Patient Sex Research Articles

Sex differences in adverse events among cancer patients receiving immune checkpoint inhibitors: the MOUSEION-07 systematic review and meta-analysis.

Immune checkpoint inhibitors have revolutionized cancer treatment, but they are associated with a range of immune-related adverse events (irAEs), and emerging evidence suggests significant sex differences in the incidence, type, and severity of these toxicities, suggesting an influential factor and understanding sex-related differences in irAEs as crucial for optimizing patient care and improving clinical outcomes. In MOUSEION-07 study, we aimed to assess the association between sex and treatment-related adverse events in cancer patients treated with immunotherapy through a large up-to-date meta-analysis of available clinical trials. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis. The protocol was registered with PROSPERO no. CRD42024549518. Sixteen studies encompassing a total of 4658 patients were included, and 2133 adverse effects were highlighted. The analysis observed a not statistically significant difference in terms of immune-related adverse events (irAEs) between males and females (Odds Ratio 1.19; CI 0.88-1.63) and revealed the presence of publication bias (β = -2.53; 95% CI = [-4.03; -1.04]; P = 0.006). Sex differences in immunotherapy-related adverse events are a significant factor in cancer treatment, necessitating a personalized approach to patient care. Further research is needed to fully understand the mechanisms driving these differences and to develop optimized strategies for monitoring and managing irAEs in both females and males.

Humanin-G Ameliorates Hemorrhage-Induced Acute Lung Injury in Mice Through AMPKα1-Dependent and -Independent Mechanisms

Background/Objectives: The severity of acute lung injury is significantly impacted by age and sex in patients with hemorrhagic shock. AMP-activated protein kinase (AMPK) is a crucial regulator of energy metabolism but its activity declines with aging. Humanin is a mitochondrial peptide that exerts cytoprotective effects in response to oxidative stressors and is associated with longevity. Using a mouse model of hemorrhagic shock that mimics the clinical condition of adult patients, we investigated whether treatment with a humanin analog, humanin-G, mitigates lung injury and whether its mechanisms of action are dependent on the catalytic AMPKα1 subunit activation. Methods: Male and female AMPKα1 wild-type (WT) and knock-out (KO) mice (8–13 months old) were subjected to hemorrhagic shock by blood withdrawal, followed by resuscitation with shed blood and lactated Ringer’s solution. The mice were treated with PEGylated humanin-G or vehicle and euthanized 3 h post-resuscitation. Results: Sex- and genotype-related differences were observed after hemorrhagic shock as lung neutrophil infiltration was more pronounced in the male AMPKα1 WT mice than the female WT mice; also, the male AMPKα1 KO mice experienced a significant decline in mean arterial blood pressure when compared to the male WT mice after resuscitation. The scores of histological lung injury were similarly elevated in all the male and female AMPKα1 WT and KO mice when compared to the control mice. At molecular analysis, acute lung injury was associated with the downregulation of AMPKα1/α2 catalytic subunits in the WT mice, whereas an increased activation of the signal transducer and activator of transcription-3 (STAT3) was observed in all the vehicle-treated groups. The in vivo administration of humanin-G ameliorated histological lung damage in all the groups of animals and ameliorated mean arterial blood pressure in the male AMPKα1 KO mice. The in vivo administration of humanin-G lowered lung neutrophil infiltration in the male and female AMPKα1 WT mice only but not in the KO mice. The beneficial results of humanin-G correlated with the lung cytosolic and nuclear activation of AMPKα in the male and female AMPKα1 WT groups, whereas STAT3 activation was not modified. Conclusions: In adult age, hemorrhage-induced acute lung injury manifests with sex-dependent characteristics. Humanin-G has therapeutic potential and the AMPKα1subunit is an important requisite for its inhibitory effects on lung leucosequestration, but not for the amelioration of lung alveolar structure or the hemodynamic effects of the peptide.

Sex differences in pneumonia risk during COVID-19 in Mexico.

