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International Immunopharmacology Jun 2024Immune checkpoint therapy (ICT) has been shown to produce durable responses in various cancer patients. However, its efficacy is notably limited in hepatocellular...
Immune checkpoint therapy (ICT) has been shown to produce durable responses in various cancer patients. However, its efficacy is notably limited in hepatocellular carcinoma (HCC), with only a small percentage of patients responding positively to treatment. The mechanism underlying resistance to ICT in HCC remains poorly understood. Here, we showed that combination treatment of ICG-001, an inhibitor of the Wnt/β-catenin signaling pathway, with anti-PD-1 antibody effectively suppresses tumor growth and promotes the infiltration of immune cells such as DCs and CD8 T cells in the tumor microenvironment (TME). By inhibiting the activity of β-catenin and blocking its binding to the transcription factor IKAROS family zinc finger 1 (IKZF1), ICG-001 upregulated the expression of CCL5. Moreover, IKZF1 regulated the activity of the CCL5 promoter and its endogenous expression. Through inhibition of the WNT/β-catenin signaling pathway, upregulation of the expression of CCL5 was achieved, which subsequently recruited more DCs into the TME via C-C motif chemokine receptor 5 (CCR5). This, in turn, resulted in an increase in the infiltration of CD8 T cells in the TME, thereby enhancing the antitumor immune response. Analysis of a tissue microarray derived from HCC patient samples revealed a positive correlation between survival rate and prognosis and the expression levels of CCL5/CD8. In conclusion, our findings suggest that combined application of ICG-001 and anti-PD-1 antibody exhibits significantly enhanced antitumor efficacy. Hence, combining a WNT/β-catenin signaling pathway inhibitor with anti-PD-1 therapy may be a promising treatment strategy for patients with HCC.
PubMed: 38941667
DOI: 10.1016/j.intimp.2024.112534 -
Journal of Neurosurgery Jun 2024The highly intricate nature of the cervical spinal cord can cause arteriovenous shunts in these segments that may be associated with heightened clinical risks and...
OBJECTIVE
The highly intricate nature of the cervical spinal cord can cause arteriovenous shunts in these segments that may be associated with heightened clinical risks and treatment complexities. In this article, the authors aimed to provide a comprehensive analysis of the detailed natural course, treatment, and clinical outcomes of cervical spinal cord arteriovenous shunts (SCAVSs) based on the largest cohort to date.
METHODS
Two hundred forty consecutive patients were included. Data on clinical presentation, angioarchitecture, treatment, and follow-up were retrospectively reviewed.
RESULTS
The cohort demonstrated a greater prevalence of acute onset (63.3% vs 36.7%). Spontaneous recovery was observed in 63.7% of patients after onset, with a significantly elevated recovery rate observed among patients experiencing acute onset (72.4% vs 48.9%, p < 0.001). The risks of acute and gradual clinical deterioration after onset was 11.9%/year and 13.4%/year, respectively. Microsurgery was performed in 39.6% of patients, while the remaining 60.4% exclusively underwent embolization. The complete obliteration rate was 65.3% after microsurgery and 21.4% after embolization. The rate of treatment-related deterioration was 14.7% after microsurgery and 6.2% after embolization. After partial treatment, the acute and gradual deterioration rates were 4.1%/year and 6.6%/year, respectively. Lack of spontaneous recovery after onset was an independent predictor of embolization-related deterioration (OR 17.905, p = 0.007) and long-term gradual deterioration after partial treatment (HR 2.325, p = 0.021). After a median follow-up period of 32.55 months, prognosis was unfavorable in 16.7% of patients, with the sole independent risk factor being the absence of spontaneous recovery after onset (OR 2.476, p = 0.018).
CONCLUSIONS
The outcomes of patients with cervical SCAVS were generally favorable, even in patients with only partial obliteration of the lesions. However, patients who did not show a trend toward spontaneous recovery after onset had a significantly elevated risk of unfavorable prognosis, highlighting the need for prompt clinical intervention.
PubMed: 38941649
DOI: 10.3171/2024.4.JNS232552 -
Journal of Neurosurgery Jun 2024Controversy surrounds the prognostic value of contrast-enhanced T1-weighted (T1CE) imaging-based subventricular zone (SVZ) classification in isocitrate dehydrogenase...
Subventricular zone-associated classification in isocitrate dehydrogenase-wildtype glioblastomas: improved prognostic value through integration of FLAIR with contrast-enhanced imaging.
OBJECTIVE
Controversy surrounds the prognostic value of contrast-enhanced T1-weighted (T1CE) imaging-based subventricular zone (SVZ) classification in isocitrate dehydrogenase (IDH)-wildtype glioblastomas (GBMs). In this study, the authors aimed to assess the potential of incorporating FLAIR imaging into T1CE imaging-based classification for improving prognostic accuracy.
