Clinical Significance In Patients Research Articles

Clinical impact of a dose-escalation strategy for lenvatinib in differentiated thyroid cancer.

Treatment options for patients with differentiated thyroid cancer (DTC) who experience disease progression on lenvatinib treatment are limited. Although dose escalation of treatment with tyrosine kinase inhibitors at disease progression has been reported across cancer types, clinical significance in patients with DTC has not been investigated. We retrospectively reviewed patients with DTC who experienced disease progression on lenvatinib treatment from September 2011 to June 2022. We compared subjects who received dose-escalation treatment with standard treatment of termination at the time of initial disease progression. The escalated dose was decided by referencing to the previous effective and tolerated dose. Thirty-three patients were identified, 15 with dose escalation and 18 with lenvatinib termination. In both groups, the starting dose of lenvatinib was 24mg/day, and the median dose at initial disease progression was 10mg/day. In the former, the median dose escalation was 6mg/day (range: 4-12). Objective response rate, clinical benefit rate by escalation, and median treatment duration of the dose-escalation phase were 13.3%, 73.3%, and 9.9months (95% confidence interval [CI] 5.71-27.6), respectively. Median overall survival from initial disease progression was significantly longer in the dose-escalation group (median OS: 20.4months [95% CI 7.0-NA] vs. 3.9months [95% CI 1.7-7.9], log-rank p-value; 0.0004, hazard ratio; 0.22 [95% CI 0.09-0.55]). There were no grade 5 adverse events, and one patient discontinued due to a grade 3 lung abscess. The dose-escalation strategy appears to be a safe and effective treatment option after disease progression in patients treated with lenvatinib for DTC.

Radiographic abnormalities and their clinical significance in patients with Parkinson disease who receive deep brain stimulation implants.

Preoperative MR images obtained in patients with Parkinson disease (PD) undergoing deep brain stimulation (DBS) often reveal incidental radiographic abnormalities (RAs). These findings range from small changes to gross pathologies. The effect of these findings on patients' clinical outcomes is unknown. The authors characterized RAs in patients with PD who underwent DBS and assessed clinical outcomes. Records of patients at the authors' institution with PD who underwent MRI for DBS electrode implantation from 2010 through 2022 were reviewed. RAs were identified from the official preoperative MRI reports. RAs were grouped into four general categories (ischemic changes, atrophy or degenerative changes [ADCs], structural abnormalities, and tumors) and correlated with clinical outcomes (including subjective clinical response, levodopa equivalent dose [LED], and Unified Parkinson's Disease Rating Scale Part III [UPDRS] score) at the 1-year and last available follow-ups. In this review, 160 patients were identified for initial analysis, with 135 presenting with ≥ 1 RAs. Of these 135 patients, 69.4% (111/160) had ischemic vascular changes, 39.4% (63/160) had ADCs, 16.9% (27/160) had structural changes, and 1.9% (3/160) had tumors. No differences in preoperative LED or UPDRS score were observed between these groups. After DBS, no differences in outcomes were observed between patients with RAs and those without RAs for both the 1-year and last follow-up time points, including mortality rates and times. Structural lesions were associated with lower mortality rates (OR 0.1, p = 0.04). ADCs were associated with a worse subjective clinical response at the 1-year (OR 0.50, p = 0.04) and last (OR 0.49, p = 0.03) follow-ups, but subjectively worse responses were not correlated with worse objective outcome measures. Most RAs have no significant effect on clinical outcomes in PD patients undergoing DBS. Generalized ADCs may be associated with poorer subjective responses and may warrant further discussion with the patient if diagnosed on preoperative MRI.

