Results In Patients Research Articles

Validity and reliability of the Danish version of the Short Form Brief Pain Inventory

BackgroundPain is impacted by bio-psycho-social factors and is closely related to disability and poor quality of life. Therefore, a patient-reported outcome measure (PROM) is needed to capture these aspects effectively. The Short Form Brief Pain Inventory (SF-BPI) serves this purpose as a tool for pain assessment. However, the Danish translation (SFBPI-DK) has not undergone validation. ObjectiveAssess the validity and reliability of SFBPI-DK. MethodsIn patients with spine-related pain, construct validity was tested using Confirmatory Factor Analysis (CFA) and convergent validity through correlations with EuroQol 5-domain 5-level (EQ-5D-5L), EQ-5D-5L VAS, Work Ability Score (WAS), and Insomnia Severity Index (ISI-7). Internal consistency was assessed with Cronbach's alpha. In individuals with musculoskeletal pain, test-retest reliability and Minimal Detectable Change (MDC) were evaluated. Floor and ceiling effects were reported for both groups. ResultsIn patients with spine-related pain (n = 329), construct validity of the SFBPI-DK was confirmed through CFA of a modified 3-factor structure. Convergent validity showed “fair” to “moderate strong” associations with EQ-5D-5L, EQ-5D-5L VAS, WAS, and ISI-7. Internal consistency was satisfactory (Cronbach's alpha 0.89–0.91). In individuals with musculoskeletal pain (n = 119), good temporal stability was demonstrated with ICCs of 0.76–0.88. The MDC for the Severity score, Interference score, and the Physical- and Affective Interference subscores were 3.37, 2.41, 3.57, and 4.01, respectively. ConclusionThe SFBPI-DK is a valid tool for assessing pain in patients with persistent spine-related pain and a reliable tool for individuals with persistent musculoskeletal pain among Danish-speaking populations.

A preliminary study of fMRI and the relationship with depression and anxiety in Meniere's patients

PurposeTo examine alterations in Blood Oxygen Level-Dependent (BOLD) resting-state functional magnetic resonance imaging (rs-fMRI) signals, utilizing regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) metrics, within activated brain regions. Additionally, this study aims to explore the relationship between these neural changes and clinical characteristics, as well as emotional states, in patients diagnosed with unilateral Meniere's disease (MD). MethodThe study included 24 patients diagnosed with left Meniere's disease (L-MD), 25 patients diagnosed with right Meniere's disease (R-MD), and 23 healthy control subjects. Resting-state blood‑oxygen-level-dependent functional magnetic resonance imaging (rest-BOLD-fMRI) data were preprocessed. A two-sample t-test was employed to compare the regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) between the patient groups and the control group. Brain regions exhibiting significant differences were further analyzed for correlations with disease duration, vertigo severity, vertigo duration, hearing loss grade, and levels of anxiety and depression. ResultsIn patients with L-MD, fALFF values were significantly decreased in the right cerebellar hemisphere, middle occipital gyrus, among other regions. In patients with right-sided Ménière's disease (R-MD), fractional amplitude of low-frequency fluctuation (fALFF) values were elevated in the right middle inferior temporal gyrus and fusiform gyrus. Regional homogeneity (ReHo) values exhibited both increases and decreases in the temporal gyrus, parahippocampal gyrus, occipital gyrus, superior marginal gyrus, anterior central gyrus, and fusiform gyrus. In studies examining relational aspects, the parahippocampal gyrus, inferior temporal gyrus, middle occipital gyrus, superior middle occipital gyrus, superior marginal gyrus, and occipital gyrus demonstrated positive or negative correlations with clinical characteristics and emotional states. ConclusionsPatients with unilateral Meniere's disease (MD) exhibited both increased and decreased activation in various brain regions when compared to control subjects. A correlation was identified between these neural activation patterns and clinical characteristics, as well as emotional state, which holds significant implications for clinical treatment, prognosis, and rehabilitation strategies for MD patients.