This study aimed to evaluate the pneumonia risk based on the patient's sex during the COVID-19 pandemic and the early months of the endemic phase of the disease in Mexico. A retrospective cohort study was conducted using a dataset resulting from the epidemiological surveillance of COVID-19 (February 2020 to August 2023). Data from 1.6million adults with laboratory-positive disease, were analyzed. Risk ratios (RR) and 95% confidence intervals (CI), computed through generalized linear regression models, were used. The overall risk of pneumonia was 9.3% (95% CI 9.2-9.4%), with sex-specific estimates of 7.0% (95% CI 6.9-7.1%) for women and 12.0% (95% CI 11.9-12.1%) for men. This disparity was consistently observed throughout all phases of the pandemic, including the endemic phase of the disease. After adjusting for age, predominant viral genotype at illness onset and preexisting medical conditions, men had a 3.3% higher risk of severe manifestations when compared to women (RR = 1.033, 95% CI 1.032-1.034). Our research highlights the potential role of patients' sex as a factor influencing pneumonia risk during and after the COVID-19 pandemic in Mexico. These findings may provide useful considerations for healthcare planning and policy development focused on addressing the impact of the disease on vulnerable populations.

Meningiomas: Sex-Specific Differences and Prognostic Implications of a Chromosome X Loss.

Meningiomas are the most common primary intracranial tumours in adults. Several studies proposed new stratification systems with a more accurate risk prediction than the WHO grading, e.g. based on methylation and copy number variations (CNVs). Yet, common shortcomings in these analyses are either a lack of stratification by sex of patients or excluding the gonososmes from CNV assessment. Within this study, DNA methylation array data from 7,424 meningioma samples as well as targeted sequencing, clinical annotations and morphology subtyping of 796 samples were examined for differences between females and males regarding mutations, methylation classes, copy number variations and histology. Meningiomas from females accounted for about 53 % of the malignant tumours and present a loss of one X chromosome in 57 % of these malignant cases. In the group of benign tumours, females comprised about 75 % of the patients. Therein, a loss of one X chromosome was detected in only about 10 % of the cases but was associated with a significantly worse progression free survival. Although genomic instability is a common feature of malignant meningiomas, particularly loss of the X chromosome in tumours of female patients in otherwise histologically and molecularly low-risk tumours confers higher risk. Hence, the gonosomal copy number status can be leveraged for increased diagnostic accuracy.

Abstract Su707: Sex Differences in Bystander Cardiopulmonary Resuscitation and Survival to Hospital Discharge for Public Out-of-Hospital Cardiac Arrests in North Carolina and Singapore

Introduction: Although it is known that women are less likely than men to receive bystander cardiopulmonary resuscitation (BCPR) in public, few studies have examined differences in receipt of BCPR and survival to hospital discharge for public out-of-hospital cardiac arrests (OHCAs) by patient sex between distinct regions. Objectives: We assessed if patient sex was associated with BCPR (primary outcome) and survival to hospital discharge (secondary outcome) for public OHCAs in North Carolina (NC) and Singapore (SG). We hypothesized that females in both regions would have lower receipt of BCPR and were less likely to survive to hospital discharge compared with men. Methods: We conducted a retrospective cohort study of the Cardiac Arrest Registry to Enhance Survival dataset (NC, 2013-2022) and Pan-Asian Resuscitation Outcomes Study (SG, 2010-2020). We excluded pediatric, traumatic, emergency medical services (EMS) witnessed cases, arrests in healthcare facilities and residential cases. Using logistic regression, we examined the association of sex with BCPR and survival to hospital discharge controlling for potential confounding variables such as age, race and the year of arrest. Results: There were 65,627 OHCAs in NC; upon exclusion 6,828 remained (78% males; mean age: 57±15, males, 54.7±18, females). In SG, there were 24,177 OHCAs; upon exclusion 3,617 cases remained (87% males; mean age: 57±14, males, 61±16.4, females). In NC, public BCPR rates were 48% for males and 44% for females. Females had a 13% adjusted lower odds of receiving less BCPR (adjusted OR 0.87 (CI 0.77, 0.99)). In SG, BCPR rates were 59% for males and 52% for females. Similarly, females had a 22% lower adjusted odds of receiving BCPR (adjusted OR 0.78 (CI 0.62, 0.98)). In NC, survival to hospital discharge rates for public OHCAs were 24% for males and 26% for females. Females had a 17% lower adjusted odds ratio of survival to hospital discharge compared to males (adjusted OR 1.17 (95% CI 1.01, 1.35)). In SG, public survival to hospital discharge rates were 12% for males and 9% for females. Females had a 36% adjusted lower odds of survival to hospital discharge compared to males (adjusted OR 0.64 (95% CI 0.43, 0.94)). Conclusion: In public OHCAs, females were less likely to receive BCPR than males in both regions. However, females were less likely to survive to hospital discharge in SG, whereas the opposite was seen in NC. Further research is needed to elucidate factors for these differences.