#2643 CD4+ T cells are associated with mortality in males with type 2 cardiorenal syndrome independently of the Seattle Heart Failure Model score

Abstract Background and Aims Immune system dysregulation appears to contribute to the pathogenesis and prognosis of the reciprocal dysfunction that occurs in cardiorenal syndrome (CRS). However, there is little evidence available regarding the potential alterations of the cellular components of the immune system and their clinical significance in patients with CRS. The Seattle Heart Failure Model (SHFM) is a well-established, multivariable risk model for predicting survival in heart failure (HF) patients, including lymphocytes but not indices of kidney function among its variables. The aim of our prospective study was to examine the incremental value of a selected panel of immune cell subsets on the mortality risk prediction of the SHFM in a cohort of type 2 CRS patients. Method 36 stable male patients with CRS type II were included in the final analysis of our prospective study. Exclusion criteria included history of malignancy, autoimmunity and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16+ and CD14+CD16++ absolute values and percentages out of total monocytes and NK cells (CD3+CD16+56+), CD3-CD19+ B lymphocytes, CD3+ CD4+ T cells, CD3+CD8+ T cells and T regulatory cells (Tregs) (CD4+CD25+FoxP3+) absolute values and percentages out of total lymphocytes were measured by flow cytometry. The Seattle Heart Failure Model (SHFM) score was derived from the online updated calculator https://depts.washington.edu/shfm. After baseline evaluation, patients were followed until the end of the established observation period, progression to end-stage kidney disease (ESKD) or until the study endpoint was reached, which was defined as a combined outcome of all-cause mortality and cardiovascular mortality. Logistic regression analysis was used to identify predictors of observed mortality and SHFM predicted mortality among various cell subtypes in CRS patients. Comparison of the prognostic accuracy of various models was performed using area under the curve (AUC) analysis. Results The mean age of our cohort was 73 ± 9 years with an eGFR 36.8 ± 12.9 ml/min/1.73 m2. Most patients had HF with reduced ejection fraction (52%) and described symptoms of HF indicative for NYHA class II and III (55% and 45%) respectively. During a mean follow-up of 29.8 ± 3.4 months, 21 patients (i.e. 58%) died while 5 patients (i.e. 14%) progressed to ESKD. The score for 1-year mortality derived from SHFM was significantly correlated with the observed mortality (r = 0.500, p = 0.002) but not with the occurrence of ESKD during follow-up. Total lymphocytes (r −0.516, p = 0.001), T-lymphocytes (r −0.543, p = 0.002), CD4+ T cells (r −0.518, p = 0.001), CD8+ T cells (r −0.409, p = 0.013) and T-regs (r −0.376, p = 0.024) counts were all significantly related to the mortality score derived from SHFM apart from relating to the observed mortality in our population (p < 0.05 for all relations with observed mortality). The proinflammatory, intermediate CD14++CD16+ monocytes counts were associated with the observed mortality (r 0.383, p = 0.021) but not with SHFM score derived mortality. After adjustment for the SHFM score derived mortality, only the CD4+ T cell count was significantly and independently associated with the observed mortality (OR 0.99, p = 0.045) whereas T-regs count showed a non-significant trend for an independent association with the observed mortality after adjustment (OR 0.95, p = 0.063). The addition of CD4+ T cells count, or Tregs count on SHFM improved AUC for mortality but not significantly [AUC SHFM 0.833, SHFM + CD4+ T cells 0.933 (p = 0.155 vs SHFM), SHFM + Tregs 0.933 (p = 0.145 vs SHFM)]. Conclusion In a small group of male patients with type 2 CRS, CD4+ T lymphocyte count was independently associated with mortality even after adjustment for the established mortality score derived from SHFM. However, the combination of both SHFM and CD4+ T cells count did not improve significantly the accuracy of the prediction models, probably attributed to our small sample size. Larger clinical studies are needed to validate the importance of specific lymphocyte subpopulations in the prognosis and management of patients with cardiorenal syndrome.

Prenatal Screening and Diagnosis: Time for a Paradigm Shift.