Centrilobular nodules are predictive chest CT findings related to adult T-cell leukemia/lymphoma development in human T-lymphotropic virus type I carriers

AIMTo evaluate predictive chest CT findings associated with the development of adult T-cell leukemia/lymphoma (ATLL) in human T-lymphotropic virus type I (HTLV-1) carriers. MATERIALS AND METHODSThis retrospective study examined 171 adult T-cell leukemia/lymphoma and 158 HTLV-1 carriers who were treated from November 2004 to April 2021. The radiological features of 888 chest CT scans in total were retrospectively assessed by two chest radiologists who were unaware of the underlying diagnoses, and compared between the groups. RESULTSIn patients with aggressive type ATLL (acute type and lymphoma type), lymph node enlargement was the most frequently observed abnormality (65.2%), followed by ground-glass opacity (33.3%) and pleural effusion (30.4%). In patients with indolent type (chronic type and smoldering type), lymph node enlargement and bronchiectasis were the most frequently observed abnormalities (5.6% and 5.6%, respectively). In each type, centrilobular nodules were observed in none and in one patient, respectively. In the 158 HTLV-1 carriers, centrilobular nodules (n=62; 39.2%) were the most frequently observed abnormality. Centrilobular nodules were significantly frequently observed in HTLV-1 carriers compared with ATLL patients. No HTLV-1 carrier with centrilobular nodules on CT developed ATLL during the duration of care. A comparative analysis between CT scans performed before ATLL development in ATLL patients and those of HTLV-1 carriers showed that no centrilobular nodules were observed on the pre-ATLL CT scans, and a statistically significant difference in centrilobular nodules was found between these two groups. CONCLUSIONThe presence of centrilobular nodules may be an indicative CT finding in HTLV-1 carriers who are less likely to develop ATLL.

Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis

AimSepsis results in high mortality and is associated with organ dysfunction caused by infection. The present study aimed to elucidate whether early-stage sympathetic activation is associated with the prognosis of sepsis and its possible mechanisms. MethodsPatients with sepsis and healthy controls were included. Sepsis in rats was induced by lipopolysaccharide. Dexmedetomidine, a α2-adrenergic receptor agonist, was used in patients and rats with sepsis to evaluate the role of the sympathetic nervous system in sepsis. Holter monitoring was used to detect heart rate variability, while plasma samples were obtained to measure levels of norepinephrine and inflammatory markers. Mean arterial pressure, heart rate, and renal sympathetic nerve activity were recorded. Immunofluorescence was used to detect the activation of neurons in the rostral ventrolateral medulla (RVLM). ResultsIn patients with sepsis, plasma levels of norepinephrine and interleukin-1β were higher compared with those in controls and positively correlated with acute physiology and chronic health evaluation (APACHEII). SDNN and SDANN were significantly reduced as well as negatively correlated with APACHEII. Meanwhile, rats with sepsis showed increased of sympathetic outflow and plasma levels of norepinephrine, with increased c-fos levels in the RVLM. Treatment with dexmedetomidine could improve prognosis. Lesion of tyrosine hydroxylase-positive neurons in the RVLM attenuated sympathetic activation and target organs damage in septic rats as well as improved survival. ConclusionThe results suggest that tyrosine hydroxylase-positive neurons in the RVLM might contribute to the prognosis of sepsis via activation of the sympathetic nervous system, while dexmedetomidine could ameliorate sepsis via inhibiting sympathetic activation.

Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo

BackgroundPathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies. MethodsThe OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma. In OpACIN-neo, all patients underwent therapeutic lymph node dissection (TLND) without subsequent adjuvant therapy. In contrast, PRADO explored a response- directed strategy, where patients achieving a major pathologic response (MPR) omitted TLND and adjuvant therapy, while those without a pathologic response (pNR) received TLND and adjuvant therapy. Here, we provide a descriptive post-hoc comparison of 3-year survival outcomes between the non-personalized approach in OpACIN-neo and the response-directed approach in PRADO. ResultsFor patients who achieved an MPR, the 3-year recurrence-free survival (RFS) was 93 % for those without TLND versus 96 % for those with TLND (log-rank p = 0.47), and distant metastasis-free survival (DMFS) was 98 % compared to 96 % (log-rank p = 0.49), respectively. For patients with pNR, 3-year RFS rates were 64 % for those receiving adjuvant systemic therapy and 35 % for patients without (log-rank p = 0.10). DMFS rates were 70 % versus 52 % (log-rank p = 0.24), respectively. ConclusionsThese data suggest that TLND and adjuvant therapy may be safely omitted in most patients achieving an MPR, while adjuvant systemic therapy following TLND appears to improve RFS and DMFS in patients with pNR. Although these results are hypothesis-generating and require further validation, they offer a potential foundation for developing personalized neoadjuvant immunotherapy approaches.