Abstract 4120534: Long-Term Outcomes After Medication, Coronary Stenting or Surgery for Men and Women With Three-Vessel Coronary Disease

Background: Sex is a vital prognostic factor in patients with coronary heart disease, however, the data on sex-treatment interaction among real-world patients with three-vessel coronary disease (TVD) are limited. Objectives: This study aimed to investigate the long-term outcomes after medication therapy (MT), percutaneous coronary intervention (PCI), and coronary artery bypass grafting surgery (CABG) according to sex in patients with TVD. Methods: Consecutive 8943 patients with TVD [2421 (27.1%) MT, 3825 (42.8%) PCI, and 2697 (30.2%) CABG] were enrolled from April 2004 to February 2011 at Fu Wai Hospital. The primary endpoint was cardiac death and major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction (MI), stroke or repeat revascularization. The secondary endpoints were the components of MACCE. Results: Among 8943 TVD patients, 7122 (79.6%) were men and 1821 (20.4%) were women. While the number of women undergoing PCI was comparable to men, women opted for more MT and fewer CABG (Figure 1). During a median 6.6-year follow-up, CABG showed a lower risk of MACCE compared to PCI, with a similar treatment effect for women and men (female HR: 0.76; 95% CI: 0.60 to 0.97; male HR: 0.61, 95% CI: 0.55 to 0.69; p for interaction=0.222) (Figure 2 and Figure 3). CABG also showed lower risks of all-cause death, MI, and repeat revascularization, and a higher risk of stroke, which had no significant interaction with sex. PCI, compared to MT, was associated with lower risks of MACCE, all-cause death, and stroke and a higher risk of MI and repeat revascularization, without significant gender disparities. CABG versus MT was associated with lower risks of MACCE, all-cause death, MI and repeat revascularization and a higher risk of stroke, with a similar treatment effect for female and male patients (Figure 3). Conclusion: There was no significant sex differences in the risks of long-term outcomes of PCI vs. CABG, PCI vs. MT, and CABG vs. MT in real-world TVD patients.

Relationships among eye dimensions in magnetic resonance images by sex, age, and strabismus type in Japanese patients with acquired strabismus and high myopia.

To investigate the relationships among eye dimensions in magnetic resonance imaging (MRI) scans by sex, age, and strabismus type in Japanese patients with acquired strabismus and high myopia. Retrospective clinical case series. We included 58 eyes of 29 patients with acquired strabismus and high myopia (mean age ± standard deviation: 60.2 ± 14.7 years, axial length [AL]: 28.69 ± 2.12 mm). For all eyes, the equatorial diameter of the globe/AL ratio (EAR) and the globe/orbit volume ratio (GOR) were measured using MRI. EAR and GOR values were compared between the following groups: 9 men vs. 20 women; 8 younger (< 56 years) vs. 21 older (≥ 56 years) patients; and non-esotropia strabismus (NES: 7 patients) vs. esotropia (ET: 13 patients) vs. restrictive strabismus (RS: 9 patients) groups. Female patients had a smaller EAR (0.87 ± 0.07) and larger GOR (0.38 ± 0.04) than male patients (0.92 ± 0.05 and 0.35 ± 0.03, both P < 0.01). Older patients had a smaller EAR (0.87 ± 0.07) than younger ones (0.93 ± 0.04, P < 0.01), without significant differences in GOR. EAR (NES: 0.92 ± 0.06, ET: 0.86 ± 0.06, RS: 0.89 ± 0.09) significantly differed among the three strabismus groups (P = 0.02: post-hoc test: NES vs. ET, P = 0.02; NES vs. RS, P = 0.49; RS vs. ET, P = 0.67), but no significant differences in GOR were found (P = 0.12). Among patients with acquired strabismus and high myopia, women, older patients, and those with esotropia exhibit a smaller EAR and longer sphere shape with AL as the major axis. The parameter EAR might be useful for evaluating the pathogenesis of strabismus associated with high myopia.

