Clinical Significance Research Articles

The clinical significance of elastic lamina invasion in patients with pStage II colorectal cancer: a notable prognostic indicator

BackgroundSome colorectal cancers (CRCs) are clinically diagnosed as cT4a with serosal invasion (SI). However, the cT4a is most often underdiagnosed pathologically as pT3 without SI by hematoxylin–eosin (H&E) staining alone. Using Elastica van Gieson (EVG) staining, some pT3 tumors invade the elastic lamina (EL), which extends just below the serosal layer. Recently, EL invasion (ELI) has been described as a poor prognostic factor for disease-free survival (DFS) and overall survival (OS) in patients with pStage II CRC. However, its clinicopathological significance remains unclear due to the limited number of studies and poor understanding of ELI.ObjectiveThis study investigated the association between the ELI and patient prognosis.MethodsAfter 1982, pathological diagnosis was routinely performed using H&E and EVG staining methods, and long-term follow up was performed until 2016. All clinicopathological features including ELI were prospectively registered into our computer and 569 patients with pStage II CRC were collected from the database. Based on the ELI status, pT3 was divided into three pathological categories: pT3ELI − was defined as pT3a, pT3ELI + as pT3b and unidentified EL (pT3EL −) as pT3u.ResultsUsing H&E staining alone, gross cT4a was most often pathologically underdiagnosed as pT3 (93.8%) and very rarely as pT4a, resulting in a large diagnostic discrepancy. Using EVG staining, 60.7% of the cT4a tumors were diagnosed as pT3b. The 10-year DFS and OS rates were similar for pT3a and pT3u patients. However, the 10-year DFS and OS rates of pT3b patients were significantly lower than those of pT3a patients (75.6% vs. 95.6%, p < 0.0001 and 58.4% vs. 70.6%, p = 0.0024, respectively) but did not differ from those of pT4a patients (70.6%, p = 0.5799 and 52.0%, p = 0.1116, respectively). Multivariate analysis revealed that the ELI was the strongest independent risk factor for recurrence and CRC-specific death (p < 0.0001).ConclusionsA better understanding of the ELI allows us to reconsider the diagnostic discrepancy of serosal invasion, i.e., pT3b should be considered pT4a. The ELI-based subclassification of pT3 is expected to be incorporated into the TNM staging system in the future. The ELI is a notable prognostic indicator in patients with pStage II CRC.

Comparison of Early Postoperative Outcomes of Omentopexy and Clips along the Staple Line During Laparoscopic Sleeve Gastrectomy: A Randomized Study.

We aimed to compare the omentopexy and clipping reinforcement methods performed along the staple line during laparoscopic sleeve gastrectomy (LSG) in terms of the effectiveness on postoperative bleeding. In this prospective randomized controlled study, patients were divided into two groups: clips group (CG) and omentopexy group (OG). The groups were compared in terms of postoperative bleeding, duration of surgery, length of hospital stay, hospital readmissions in the postoperative first 30-days. A total of 148 patients were included in the study. Postoperative bleeding was observed in 11 patients (14.9%) of CG and 2 patients (2.7%) of the OG, and the difference between the groups was found to be significant (p = 0.009). Similarly, the number of patients with bleeding that did not require intervention was 9 (12.2%) in CG and 2 (2.7%) in OG, and the difference between the groups was also significant (p = 0.028). The duration of surgery in the CG was 30 (27 to 36) minutes, whereas in the OG, it was 43 (39 to 45) minutes, with a significant difference noted (p < 0.001). Additionally, the rate of patients readmitted to the hospital within the first 30days was 16 (21.6%) in the CG and 7 (9.5%) in the OG, with a significant difference observed (p = 0.041). In terms of bleeding requiring intervention, there was no difference between omentopexy and clipping techniques. In addition, omentopexy showed more satisfactory results than clipping in terms of non-interventional bleeding, but its clinical significance is unclear.

Targeting the IL-5 pathway in eosinophilic asthma: A comparison of anti-IL-5 versus anti-IL-5 receptor agents.