Investigating racial differences in mortality and survival outcomes following radical prostatectomy: a systematic review and meta-analysis

BackgroundNotable variations in cancer rates, survival rates, mortality exist among certain populations in the US. We aim to examine how prostate cancer prognosis differs among black and white men from various ethnic backgrounds undergoing radical prostatectomy.MethodsWe performed a comprehensive search across MEDLINE and Google Scholar databases from inception to March 2023 for observational studies including black and white men undergoing radical prostatectomy. Outcomes of interest included either overall survival, prostate cancer survival, biochemical recurrence, or all-cause mortality. Studies were pooled using hazard ratios (HR) with 95% confidence intervals (CIs) using Review Manager (RevMan) version 5.4.1.ResultsIn patients undergoing radical prostatectomy, the risk of all-cause mortality was significantly greater in blacks in comparison to whites ([HR] 1.16, 95% CI 1.12–1.21; I2 = 51%; p < 0.00001). Pooled analysis shows higher rate of prostate-specific mortality in blacks treated compared to whites ([HR]: 1.08, 95% CI 0.86–1.37; I2 = 81%; p = 0.50). The risk of biochemical recurrence was significantly higher in blacks undergoing radical prostatectomy than in whites (HR: 1.27; 95% CI 1.11–1.45; I2 = 58%; p = 0.0007). On regional subgroup analysis, the mid-west and multi-institutional centers revealed a higher rate of biochemical recurrence in blacks than in whites. No significant difference was noted between blacks and whites for overall survival.ConclusionsOur research demonstrated elevated rates of all-cause mortality, prostate-specific mortality, and biochemical recurrence, with no significant differences in overall survival between blacks and whites. Further research is warranted to assess ethnic and geographic differences at a large scale.

Hepatitis D Virus infection triggers CXCL9-11 upregulation in hepatocytes and liver infiltration of CXCR3+ CD4 T cells

Background & AimsThe role of hepatocytes in producing chemokines and in triggering liver inflammation and damage in chronic hepatitis D (CHD) is not fully understood. Herein, we investigated the contribution of primary human hepatocytes (PHHs) infected with hepatitis D virus (HDV) in triggering inflammation by producing the chemokines CXCL9-11. MethodsWe performed qPCR, RNA in situ hybridisation (ISH), activation-induced marker (AIM) assays, and FACS analysis to investigate the CXCR3/CXCL9-11 receptor/ligand axis of T cells in peripheral blood and livers from patients with chronic hepatitis B (n=27 and 18, respectively) and CHD (n=20 and 18, respectively). Chemokine expression was investigated in cultured HDV-infected PHHs and in livers of HBV- or HBV/HDV-infected humanized mice, in the presence or absence of adoptively transferred human immune cells (n=35 in total). ResultsIn patient and chimeric mouse livers, higher expression levels of CXCL9-11 were found in an HBV/HDV-co-infected setting versus HBV-mono-infected. Similarly, high levels of CXCL9-11 were observed in HDV-infected PHHs in vitro. Analysis by RNA-ISH on patient livers revealed that HDV-infected hepatocytes were a significant contributor to the chemokine expression. The corresponding chemokine receptor CXCR3 was found upregulated specifically on peripheral bulk CD4 T cells of CHD patients. CXCR3-upregulation was unspecific and was not detected on HDAg- or HBsAg-specific CD4 T cells by AIM assay. Lastly, adoptive transfer of human T cells in humanized mice led to recruitment of non-HBV/HDV-specific CD4+ T cells only in the setting of HBV/HDV co-infection, but not in HBV-mono-infected mice. ConclusionsHDV infection upregulated the intrahepatic expression of the CXCL9-11/CXCR3 receptor/ligand axis. Higher amounts of HBV/HDV-unspecific CD4 T cells expressing CXCR3 may contribute to the aggravated liver inflammation frequently observed in CHD patients. Impact and implicationsChronic hepatitis D causes the most severe form of viral hepatitis and treatment options are still limited, therefore a more precise understanding of CHD immunopathology is needed. In this study, we demonstrated that HDV infection triggers CXCL9-11 expression in hepatocytes and liver infiltration of CXCR3 expressing CD4 T cells in preclinical models as well as patient biopsies. Since recruitment of Th1-polarized CD4 T cells to the liver has been also described for other severe liver diseases like autoimmune hepatitis, it may represent an important mechanism of aggravating liver diseases. The data of this study set hereby the basis for future studies analysing phenotype and function of intrahepatic T cells in CHD.