Recent advances in genetics and imaging have ushered substantial breakthroughs in screening and diagnosis for chromosomal and structural abnormalities. Thus, it is imperative that health care providers caring for pregnant individuals should reexamine established practices in prenatal screening and diagnosis. In the past, screening for chromosomal abnormalities was based almost entirely on Down syndrome. Pregnant individuals aged > 35 years were considered at "high risk" or of "advanced maternal age" based on age alone; however, the advent of tests with high sensitivity for prenatal detection of chromosomal abnormalities should lead to abandoning that concept, at least from the perspective of chromosomal abnormalities. Given that first-trimester and second-trimester screenings will fail to detect between 5 and 20% of Down syndrome, in most situations, noninvasive testing with cell-free DNA should be the first-line screen for Down syndrome. The fact that over 99% of fetuses with Down syndrome will be detected prenatally with cell-free DNA gives other fetal chromosomal and structural abnormalities increasing prominence. Chromosomal microarray analysis (CMA) permits prenatal detection of several clinically important chromosomal aberrations that cannot be detected by karyotype and may exist in structurally normal fetuses with low-risk cell-free DNA screening. As such, CMA should be more readily conducted when invasive testing is performed, regardless of the presence of a structural abnormality. Isolated sonographic "soft markers" have no clinical significance in patients who have normal cell-free DNA screening, can cause unwarranted anxiety and a negative impact on pregnancy, and perhaps it is time to stop discussing them. Detailed first-trimester ultrasound allows early detection of several severe fetal anomalies and, therefore, in settings with adequately trained personnel and resources, should be used more frequently. This opinion traces the evolution of prenatal screening and diagnosis and advocates for a paradigm shift that aligns with recent developments in prenatal screening and diagnostic capabilities. KEY POINTS: · Noninvasive prenatal testing with cell-free DNA should be available to all pregnant individuals.. · Chromosomal microarray should be available to all pregnant individuals undergoing amniocentesis.. · Patients >35 years with low-risk screening are not at "high risk" for chromosomal abnormalities..

Apoptosis Pathway-Associated Proteins Are Frequently Expressed in Melanoma: A Study of 32 Cases With Focus on Acral Lentiginous Melanoma.

Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and clinical significance in patients with ALM. Thus, we assessed protein expression of BCL2, MCL1, BIM, and BRAF V600E by immunohistochemistry in 32 melanoma samples from White and Hispanic populations, including ALM and non-ALM (NALM). BCL2, MCL1, and BIM were expressed in both ALM and NALM tumors, and no significant differences in expression of any of these proteins were detected between the groups, in our relatively small cohort. There were no significant associations between protein expression and BRAF V600E status, overall survival, or ethnicity. In summary, ALM and NALM demonstrate frequent expressions of apoptosis-related proteins BCL2, MCL1, and BIM. Our findings suggest that patients with melanoma, including ALM, may be potential candidates for apoptosis-directed therapies.

Valvulitis: un nuevo criterio ecocardiográfico para el diagnóstico de endocarditis infecciosa de bioprótesis de válvula aórtica

Introduction and objectivesDiffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. MethodsFrom 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. ResultsThe prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. ConclusionsValvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.

Identification of skewed X chromosome inactivation using exome and transcriptome sequencing in patients with suspected rare genetic disease.

X-chromosome inactivation (XCI) is an epigenetic process that occurs during early development in mammalian females by randomly silencing one of two copies of the X chromosome in each cell. The preferential inactivation of either the maternal or paternal copy of the X chromosome in a majority of cells results in a skewed or non-random pattern of X inactivation and is observed in over 25% of adult females. Identifying skewed X inactivation is of clinical significance in patients with suspected rare genetic diseases due to the possibility of biased expression of disease-causing genes present on the active X chromosome. The current clinical test for the detection of skewed XCI relies on the methylation status of the methylation-sensitive restriction enzyme (Hpall) binding site present in proximity of short tandem polymorphic repeats on the androgen receptor (AR) gene. This approach using one locus results in uninformative or inconclusive data for 10-20% of tests. Further, recent studies have shown inconsistency between methylation of the AR locus and the state of inactivation of the X chromosome. Herein, we develop a method for estimating X inactivation status, using exome and transcriptome sequencing data derived from blood in 227 female samples. We built a reference model for evaluation of XCI in 135 females from the GTEx consortium. We tested and validated the model on 11 female individuals with different types of undiagnosed rare genetic disorders who were clinically tested for X-skew using the AR gene assay and compared results to our outlier-based analysis technique. In comparison to the AR clinical test for identification of X inactivation, our method was concordant with the AR method in 9 samples, discordant in 1, and provided a measure of X inactivation in 1 sample with uninformative clinical results. We applied this method on an additional 81 females presenting to the clinic with phenotypes consistent with different hereditary disorders without a known genetic diagnosis. This study presents the use of transcriptome and exome sequencing data to provide an accurate and complete estimation of X-inactivation and skew status in a cohort of female patients with different types of suspected rare genetic disease.

