Risk Factors For Disease Progression Research Articles

Misclassified Alcohol-related Liver Disease is Common in Presumed Metabolic Dysfunction-associated Steatotic Liver Disease and Highly Increases Risk for Future Cirrhosis

Background and aimsAlcohol overconsumption is a risk factor for disease progression in patients with presumed metabolic dysfunction-associated steatotic liver disease (MASLD). How commonly this occurs and how it affects progression to major adverse liver outcomes (MALO) is not well known. MethodsWe did a register-based cohort study, including all patients with a diagnosis of MASLD in Sweden between 1987 and 2020. Patients were stratified on co-occurrence of diagnoses of alcohol-related liver disease (ALD) or alcohol use disorder (AUD) prior to MASLD diagnosis. Incident MALO:s were derived from national registers. Cox regression was used to calculate hazard ratios for incident MALO. ResultsA total of 15,107 patients with MASLD were identified. Median age was 55 years and 52% were female. 1,843 (12%) had a prior diagnosis of ALD or AUD. During follow-up, a further 787 (5.2%) received a diagnosis of ALD or AUD. Patients with previous ALD or AUD diagnoses at or before baseline had considerably higher rates of MALO compared to patients without (19.5% vs 7.8%, aHR=3.12, 95%CI=2.74-3.55). Acquiring an ALD or AUD diagnosis after MASLD diagnosis was associated with higher rates of MALO (aHR=5.81, 95%CI=4.90-6.88). ConclusionsALD or AUD is commonly diagnosed prior to or after MASLD diagnosis. Such patients have considerably higher rates of progression to MALO. Correctly separating between MASLD and ALD is vital to assess prognosis.

Childhood-onset IgA nephropathy: is long-term recovery possible?

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. While studies have primarily focused on identifying risk factors for disease progression, very few data exist on the likelihood of achieving complete recovery from the disease. We conducted a single-center retrospective study on all consecutive patients with biopsy-proven IgAN diagnosed between 1986 and 2018 in our pediatric center. Biopsies were classified according to the MEST-C Oxford classification score. "Complete clinical remission" was defined as the absence of proteinuria, hematuria, and hypertension in patients with normal kidney function who had been off therapy for more than 2 years. Overall, 153 patients with age at onset of 10.6 ± 4 years were enrolled in the study. Of these, 41 achieved "complete clinical remission." The estimated probability of complete clinical remission at 10 years was 43% (95%CI 33-54). However, seven patients relapsed within 10 years. Multivariable analysis showed that higher age at onset (HR 0.89, 95%CI 0.80-0.98, p = 0.017) and segmental glomerulosclerosis lesions (HR 0.28, 95%CI 0.10-0.79, p = 0.017) decreased significantly the chances of achieving complete clinical remission. Immunosuppressive therapy was not significantly associated with clinical outcomes. Approximately one-third of patients with pediatric-onset IgAN achieve prolonged remission, in particular, very young children at disease onset without sclerotic glomerular lesions. Longer term follow-up is needed to assess if these patients have achieved permanent remission.

Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience.

Peptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment. We retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups. A total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively. The study's results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly.

The Effect of Radial Inclination on the Stage of Kienbock Disease at the Time of Initial Diagnosis.

Negative ulnar variance is a widely accepted risk factor for the development of Kienbock disease (KD). Variation in radial inclination has been proposed as a risk factor, but evidence thus far has been inconclusive. We aim to clarify the relationship between radial inclination and KD. A retrospective analysis of all KD patients from a single institution from 2007 to 2021 was conducted. Radiographs were reviewed to measure anatomic parameters and stage of disease. An exploratory multinomial regression model was created to examine the association of patient age, radial height, ulnar variance, radial inclination, volar tilt, scapholunate angle, duration of symptoms prior to evaluation, history of wrist trauma, and diagnosis of diabetes with stage of disease. Fifty-seven cases of KD were identified, with a mean duration of disease of 33.3 months. A history of trauma to the wrist was common (53%) and significantly associated with stage of disease at initial presentation. Twenty-seven cases (47%) were stage IIIB or greater. The average initial radial inclination, radial height, and ulnar variance was 21.9°, 10.7 mm, and -1.23 mm, respectively. A multinominal logistic regression model revealed decreased initial radial inclination is associated with Lichtman stage IIIB or greater at the time of initial patient presentation. A correlation exists between decreased radial inclination and more advanced KD at presentation, suggesting this may be a risk factor for disease progression. This correlation is strengthened by our finding of decreased ulnar variance being associated with later stage at presentation, which is one of the most widely accepted proposed risk factors for development and progression of disease. IV.