The association between change in temporal muscle mass and treatment of acromegaly

PurposeWe aimed to evaluate the relationship between temporal muscle thickness and GH/IGF-1 elevation and the effect of acromegaly treatment on temporal muscle thickness. MethodsPatients with acromegaly and healthy controls were included in the study. While laboratory parameters, clinical findings and temporal muscle thickness of acromegaly patients at the time of diagnosis and one year after treatment were evaluated, laboratory parameters and temporal muscle thickness of healthy controls were evaluated only during the period when they were included in the study. Temporal muscle thickness was measured using pituitary MRI. Temporal muscle thickness of patients with acromegaly was compared with healthy controls. We also evaluated how temporal muscle thickness changes with treatment in patients with acromegaly and the association between laboratory parameters and temporal muscle thickness. ResultsIn patients with acromegaly, measurements of left, right, and mean temporal muscle thickness at the time of diagnosis were found to be significantly higher than those of healthy controls' measurements at the time of their inclusion in the study (p = 0.007, p = 0.014 and p = 0.018, respectively). However, no significant difference was found when comparing the temporal muscle thickness of the 1st year of acromegaly treatment with the temporal muscle thickness of healthy controls at the time of their inclusion in the study (p = 0.155, p = 0.189, p = 0.198, respectively). In addition, a significant decrease was detected in the left, right and mean temporal muscle thicknesses of patients with acromegaly before and after treatment. While the temporal muscle thickness at the time of diagnosis was thicker in patients with acromegaly receiving surgical + medical treatment than in patients receiving exclusively surgical treatment, statistical significance was only found in the left temporal muscle thickness (p = 0.042). ConclusionTemporal muscle thickness was found to be associated with treatment modalities in patients with acromegaly.

Long-Term Survival Outcomes With First-Line Nivolumab Plus Ipilimumab–Based Treatment in Patients With Metastatic NSCLC and Tumor Programmed Death-Ligand 1 Lower Than 1%: A Pooled Analysis

IntroductionNivolumab plus ipilimumab–based treatment regimens have shown long-term, durable efficacy benefits in patients with metastatic NSCLC. Here we report clinical outcomes from a pooled analysis of patients with metastatic NSCLC and tumor programmed death-ligand 1 (PD-L1) lower than 1% treated with first-line nivolumab plus ipilimumab with or without two cycles of chemotherapy versus up to four cycles of chemotherapy in the randomized phase 3 CheckMate 227 and CheckMate 9LA studies. MethodsPatients were aged 18 years or older and had stage IV or recurrent NSCLC with no sensitizing EGFR/ALK alterations. Assessments included overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety. ResultsIn patients with tumor PD-L1 lower than 1% in the nivolumab plus ipilimumab with or without chemotherapy (n = 322) versus chemotherapy (n = 315) arms, median OS was 17.4 versus 11.3 months, respectively, (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.54–0.76; 5-y OS rate, 20% versus 7%) at a median follow-up of 73.7 months. The OS benefit was observed across key subgroups, including difficult-to-treat populations such as those with baseline brain metastases (HR = 0.44, 95% CI: 0.26–0.75) or squamous NSCLC (HR = 0.51, 95% CI: 0.36–0.72). In the overall pooled population, the median PFS was 5.4 versus 4.9 months (HR = 0.72, 95% CI: 0.60–0.87; 5-y PFS rate, 9% versus 2%), the objective response rate was 29% versus 22%, and the median duration of response was 18.0 versus 4.6 months. No new safety signals were observed. ConclusionNivolumab plus ipilimumab with or without chemotherapy provides a long-term, durable clinical benefit in patients with metastatic NSCLC and tumor PD-L1 lower than 1%, supporting the use of this strategy as a first-line treatment option in this population with high unmet need. Clinical Trial Registrations: NCT02477826, NCT03215706

A Machine Learning-derived Risk Score Improves Prediction of Outcomes After LVAD Implantation: An Analysis of the INTERMACS Database