Eosinophilic asthma is characterized by frequent exacerbations, poor symptom control and accelerated lung function decline. It is now recognized that the immune response underlying eosinophilic asthma involves a complex network of interconnected pathways from both the adaptive and innate immune systems. Within this response, interleukin-5 (IL-5) plays a central role in eosinophil differentiation, activation and survival and has emerged as a key target for therapies treating severe asthma. The monoclonal antibodies mepolizumab and reslizumab target the ligand IL-5, preventing its interaction with eosinophils; in contrast, benralizumab binds to the IL-5 receptor (IL-5R), preventing IL-5 from binding and leading to substantially greater eosinophil reduction by enhanced antibody-dependent cell-mediated cytotoxicity. Although no direct head-to-head clinical trials of asthma have been published to formally evaluate the clinical significance of these different therapeutic approaches, the potential benefits of partial versus complete eosinophil depletion continue to remain an important area of study and debate. Here, we review the existing real-world and clinical study data of anti-IL-5/anti-IL-5R therapies in severe eosinophilic asthma.

FTO/m6A mediates miR-138-5p maturation and regulates gefitinib resistance of lung adenocarcinoma cells by miR-138-5p/LCN2 axis

BackgroundLung cancer (LC) occupies an important position in the lethality of cancer patients. Acquired resistance to gefitinib in lung adenocarcinoma (LUAD) seriously affects the therapeutic efficacy of LC. Thus, it is of major scientific and clinical significance to probe the mechanism of gefitinib resistance in LUAD for ameliorating the prognosis of patients.MethodsThe expression of miRNAs in gefitinib-resistant LUAD cells was validated using qRT-PCR. Cell viability was assessed through CCK-8, whereas cell death was examined through PI staining. Changes in the ferroptosis process were evaluated by detecting the intracellular Glutathione (GSH), Malondialdehyde (MDA), and Reactive Oxygen Species (ROS) levels. Downstream targets of miR-138-5p were verified via luciferase reporter and RNA pull-down assays. RIP and qRT-PCR were employed to evaluate pri-miR-138-5p binding to DiGeorge critical region 8 (DGCR8) and the pri-miR-138-5p m6A modification level. Additionally, the impact of fat mass and obesity-associated protein (FTO) on LUAD gefitinib sensitivity was assessed in vivo by constructing a xenograft model.ResultsWe observed that miR-138-5p was notably diminished in gefitinib-resistant cells. Overexpression of miR-138-5p suppressed viability while facilitated cell death and intracellular ferroptosis in gefitinib-resistant cells. Moreover, lipocalin 2 (LCN2) was the downstream target of miR-138-5p. The biological functions of miR-138-5p on gefitinib-resistant cells was reversed by introduction of LCN2. FTO suppressed the binding of DGCR8 to pri-miR-138-5p through m6A modification, thereby restraining the processing of miR-138-5p. Meanwhile, silencing of FTO enhanced the sensitivity of LUAD to gefitinib treatment.ConclusionFTO suppressed the processing of miR-138-5p and then modulated the proliferation, death, and ferroptosis of gefitinib-resistant cells through the miR-138-5p/LCN2 pathway, which may put forward novel insights for clinically ameliorating the therapeutic effect of gefitinib in LUAD.

Morphological Variability of the Sural Nerve and Its Clinical Significance

The sural nerve provides sensory innervation to the skin on the distal posterolateral third of the lower extremity. The morphological variants are characterized by high variability. However, it most commonly arises from a union of the medial sural cutaneous nerve and the peroneal communicating branch of the common fibular nerve. This article overviews the anatomical and clinical significance of the sural nerve. Despite the remarkable development of genetic diagnostics, sural nerve biopsy is still a very important tool to diagnose peripheral neuropathies such as diabetic, vascular and inflammatory neuropathies. Furthermore, the sural nerve is also commonly transplanted due to its characteristics. Such a procedure is applicable in cases of segmental nerve loss, but it is also used to restore potency in patients after radical prostatectomy. The knowledge of anatomical variants of the sural nerve is also crucial as it allows to minimize its damage during surgical procedures. Furthermore, during an ankle surgery, a nerve block can be used to complement anesthesia. The major aim of this work is to review contributions of the sural nerve to physiological and pathophysiological processes.