Predictive value of dynamic changes in peripheral blood inflammation and blood lipid-related indices for the lung cancer treatment efficacy.

To investigate the dynamics of inflammation and lipid-related indicators in lung cancer patients and their impact on treatment efficacy. A retrospective analysis was conducted on 133 lung cancer patients who seek for primary treatment at Wujin Hospital Affiliated to Jiangsu University from January 2019 to August 2022. The inflammation and blood lipid-related indicators were collected 1 week before treatment and after 2 cycles of treatment. We compared the changes in these indicators among patients with different treatment methods and outcomes. The diagnostic value of the dynamic changes in each index for disease progression was calculated using the ROC curve. The risk factors influencing disease development were identified using multifactorial logistic regression analysis. After 2 cycles of treatment, the white blood cell count (WBC, P<0.001), neutrophil count (NC, P<0.001), neutrophil-to-lymphocyte ratio (NLR, P<0.001) in the disease progression (PD) group were significantly increased, triglyceride (TG, P=0.023), apolipoprotein A1 (APO-A1, P=0.009) was significantly decreased. The results showed that ∆NC had the highest sensitivity (88.24%) in predicting disease progression, and ∆WBC had the best specificity (77.78%). Multivariate regression analysis showed that ΔWBC (P<0.001), ΔTG (P=0.041), and treatment method (P=0.010) were independent risk factors for disease progression (PD). The changes of WBC and TG before and after treatment are promising indicators for predicting the progression of lung cancer and may offer a new direction for lung cancer treatment.

Histologic features and predicting prognosis in ulcerative colitis patients with mild endoscopic activity.

We aimed to evaluate the histologic features predictive of prognosis and correlate them with endoscopic findings in patients with ulcerative colitis (UC) having complete or partial mucosal healing (MH). We prospectively collected and reviewed data from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsy. Complete and partial MH were defined as Mayo endoscopic subscores (MESs) of 0 and 1, respectively. Histologic variables, including the Nancy index (NI), predicting disease progression (defined as the need for medication upgrade or hospitalization/surgery), were evaluated and correlated with endoscopic findings. Overall, 441 biopsy specimens were collected from 194 patients. The average follow-up duration was 14.7 ± 7.4 months. There were 49 (25.3%) and 68 (35.1%) patients with MESs of 0 and 1, respectively. Disease progression occurred only in patients with an MES of 1. NI ≥ 3 was significantly correlated with disease progression during follow-up. Mucosal friability on endoscopy was significantly correlated with NI ≥ 3 (61.1% in NI < 3 vs. 88.0% in NI ≥ 3; p = 0.013). Histological activity can help predict the prognosis of patients with UC with mild endoscopic activity. Mucosal friability observed on endoscopy may reflect a more severe histological status, which can be a risk factor for disease progression.

Pre-treatment pan-immune-inflammation value as a prognostic marker of pazopanib in soft tissue sarcoma.

Increasingly, more evidence has shown that inflammation stress and the tumor microenvironment pose a negative effect on targeted therapy. The neutrophil-to-lymphocyte ratio is considered to be a surrogate biomarker of inflammation and can predict pazopanib treatment effect in non-adipocytic soft-tissue sarcoma (STS). The role of the pan-immune-inflammation value (PIV) in STS is still yet to be determined. We sought whether the pre-treatment PIV could be applied to predict the response of pazopanib in STS. We conducted a retrospective analysis of 75 patients who had been treated with pazopanib for recurrent or metastatic non-adipocytic STS. Our cohort was stratified into either a pre-treatment high PIV group with PIV ⩾310 (n = 45) or a low PIV group with PIV <310 (n = 30). We compared their clinical features and outcomes. Cox regression analysis was employed to determine the risk factors of disease progression and mortality. Kaplan-Meier survival curves were utilized to assess both the progression-free survival (PFS) and overall survival (OS). The results revealed that a pre-treatment high PIV (⩾310) is a risk factor for progression under pazopanib (hazard ratio: 1.91; 95% confidence interval: 1.08-3.36; p = 0.025). The median PFS and OS of the pre-treatment high PIV group were found to be significantly lower than the low PIV group (0.33 vs 0.75 years; p = 0.023, 0.46 vs 1.63 years; p = 0.025). High pre-treatment PIV in STS patients may indicate an elevated risk of disease progression and mortality. Pre-treatment PIV reflects inflammation stress and acts as a practical biomarker for STS patients treated with pazopanib.