BackgroundSignificant variability in outcomes after left ventricular assist device (LVAD) implantation emphasize the importance of accurately assessing patients' risk before surgery. This study assesses the Machine Learning Assessment of Risk and Early Mortality in Heart Failure (MARKER-HF) mortality risk model, a machine learning-based tool using 8 clinical variables, to predict post-LVAD implantation mortality and its prognostic enhancement over the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS) profile. MethodsAnalyzing 25,365 INTERMACS database patients (mean age 56.8 years, 78% male), 5,663 (22.3%) and 19,702 (77.7%) received HeartMate 3 and other types of LVAD, respectively. They were categorized into low, moderate, high, and very high-risk groups based on MARKER-HF score. The outcomes of interest were in-hospital and 1-year postdischarge mortality. ResultsIn patients receiving HeartMate 3 devices, 6.2% died during the index hospitalization. In-hospital mortality progressively increased from 4.4% in low-risk to 15.2% in very high-risk groups with MARKER-HF score. MARKER-HF provided additional risk discrimination within each INTERMACS profile. Combining MARKER-HF score and INTERMACS profile identified patients with the lowest (3.5%) and highest in-hospital mortality rates (19.8%). The postdischarge mortality rate at 1 year was 5.8% in this population. In a Cox proportional hazard regression analysis adjusting for both MARKER-HF and INTERMACS profile, only MARKER-HF score (hazard ratio 1.27, 95% confidence interval 1.11–1.46, P < .001) was associated with postdischarge mortality. Similar findings were observed for patients receiving other types of LVADs. ConclusionsThe MARKER-HF score is a valuable tool for assessing mortality risk in patients with HF undergoing HeartMate 3 and other LVAD implantation. It offers prognostic information beyond that of the INTERMACS profile alone and its use should help in the shared decision-making process for LVAD implantation.

Oropharyngeal Dysphagia in Hospitalized Older Adults with Dementia: A Prospective Cohort Study

ObjectiveOropharyngeal dysphagia (dysphagia) is highly prevalent (up to 86%) in hospitalized patients with Alzheimer disease and related dementias (ADRD). This study aims to describe the management and clinical course of dysphagia in hospitalized patients with ADRD. DesignProspective observational cohort study. Setting and ParticipantsThe study was conducted across 10 hospitals within a large health system in New York. Participants were older adults with ADRD admitted to the medicine service and diagnosed with dysphagia to liquids on speech-language pathologist (SLP) assessment and were recruited between January and June 2023. MethodsBaseline characteristics [eg, dementia Functional Assessment Staging Tool (FAST)], dysphagia management (eg, prescribed diet), and clinical course (eg, dysphagia improvement, respiratory complications) were collected. ResultsOf patients with ADRD and dysphagia (n = 62), the average age was 86.5 and 66.1% were FAST Stage 7. On admission, 48.4% had pneumonia, 79.0% had delirium, and 69.4% were made nil per os (NPO) for aspiration risk. Of those who received SLP reassessment after diet initiation (n = 25), 76% demonstrated dysphagia improvement; 75% of patients with FAST stage 7 demonstrated improvement. Respiratory complications occurred in 21.0% of patients on the following diets: NPO, nasogastric tube feeding, dysphagia diets, and comfort feeds. In univariate analyses, hospital-acquired dehydration, no dysphagia improvement, and delirium were associated with respiratory complications. Conclusions and ImplicationsThe potential for dysphagia improvement in hospitalized patients with ADRD (even those with advanced dementia) highlights the critical need for standardizing reassessment. Further studies are needed to evaluate factors associated with respiratory complications in this population.

Pathomechanism of infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion evaluated by MR spectroscopy

BackgroundInfantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has recently been reported as a distinct type of TBI in infancy. However, the pathological and prognostic factors of TBIRD remain unknown. We aimed to compare patients with and without TBIRD and evaluate the pathomechanism of TBIRD using magnetic resonance spectroscopy (MRS). MethodsTen Japanese patients with TBI were admitted to our hospital and underwent MRS between September 2015 and September 2022 (age range, 3–15 months; median age, 8.5 months). TBIRD was diagnosed in six patients. MRS data were compared among patients with TBIRD, patients without TBIRD, and controls. Neurological prognosis was classified into grades 1 (normal) to 3 (severe). ResultsIn patients with TBIRD, MRS revealed an increase in the glutamine (Gln) level on days 3–29, which subsequently became close to normal. The degree of Gln elevation in the non-TBIRD group was smaller (117–158 % of controls) than that in the TBIRD group (210–337 %) within 14 days. MRS in the TBIRD group showed decreased N-acetyl aspartate (NAA) concentrations. The degree of NAA decrease was more prominent in grade 3 than in grades 1 and 2. NAA levels in the non-TBIRD group were almost normal. ConclusionsPatients with TBI and markedly elevated Gln levels on MRS may develop TBIRD. Neuro-excitotoxicity is a possible pathological mechanism of TBIRD. Decreased NAA levels may be useful for predicting the prognosis of patients with TBIRD.