Prognostic significance of the modified Glasgow Prognostic Score in NSCLC patients undergoing immune checkpoint inhibitor therapy: a meta-analysis

BackgroundThe modified Glasgow Prognosis Score (mGPS), which considers both inflammatory response and nutritional status, has been linked to the prognosis of various tumors. The relationship between mGPS and non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) is still a subject of debate. This meta-analysis aims to comprehensively assess the association between mGPS and survival in NSCLC treated with ICIs.MethodsA thorough review of studies from PubMed, Web of Science, Scopus, and Embase was conducted up to June 4, 2024. Fixed-effect or random-effect models were employed, combining hazard ratios (HRs) and 95% confidence intervals (CI), to assess the prognostic value of mGPS for OS and PFS in patients with NSCLC receiving immunotherapy.ResultsA total of 1,022 patients from 11 studies were recruited. Combined results showed that mGPS elevation was significantly associated with poor OS (HR = 1.63, 95%CI: 1.42-1.87, P &amp;lt; 0.01) and PFS (HR = 1.71, 95%CI: 1.31-2.24, P &amp;lt; 0.01). Subgroup analysis and sensitivity analysis further determined the predictive effect of elevated mGPS on OS and PFS deterioration in NSCLC patients receiving immunotherapy.ConclusionmGPS can be used as a good noninvasive biomarker to demonstrate prognostic and clinical significance in patients with NSCLC undergoing immunotherapy.Systematic review registrationhttp://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023432661.

Ocular Movement Examination in Peripheral Vestibular Disorders as a Tool to Improve Diagnosis: A Literature Review

Background and Objectives: This study reviews the current literature on ocular movements, specifically focusing on nystagmus associated with peripheral vestibular disorders, to enhance diagnostic accuracy. The evaluation of ocular movements, particularly nystagmus, provides essential insights into the function and dysfunction of the vestibular system, helping clinicians distinguish between peripheral and central causes of vertigo and imbalance. Materials and Methods: A comprehensive search of PubMed was conducted using key terms such as “ocular movements”, “nystagmus”, “vestibular nystagmus”, and “peripheral vestibular disorders”. Results: The search yielded 2739 titles, and after a rigorous selection process, 52 articles were reviewed in full. Discussion: The review highlights different classifications and types of nystagmus, including physiological and pathological forms, and their diagnostic relevance in vestibular disorders such as benign paroxysmal positional vertigo (BPPV), vestibular neuritis, and Meniere’s disease. Diagnostic techniques like video/electro-oculography are emphasized for their role in assessing vestibular function and identifying abnormalities. The study underscores the importance of detailed ocular examination in the diagnosis of peripheral vestibular disorders and proposes an algorithm to aid this process. Conclusions: While not a systematic review, this study highlights the importance of detailed ocular examination in diagnosing peripheral vestibular disorders and presents an algorithm to facilitate this process. It also emphasizes the need for continued research and advancements in vestibular medicine to further understand ocular movements and their clinical significance, ultimately contributing to improved patient outcomes.

Diaphragmatic Palsy Due to a Paraneoplastic Autoimmune Syndrome Revealed by Checkpoint Inhibitors

Background and Clinical Significance: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but may underlie diverse and potentially life-threatening immune-related adverse events (irAEs). They may cause various conditions leading to respiratory failure, including myasthenic syndromes and myositis. However, diaphragmatic paralysis (DP) has rarely been reported. To describe patients with diaphragmatic paralysis in a pharmacovigilance registry, we searched the prospective REISAMIC registry at the Gustave Roussy Cancer Center (Villejuif, France) for cases of diaphragmatic palsy (DP) occurring from September 2014 to December 2021. Case Presentation: We identified three patients, in whom DP was confirmed by diaphragmatic ultrasonography, pulmonary function tests, and/or diaphragmatic electroneuromyogram. Diaphragmatic palsy was life-threatening in all patients, as it caused respiratory failure requiring mechanical ventilation. In all cases, a pre-existing subclinical paraneoplastic syndrome was detected. Onconeural antibodies (anti-titin and anti-VGCC) were detected in these patients before and after the initiation of ICI therapy, suggesting a mixed paraneoplastic syndrome with features overlapping those of myasthenic syndrome (myasthenia gravis in one patient and Lambert–Eaton syndrome in another) and myositis. Conclusions: Diaphragmatic palsy is a severe irAE potentially resulting from different mechanisms, including myositis and neuromuscular junction involvement (myasthenia gravis, Lambert–Eaton). Antineuronal antibodies associated with such conditions were already present in our patients prior to immunotherapy initiation, suggesting ICIs could trigger flare-ups of pre-existing silent paraneoplastic autoimmune conditions.

Ultrathin crystalline silicon-based omnidirectional strain gauges for implantable/wearable characterization of soft tissue biomechanics.