The functional role of P2 purinergic receptors in the progression of gastric cancer.

Studies have confirmed that P2 purinergic receptors (P2X receptors and P2Y receptors) expressed in gastric cancer (GC) cells and GC tissues and correlates with their function. Endogenous nucleotides including ATP, ADP, UTP, and UDP, as P2 purinergic receptors activators, participate in P2 purinergic signal transduction pathway. These activated P2 purinergic receptors regulate the progression of GC mainly by mediating ion channels and intracellular signal cascades. It is worth noting that there is a difference in the expression of P2 purinergic receptors in GC, which may play different roles in the progression of GC as a tumor promoting factor or a tumor suppressor factor. Among them, P2 × 7, P2Y2 and P2Y6 receptors have certain clinical significance in patients with GC and may be used as biological molecular markers for the prediction of patients with GC. Therefore, in this paper, we discuss the functional role of nucleotide / P2 purinergic receptors signal axis in regulating the progression of GC and that these P2 purinergic receptors may be used as potential molecular targets for the prevention and treatment of GC.

Valvulitis: a new echocardiographic criterion for the diagnosis of bioprosthetic aortic valve infective endocarditis

Introduction and objectivesDiffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. MethodsFrom 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. ResultsThe prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. ConclusionsValvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.

In patients with mild disability NMOSD: is the alteration in the cortical morphological or functional network topological properties more significant.

To assess the alteration of individual brain morphological and functional network topological properties and their clinical significance in patients with neuromyelitis optica spectrum disorder (NMOSD). Eighteen patients with NMOSD and twenty-two healthy controls (HCs) were included. The clinical assessment of NMOSD patients involved evaluations of disability status, cognitive function, and fatigue impact. For each participant, brain images, including high-resolution T1-weighted images for individual morphological brain networks (MBNs) and resting-state functional MR images for functional brain networks (FBNs) were obtained. Topological properties were calculated and compared for both MBNs and FBNs. Then, partial correlation analysis was performed to investigate the relationships between the altered network properties and clinical variables. Finally, the altered network topological properties were used to classify NMOSD patients from HCs and to analyses time- to-progression of the patients. The average Expanded Disability Status Scale score of NMOSD patients was 1.05 (range from 0 to 2), indicating mild disability. Compared to HCs, NMOSD patients exhibited a higher normalized characteristic path length (λ) in their MBNs (P = 0.0118, FDR corrected) but showed no significant differences in the global properties of FBNs (p: 0.405-0.488). Network-based statistical analysis revealed that MBNs had more significantly altered connections (P< 0.01, NBS corrected) than FBNs. Altered nodal properties of MBNs were correlated with disease duration or fatigue scores (P< 0.05/6 with Bonferroni correction). Using the altered nodal properties of MBNs, the accuracy of classification of NMOSD patients versus HCs was 96.4%, with a sensitivity of 93.3% and a specificity of 100%. This accuracy was better than that achieved using the altered nodal properties of FBNs. Nodal properties of MBN significantly predicted Expanded Disability Status Scale worsening in patients with NMOSD. The results indicated that patients with mild disability NMOSD exhibited compensatory increases in local network properties to maintain overall stability. Furthermore, the alterations in the morphological network nodal properties of NMOSD patients not only had better relevance for clinical assessments compared with functional network nodal properties, but also exhibited predictive values of EDSS worsening.

Myositis Autoantibody Profiles and Clinical Significance in Patients with Inflammatory Myopathies in Southwest China.