Serum Phosphorus Might Be a Predictor of Kidney Disease Progression in IgA Nephropathy

Introduction: High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease, whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN. Methods: A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus and kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline or kidney failure, was evaluated using Cox models. Results: Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238–5.400, p = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783–0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756–0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95% CI, 1.791–14.944; p = 0.002). Conclusion: Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression.

Long-term non-progression and risk factors for disease progression among children living with HIV in Botswana and Uganda: A retrospective cohort study

ObjectivesWe utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda. MethodsElectronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era. ResultsBetween the two countries, 14,246 antiretroviral therapy-naïve children infected with HIV were enrolled into clinical care. The overall proportion of LTNP was 6.3% (9.5% in Botswana vs 5.9% in Uganda). The median progression-free survival for the cohort was 6.3 years, although this was lower in Botswana than in Uganda (6.6 vs 8.8 years; P <0.001). At baseline, the adjusted subdistribution hazard ratio (aHRsd) of progression was increased among underweight children (aHRsd 1.42; 95% confidence interval [CI]: 1.32-1.53), enrolled after 2010 (aHRsd 1.32; 95% CI 1.22-1.42), and those from Botswana (aHRsd 2; 95% CI 1.91-2.10). ConclusionsIn our study, the prevalence of pediatric LTNP was lower than that observed among adult populations, but progression-free survival was higher than expected. Underweight, year of enrollment into care, and country of origin are independent predictors of progression among children.

A Real-World Evaluation of Risk Factors for Disease Progression in Patients with Polycythemia Vera (PV) Enrolled in REVEAL

Background: PV is a myeloproliferative neoplasm complicated by symptom burden, splenomegaly, vascular events, and disease progression to myelofibrosis (MF). Current risk models for PV include advanced age and history of thrombotic events (TEs), yet information on risk factors for PV progression is limited. In this analysis, we assessed the rate of PV progression to MF during the P rospective Obs ervational Study of Patients With Polycythemia Vera in US Clinic al Practices Trial (REVEAL) and assessed baseline demographics and disease characteristics as risk factors for PV progression. Methods: Criteria for enrollment in REVEAL included a physician-reported PV diagnosis. PV progression was defined by meeting any of the following criteria during the study: 1) Death from MF/myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML); 2) new/worsening splenomegaly, plus 2 of the following criteria: white blood cell (WBC) count &amp;gt;11×10 9/L, platelets (PLT) &amp;lt;100×10 9/L, hemoglobin (Hb) &amp;lt;10 g/dL; 3) evidence of progression to MF from bone marrow (BM) biopsy; 4) new/worsening splenomegaly, plus blasts &amp;gt;1%. Univariate and multivariate logistic regressions were performed to assess risk factors of PV progression. Results: Of the 2510 patients enrolled in REVEAL, 1191 (47.5%) were reported to have a JAK2 mutation at enrollment. To confirm PV diagnosis, digital droplet PCR for JAK2 p.V617F was performed on all patients with the first available biospecimen from an optional biological specimen substudy; 1520/1871 (81.2%) were positive. A further 367 patients with a physician-reported JAK2 mutation and 135 with a PV diagnosis confirmed by BM aspirate/biopsy were included; 488 patients (19.4%) who did not meet any criteria were excluded. Of the 2022 patients with confirmed diagnosis, median (range) follow-up was 44.1 (0-59.5) months; 134 (6.6%) progressed to MF (BM evidence of MF, n=69 [3.4%]; new/worsening splenomegaly, plus 2 of the following criteria WBC count &amp;gt;11×10 9/L, PLT &amp;lt;100×10 9/L, Hb &amp;lt;10 g/dL, n=44 [2.2%]; new/worsening splenomegaly, plus blasts &amp;gt;1%, n=37 [1.8%]; death from MF/MDS/AML, n=22 [1.1%]). A nonsignificant trend toward higher mean JAK2 p.V617F variant allele frequency was observed in patients with vs without progression (Table 1). Compared with patients without progression to MF, patients with progression were of similar age (69.5 vs 68.0 y) and had a longer time from PV diagnosis to enrollment (median, 7.2 vs 3.7 y; P&amp;lt;0.0001; Table 1). The percentage of patients with vs without progression enrolled via academic practices was 23.1% vs 16.9%; the percentage of patients with vs without progression who had no cytoreductive treatment prior to enrollment was 85.1% vs 91.2%. PV risk stratification (age &amp;gt;60 y or history of TEs) at enrollment was similar for patients with vs without progression (high risk, 61.9% vs 63.5%). However, a higher percentage of patients with vs without progression had a history of TEs at enrollment (29.9% vs 19.7%; P=0.0050). Univariate analysis also identified hematocrit (HCT) ≤0.45 L/L (63.9% vs 53.5%; P=0.0288) and WBC count &amp;gt;11×10 9/L (50.4% vs 31.8%; P&amp;lt;0.0001) at enrollment as significantly different between patients with vs without progression, respectively (Figure 1). In univariate analyses, time from PV diagnosis, TE history, HCT ≤0.45 L/L, WBC count &amp;gt;11×10 9/L at enrollment were each associated with increased PV progression risk (Figure 1). These factors were retained as significant covariates in multivariate analyses with stepwise model selection (OR [90% CI]: time from PV diagnosis to enrollment, 1.030 [1.016-1.044], P&amp;lt;0.0001; history of TEs at enrollment, 1.96 [1.281-2.998], P=0.0019; HCT &amp;gt;0.45 vs ≤0.45 L/L, 0.637 [0.421-0.964], P=0.0330; WBC &amp;gt;11 vs ≤11×10 9/L, 2.205 [1.477-3.292], P&amp;lt;0.0001). Conclusions: This real-world analysis of prospective data from REVEAL found that 6.6% of patients with PV progressed to MF over the median 44.1 months of follow-up. Time from diagnosis to enrollment and history of TEs were each significantly associated with an increased risk of PV progression; the latter finding regarding TE history was unexpected and represents a potentially novel risk factor for PV progression. HCT ≤0.45 L/L and WBC &amp;gt;11×10 9/L at enrollment were also significantly associated with an increased progression risk. Additional analysis is ongoing to better understand the causal relationships between these risk factors and PV progression.