METHODS
A retrospective analysis was conducted on 281 patients with IDH-wildtype GBM. T1CE imaging-based classification was performed, and T2-weighted/FLAIR imaging was integrated to evaluate its prognostic estimation ability. Based on the relationship between the tumors and SVZ, patients were categorized into SVZ+ and SVZ- cohorts based on T1CE and T2-weighted/FLAIR imaging findings. Kaplan-Meier and Cox proportional hazards regression analyses were used to assess progression-free survival (PFS) and overall survival (OS), respectively. Patients were then categorized into three subgroups based on their combined classifications: group 1 (SVZ+ on T1CE and T2-weighted/FLAIR imaging), group 2 (SVZ- on T1CE but SVZ+ on T2-weighted/FLAIR imaging), and group 3 (SVZ- on T1CE and T2-weighted/FLAIR imaging). Subgroup analysis was used to evaluate differences in clinical and molecular factors as well as in prognoses.
RESULTS
The T1CE imaging-based classification failed to stratify OS between SVZ+ and SVZ- cohorts (16.0 vs 20.0 months, p = 0.36). Survival analysis revealed similar prognoses for patients in groups 1 and 2, and patients in group 2 exhibited worse OS compared with those in group 3 (19.0 vs 23.5 months, p = 0.024). Logistic regression identified lower Karnofsky Performance Status (KPS) (p = 0.011), tumor diameter (p = 0.002), and telomerase reverse transcriptase (TERT) promoter mutation (p = 0.003) to be associated with a higher incidence of group 2 GBMs. Additionally, T2-weighted/FLAIR imaging-based classification provided significant prognostic value (17.0 vs 23.5 months p = 0.021) and was found to be an independent prognostic factor in the Cox multivariate analysis (HR 1.79, 95% CI 1.08-2.96; p = 0.024).
CONCLUSIONS
This study underscores the limitations of T1CE imaging-based SVZ-associated classification in predicting prognosis for IDH-wildtype GBMs. The authors therefore propose an integrated approach that involves T2-weighted/FLAIR imaging that can provide improved prognostic ability. Notably, the presence of TERT promoter mutation was identified as a critical factor in nonenhancing tumor infiltration into the SVZ. Further validation through extensive cohort studies is recommended to confirm these findings.
PubMed: 38941641
DOI: 10.3171/2024.4.JNS232658 -
Journal of Neurosurgery Jun 2024The objective of this study was to develop a nomogram to predict long-term facial nerve (FN) function after vestibular schwannoma (VS) resection.
OBJECTIVE
The objective of this study was to develop a nomogram to predict long-term facial nerve (FN) function after vestibular schwannoma (VS) resection.
METHODS
A retrospective cohort study of two tertiary academic skull base referral centers was performed. Consecutive adults > 18 years of age with sporadic unilateral VS who underwent resection between September 2016 and May 2021 were included. FN function in the immediate postoperative period and at the most recent evaluation was measured.
RESULTS
A total of 306 patients (mean age 49 years, 63% female) were included, with a mean follow-up of 18 months. The mean maximum tumor diameter was 19 mm (range 1-50 mm), and 80 (26.1%) tumors were > 25 mm. Overall, 85% of patients showed good immediate postoperative FN function (House-Brackmann [HB] grade I or II) and 89% maintained good FN function at > 12 months of follow-up. An intraoperative FN electromyographic (EMG) response ≥ 100 µV to 0.05 mA of stimulation (OR 18.6, p < 0.001) was the strongest predictor of good HB grade in the immediate postoperative period. EMG response ≥ 100 µV (OR 5.70, p < 0.001), tumor size ≤ 25 mm (OR 3.09, p < 0.05), and better immediate postoperative HB grade (OR 1.48, p = 0.005) predicted good long-term FN function on multivariable analysis. A point-of-care nomogram based on these data predicted long-term FN function with a sensitivity of 89% and specificity of 69%.
CONCLUSIONS
Better immediate postoperative HB grade, intraoperative FN EMG response ≥ 100 µV, and tumor size ≤ 25 mm strongly predicted good long-term FN function after VS resection. A point-of-care nomogram based on these variables could serve as a useful tool for postoperative counseling and prognosis of long-term FN recovery.
PubMed: 38941635
DOI: 10.3171/2024.4.JNS232208 -
JMIR Public Health and Surveillance Jun 2024Globally, over 39% of individuals are obese. Metabolic syndrome, usually accompanied by obesity, is regarded as a major contributor to noncommunicable diseases. Given...