The purpose of this study is to analyze the distribution of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in patients with idiopathic inflammatory myopathies (IIMs) in southwest China and to explore the relevance between each subtype, each clinical feature, and to explore the relevance between the laboratory indexes. For this study, 200 patients with IIMs were tested for myositis autoantibodies. Clinical manifestations and laboratory metrics were collected and the correlations between autoantibodies and clinical phenotypes were analyzed. MSAs were found in 73.5% of the patients. The most frequently MSAs were anti-MDA5 (26.8%), followed by anti-ARS (18.5%). Anti-Ro52 was the most prevalent in MAAs (46.2%). Interstitial lung disease (ILD) and arthralgia were more frequent in anti-MDA5 and anti-Jo-1 positive groups (each p < 0.05). Anti-TIF1-γ and anti-NXP2 were associated with dysphagia (each p < 0.05). Different antibody subtypes were associated with laboratory indicators of response to muscle damage and immune status. Logistic regression showed that anti-MDA5 and anti-Jo-1 were independent risk factors for ILD (OR = 4.542, p = 0.004; OR = 4.290, p = 0.018, respectively) and arthralgia (OR = 7.856, p = 0.000; OR = 5.731, p = 0.004, respectively), whereas anti-TIF1-γ and anti-NXP2 were independent risk factors for dysphagia (OR = 4.521, p = 0.009; OR = 6.889, p = 0.017, respectively). Different antibody subtypes were associated with specific clinical features. Anti-MDA5 and anti-Jo-1 were independent risk factors for ILD and arthralgia. Anti-TIF1-γ and anti-NXP2 were independent risk factors for dysphagia.

Brain network hierarchy reorganization in subthreshold depression

BackgroundHierarchy is the organizing principle of human brain network. How network hierarchy changes in subthreshold depression (StD) is unclear. The aim of this study was to investigate the altered brain network hierarchy and its clinical significance in patients with StD. MethodsA total of 43 patients with StD and 43 healthy controls matched for age, gender and years of education participated in this study. Alterations in the hierarchy of StD brain networks were depicted by connectome gradient analysis. We assessed changes in network hierarchy by comparing gradient scores in each network in patients with StD and healthy controls. The study compared different brain subdivisions if there was a different network. Finally, we analysed the relationship between the altered gradient scores and clinical characteristics. ResultsPatients with StD had contracted network hierarchy and suppressed cortical range gradients. In the principal gradient, the gradient scores of default mode network were significantly reduced in patients with StD compared to controls. In the default network, the subdivisions of reduced gradient scores were mainly located in the precuneus, superior temporal gyrus, and anterior and posterior cingulate gyrus. Reduced gradient scores in the default mode network, the anterior and posterior cingulate gyrus were correlated with severity of depression. ConclusionsThe network hierarchy of the StD changed and was significantly correlated with depressive symptoms and severity. These results provided new insights into further understanding of the neural mechanisms of StD.

Retracted: Study on the Changes of Liver and Kidney Function-Related Indicators and Clinical Significance in Patients with OSAHS.

[This retracts the article DOI: 10.1155/2022/9536617.].

Clinical application of circulating tumor cells.

This narrative review aims to provide a comprehensive overview of the current state of circulating tumor cell (CTC) analysis and its clinical significance in patients with epithelial cancers. The review explores the advancements in CTC detection methods, their clinical applications, and the challenges that lie ahead. By examining the important research findings in this field, this review offers the reader a solid foundation to understand the evolving landscape of CTC analysis and its potential implications for clinical practice. The comprehensive analysis of CTCs provides valuable insights into tumor biology, treatment response, minimal residual disease detection, and prognostic evaluation. Furthermore, the review highlights the potential of CTCs as a non-invasive biomarker for personalized medicine and the monitoring of treatment efficacy. Despite the progress made in CTC research, several challenges such as standardization, validation, and integration into routine clinical practice remain. The review concludes by discussing future directions and the potential impact of CTC analysis on improving patient outcomes and guiding therapeutic decision-making in epithelial cancers.