The Important Role of Egfr Change in Patients with Multiple Myeloma

Background. Renal impairment is a common complication in multiple myeloma (MM) patients and related to a higher mortality. However, whether the change of estimated glomerular filtration rate (eGFR) is associated with prognosis is not clear currently. Patients and Methods. A total of 1552 myeloma patients in West China Hospital from July 1, 2008 to September 1, 2022 were retrospectively included in this study, patients with dialysis or complicated with other malignancy were excluded. All patients had at least 3 measurements of creatinine and eGFR between 6 months and 2 years after baseline. The 1-year change in eGFR (slope) was calculated by linear regression, patients were divided into 3 groups by the eGFR slope (sustained group: eGFR slope was -5 ~ 5 ml/min per 1.73 m2 per year over 2 years; increased group: eGFR Slope &amp;gt; 5 ml/min per 1.73 m2 per year over 2 years; decreased group: eGFR Slope &amp;lt; -5 ml/min per 1.73 m2 per year over 2 years ), the Kaplan-Meier survival analysis, multiple Cox regression model and Restricted cubic spline (RCS) analysis were applied to explore the association of eGFR slope with the best efficacy and progression of myeloma patients. Results. After a median follow-up of 21 months, 977(62.95%) patients had reached VGPR or CR (the best efficacy), 24.1% patients experienced progression, the survival status is currently being followed up. The eGFR decline more than 5 ml/min per 1.73 m2 per year over 2 years (decreased group) was showed to have a higher risk of disease progression (P=0.01, Figure 1a) and to be an independent risk factor for disease progression, both in patients with (eGFR&amp;lt;60 ml/min per 1.73 m2) or without (eGFR&amp;gt;60 ml/min per 1.73 m2) renal failure (Table 1). The RCS analysis showed that the decline of eGFR within 2 years was positively related to the risk of disease progression, while the eGFR rise with a certain range could reduce the risk of progression (0-6.4 ml/min per 1.73 m2 per year) (Figure 1b). Inversely, the eGFR increased group showed a higher possibility of acquiring very good partial remission (VGPR) or complete remission (CR) (Figure 1c, P&amp;lt;0.001), and was a beneficial factor of reaching VGPR or CR for MM patients (HR 1.3, 95%CI 1.05-1.62, P=0.015, Table 1). The RCS analysis showed that eGFR slope was linearly correlated with patients' VGPR or CR rate (Figure 1d). Notably, in patients without renal insufficiency at baseline (eGFR&amp;gt;60 ml/min per 1.73 m2), eGFR improvement did not increase the rate of VGPR or CR (Table 1). Conclusions. eGFR decreasing &amp;gt;5 ml/min per 1.73 m2 per year over 2 years could increase the risk of disease progression in MM patients with or without renal impairment, while eGFR increasing at a certain range could reduce progression risk. For myeloma patients with renal impairment, eGFR increasing may improve the rate of VGRP or CR in MM patients.