CT pulmonary angiography in the inpatients: A 5-year retrospective view at the end of COVID-19 public health emergency.

To retrospectively evaluate the trends in utilization and results of computed tomography pulmonary angiography (CTPA study) for detection of acute pulmonary embolism (PE) in the hospital inpatients during different phases of COVID-19 public health emergency. We conducted an Institutional Review Board (IRB)-approved retrospective review of CTPA studies for our hospital inpatients in the years from 2019 to 2023, ranging from the prepandemic year (2019) to the year coinciding with the end of public health declarations (2023). Collected characteristics included patient age, patient sex, and result of the study. The utilization of CTPA studies for inpatients was higher in 2020 to 2023, compared to 2019 (3.8% in 2023 compared to 2.4% in 2019, P < .001). The increase in utilization was also statistically significant in each group, when stratified by age and sex (OR = 1.46 for female, OR = 1.71 for male, OR = 1.93 for elderly, and OR = 1.29 for non-elderly inpatients in 2023, compared to 2019). The positivity rate of acute PE in the inpatients was overall higher in 2021, 2022, and 2023, compared to 2019 (for example, 18.5% in 2023 compared to 14.3% in 2019, P = .01). When stratified by age and sex, only the non-elderly patients continued to have a significantly higher rate of acute PE in 2023, compared to 2019 (OR = 1.39). While studies spanning longer time frames and involving multiple institutions are needed to understand and generalize this conclusion, we conclude that the utilization and positivity rates of CTPA studies in inpatients remains high at the end of the COVID-19 pandemic public health emergency.

Advancements in MELD score and its impact in Hepatology.

There continues to be an ongoing need for fair and equitable organ allocation. The Model for End-stage Liver Disease (MELD) score has evolved as a calculated framework to evaluate and allocate patients for liver transplantation objectively. The original MELD score has undergone multiple modifications as it is continuously scrutinized for its accuracy in objectively representing the clinical context of patients with liver disease. Several refinements and iterations of the score have been developed, including the widely accepted MELD-Na score. In addition, the most recent updated iteration, MELD 3.0, has been created. The MELD 3.0 calculator incorporates new variables such as patient sex and serum albumin levels and assigns new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is anticipated that the use of MELD 3.0 scores will reduce overall waitlist mortality and enhance access for female liver transplant candidates. However, despite the emergence of the MELD score as one of the most objective measures for fair organ allocation, various countries and healthcare systems employ alternative methods for stratification and organ allocation. This review article highlights the origins of the MELD score, its iterations, the current MELD 3.0, and future directions for managing liver transplantation organ allocation.

CD70-Targeted Immuno-PET/CT Imaging of Clear Cell Renal Cell Carcinoma: A Translational Study.

The diagnosis and surveillance of clear cell renal cell carcinoma (ccRCC) remains a clinical challenge. The high and specific expression of the cluster of differentiation 70 (CD70) in ccRCC makes it a potential diagnostic and therapeutic target. Methods: We detected and analyzed CD70 expression in various renal cell carcinomas (RCCs) and normal kidneys using immunohistochemical staining. Two novel CD70-specific single-domain antibodies, RCCB3 and RCCB6, were produced and labeled with 68Ga to develop radiotracers. We performed immuno-PET/CT imaging with [68Ga]Ga-NOTA-RCCB3 and [68Ga]Ga-NOTA-RCCB6 in subcutaneous ccRCC patient-derived xenograft models. We recruited 8 RCC patients in a pilot clinical trial (ClinicalTrials.gov identifier: NCT06148220) to evaluate the diagnostic utility of [68Ga]Ga-NOTA-RCCB3 and [68Ga]Ga-NOTA-RCCB6 immuno-PET/CT. Results: Expression of CD70 is associated with sex, tumor differentiation, tumor thrombus, necrosis, distant metastasis, and overall survival of RCC patients. RCCB3 and RCCB6 had high affinities for recombinant human CD70. Immuno-PET/CT imaging with [68Ga]Ga-NOTA-RCCB3 and [68Ga]Ga-NOTA-RCCB6 rapidly visualized subcutaneous ccRCC with clarity. Tumor uptake of [68Ga]Ga-NOTA-RCCB6 was significantly reduced after the blockade of CD70. [68Ga]Ga-NOTA-RCCB6 PET/CT in ccRCC patients outperformed traditional 18F-FDG PET/CT in specifically identifying CD70-positive ccRCC metastases. Conclusion: CD70-targeted immuno-PET/CT imaging with [68Ga]Ga-NOTA-RCCB6 or [68Ga]Ga-NOTA-RCCB3 is a precise and superior method for evaluating tumor burden and suspected metastases in ccRCC patients. This advancement in imaging technology has the potential to improve the clinical decision-making process for this patient cohort significantly.