Genetic insights and clinical implication of inherited hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy is one of the most common inherited genetic diseases of myocardium. It is the leading cause of unexpected mortality among young people and athletes. H.C.M. has been regarded as a sarcomere illness for the past few decades, usually with incomplete penetrance and varied expressivity arising from autosomal dominance. For the purpose of risk and treatment stratification, all diagnostic techniques—such as tissue biopsy, genetic counselling, magnetic resonance imaging, transthoracic and transoesophageal echocardiography, heart catheterization, and genetic counselling—must be used. Additionally, each patient's results should be customized based on their genotype and phenotype. About one-third of people have left ventricular outflow tract blockage at rest, and another third may be prompted to develop it. Interstitial fibrosis and myocyte hypertrophy and disarray are among the histological characteristics of H.C.M. Another common complication of the hypertrophy is left ventricular diastolic dysfunction. The pathogenesis of H.C.M is complex, and its clinical profile is variable. Functional disability resulting from heart failure and stroke (induced by atrial fibrillation) is also attributed to H.C.M. The goal of the current treatments for H.C.M., which include medication, myectomy, alcohol septal ablation, and implanted cardiac defibrillators (I.C.Ds) to avoid SCD, is to slow down the disease's progression and relieve symptoms. Multidisciplinary approaches are best suited for the diagnosis and treatment of patients with H.C.M. More individualized care and better results for this patient population have been made possible by this, as well as the enhanced safety and effectiveness of medicinal, percutaneous, and surgical therapy for H.C.M. In this review the molecular pathophysiology of H.C.M will be reviewed in light of current knowledge. In addition, describing how genetic testing is used for diagnosis and outlining the range of clinical manifestations.

Evaluation of Paravertebral Muscle Structure Asymmetry in Idiopathic Scoliosis Using Imaging Techniques

ObjectiveThis study aimed to assess variances in paravertebral muscle structure in individuals with idiopathic scoliosis（IS） through imaging techniques. MethodsA cohort of 112 patients diagnosed with IS and treated at our institution between January and December 2023 were included in the analysis. During the same period, 37 patients with secondary scoliosis（SS）were included as controls. Imaging data were used to measure the Cobb angle of the apical vertebrae in scoliosis patients, along with the area and fat infiltration of the paravertebral muscles on both sides. Finally, the cross-sectional area of the paravertebral muscles and the degree of fat infiltration were comparatively evaluated. ResultsIn patients with IS, the paravertebral muscles on the concave side of the main curve were significantly larger than those on the convex side (P < 0.05). The concave/convex muscle area ratio in IS patients showed a positive correlation with the Cobb angle and scoliosis duration (both P < 0.05). There was no significant difference in the muscle area ratio between patients with IS and those with SS (P > 0.05). In IS, the paravertebral muscles on the concave side of the main curve exhibited more fat infiltration than those on the convex side, with this fat infiltration positively correlating with body mass index (BMI), Cobb angle, age, and scoliosis duration. Similarly, the degree of fat infiltration in the paravertebral muscles on the concave side of SS was greater than that observed on the convex side. Furthermore, the degree of fat infiltration in the paravertebral muscles associated with SS was more pronounced compared to that seen in IS (P < 0.05). ConclusionIn IS patients, the paravertebral muscles on the concave side are more prominent and exhibit more fat infiltration compared to those on the convex side. This fat infiltration positively correlates with the Cobb angle, scoliosis duration, BMI, and age, possibly indicating scoliosis progression.