Monitoring soft-tissue biomechanics is of interest in biomedical research and clinical treatment of diseases. An important focus is biointegrated strain gauges that track time-dependent mechanics of targeted tissues with deforming surfaces over multidirections. Existing methods provide limited gauge factors, tailored for sensing within specific directions under quasi-static conditions. We present development and applicability of implantable/wearable strain gauges that integrate multiple ultrathin monocrystalline silicon-based sensors aligned with different directions, in stretchable formats for dynamically monitoring direction angle-sensitive strain. We experimentally and computationally establish operational principles, with theoretical systems that enable determination of intensities and direction of applied strains at an omnidirectional scale. Wearable evaluations range from cardiac pulse to intraocular pressure monitoring of eyeballs. The device can evaluate cardiac disorders of myocardial infarction and hypoxia of living rats and locate the pathological orientation associated with infarction, in designs with possibilities as biodegradable implants for stable operation. These findings create clinical significance of the devices for monitoring complex dynamic biomechanics.

Frequency of Major Transmitted Integrase Resistance in Poland Remains Low Despite Change in Subtype Variability

With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend (p &lt; 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation.

Exome sequencing for nonimmune hydrops fetalis and clinical utility of data reanalysis.

Nonimmune hydrops fetalis (NIHF) presents as life-threatening fluid collections in multiple fetal compartments and may be led by numerous etiologies. To establish the diagnostic yield of exome sequencing for single-gene disorders in unexplained NIHF and to evaluate the clinical utility of data reanalysis. A series of 53 unexplained cases of NIHF were enrolled, including 39 cases met a strict definition of NIHF, and 14 cases with increased nuchal translucency (NT) and/or cystic hygroma in combination with other fluid collections. Trio ES from fetal samples and parental blood was performed, and clinical reports were returned by geneticists and genetic counselors. Multidisciplinary team forums were conducted for accurate diagnoses and improved patient management. The clinical follow-up assessments were conducted, and the reanalysis was performed for cases with a non-positive result. Diagnostic variants were identified in 22.6% (12/53) of the cases, and variants of potential clinical significance were detected in an additional 13.2% (7/53) of the cases. Of them, 3 possible diagnoses (3/41, 7.3%) were obtained during reanalysis. Notably, half of the diagnosed cases were from the group exhibiting only skin edema and increased nuchal translucency and/or cystic hygroma. The diagnostic rate in this group was 42.8% (6/14), while in the classically defined NIHF group, the rate was 15.4% (6/39). The pregnancy termination and live birth rates of the cases with positive genetic testing results were found to be statistically significantly different from those with negative results (91.7% vs 53.6% and 8.3% vs 36.6%, P < 0.05 for both). ES provides high incremental diagnostic yield for NIHF after standard-of-care testing, and reevaluating non-diagnostic exomes in light of updated knowledge can maximize diagnostic yield. Identifying the etiology of NIHF facilitates prenatal diagnosis, improves the management of NIHF cases, and predicts recurrence risk in future pregnancies.

Tuina versus physiotherapy or a combination of both for the management of chronic nonspecific low back pain: A randomized controlled trial

To rigorously evaluate the short-term and long-term effectiveness of Tuina (TN), alone and in combination with physiotherapy (PT), for Chronic nonspecific low back pain (CNLBP) through a comprehensive, high-quality clinical trial. This randomized, single-blind trial was conducted from September 2020 to July 2023, involving 204 CNLBP patients from the First Affiliated Hospital of Jinan University. Participants underwent a baseline assessment, 6 treatment sessions over 8 weeks, a post-treatment evaluation in the 9th week, and a 20-week follow-up. Participants were randomly assigned to TN, PT, or a combination of TN and PT (TP) groups. Each treatment involved 6 sessions with a minimum 7-day interval, each lasting 30minutes. Primary outcome was the change in Visual Analog Scale (VAS) for pain. Secondary outcomes included the Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), Range of Motion (ROM) of the spine, Traditional Chinese Medicine Syndrome Scale (TCMSS), and adverse events (AE). Among the 204 participants, 67.16% were female, and 88.73% completed the 20-week follow-up. All groups showed significant reductions in VAS scores post-treatment and at follow-up. Secondary outcomes improved significantly, with notable decreases in ODI and TCMSS scores. Pairwise comparisons within groups indicated statistical significance, particularly in ODI scores, with clinical relevance. No significant differences were found between the groups. ROM and SF-36 showed statistical but not clinical significance. Only one AE (0.49%) was reported, with no severe incidents. All treatment groups, including TN, TP, and PT, demonstrated significant reductions in VAS scores for CNLBP patients, with effects lasting up to 20 weeks. While TN and TP showed substantial improvements in secondary outcomes, particularly in ODI scores, no significant differences were found between the groups. These findings suggest that all treatments can be effective for managing CNLBP, supporting clinical practitioners in selecting appropriate interventions for patients, especially for those unable to engage in active exercises, utilizing passive movements like TN to enhance health outcomes.