Pooled safety analysis from the VOLTAIRE clinical trials of adalimumab-adbm and adalimumab reference product in patients with rheumatoid arthritis, Crohn’s disease, and chronic plaque psoriasis

ABSTRACT Objectives This analysis reported the incidence of safety endpoints across five phase 3 randomized controlled clinical trials in patients with rheumatoid arthritis (RA), Crohn’s disease (CD), and chronic plaque psoriasis (PsO) who received ≥ 1 dose of adalimumab-adbm or adalimumab reference product (RP). Methods Exposure-adjusted incidence rates for safety endpoints were calculated per 100 patient-years and reported by disease indication and treatment arm. Subgroup analyses by patient age and sex were also conducted. Results The mean length of follow-up was 62 weeks, 48 weeks, and 32 weeks for patients with RA, CD, and PsO, respectively. Rates of SAEs and discontinuations due to AEs were similar among patients with RA and PsO, but slightly higher among those with CD. Incidence rates of all safety endpoints were consistent between the adalimumab-adbm and adalimumab RP treatment arms within each indication Subgroup analyses of patients with RA, CD, and PsO showed no between-group differences by age and sex. Conclusions In patients with RA, CD, and PsO, there were no differences between biosimilar adalimumab-adbm or the adalimumab RP regarding the rate of adverse events, serious adverse events, discontinuations due to adverse events, deaths, or any adverse events of special interest.

Factors influencing clavicular tunnel widening after single bundle coracoclavicular ligament reconstruction.

The coracoclavicular ligament reconstruction (CLR) technique for the treatment of acromioclavicular joint (ACJ) dislocation has gained immense clinical popularity. However, this technique also has some limitations including complications such as distal clavicle fractures, coracoid fractures, bone tunnel widening, implant failure, and loss of reduction. A study was conducted to analyse the extent of CTW after single-bundle CLR by measuring radiographic parameters to determine its relationship with clinical variables to reduce the risk of clavicular tunnel widening (CTW), thereby providing important insights for clinical practice. This retrospective analysis was conducted at Affiliated Fuyang People's Hospital of Bengbu Medical University, and data from 96 patients who underwent single-bundle CLR for type III-VI ACJ dislocation between January 2018 and December 2023 were initially collected. Finally, 84 patients met the inclusion criteria (63 male and 21 female, mean age: 49.5 ± 12.36 years). The clavicle tunnel (CT) width and coracoclavicular distance (CCD) was measured immediately postoperatively and at 6 months follow up using radiographic imaging, and the degree of expansion at 6 months was recorded. Preoperative variables including patient sex, age, injury cause, injury side, body mass index (BMI), Rockwood classification, extent of the CCD after surgery, and the CT location were recorded to analyze their correlation with the extent of CTW at 6 months follow up. With an average follow-up duration of 10 months (range: 6-18 months). Both the extent of the CCD and CTW measured at 6 months postoperatively were differently enlarged, compared to early postoperative period (EPO) (P < 0.05). The results showed that there were no statistically significant differences in the CTW at 6 months postoperatively with respect to patients' sex, causes of injury, sides of injury, and Rockwood classification types(P > 0.05). However, the location of CT was significantly associated with the extent of CTW at 6 months postoperatively (P < 0.05). The location of CT drilling is a significant factor that affects tunnel widening. When the drilling site is situated closer to the conoid tubercle, the extent of CTW is greater than when the tunnel is located farther from the conoid tubercle.