Trimethylamine-N-oxide (TMAO) and basic fibroblast growth factor (bFGF) are possibly involved in corticosteroid resistance in adult patients with immune thrombocytopenia

PurposeImmune thrombocytopenia (ITP) is an autoimmune disease characterized by accelerated platelet clearance. Gut dysbiosis was associated with its pathogenesis, but the underlying mechanisms have not been fully elucidated. Patients with ITP exhibit varying degrees of responsiveness to corticosteroid treatment. Therefore, prognostic indexes for corticosteroid responsiveness in ITP could offer valuable guidance for clinical practices. MethodsThe present study examined the signature of six types of gut-microbiota metabolites and forty-eight types of cytokines, chemokines, and growth factors and their clinical significance in patients with ITP. ResultsBoth patients with good and poor corticosteroid responsiveness exhibited significantly elevated/suppressed secretion of twenty-two cyto(chemo)kins/growth factors in comparison to healthy controls. Additionally, patients with ITP demonstrated a significant decrease in plasma levels of trimethylamine-N-oxide (TMAO), which was found to be negatively correlated to circulating platelet counts, and positively correlated with Interleukin (IL)-1β and IL-18. Notably, patients who exhibited poor response to corticosteroid treatment displayed elevated levels of TMAO and basic fibroblast growth factor (bFGF) in comparison to responders. Additionally, we found that the amalgamation of TMAO, bFGF and interleukin (IL)-13 could serve as a valuable prognostic tool for predicting CS responsiveness. ConclusionPatients with ITP were characterized overall by an imbalanced secretion of cyto(cheo)kins/growth factors and inadequate levels of TMAO. The varying degrees of responsiveness to corticosteroid treatment can be attributed to different profiles of basic FGF and TMAO that might be related to overburdened oxidative stress and inflammasome overactivation, and ultimately mediate corticosteroid resistance.

Valvulitis: a new echocardiographic criterion for the diagnosis of prosthetic valve infective endocarditis

Abstract Background Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been previously described in some patients with aortic bioprosthetic valve endocarditis (PVE). This echocardiographic finding has been termed valvulitis. Objectives Our aim was to estimate the prevalence of valvulitis, to precisely describe its echocardiographic characteristics, and to determine their clinical significance in patients with aortic bioprosthetic valve endocarditis. Methods From 2011 to 2022, 388 consecutive patients with IE admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with aortic bioprosthetic valve endocarditis (n=86) were selected, and their TEE images were thoroughly evaluated by three independent cardiologists to identify all potential cases of valvulitis. The diagnosis of valvulitis was considered to be present when all three were in complete agreement. Results Prevalence of isolated valvulitis in the total cohort was 12.8%, and 20.9% of patients had valvulitis accompanying other classical echocardiographic findings of IE. A description of the main clinical and imaging findings of 11 patients with valvulitis and no other echocardiographic signs of IE is shown at the Table. Diagnosis status corresponds to the criteria for the diagnosis of IE according to the ESC 2015 IE guidelines, including 18F-FDG PET/CT. TEE long-axis and short-axis views of a patient with bioprosthetic valvulitis (homogeneous and hypoechoic thickening of the aortic leaflets) resulting in severe aortic stenosis are shown at the Figure, Panel A. At Panel B, abnormal FDG uptake (white arrow) at the prosthetic valve is seen on PET/CT scan of the same patient. At Panel C, histology of the aortic bioprosthetic leaflet of the same patient with valvulitis is presented (hematoxylin and eosin stain of the aortic leaflet; granulation tissue is well demonstrated (red bracket) covering the aortic fibrosa (red asterisk)). Moderate or severe valve stenosis was more common in those with valvulitis (81.8 vs 34.9%, p&amp;lt;0.001). Patients with isolated valvulitis tended to have a lower IE-related in-hospital mortality (9.1 vs 23.3%, p=0.219) and cardiac surgery was less frequently performed than in the other subjects with aortic PVE (27.3 vs 58.1%, p=0.17), but these results were not statistically significant. Conclusions Valvulitis can be the only echocardiographic finding in infected biological aortic prosthesis and needs to be recognized by imagers for early patient diagnosis. The identification of this sort of lesion is important since the clinical profile and management of these patients is different from that of patients with classical PVE.TableFigure

Cardiac involvement and its clinical significance in patients with anorexia nervosa.