514. Nirmatrelvir/ritonavir or Molnupiravir for Treatment of Non-hospitalized Patients with COVID-19 at Risk of Disease Progression

Abstract Background In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents. Methods Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with &amp;gt;1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers’ preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was severe, critical, or fatal disease within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups and 1:1 matched groups. Cohort construction Results Between January 1 and November 30, 2022, 9,172 individuals were eligible for inclusion (6,692 prescribed NMV/r; 2,480 prescribed MPV). The ARD for severe, critical, or fatal disease for NMV/r vs MPV was -0.18 (95% CI -0.45 to 0.09). There was no statistically significant difference in ARD among strata by age, race, sex, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value=0.43). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.12, 95% CI -0.71 to 0.47). Conclusion We found no significant difference in short term risk of severe, critical or fatal disease in non-hospitalized individuals with COVID-19 at risk of disease progression treated with either NMV/r or MPV. Disclosures Adeel A. Butt, MBBS, MS, Gilead Sciences: Grant/Research Support|Merck and Company: Grant/Research Support

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective study

PurposeWe aimed to investigate the efficacy and side effects of concurrent chemoradiotherapy, with or without nimotuzumab, for the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy.MethodsThis study retrospectively enrolled 109 patients with NPC from our hospital from July 2019 to May 2021.All patients were treated with docetaxel, cisplatin, and fluorouracil(TPF) neoadjuvant chemotherapy for 2 cycles, and concurrent chemoradiotherapy was performed 2 weeks after chemotherapy. According to whether nimotuzumab was added in concurrent chemoradiotherapy, they were divided into the nimotuzumab group and the control group, with 52 cases in the nimotuzumab group and 57 cases in the control group.The efficacy and adverse reactions of the two groups were retrospectively analyzed.ResultsThe objective remission and complete remission rates in the nimotuzumab and control groups were 100% vs 98.2% (p = 1.000), and 92.3% vs 78.9% (p = 0.049), respectively. The 3-year distant metastasis-free survival of the nimotuzumab and control groups was 91.6% and 77.3% (p = 0.047), respectively.The 3-year progression-free survival, locoregional relapse-free survival, and overall survival of the nimotuzumab and control groups were 87.6% vs 75.5% (p = 0.110), 90.5% vs 86.9% (p = 0.566), and 94.5% vs 87.1% (p = 0.295), respectively. In the nimotuzumab group, subgroup analysis showed that patients aged < 60 years (hazard ratio [HR] = 0.350, 95% confidence interval [CI]: 0.131–0.934, p = 0.036) and those with a neutrophil-to-lymphocyte ratio (neutrophil/lymphocyte ratio) ≤ 4 (HR = 0.365, 95% CI: 0.144–0.923, p = 0.033) achieved a better result. Additionally, multivariate analysis demonstrated that neutrophil/lymphocyte ratio was an independent risk factor for disease progression (HR = 7.485, p = 0.012) and distant metastasis (HR = 17.540, p = 0.009).No grade 4 adverse reactions were observed in either group. Grade 3 oral mucosal reactions, as well as pharyngeal and esophageal reactions were slightly higher in the nimotuzumab group than in the control group, but the difference was not statistically significant. No significant differences were observed in the incidence of adverse reactions such as leukopenia, HB reduction, thrombocytopenia between the two groups (P > 0.05).ConclusionThe concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma achieved a higher complete remission rate and significantly improved distant metastasis-free survival compared with concurrent chemoradiotherapy alone. Additionally, an increasing trend was observed in progression-free survival, and the incidence of side effects was similar in both groups.