HyProCure for Flatfoot Deformity: A Clinical Characteristics Analysis in China.

Flatfoot is a common foot disorder involving progressive foot deformity of the three-dimensional structures of the forefoot, midfoot, and hindfoot. Currently, Chinese surgeons and patients favor subtalar arthroereisis (SA) due to its minimally invasive and low-damage characteristics. HyProCure device is widely used. However, there is limited analysis of large sample sizes. This study utilized statistical evaluation with a large sample size to analyze clinical characteristics trends of SA for flatfoot, including baseline indicators, selection of HyProCure size and surgical strategy, complications, and implant removal. This study will enhance the understanding of SA in China. A retrospective analysis of 732 patients (1008 ft) who underwent SA from June 2015 to June 2023, with 509 pediatric and adolescent patients (772 ft) and 223 adult patients (236 ft). Based on the patient's age, patients aged ≤ 18 were included in the children and adolescent group, while adult acquired flatfoot deformity (AAFD) patients aged > 18 were included in the adult group. General data was collected, including patient sex, age, side, body mass index (BMI), surgery date, HyproCure size, and surgical data, and trends were analyzed. Postoperative complications and HyProCure removal were collected as outcome measures during follow-up. The age of patients treated with SA was gradually getting younger, with male patients predominating, mainly concentrated in the 11-14 age group. HyProCure 7 has the highest usage rate. In the children and adolescent group, 288 ft (37.31%) only underwent SA. In the adult group, 18 ft (7.63%) only underwent SA. Complications include sinus tarsi pain, peroneal spasms, achilles tendon tension, and muscle strength decline. The complication rate in the children and adolescent group was 5.05%, while in the adult group it was 28.81%. Overall, it was 10.62%. The removal rate of HyProCure in the children and adolescent group is 1.04%, in the adult group is 15.25%, and overall is 4.37%. The trend in flatfoot treated with SA was towards children and adolescent male patients, and sinus tarsi pain was the most common complication after SA. The complication rate and removal rate in the children and adolescent group were lower than those in the adult group. HyProCure can be removed without additional adverse effects.

Sex-related differences in early morphological and clinical outcomes in patients with type A intramural haematoma: an observational cohort study.

To investigate sex-based differences in presenting characteristics and early outcomes of type A intramural haematoma. Patients with type A intramural haematoma in an institutional cohort were consecutively enrolled between December 2013 and July 2022. Presenting characteristics, morphological progression and all-cause death during hospitalization were evaluated according to patient sex. Among 473 patients, 48.0% were female. Females were older (65.9 ± 9.1 vs 58.5 ± 11.5 years, P < 0.001) with larger ascending aortic diameters (52.2 ± 6.6 vs 48.3 ± 6.1 mm, P < 0.001), thicker haematomas (11.5 ± 4.9 vs 9.5 ± 3.4 mm, P < 0.001) and more frequent focal intimal disruptions (45.4% vs 29.7%, P < 0.001). Within 30 days of initial medical therapy, 89.8% of males vs 70.1% of females showed morphological regression or stable condition on repeat computed tomography angiography. The in-hospital mortality was 9.7% in females (n = 22) and 2.8% in males (n = 7). Kaplan-Meier analysis revealed higher early mortality in females (P = 0.002). Multivariable Cox regression showed female sex as an independent risk factor for early death (hazard ratio: 2.8, 95% confidence interval: 1.2-6.8, P = 0.021). Subgroup analysis revealed no heterogeneity according to subgroups including older age (71-90 years), ascending aortic diameter ≥50 mm, presence of focal intimal disruption, presence of pericardial effusion, haematoma thickness ≥11 mm and hypertension. Female patients with type A intramural haematoma presented with worse characteristics, higher early morphological progression and an increased risk of early death compared to males.