BACKGROUND
Globally, over 39% of individuals are obese. Metabolic syndrome, usually accompanied by obesity, is regarded as a major contributor to noncommunicable diseases. Given this relationship, the concepts of metabolically healthy and unhealthy obesity, considering metabolic status, have been evolving. Attention is being directed to metabolically healthy people with obesity who have relatively low transition rates to noncommunicable diseases. As obesity rates continue to rise and unhealthy behaviors prevail among young adults, there is a growing need for obesity management that considers these metabolic statuses. A nomogram can be used as an effective tool to predict the risk of transitioning to metabolically unhealthy obesity from a metabolically healthy status.
OBJECTIVE
The study aimed to identify demographic factors, health behaviors, and 5 metabolic statuses related to the transition from metabolically healthy obesity to unhealthy obesity among people aged between 20 and 44 years and to develop a screening tool to predict this transition.
METHODS
This secondary analysis study used national health data from the National Health Insurance System in South Korea. We analyzed the customized data using SAS (SAS Institute Inc) and conducted logistic regression to identify factors related to the transition from metabolically healthy to unhealthy obesity. A nomogram was developed to predict the transition using the identified factors.
RESULTS
Among 3,351,989 people, there was a significant association between the transition from metabolically healthy to unhealthy obesity and general characteristics, health behaviors, and metabolic components. Male participants showed a 1.30 higher odds ratio for transitioning to metabolically unhealthy obesity than female participants, and people in the lowest economic status were also at risk for the transition (odds ratio 1.08, 95% CI 1.05-1.1). Smoking status, consuming >30 g of alcohol, and insufficient regular exercise were negatively associated with the transition. Each relevant variable was assigned a point value. When the nomogram total points reached 295, the shift from metabolically healthy to unhealthy obesity had a prediction rate of >50%.
CONCLUSIONS
This study identified key factors for young adults transitioning from healthy to unhealthy obesity, creating a predictive nomogram. This nomogram, including triglycerides, waist circumference, high-density lipoprotein-cholesterol, blood pressure, and fasting glucose, allows easy assessment of obesity risk even for the general population. This tool simplifies predictions amid rising obesity rates and interventions.
Topics: Humans; Republic of Korea; Male; Female; Adult; Young Adult; Obesity, Metabolically Benign; Metabolic Syndrome; Nomograms; Obesity; Health Behavior; Risk Factors
PubMed: 38941611
DOI: 10.2196/52103 -
Neurology(R) Neuroimmunology &... Sep 2024Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw...
BACKGROUND AND OBJECTIVES
Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS).
METHODS
We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests.
RESULTS
In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]:1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], 3.82e). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR: 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], = 0.04). Compared with raw values with arbitrary cutoffs, applying the score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score).
DISCUSSION
In conclusion, our work demonstrated reference cohort-based scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.
Topics: Humans; Female; Male; Tomography, Optical Coherence; Adult; Middle Aged; Disease Progression; Prognosis; Multiple Sclerosis; Retina; Severity of Illness Index
PubMed: 38941572
DOI: 10.1212/NXI.0000000000200269 -
Cancer Jun 2024Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy.
BACKGROUND
Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy.
METHODS
A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed.
RESULTS
A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses.
CONCLUSIONS
Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.
PubMed: 38941496
DOI: 10.1002/cncr.35454 -
Medicine Jun 2024Isolated popliteal artery occlusions are rare compared with femoropopliteal occlusive diseases. Although endovascular procedures have gained importance in treatment,...
Isolated popliteal artery occlusions are rare compared with femoropopliteal occlusive diseases. Although endovascular procedures have gained importance in treatment, conventional surgery remains the gold standard. In this study, we reviewed popliteal endarterectomy and patch plasty using a posterior approach. Fourteen patients who underwent surgery for isolated popliteal artery occlusions were retrospectively examined. Patients were assessed in terms of age, sex, and risk factors, such as accompanying diseases and smoking, surgical method and anesthesia, incision type, preoperative and postoperative pulse examination, ankle-brachial indices, patency, wound infection, postoperative complications, and the treatment applied. Twelve (85.7%) patients were male, and 2 (14.3%) were female. Limb ischemia was critical (ABI < 0.7) in 11 (78.5%) patients. The average duration of postoperative hospitalization was 8 ± 3.7 days on average, and the average length of follow-up was 17 ± 3.4 months. Thrombosis and complications requiring secondary intervention did not develop during the early postoperative period. While the patency rate in the first 6 months of follow-up was 100%, it was 92.8% in the 1st year and 85.7% in the 2nd year. Surgical treatment with the posterior approach in isolated popliteal artery lesions is preferred by vascular surgeons as a prioritized treatment method, with a sufficient recanalization rate and low perioperative morbidity and mortality rates. Furthermore, it is promising because it does not prevent below-knee femoropopliteal bypass, which is the subsequent stage of treatment. Moreover, the great saphenous vein was protected, and the acceptable early- and mid-term results were encouraging.