Analysis of clinical characteristics and risk factors between elderly patients with severe and nonsevere Omicron variant infection

BACKGROUND Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to millions of confirmed cases and deaths worldwide. Elderly patients are at high risk of developing and dying from COVID-19 due to advanced age, decreased immune function, intense inflammatory response, and comorbidities. Shanghai has experienced a wave of infection with Omicron, a new variant of SARS-CoV-2, since March 2022. There is a pressing need to identify clinical features and risk factors for disease progression among elderly patients with Omicron infection to provide solid evidence for clinical policy-makers, public health officials, researchers, and the general public. AIM To investigate clinical characteristic differences and risk factors between elderly patients with severe and nonsevere Omicron SARS-CoV-2 variant infection. METHODS A total of 328 elderly patients with COVID-19 admitted to the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 2022 to June 2022 were enrolled and divided into a severe group (82 patients) and a nonsevere group (246 patients) according to the diagnosis and treatment protocol of COVID-19 (version 7). The clinical data and laboratory results of both groups were collected and compared. A chi-square test, t test, Mann-Whitney U test, hierarchical log-rank test, univariate and multivariate logistic regression, and hierarchical analyses were used to determine significant differences. RESULTS The severe group was older (84 vs 74 years, P &lt; 0.001), included more males (57.3% vs 43.9%, P = 0.037), had a lower vaccination rate (P &lt; 0.001), and had a higher proportion of comorbidities, including chronic respiratory disease (P = 0.001), cerebral infarction (P &lt; 0.001), chronic kidney disease (P = 0.002), and neurodegenerative disease (P &lt; 0.001), than the nonsevere group. In addition, severe disease patients had a higher inflammatory index (P &lt; 0.001), greater need for symptomatic treatment (P &lt; 0.001), longer hospital stay (P = 0.011), extended viral shedding time (P = 0.014), and higher mortality than nonsevere disease patients (P &lt; 0.001). No difference was observed in the application of Paxlovid in the severe and nonsevere groups (P = 0.817). Oxygen saturation, cerebral infarction, and D-dimer were predictive factors for developing severe disease in patients with COVID-19, with D-dimer having an excellent role (area under the curve: 90.1%, 95%CI: 86.1-94.0%). In addition, D-dimer was a risk factor for developing severe COVID-19 according to multivariate stratified analysis. CONCLUSION The clinical course of severe COVID-19 is complex, with a higher need for symptomatic treatment. D-dimer is a suitable biomarker for identifying patients at risk for developing severe COVID-19.

Lineage-specific regulation of PD-1 expression in early-stage hepatocellular carcinoma following 90yttrium transarterial radioembolization – Implications in treatment outcomes

BackgroundHepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths in the world. Liver-directed therapies, including 90Yttrium (90Y) radioembolization, play an integral role in the management of HCC with excellent response rates. This has led to clinical trials of immunotherapy in combination with 90Y. Elevated PD-1 expression and lymphopenia were recently shown as risk factors for disease progression in early-stage HCC treated with liver-directed therapies. The aim of this study was to investigate PD-1 expression dynamics in bridge/downstage to transplant in HCC patients receiving first-cycle 90Y and evaluate the impact of these changes on response rates and time-to-progression (TTP). MethodsPatients with HCC receiving first-cycle 90Y as a bridge to liver transplantation (n = 99) were prospectively enrolled. Blood specimens were collected before 90Y and again during routine imagining follow-up to analyze PD-1 expression via flow cytometry. Complete and objective response rates (CR and ORR) were determined using mRECIST. ResultsIn 84/88 patients with available follow-up imaging, 83% had a localized ORR with 63% having localized CR. For overall response, 71% and 54% experienced ORR and CR, respectively. Post-90Y PD-1 upregulation in CD8 + associated with HCC progression and decreased TTP. Treatment with 90Y was associated with an anticipated significant post-treatment drop in lymphocytes (P < 0.001) that was independent of PD-1 expression for either CD4+ or CD8+ T cells (P = 0.751 and P = 0.375) and not associated with TTP risk. The change in lymphocytes was not correlated with PD-1 expression following treatment nor TTP. ConclusionsElevated PD-1 expression on peripheral T cells is associated with increased risk of HCC progression and shorter time to progression in bridging/downstaging to transplant HCC patients undergoing first-cycle 90Y. Treatment-induced lymphopenia was not associated with treatment response, or increased progression risk, suggesting this anticipated adverse event does not impact short-term HCC outcomes.