Comparison of 24 vs 72-hr octreotide infusion in acute esophageal variceal hemorrhage - A multi-center, randomized clinical trial

BackgroundCurrent guidelines lack clarity about the optimal duration of octreotide therapy for patients with esophageal variceal hemorrhage (EVH). To address this lack of evidence, we conducted a randomized clinical trial (RCT) of 24-hr versus 72-hr continuous infusion of octreotide for patients with EVH. MethodsThis multi-center, prospective RCT (NCT03624517), randomized patients with EVH to 24-hr versus 72-hr infusion of octreotide. Patients were required to undergo esophageal variceal band ligation prior to enrollment. The primary endpoint was rebleeding rate at 72 hr. The study was terminated early due to an inability to recruit during and after the COVID-19 epidemic. ResultsFor patients randomized to 72-hr (n = 19) of octreotide vs 24-hr (n = 15), there were no differences in the need for transfusion, average pRBC units transfused per patient (3 units vs 2 units), infection (5 % vs 0 %), mechanical ventilation (11 % vs 7 %), or the need for vasopressors (5 % vs 3 %), respectively (none of these differences were statistically significantly different). There were 2 re-bleeding events in the 72-hr group (11 %), and no re-bleeding events in the 24-hr group (p = 0.49). 8/15 of patients receiving 24 hr of octreotide were discharged at or before hospital day 3 while none in the 72-hr group was discharged before day 3 (p < 0.001). There was one death (in the 72-hr group) within 30 days. ConclusionsA 24-hr infusion is non-inferior to a 72-hr infusion of octreotide for prevention of re-bleeding in patients with EVH. We propose that shortened octreotide duration may help reduce hospital stay and related costs in these patients.

Airway proteomics reveals broad residual anti-inflammatory effects of prednisolone in mepolizumab-treated asthma

BackgroundMepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces asthma exacerbations. Residual airway inflammation on mepolizumab may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations. ObjectiveOur study aimed to explore the corticosteroid-responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway. MethodThe MAPLE trial was a multi-centre, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for SEA. We analysed paired sputum (n=16) and plasma (n=25) samples from the MAPLE trial using high-throughput Olink® proteomics. We also analysed additional sputum proteins using ELISA. ResultsIn patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type-2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated.Type-2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated. ConclusionAt stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations.

Dialog between mantle cell lymphoma cells and lymphoma-associated macrophages underlies ibrutinib resistance

IntroductionPatients with mantle cell lymphoma (MCL) frequently develop resistance to ibrutinib. Lymphoma-associated macrophages (LAMs) may play a causal role in this resistance but remain underexplored in current literature. ObjectivesTo elucidate the role of LAMs in mediating ibrutinib resistance in MCL. MethodsWe investigated macrophage polarization through multiparameter flow cytometry (MPFC) using antibodies against CD206 and CD86 in blood and tissue samples from patients with MCL, both resistant and sensitive to ibrutinib. Subsequently, we developed an in vitro co-culture model utilizing MCL cell lines to identify cytokines associated with ibrutinib resistance and macrophage M2 polarization. The mechanisms underlying resistance were examined using MPFC, RNA sequencing, and Western blot analysis. Additionally, we assessed whether SB225002, a CXCR2 inhibitor, could reverse ibrutinib resistance through CCK-8 and caspase-3 assays, as well as in a mouse xenograft model involving an ibrutinib-resistant MCL cell line. ResultsIn patients exhibiting ibrutinib resistance, the ratio of M2 to M1 LAMs was significantly higher compared to sensitive patients. In co-cultures of LAMs and MCL cells, the percentage of M2 macrophages, the IC50 value for ibrutinib, and the concentrations of IL-8 and CXCL5 were significantly elevated. Mechanistically, CXCL5 secreted by LAMs interacted with the CXCR2 on MCL cells, leading to the activation of the Akt, p38, and STAT3 signaling pathways in the presence of ibrutinib; this activity was diminished upon blockade of the CXCL5/CXCR2 axis. The combination of SB225002 and ibrutinib significantly enhanced MCL cell apoptosis, suppressed lymphoma growth in the xenograft model, and reprogrammed macrophage phenotype compared to treatment with ibrutinib alone. ConclusionOur data indicate that M2-polarized LAMs are associated with ibrutinib resistance in a model of MCL, and that a CXCR2 inhibitor can reverse this resistance. These findings suggest a potential new therapeutic strategy.