Effect of moderate-intensity aquatic treadmill exercise on cognitive function and cerebral blood flow for healthy older adults

To compare the effect of moderate-intensity aquatic treadmill exercise (ATM) on cerebral blood flow (CBF) and cognitive function in healthy older adults to that of moderate-intensity land-based treadmill exercise (LTM). This randomized controlled trial study was conducted between May 2023 and Oct 2023. Twenty-eight participants aged 60–80 were randomly assigned to either ATM group (N = 14) or LTM group (N = 14). Cognitive function and cerebral blood flow were assessed before and after the exercise. The outcome measures used in this study were the Digit Symbol Substitution Test (DSST) and the Digit Span Test (DST) to assess cognitive performance, and the mean middle cerebral artery blood velocity (MCAvmean) to evaluate CBF. A mixed effects model was used to analyze the within-group and between-group differences in cognitive function and CBF outcomes pre-to-post treadmill by SPSS. The DSST demonstrated a statistically significant improvement within both the ATM [β ± SE: −13.643 ± 2.407, 95 % CI: −18.749, −8.537] and LTM [β ± SE: −19.25 ± 3.66, 95 % CI: −26.424, −12.076] groups, indicating clinical significance in both groups. Both ATM and LTM groups exhibited post-exercise improvements within their respective groups for forward Digit Span Test (FDST) [ATM β ± SE: −0.143 ± 0.362, 95 % CI: −0.92, 0.634; LTM β ± SE: −0.286 ± 0.37, 95 % CI: −1.078, 0.506] and backward Digit Span Test (BDST) (ATM β ± SE: −1.741 ± 5.377, 95 % CI: −13.27, 9.792; LTM β ± SE: −6.729 ± 5.370, 95 % CI: −4.788, 18.24). In terms of MCAvmean, there is a higher improvement of CBF in ATM group [β ± SE: −138.669 ± 67.9217, 95 % CI: −288.164, 10.826] than LTM group [β ± SE: −9.305 ± 70.076, 95 % CI: −153.617, 135.007]. Hence, a single bout of moderate-intensity ATM and LTM can enhance cognitive function and CBF in healthy older adults, suggesting their potential as preventive strategies against age-related declines.

Clinical significance of analysis of long non-coding RNA PSMB8-AS1, MBNL1-AS1, and OLMALINC expression by polymerase chain reaction in non-small cell lung cancer

Rationale: Long non-coding RNAs (lncRNAs) influence tumor cell properties during the onset and progression of lung malignancies; however, their diagnostic and prognostic significance has not been determined. We have previously shown that when non-small cell lung cancer (NSCLC) cells acquire a more malignant phenotype (under the influence of macrophagal cytotoxic activity) compared to the original cell lines, the expression of several lncRNAs, in particular PSMB8-AS1, MBNL1-AS1, and OLMALINC, is altered compared to the original cell lines. Aim: A comparative analysis of lncRNAs PSMB8-AS1, MBNL1-AS1, and OLMALINC expression in tissue samples from lung tumors and conditionally normal areas of the lungs and an assessment of the lncRNAs clinical significance. Methods: We have analyzed surgical samples of the tumor and conditionally normal tissue from 16 patients with a verified diagnosis of NSCLC. The expression level of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was assessed by real-time polymerase chain reaction. To analyze the long-term treatment results and clinical significance of the studied genes, the patients were divided into two comparison groups depending on the relative level of lncRNAs expression (above or below the median). Results: The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC in the lung tumor tissue was significantly reduced compared to the conditionally normal tissues (p = 0.0034; p = 0.002 and p = 0.0172, respectively). Analysis of the association between the expression of these lncRNAs with clinical and morphological characteristics, such as disease stage, tumor size, presence of regional and distant metastases was unable to identify any regular patterns. The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was not a significant prognostic factor (p = 0.364; p = 0.759 and p = 0.184, respectively). However in the case of high OLMALINC and PSMB8-AS1 expression, median survival was 47 months, while in the case of their low expression, median survival was not achieved during the follow-up. The expression of lncRNA PSMB8-AS1 in NSCLC tumors positively correlated with the expression of lncRNA OLMALINC (r = 0.680, p = 0.007), which may indicate their functional interplay or the presence of common regulatory mechanisms. Conclusion: The NSCLC tumors demonstrated aberrant expression of PSMB8-AS1, MBNL1-AS1, and OLMALINC lncRNAs. A more detailed study of their expression in various cell types and their regulatory role would allow for validation of new therapeutic targets in NSCLC, as well as for development of alternative therapies.