High-dose chemotherapy with transplantation of autologous hematopoietic stem cells in the first line of follicular lymphoma therapy

Introduction. The follicular lymphoma (FL) is the most common indolent lymphatic tumor with high sensitivity to immunochemotherapy un most cases. Although overall survival (OS) is generally long, the disease is characterized by multiple relapses. High-dose chemotherapy (HDCT) with transplantation of autologous hematopoietic stem cells (auto-HSCT) is used for recurrent FL. Aim: to evaluate the efficacy and safety of HDCT with aHSCT in the first line of FL therapy; identify risk factors for disease progression and refractoriness. Material and methods. A prospective single-center study (conducted from May 2015 to January 2023) included 35 patients aged 18–65 years (median 43) with PL 1–3A grade t(14;18)+ with stages III–IV or stage II with bulky, having at least one criterion for the need to start therapy (according to GELF). Patients were treated according to the FL-2015 protocol: 4 R-CHOP, 2 R-DHAP and BeEAM with auto-HSCT. The primary endpoint was the rate of overall response (OR) and/or complete remission (CR) at the end of chemotherapy. Secondary end points were 3-year survival rates: OS, relapse-free survival (RFS), progression-free survival (PFS), and event-free survival (EFS). Minimal residual disease (MRD) in blood and/or bone marrow was assessed by PCR based on immunoglobulin heavy chain (IGH) gene rearrangements and/or BCL2::IGH rearrangements. Statistical analysis (by intent to treat) was performed on January 12, 2023. Results. 86 % of patients had stage IV tumor and 79 % had 3–5 FLIPI factors. After the end of treatment, OR and PR were 90 % and 90 %, the incidence of POD24 was 3 %. After the end of induction (4 courses of R-CHOP), MRD-negativity was achieved in 77 % and 53 % of patients as determined by PCR-IGH and BCL2::IGH. After the full completion of the FL-2015 protocol, MRD was not detected in 96 % of patients (according to PCR-IGH). Three-year overall survival, disease-free survival, progression-free survival and event-free survival were respectively: 90 %, 90 %, 95 % and 85 % (with the same standarderror of 9 %) at a median follow-up (by inverse Kaplan-Meier estimate) of 19 months (range: from 1 to 91 months) There were no deaths due to early toxicity within 100 days of auto-HSCT. Prognostically unfavorable independent statistically significant (р &lt; 0.01; Wald test; hazard ratio &gt; 1) predictors of progression and refractoriness according to the results of multivariate analysis using the Fine-Grey competing risk model (р = 0.052 for the model) were: bone marrow disease, ECOG high risk, patient age &gt; 50 years, stage 4 disease, elevated serum lactate dehydrogenase and B-symptoms. Conclusion. The use of HDCT with auto-HSCT in the first line in patients with FL is highly effective and can significantly reduce the incidence of POD24 and early mortality from the tumor. The study is ongoing.

Epigenetic alterations in urothelial bladder cancer associated with disease outcomes.

Bladder cancer (BLCA) is a molecular heterogeneous disease with known genetic distinctive signatures. However, DNA methylation is highly prevalent across a wide range of tumors, suggesting its potential in oncogenesis. Here, we aimed to interrogate the role of nine epigenetic alterations as diagnostic and prognostic markers in BLCA. DNA methylation, gene expression, and clinicopathological information were retrieved from The Cancer Genome Atlas data portal. Methylation values and gene expression were assessed to determine their association with normal and malignant tissue. Additionally, we studied the association between methylation values and clinicopathological variables. For the prognostic model, Kaplan-Meier Survival curves were generated. Lastly, univariate and multivariate analysis were performed to evaluate the simultaneous impact of methylation and clinicopathological variables on the risk of tumor progression and survival. Nine CpG sites' methylation -values involved in our study demonstrated different methylation signatures between normal and malignant urothelium. Hypermethylated CpGs were overrepresented in tumor tissue (p < 0.0001). Opposingly, 4 CpG sites showed lower methylation values in tumor samples (p < 0.0001). Cg12743248high and cg17192862low are risk factors for progression-free survival, whereas cg12374721high (HR:3.003 (1.283-7.030)) also demonstrated to be the most valuable independent risk factor for disease progression and a risk factor for overall survival. We have identified that methylated cg12374721 shows promise as a diagnostic and independent prognostic marker in BLCA progression.