Appropriateness and outcomes of hospitalized patients telemetry monitored for cardiac arrhythmias in accordance with the American Heart Association Practice Standards–A multicenter study

BackgroundTo the best of our knowledge, no prospective research studies have compared clinical practice to the American Heart Association (AHA) updated practice standards for in-hospital telemetry monitoring. ObjectivesOur aims were therefore (1) to investigate how patients were assigned to telemetry monitoring in accordance with the AHA's updated practice standards, (2) to determine the number and type of arrhythmic events, and (3) to describe subsequent changes in clinical management. MethodsThis prospective multicenter study included 1154 patients at three university hospitals in Norway. Data were collected 24/7 over a four-week period, with follow-up measurements from telemetry admission until hospital discharge. ResultsOf patients assigned to telemetry, 67 % (n = 767) met practice standards, corresponding to AHA Class I or II. Patients were predominantly men (65 %, n = 748), and the mean age was 65 years (SD ±16). The study included both patients with cardiac and non-cardiac diagnoses from various medical and surgical departments throughout the hospitals. Ninety-one percent of the patients in Class III were monitored based on indications that were reclassified from Class II to Class III (not indicated) in the updated practice standards (patients admitted with chest pain or post-percutaneous coronary intervention (PCI) without complications). Overall, arrhythmic events occurred in 37 % (n = 424) of patients, and they occurred in all classes. Eighteen percent (n = 59) of arrhythmic events occurred in Class III. Of all arrhythmias, 3 % (n = 14) were life threatening, and all of them occurring within Class I. Telemetry monitoring led to changes in clinical management in 22 % (n = 257) of patients due to clinical alarms, of which 71 % (n = 182) were related to medication management. ConclusionsMost patients were appropriately monitored according to the AHA practice standards, meeting Class I and II. Arrhythmias occurred in all classes, but life-threatening arrhythmias only occurred in patients in Class I. However, a daily re-assessment of each patient's telemetry indication is warranted.

Population-specific equations of age-related maximum handgrip force: a comprehensive review.

The measurement of handgrip force responses is important in many aspects, for example: to complement neurological assessments, to investigate the contribution of muscle mass in predicting functional outcomes, in setting realistic treatment goals, evaluating rehabilitation strategies. Normative data about handgrip force can assist the therapist in interpreting a patient's results compared with healthy individuals of the same age and gender and can serve as key decision criteria. In this context, establishing normative values of handgrip strength is crucial. Hence, the aim of the this study is to develop a tool that could be used both in rehabilitation and in the prevention of work-related musculoskeletal disorders. This tool takes the form of population-specific predictive equations, which express maximum handgrip force as a function of age. In order to collect data from studies measuring maximum handgrip force, three databases were searched. The search yielded 5,058 articles. Upon the removal of duplicates, the screening of abstracts and the full-text review of potentially relevant articles, 143 publications which focussed on experimental studies on various age groups were considered as fulfilling the eligibility criteria. A comprehensive literature review produced 1,276 mean values of maximum handgrip force. A meta-analysis resulted in gender- and world region-specific (general population, USA, Europe and Asia) equations expressing maximum force as a function of age. The equations showed quantitative differences and trends in maximum handgrip force among age, gender and national groups. They also showed that values of maximum handgrip force are about 40% higher for males than for females and that age-induced decrease in force differs between males and females, with a proved 35% difference between the ages of 35 and 75. The difference was lowest for the 60-64 year olds and highest for the 18-25 year-olds. The equations also showed that differences due to region are smaller than those due to age or gender. The equations that were developed for this study can be beneficial in setting population-specific thresholds for rehabilitation programmes and workstation exposure. They can also contribute to the modification of commonly used methods for assessing musculoskeletal load and work-related risk of developing musculoskeletal disorders by scaling their limit values.

The relationship between uric acid and bone mineral density in the intermediate stage of CKD 1–3

BackgroundSome studies have suggested that uric acid has antioxidant properties that can prevent bone loss, but the relationship between uric acid and bone mineral density is controversial. The aim of this study was to investigate the relationship between UA and BMD in patients with CKD stage 1–3.MethodsWe extracted 13,047 participants from the NHANES database, including 7342 male subjects and 5705 female subjects. Weighted multiple linear regression analysis was used to investigate the correlation between UA and BMD in patients with CKD stages 1–3.ResultsIn patients with CKD stage 1–3, UA was significantly correlated with BMD. In the male group, UA was positively associated with BMD (β, 7.94 [95%CI, 4.95, 10.94]). In the female group, there was a negative relationship between them (β, -5.33 [95%CI, -8.77, -1.89]). The relationship between UA and BMD in male group showed an inverted U-shaped curve, and UA was positively correlated before 6.1 mg/dl and negatively correlated after 6.1 mg/dl. The relationship was basically negative in the female group.ConclusionsFor the patients with CKD stage 1–3, the relationship between UA and BMD showed an inverted U-shaped curve in the males, while the relationship was largely negative in the females.