Mode of delivery and behavioral and neuropsychological outcomes in children at 10 years of age.

Previous studies have reported that mode of delivery, particularly cesarean delivery (CD), is associated with neurodevelopmental outcomes in children. This study evaluates behavioral and neuropsychological test scores in children based on mode of delivery. Children enrolled in the Raine Study from Western Australia, born between 1989 and 1992 by instrumental vaginal delivery (IVD), elective CD, and non-elective CD, were compared to those with spontaneous vaginal delivery (SVD). The primary outcome was the Child Behavior Checklist (CBCL) administered at age 10. Secondary outcomes included evaluations of language, motor function, cognition, and autistic traits. Multivariable linear regression was used to evaluate score differences by mode of delivery adjusted for sociodemographic and clinical characteristics, and Poisson regression was used to evaluate for increased risk of clinical deficit. Of 2,855 children, 1770 (62.0 %) were delivered via SVD, 480 (16.8 %) via IVD, 346 (12.1 %) via elective CD, and 259 (9.1 %) via non-elective CD. Non-elective CD was associated with higher (worse) CBCL Internalizing (+2.09; 95 % CI 0.49, 3.96; p=0.01) scores, and elective CD was associated with lower (worse) McCarron Assessment of Neuromuscular Development (MAND) (-3.48; 95 % CI-5.61,-1.35; p=0.001) scores. Differences were not seen in other outcomes, and increased risk of clinical deficit was not observed with either the CBCL Internalizing or MAND scores. Differences in behavior and motor function were observed in children delivered by CD, but given that score differences were not associated with increased incidence of clinical deficit, clinical significance may be limited.

Serum Derivatives–Reactive Oxygen Metabolite Levels as a Marker of Clinical Conditions in Patients with Bronchial Asthma, COPD, or Asthma–COPD Overlap: A Prospective Study

Background: Oxidative stress plays an important role in the pathophysiology of bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO), but its relevance has not been fully elucidated. The aim of this study was to measure the levels of oxidative stress and investigate its clinical significance in patients with BA, COPD, or ACO. Methods: We recruited 214 patients between June 2020 and May 2023 (109 patients with BA, 63 with COPD, and 42 with ACO). To assess clinical conditions, we evaluated patient characteristics, results of respiratory function tests and blood tests, and administered several questionnaires. We evaluated oxidative stress using the test for derivatives–reactive oxygen metabolites (d–ROMs) in serum. Results: The d–ROMs levels were significantly higher in patients with COPD or ACO than in patients with BA. There was no difference in serum d–ROMs levels between the COPD and ACO groups. In BA, d–ROMs levels were positively correlated with interleukin (IL)-6, IL-8, serum amyloid A (SAA), and C-reactive protein (CRP) levels; white blood cell (WBC) and neutrophil counts; and St. George’s Respiratory Questionnaire (SGRQ) scores, and they were negatively correlated with forced expiratory volume in 1 s (%FEV1) and asthma control test (ACT) score. In COPD, d–ROMs levels were positively correlated with IL-6, SAA, and CRP levels; WBC, neutrophil, and eosinophil counts; and COPD assessment test (CAT) and SGRQ scores, and they were negatively correlated with forced vital capacity (%FVC), %FEV1, and %FEV1/FVC scores. In ACO, d–ROMs levels were positively correlated with IL-6, SAA, tumor necrosis factor alpha (TNF-α), and CRP levels; and CAT and SGRQ scores, and they were negatively correlated with %FVC and %FEV1 scores. Conclusions: Serum d–ROMs levels may serve as a marker reflecting clinical conditions such as systemic inflammation, symptom severity, and airflow limitation in patients with BA, COPD, and ACO.