P281 Multicentric analysis of the influence of sex in patients with metastatic invasive urothelial cancer in Northern Spain

P281 Multicentric analysis of the influence of sex in patients with metastatic invasive urothelial cancer in Northern Spain

Comprehensive Surgical Management of Thoracic Schwannomas: A Retrospective Multicenter Study on 98 Lesions.

The optimal surgical management of thoracic schwannomas (TSs) remains contentious, with various approaches proposed. Video-assisted thoracoscopic surgery (VATS) and combined VATS with neurosurgical procedures have shown promise, particularly for Eden type IV and III lesions. However, unanimous consent on the most effective surgical intervention and understanding of prognostic factors for tumor recurrence needs to be improved. The aim of this study was to elucidate the optimal surgical approach according to the Eden type and investigate predictive factors for TS recurrence. This retrospective, multicentric, observational study analyzed 98 surgically treated patients with TS from 2011 to 2023, assessing preoperative and 6-month follow-up clinical (recurrences, pain, and myelopathy recovery) and surgical parameters (operative time, intraoperative blood loss, extent of resection). Surgical procedures included thoracic laminectomy or hemilaminectomy for type I, laminectomy or thoracic transpedicular (TPD) approach for type II, laminectomy alone or combined laminectomy with VATS for type III, and VATS or thoracotomy (open thoracotomy [OT]) for type IV. Descriptive and deductive analyses were conducted between and within the 4 cohorts, with multivariate analysis assessing the contribution of predictor variables. No significant differences were found between hemilaminectomy and laminectomy for all analyzed parameters for type I. Type II lesions treated with TPD exhibited similar outcomes to laminectomy, albeit with longer procedure times. Type III lesions benefited from combined approaches compared with neurosurgical-only approaches. Video-assisted thoracoscopic surgery emerged as more favorable than OT for type IV lesions. Multivariate analysis revealed that patient sex, tumor location, extent of resection, and pathology significantly influenced recurrence rates. For Eden type III TSs, neurosurgical and VATS combined surgery achieved better outcomes than neurosurgery alone; for Eden type IV TSs, VATS achieved better results than OT. For Eden types I and II, hemilaminectomy and bilateral laminectomy and laminectomy and TPD achieved similar outcomes, respectively.

Immunogenicity of adalimumab reference product and adalimumab-adbm in patients with rheumatoid arthritis, Crohn’s disease and chronic plaque psoriasis: a pooled analysis of the VOLTAIRE trials

ObjectiveThis post hoc analysis compared the immunogenicity of the biosimilar adalimumab-adbm (Cyltezo) with the adalimumab reference product (RP; Humira) across indications, including rheumatoid arthritis (RA), Crohn’s disease (CD) and plaque psoriasis (PsO), and by patient sex in the VOLTAIRE trials programme.MethodsIn each active-comparator randomised controlled trial (RCT), immunogenicity was assessed at various time points by the proportion of patients with antidrug antibodies (ADAs) and neutralising antibodies (nAbs), using acid dissociation followed by electrochemiluminescence assay. Assay sensitivity was 50 ng/mL, and drug tolerance was ≥30 µg/mL (free drug) at the low positive control level.ResultsMinor differences in immunogenicity parameters (ADAs, ADA titres and nAbs) were evident between adalimumab-adbm and adalimumab RP across these three immune-mediated inflammatory diseases (IMIDs). The proportion of ADA-positive and nAb-positive patients increased from baseline over time in all three RCTs, as expected, and was similar in the RA and CD RCTs but with higher numbers of ADA-positive and nAb-positive patients reported in the PsO trial. Subgroup analysis by patient sex showed the same trend.ConclusionsDifferences among the RCTs may partially be explained by concomitant background therapy (methotrexate) in the RA trial, stable doses of azathioprine, 6-mercaptopurine or methotrexate in 36% of patients with CD and absence of background therapy in the PsO RCT. The analyses further confirm the biosimilarity of adalimumab-adbm with the adalimumab RP across IMIDs and provide supporting evidence that adalimumab-adbm is an interchangeable biosimilar with consistent clinical results in patients originally treated with the RP.Trial registration numbersVOLTAIRE-RA (NCT02137226; EudraCT 2012-002945-40); VOLTAIRE-CD (NCT02871635; EudraCT 2016-000612-14); VOLTAIRE-PsO (NCT02850965; EudraCT 2016-000613-79).