The prevalence of cardiac involvement, except for sinus bradycardia, was notably low in our cohort. The presence of cardiac aberrations is correlated with several clinical variables: lower body mass index (BMI) and the presence of amenorrhea and hypotension at admission. Patients presenting with these variables may be at high risk for cardiac findings per echocardiography. Dividing the patients into high and low risk groups may enable targeted evaluation, while avoiding unnecessary cardiac investigations in low-risk patients. • Cardiac involvement in anorexia nervosa (AN) patients is a major concern, which contributes to morbidity and mortality. • It is unknown which patients are prone to develop this complication. • Cardiac complications in our cohort are less frequent compared to previous studies, and it is correlated with lower body mass index (BMI) at admission, and the prevalence of amenorrhea and hypotension.

Immune function, gastrointestinal hormone levels, and their clinical significance in patients with gastric ulcers complicated with depression.

Gastric ulcer (GU) is a common digestive tract disease, and medical records of GU combined with depression are increasingly common. Currently, the risk factors and pathogenesis of GU complicated with depression remain unclear. Low immune function and gastrointestinal hormone levels may also be significant risk factors. Therefore, this study explored the immune function and gastrointestinal hormone levels in patients with GU combined with depression. To explore the immune function, gastrointestinal hormone level, and clinical significance of patients with GU combined with depression. A retrospective analysis was conducted on 300 patients with GU combined with depression admitted to Guizhou Provincial People's Hospital from January 2021 to June 2022 as the study subjects. According to the Hamilton Depression Scale (HAMD) score, patients were divided into mild-to-moderate (n = 210) and heavy (n = 90) groups. Basic data, immune function indices [immunoglobulin A (IgA), IgM, IgG, serum CD4+ and CD8+ percentage, and CD4+/CD8+ ratio], and gastrointestinal hormone indices [serum gastrin (GAS), cholecystokinin (CCK), and motilin (MTL) levels] were collected. The basic data of the two groups were compared, and the immune function and gastrointestinal hormone indices were analyzed. Multivariate logistic regression was used to analyze the factors influencing the severity of GU complicated with depression. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to analyze the value of the immune function index, gastrointestinal hormone index, and combined index in predicting the severity of GU complicated with depression. There were no marked differences in sex, age, body mass index, abdominal distension, abdominal pain, belching, nausea, vomiting, or sleep disorders between the heavy and mild-to-moderate groups (P > 0.05). There was a marked difference in the family history of depression between the heavy and mild-to-moderate groups (P < 0.05). There were significant differences in serum IgA and IgM levels and serum CD4+, CD8+, and CD4+/CD8+ ratios between the heavy and mild-to-moderate groups (P < 0.05). Multivariate analysis showed that IgA, IgM, GAS, and CCK serum levels influenced the severity of GU with depression (P < 0.05). The AUC of the ROC curve for serum IgA level predicting GU with depression severity was 0.808 [95% confidence interval (CI): 0.760-0.857], the AUC of the serum IgM level was 0.757 (95%CI: 0.700-0.814), the AUC of the serum GAS level was 0.853 (95%CI: 0.810-0.897), the AUC of the serum CCK level was 0.762 (95%CI: 0.709-0.822), the AUC of immune function (IgA, IgM) and gastrointestinal hormone levels (GAS, CCK) for the prediction of GU with depression severity was 0.958 (95%CI: 0.933-0.976). Important factors influencing GU complicated with depression are serum IgA, IgM, GAS, and CCK indicators. They can be used as indicators to predict the severity of GU complicated with depression.

Effects of multimodal exercise program on postural balance in patients with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial

BackgroundEvidence has shown that patients with chronic obstructive pulmonary disease present significant deficits in the control of postural balance when compared to healthy subjects. In view of this, it is pertinent to investigate the effects of different therapeutic strategies used alone or in association with pulmonary rehabilitation with the potential to improve postural balance and other outcomes with clinical significance in patients with chronic obstructive pulmonary disease. This study will investigate the effects of an 8-week (short-term) multimodal exercise program [inspiratory muscle training (IMT) plus neuromuscular electrical stimulation (NMES)] on postural balance in patients with chronic obstructive pulmonary disease enrolled in a pulmonary rehabilitation program compared to individualized addition of IMT or NMES to pulmonary rehabilitation or standard pulmonary rehabilitation.MethodsThis is a randomized, single-blind, 4-parallel-group trial. Forty patients with chronic obstructive pulmonary disease will be included prospectively to this study during a pulmonary rehabilitation program. Patients will be randomly assigned to one of four groups: multimodal exercise program (IMT + NMES + pulmonary rehabilitation group) or (IMT + pulmonary rehabilitation group) or (NMES + pulmonary rehabilitation group) or standard pulmonary rehabilitation group. Patients will receive two sessions per week for 8 weeks. The primary outcome will be static postural balance and secondary outcomes will include as follows: static and dynamic postural balance, fear of falling, muscle strength and endurance (peripheral and respiratory), functional capacity, health-related quality of life, muscle architecture (quadriceps femoris and diaphragm), and laboratory biomarkers.DiscussionThis randomized clinical trial will investigate the effects of adding of short-term multimodal exercise program, in addition to pulmonary rehabilitation program, in postural balance in patients with chronic obstructive pulmonary disease enrolled in a pulmonary rehabilitation. Furthermore, this randomized control trial will enable important directions regarding the effectiveness of short-term intervention as part of the need to expand the focus of pulmonary rehabilitation to include balance management in chronic obstructive pulmonary disease patients which will be generated.Trial registrationClinicalTrials.gov NCT04387318. Registered on May 13, 2020.

Efficacy of Autologous Stem Cell Transplantation for Myeloma Patients with Suboptimal Response: A Multicenter Retrospective Analysis

Autologous stem cell transplantation (ASCT) is the standard of care for myeloma patients when partial response (PR) or better is achieved after induction therapy. However, its clinical significance in patients with suboptimal response (SR), including stable disease (SD) and progressive disease (PD) before ASCT, has not been established. Additionally, functional high-risk (FHR), including RS and early PD within 12 months, was a poor prognostic factor up to now. This study aimed to evaluate the efficacy of ASCT in myeloma patients having SR in novel agent era. This multicenter, retrospective study was conducted using the Transplant Registry Unified Management Program (TRUMP) database of the Japanese Society of Transplantation and Cellular Therapy (JSTCT) and included 3898 patients with transplant-eligible patients with newly diagnosed multiple myeloma who underwent ASCT between 2007 and 2020 and were followed up until 2021. The SR rate was 4.7% including 1.7% of PD. In survival time analysis for overall cases, The significant difference of PFS between the VGPR and PR groups were observed while there was no significant difference of OS between the VGPR and PR groups. Additionally, there was no significant difference of OS and PFS between the PR and SD groups. Therefore, we focused on the PR, SD, and PD groups as the purpose of this retrospective study was to investigate the clinical significance of ASCT in patients with SR compared with those with PR. The median age of the patients was 60 years (range, 30-77 years). In total, 1605 (97.4%), 561 (38.2%), and 512 (34.9%) patients received bortezomib, immunomodulatory drug (IMiD), and both bortezomib and IMiD, respectively. A total of 558 (38.0%) patients received reinduction therapy. There were 229 (37.7 %) patients with high-risk cytogenetic risk (HRCA). In a median follow-up period of 31.7 months, a significant difference was observed in 30-month overall survival (OS) rates between the PR, SD, and PD groups (86.3%, 78.5%, and 39.4%, respectively; p <0.001). In a comparison between the PR and SD groups, the OS in the SD group was significantly shorter than that in the PR among the patients with HRCA (p <0.001) and in the patients treated with reinduction therapy (p = 0.013). Concerning the PD group, the 30-month OS and PFS rates in the PD group were 39.4% and 17.9%. Finally, early PD within 12 months after ASCT predicted short OS, whereas OS without early PD even in the PD group was similar to that in the SD and PR groups. In conclusion, the OS in the SR was not always short, but the SR in the HRCA and the reinduction therapy groups predicted to short OS so that alternative therapeutic options to ASCT are needed. OS in the PD group was significantly short, but ASCT improved clinical outcome when early PD was not occurred even in the PD group.