CapeOX as neoadjuvant chemotherapy for locally advanced rectal cancer: might less be more?

BackgroundLocally advanced rectal cancer (LARC) poses unique challenges in treatment, with current neoadjuvant chemoradiotherapy (NA-CRT) showing limitations. The CapeOX regimen emerges as a potential less aggressive neoadjuvant chemotherapy (NAC) for LARC.MethodsWe conducted a retrospective study involving treatment-naïve patients with LARC from March 2014 to March 2021 who received 2–4 cycles of CapeOX NAC followed by radical surgery. Treatment response was evaluated using tumor regression grade (TRG), MRI-based TRG (MRI-TRG), and Neoadjuvant Rectal (NAR) score.Results94.7% of patients experienced symptom improvement and 96.4% achieved sphincter-preserving surgery. Post-NAC showed significant tumor regression and MRI confirmed a tumor length reduction (P < 0.001). Clinical and pathological staging discrepancies post-NAC suggest broader therapeutic advantages. 5-year overall and disease-free survival rates were 78.4% and 73.4%. NAR scores provided better prognostic accuracy than MRI-TRG.ConclusionCapeOX NAC presents notable benefits for LARC patients and its clinical significance may be underestimated. The NAR score demonstrates superior prognostic value over MRI-TRG.

Causes and Diagnostic Significance of Coughing in Dogs with Endocardiosis

Introduction. Endocardiosis is the most widespread acquired cardiac disease in small dog breeds, characterised by the valvular degeneration leading to mitral insufficiency. Progression of mitral regurgitation leads to cardiac remodeling, increased left ventricular filling pressures, pulmonary hypertension and, eventually, myocardial dysfunction. Decreased exercise tolerance, dyspnea, anorexia, and coughing are the most often reported signs in dogs with endocardiosis. Coughing is often reported as the primary clinical sign of congestive heart failure in dogs with endocardiosis. The concomitant respiratory tract disease and compression of the left mainstem bronchus by the giant left atrium have also been suggested as the potential causes of coughing in these patients. However, the absence of relief from cough in dogs with endocardiosis when treated with calcium sensitizers and the registered improvement in systolic cardiac function makes doubtful the cardiogenic nature of coughing in endocardiosis. In other words, the clinical and diagnostic significance of coughing in dogs with endocardiosis has not been sufficiently studied. The aim of the present research is to determine the frequency of cough incidence in dogs with endocardiosis and to establish the pathognomonic nature of this symptom in endocardiosis, its clinical significance.Materials and Methods. The medical records of 49 dogs that have attended to the veterinary clinics of the “Vita” network (Rostov region) for cardiological examination in the period from September 1, 2021 to July 31, 2024 were analysed. The research was carried out using the following equipment: premium ultrasound scanner with improved image quality on the ZST+ Mindray Vetus 9 platform, Maxivet 400 veterinary X-ray digital DR system, and Poli-Spectrum–8/V computerassisted electrocardiograph.Results. The research allowed us to find out the following: although the cardiomegaly and the increase in the size of the left ventricle in endocardiosis can aggravate and intensify the clinical manifestation of coughing in dogs with degenerative diseases of the upper respiratory tract, they are not the necessary condition for the occurrence of coughing. Coughing in dogs with endocardiosis should be considered as a clinical sign of the concomitant inflammatory or degenerative disease of the upper respiratory tract, which should be taken into account in therapy and in the attempt to improve the quality of life of these animals.Discussion and Conclusion. We have found that only 57% of the dogs with clinically evident endocardiosis suffer from coughing, whereas it does not have the uniform nature. In dogs with cardiogenic pulmonary edema, a cough is not loud, is usually acute and is associated with the flow of fluid into the medium and large-sized bronchi. The chronic loud, hoarse cough, intensifying in the morning, is typical for dogs with endocardiosis and chronic bronchitis: these animals at the same time have the non-specific inflammatory lesion of the bronchial tree and lesion of the mitral valves. Most severe coughing, with the characteristic loud sound, is observed in dogs suffering from the elements of the upper respiratory tract collapse and cardiomegaly due to endocardiosis.