Evaluation of Cold and Electric Pulp Tests for Assessing the Success of Inferior Alveolar Nerve Block for Mandibular First Molars diagnosed with Symptomatic Irreversible Pulpitis

IntroductionFear of dentistry, often due to past painful experiences, is a significant barrier preventing patients from visiting dentists. Achieving effective pain control, especially during root canal treatments, is crucial. However, inferior alveolar nerve blocks (IANB) have a low success rate, influenced by factors such as anxiety, anatomical variations, and technique limitations, leading to anesthesia failure. Although numerous studies have examined the cold test and EPT in assessing the success of local anesthesia, no standardized method has been established. This study evaluated the effectiveness of electric pulp test (EPT) and cold tests in assessing the depth of anesthesia in patients with symptomatic irreversible pulpitis (SIP) in the mandibular first molar teeth. MethodsA cross-sectional study was conducted on 50 patients with SIP who met the inclusion criteria and exhibited lip numbness. Following the administration of the IANB and confirmation of lip numbness, cold tests and EPT were performed on all patients. Subsequently, the preparation of the access cavity (gold standard test) was initiated, and patients' responses during cavity preparation were recorded as either "presence of pain or discomfort" or "absence of pain or discomfort," indicating IANB failure and success, respectively. Sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (LR-/+), and accuracy (AC) with 95% confidence intervals (CI) were calculated for each test separately as well as for sequential testing. ResultsIANB failure was determined in 56% of the patients. A comparative analysis of diagnostic tests (cold test and EPT) showed no significant difference in SN, NPV, and AC; however, the cold test had higher SP, PPV, and LR+. Combining cold test and EPT evaluations improved SN, NPV, PPV, and LR-, but SP and AC were similar to EPT alone. No correlation was found between IANB success and patient age, sex, or initial pain. ConclusionsDespite evidence of lip numbness, a significant number of IANBs failed in cases of painful pulpitis. A positive result from the cold test strongly indicated anesthesia failure. The findings of the current study suggested that when the cold test yielded a negative result, further evaluation with EPT was necessary to confirm anesthetic success and ensure complete pain control.

Ulcerative Colitis Patients are at Increased Risk for Adverse Events Following Total Hip Arthroplasty

BackgroundPatients who have the autoinflammatory bowel disease ulcerative colitis (UC) may become candidates for total hip arthroplasty (THA). Having UC may predispose patients to postoperative adverse events, but it remains unclear if these events are related more to the disease process itself or perhaps related to the medications used to treat the condition. MethodsPatients undergoing THA were identified from a large administrative dataset. Those who did not have and those who had UC were matched 4:1 based on patient age, sex, and the Elixhauser Comorbidity Index (ECI). Matched THA patients who did not have UC (n = 19,482) and those who had UC (n = 4,874) were identified. The matched groups were compared regarding 90-day adverse and five-year survival. Further analyses were performed based on classes of medications. ResultsControlling for patient age, sex, and ECI, UC patients were at significantly higher odds of 90-day adverse events: any (odds ratio [OR] 1.59), severe (OR 1.72), and minor (OR 1.63) (all P < 0.001). Despite this, no differences in 5-year survival were identified. Relative to those who did not have UC, there were increasing odds of any adverse event based on the potency of related medications: no corticosteroids /immunomodulators/5-aminosalicylic acid (5-ASA) (OR 1.42), corticosteroids only (OR 1.58), 5-ASA ± corticosteroids OR (1.72), and immunomodulators ± corticosteroids (OR 1.74, all P < 0.001). ConclusionsTotal hip arthroplasty patients who have UC were at higher odds for 90-day postoperative adverse events relative to those who did not have UC, and this risk was even greater for those on defined classes of medications. Total hip arthroplasty patients who have UC bear specific considerations, and surgeons must carefully consider and manage the patient’s medication regimen in the perioperative period of the THA.

The association between non-HDL cholesterol and high-grade pancreatic neuroendocrine neoplasms.

High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs). A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis. Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49). A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.