Topics: Humans; Popliteal Artery; Male; Female; Endarterectomy; Retrospective Studies; Aged; Middle Aged; Arterial Occlusive Diseases; Constriction, Pathologic; Treatment Outcome; Postoperative Complications; Vascular Patency
PubMed: 38941441
DOI: 10.1097/MD.0000000000038693 -
Medicine Jun 2024This study aimed to evaluate the clinical and radiological features of the patella fixation technique using Toggleloc suspension system in a single ellipsoidal blind...
BACKGROUND
This study aimed to evaluate the clinical and radiological features of the patella fixation technique using Toggleloc suspension system in a single ellipsoidal blind patellar tunnel during medial patellofemoral ligament (MPFL) reconstruction.
METHODS
This study included 52 patients (25 men, 27 women) who underwent MPFL reconstruction using a semitendinosus tendon graft. The graft was fixed to the ellipsoidal single blind tunnel opened on the medial side of the patella with an endobutton and was fixed to the femoral tunnel by using bioabsorbable screw. Clinical scores (Kujala score, Lysholm score, Tegner activity score and the visual analog scale [VAS] score) were evaluated preoperatively and at the end-follow up. Preoperative and postoperative radiological measurements (trochlea depth, sulcus angle, patellar height, patellar congruence angle, patellar tilt angle and lateral patellofemoral angle) were evaluated with X-ray (Merchant X-ray, anteroposterior and lateral radiography) and computed tomography (CT) of the knee.
RESULTS
Postoperative patellar redislocation or subluxation was not observed in any patient. Patellar congruence angle, patellar tilt angle and lateral patellofemoral angle mean values were found to return to normal values in the postoperative period and the results were statistically significant. Also statistically significant improvement in all clinical scores postoperatively. According to the Insall-Salvati index (ISI) and Caton-Deschamps index (CDI) on lateral radiography of the knee at 30° flexion, patellar height decreased in the postoperative period statistically significant. The CDI was above 1.3 in 17 (%32) of our patients. Thirteen of these values decreased to normal values. No radiological progression of patellofemoral osteoarthritis was observed in all patients at the final follow-up evaluation.
CONCLUSION
In cases of patellofemoral instability, fixation of the tendon graft in blind ellipsoid tunnel using the Toggleloc suspension system provides satisfactory patellar graft fixation strength, significant functional improvement and a low failure rate.
Topics: Humans; Female; Male; Adult; Patellofemoral Joint; Follow-Up Studies; Patella; Plastic Surgery Procedures; Young Adult; Ligaments, Articular; Treatment Outcome; Adolescent
PubMed: 38941440
DOI: 10.1097/MD.0000000000038379 -
Medicine Jun 2024Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding... (Observational Study)
Observational Study
Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding is the presence of mechanic's hands. The aim of the present study was to describe the clinical, functional, tomographic, and serological data of patients with ILD and mechanic's hands and their response to treatment and survival rates. This is a retrospective study of ILD with concurrent myopathy. Among the 119 patients initially selected, 51 had mechanic's hands. All the patients were screened for anti-Jo-1 antibodies. An expanded panel of myopathy autoantibodies was also performed in 27 individuals. Of the 51 patients, 35 had 1 or more antibodies. The most common were anti-Jo-1, anti-PL-7, and anti-PL-12, while of the associated antibodies, anti-Ro52 was present in 70% of the 27 tested individuals. A significant response to treatment was characterized by an increase in predicted forced vital capacity (FVC) of at least 5% in the last evaluation done after 6 to 24 months of treatment. A decrease in predicted FVC of at least 5%, the need for oxygen therapy, or death were all considered treatment failures. All patients were treated with corticosteroids, and 71% with mycophenolate. After 24 months, 18 patients had an increase in FVC, 11 had a decrease, and 22 remained stable. After a median follow-up of 58 months, 48 patients remained alive and three died. Patients with honeycombing on high-resolution chest tomography (log-rank = 34.65; P < .001) and a decrease in FVC ≥5% (log-rank = 18.28, P < .001) had a poorer survival rate. Patients with ILD and mechanic's hands respond well to immunosuppressive treatment.
Topics: Humans; Lung Diseases, Interstitial; Retrospective Studies; Male; Female; Middle Aged; Myositis; Aged; Treatment Outcome; Adult; Autoantibodies; Outpatients; Adrenal Cortex Hormones; Vital Capacity
PubMed: 38941439
DOI: 10.1097/MD.0000000000038642