Risk and protective factors of late in-the-bag intraocular lens dislocations – a systematic review

Topic: This article aimed to identify and review published articles addressing risk and protective factors of late in-the-bag (ITB) intraocular lens (IOL) dislocations. Clinical relevance: Prevention of this complication is of great importance considering the great number of cataract cases and its vision threatening capacity. Methods: A structured search on PubMed (MEDLINE) using both Medical Subject Headings (MeSH) and key words was conducted. Additionally, the reference lists of the resulting articles were screened for further publications. Articles were eligible if they included 20 or more patients. Hazard and odds ratios were analyzed if they were calculated in the original study. The relative frequency of risk factors was recorded if hazard or odds ratios were not available. The threshold for clinical significance was set at 10%. Risk-of-bias in individual studies was evaluated using the revised Cochrane risk-of-bias tool in randomized trials (RoB 2.0) and the Cochrane risk-of-bias in non-randomized studies of interventions tool. Results: Database search identified 3474 records and no further records were obtained from the reference lists. After exclusion of records not related to the topic, 177 articles were assessed for eligibility. Of these, 39 were considered eligible and read in full. Three studies were prospective, while all other investigations were retrospective. In total, 18 614 cases of late ITB dislocations were analyzed across all studies. The risk of bias within studies was considerable, as only three studies were prospective and statistical significance of risk factors was assessed in only five studies. Conclusions: Typical patient age of this condition is between 70 and 85 years and there appears to be a slight male predominance. Risk factors with a good level of evidence include preoperative trauma and zonular dehiscence, previous vitrectomy, retinitis pigmentosa, pseudoexfoliation, high myopia, glaucoma/previous glaucoma surgery, corneal endothelial damage, and uveitis. Hydrophilic, quadripode and haptic-angulation IOLs are further risk factors. Capsular tension rings, Nd:YAG capsulotomy, three-piece IOLs and IOLs with large optic diameters protect from ITB dislocations. Typically, no risk factors can be identified in approximately one-fourth of patients.

Exploring the significance and potential mechanisms of hippo pathway-associated genes in prognosis of glioma patients

PurposeDespite the efforts of countless researchers to develop glioma treatment strategies, the current therapeutic effect of glioma is still not ideal, and it is necessary to further explore the mechanism to guide treatment. Thus, this study aims to introduce a novel approach for predicting patient prognosis and guiding further treatment interventions.MethodsInitially, we conducted a differential gene expression analysis to identify Hippo pathway-associated genes overexpressed in tumors and determined genes correlated with prognosis. Subsequently, employing cluster analysis, we categorized samples into two groups and performed further analyses including prediction, immune cell infiltration abundance, and drug response rates. We utilized weighted gene co-expression analysis to reveal gene sets with high co-variation, delineate inter-sample gene correlation patterns, and conduct enrichment analysis. Prognostic models were built using ten machine learning algorithms combined in 101 different combinations, followed by evaluation and validation. Immune infiltration analysis, differential expression analysis of depleted T cell-related markers, drug sensitivity analysis, and exploration of pathway dysregulation were performed for different risk groups. Quality control and batch integration were performed, and single-cell data were analyzed using dimensionality reduction clustering algorithms and annotation tools to evaluate the activity of the prognostic model in malignant cells.ResultsWe conducted data filtering to identify genes overexpressed in tumors, intersecting these genes with Hippo pathway-related genes, identifying 62 genes correlated with prognosis, and performing cluster analysis to divide tumor tissues into two groups. Cluster 2 exhibited a poorer prognosis and demonstrated differences in immune cell infiltration. Utilizing weighted gene co-expression analysis on Cluster 2, we identified gene modules, conducted functional enrichment analysis, and delineated pathways. Employing a combined model based on ten machine learning algorithm combinations, we selected the optimal prognostic model system and validated the model’s predictive ability within the dataset. Through immune-related analysis and drug sensitivity analysis, we uncovered differences in immune infiltration and varying sensitivities to chemotherapy drugs. Additionally, the enrichment analysis of gene set revealed discrepancies in upregulation within relevant pathways between the high and low-risk groups. Finally, annotation and evaluation of malignant cells via single-cell analysis showed increased activity of the prognostic model and variations in distribution across different prognostic levels in malignant cells.ConclusionThis study introduces a novel approach utilizing the Hippo pathway and associated genes for glioma prognosis research, demonstrating the potential and significance of this method in evaluating the outcome for patients with glioma. These findings hold substantial clinical significance in guiding therapy and predicting outcomes for individuals diagnosed with glioma, offering significant clinical utility.