Real-world clinical effectiveness of Tixagevimab/Cilgavimab and Regdanvimab monoclonal antibodies for COVID-19 treatment in Omicron variant-dominant period.

https://clinicaltrials.gov/, identifier NCT05982704.

Opportunities to improve the prognosis of the course of COVID-19 for at-risk patients

To evaluate the efficacy and safety of a combination of virus neutralizing monoclonal antibodies in the treatment of patients with confirmed COVID-19 and risk factors for disease progression and severe disease course. The study was carried out in the Sokolniki temporary hospital of the Inozemtsev City Clinical Hospital. A retrospective comparative case-control study included 400 patients hospitalized for confirmed COVID-19 infection from November 01, 2022 to March 31, 2023. Patients were divided into two groups depending on the treatment given: the first control group (n=200) and the second group (n=200), where patients received a single intramuscular injection of tixagevimab + cilgavimab within the first days of hospitalization. When analyzing the concomitant pathology, C-reactive protein level and CT scans at the time of hospitalization, it was revealed that patients in the tixagevimab + cilgavimab treatment group were more severe compared to the control group. On the 2nd day of hospitalization, there was a decrease in the level of C-reactive protein in the control group by 36.2%, in the group receiving tixagevimab + cilgavimab - by 45.2%; p<0.05. Standard treatment was supplemented with antibacterial therapy in 47 (23.5%) patients of the first group and in 32 (16.0%) patients of the second group, which was due to the accession of bacterial infection; p<0.05. Significant differences were found in the duration of hospitalization, which averaged 8.0±0.21 bed-days in group 1 and 6.4±0.13 (p<0.05) bed-days in group 2. No adverse reactions to intramuscular injection of tixagevimab + cilgavimab were detected. The use of a combination of neutralizing monoclonal antibodies in patients with COVID-19 reduce the average bed-day in hospitalization of patients with comorbid pathology and/or immunodeficiencies and high risk of progression of infection.

The Outcome of Childhood Immunoglobulin A Nephropathy with Acute Kidney Injury at the Onset of the Disease-National Study.

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Decreased glomerular filtration rate is a known risk factor for disease progression. Aim: We aimed to examine factors that may contribute to disease progression in children that present with impaired eGFR at the onset of IgAN. Materials and methods: Of the 175 patients with IgAN from the Polish Registry of Children with IgAN and IgAVN, 54 (31%) patients with IgAN who had an onset of renal function impairment (GFR < 90 mL/min) were eligible for the study. All of them were analyzed for initial symptoms (GFR according to Schwartz formula, creatinine, proteinuria, IgA, C3), renal biopsy result with assessment by Oxford classification, treatment used (R-renoprotection, P-prednisone+R, Aza-azathioprine+P+R, Cyc-cyclophosphamide+P+R, CsA-cyclosporine+P+R, MMF-mycophenolate mofetil+P+R), and distant follow-up. Based on the GFR score obtained at the end, patients were divided into two groups: A-GFR > 90 mL/min and B-GFR < 90 mL/min. Results: In the study group, the mean age of onset was 12.87 ± 3.57 years, GFR was 66.1 ± 17.3 mL/min, and proteinuria was 18.1 (0-967) mg/kg/d. Renal biopsy was performed 0.2 (0-7) years after the onset of the disease, and MESTC score averaged 2.57 ± 1.6. Treatment was R only in 39% of children, P+R in 20%, Aza+P+R in 28%, Cyc+P+R in 9%, CsA+P+R in 7%, and MMF+P+R in 3%. The length of the observation period was 2.16 (0.05-11) years. At the follow-up, Group A had 30 patients (56%) and Group B had 24 patients (44%). There were no significant differences in any of the other biochemical parameters (except creatinine) or proteinuria values between the groups and the frequency of the MESTC score ≥ 2 and <2 was not significantly different between Groups A and B. Patients with normal GFR at the follow-up (Group A) were significantly more likely to have received prednisone and/or immunosuppressive treatment than those in Group B (p < 0.05) Conclusions: In a population of Polish children with IgAN and decreased renal function at the onset of the disease, 56% had normal GFR in remote observation. The use of immunosuppressive/corticosteroids treatment in children with IgAN and impaired glomerular filtration rate at the beginning of the disease may contribute to the normalization of GFR in the outcome, although this requires confirmation in a larger group of pediatric patients.