Clinical characteristics and prognosis of pancreatitis associated with immune checkpoint inhibitors.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy against various cancers in clinical practice. However, ICIs can cause immune checkpoint inhibitor-associated pancreatic injury, often leading to drug withdrawal, and then patients must go to specialized treatment. The patients, their primary tumors are sensitive to ICIs therapy, may experience treatment delays due to such adverse reactions. Therefore, there is a need for systematic clinical researches on immune-related pancreatic toxicity to provide a clinical basis for its prevention and treatment. METHODS: This study involved the collection of data from patients treated with ICIs and addressed pancreatic injury with preemptive treatment before continuing ICIs therapy. Then, we also statistically analyzed the incidence of pancreatic injury in patients with different courses and combined treatment, and the success rate of rechallenge treatment. RESULTS: The study included 62 patients, with 33.9% (21/62) experiencing varying degrees of pancreatic injury. Patients with pancreatic injury, 10 cases evolved into pancreatitis, representing 47.6% (10/21) in the pancreatic injury subgroup and 16.1% (10/62) of the total patient cohort. Preemptive treatment was administered to 47.6% (10/21) of patients with pancreatitis, the effective rate was 100%. Among these patients, 70% (7/10) underwent successful rechallenge with ICIs. The occurrence of pancreatic injury was positively correlated with the treatment duration (P < 0.05) but showed no significant correlation with combination therapies (P > 0.05). CONCLUSION: The likelihood of pancreatic injury increased with longer treatment durations with ICIs; no significant association was found between the incidence of ICIs-related pancreatic damage and combination therapies. Preemptive treatment for immune-related pancreatitis is feasible, allowing some patients to successfully undergo rechallenge with ICIs therapy.

EFFICACY OF FULL-ENDOSCOPIC INTERLAMINAR AND TRANSFORAMINAL DISCECTOMY FOR LUMBER DISC HERNIATION.

A previous study has reported the therapeutic effects of interlaminar/transforaminal approaches under full-endoscopic visualization to treat L5-S1 lumber disc herniation (LDH). However, the comparison of interlaminar/transforaminal approaches to treat other segments of LDH remains unclear. OBJECTIVE: To evaluate the clinical efficacy of full-endoscopic interlaminar and transforaminal lumbar discectomy to treat LDH. METHODS: A total of 93 patients with LDH who underwent fully-endoscopic lumbar interlaminar/transforaminal discectomy were retrospectively collected. Patients were divided into a Transforaminal group (n=41) and an Interlaminar group (n=52). Clinical efficacy was evaluated by visual analogue scale (VAS), the Oswestry disability index (ODI), and the modified MacNab scoring system. RESULTS: Of the 93 patients, involving segments in LDH referred to L3-4, L4-5, and L5-S1. The fluoroscopy times in the Interlaminar group were smaller than that of the Transforaminal group. We found no obvious significances between the Transforaminal and Interlaminar groups regarding operation time, incision length, postoperative landing time, hospitalization, and incision healing time. Postoperative VAS and ODI scores notably improved at follow-up. Besides, almost 90% LDH patients achieved excellent/good outcomes. CONCLUSION: The full-endoscopic visualization technique via interlaminar and transforaminal approaches safely and effectively treat LDH. Level of Evidence III, Retrospective Study.

Um estudo anterior relatou os efeitos terapêuticos das abordagens interlaminar/transforaminal sob visualização totalmente endoscópica para tratar a hérnia de disco lombar (HDL) L5-S1. No entanto, a comparação das abordagens interlaminar/transforaminal para o tratamento de outros segmentos de HDL permanece pouco clara. Objetivo: Avaliar a eficácia clínica da discectomia lombar interlaminar e transforaminal totalmente endoscópica no tratamento da HDL. Métodos: Foram recolhidos retrospetivamente 93 pacientes com HDL submetidos a discectomia lombar interlaminar/transforaminal totalmente endoscópica. Os pacientes foram divididos em um grupo transforaminal (n=41) e um grupo interlaminar (n=52). A eficácia clínica foi avaliada através da escala visual analógica (EVA), do índice Oswestry de incapacidade (ODI) e do sistema de pontuação de MacNab modificado. Resultados: Dos 93 pacientes, os segmentos envolvidos na HDL referiam-se a L3-4, L4-5 e L5-S1. Os tempos de fluoroscopia no grupo Interlaminar foram menores do que no grupo Transforaminal. Não encontramos significâncias óbvias entre os grupos Transforaminal e Interlaminar em relação ao tempo de operação, comprimento da incisão, tempo de pós-operatório, hospitalização e tempo de cicatrização da incisão. As pontuações EVA e ODI pós-operatórias melhoraram notavelmente no acompanhamento. Além disso, quase 90% dos pacientes com HDL obtiveram resultados excelentes/bons. Conclusão: A técnica de visualização totalmente endoscópica através de abordagens interlaminar e transforaminal trata a HDL de forma segura e eficaz. Nível de Evidência III, Estudo Retrospectivo.

A comprehensive analysis of immunogenic cell death and its key gene HSP90AA1 in bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is defined as a type of urinary cancer with high incidence and lack of specific biomarkers and drug targets. Immunogenic cell death (ICD) has been classified as a regulated type of cell death. Growing evidence suggested that ICD can reshape the tumor immune microenvironment, which may contribute to the development of immunotherapy strategies. The aim of this study was to reveal the specific mechanism of ICD in bladder cancer and to further predict the prognostic immunotherapy outcomes. METHODS: By consensus clustering analysis, bladder cancer patients in TCGA database were divided into different ICD subtypes. Additionally, we developed an ICD-scoring system and constructed the ICD score-based risk signature and nomogram to better characterize patients. Furthermore, we carried out a series of experiments to verify the relevant findings. RESULTS: Based on the transcriptome expression levels of ICD-related genes, a total of 403 BLCA patients in the TCGA database were divided into two subgroups with different ICD molecular patterns by consensus cluster analysis. These subgroups showed different clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related scores, and treatment response. Moreover, the established prediction model and ICD score can effectively distinguish high risk/score patients from low risk/score patients, which has excellent predictive value. Finally, we found that the key gene HSP90AA1 was highly expressed in the high-ICD score group and in bladder cancer tissues, and was confirmed to be associated with the proliferation of bladder cancer cells. CONCLUSION: To sum up, we established a new classification system for BLCA based on ICD-related genes. This stratification has significant predictive power for clinical outcomes and can effectively evaluate the prognosis and immunotherapy of BLCA patients. Finally, it was proved that HSP90AA1 was highly expressed in BLCA and would be a promising therapeutic target for BLCA.

Efficacy of full-endoscopic interlaminar and transforaminal discectomy for lumber disc herniation / Eficácia da discectomia interlaminar e transforaminal totalmente endoscópica na hérnia de disco lombar

ABSTRACT A previous study has reported the therapeutic effects of interlaminar/transforaminal approaches under full-endoscopic visualization to treat L5-S1 lumber disc herniation (LDH). However, the comparison of interlaminar/transforaminal approaches to treat other segments of LDH remains unclear. Objective: To evaluate the clinical efficacy of full-endoscopic interlaminar and transforaminal lumbar discectomy to treat LDH. Methods: A total of 93 patients with LDH who underwent fully-endoscopic lumbar interlaminar/transforaminal discectomy were retrospectively collected. Patients were divided into a Transforaminal group (n=41) and an Interlaminar group (n=52). Clinical efficacy was evaluated by visual analogue scale (VAS), the Oswestry disability index (ODI), and the modified MacNab scoring system. Results: Of the 93 patients, involving segments in LDH referred to L3-4, L4-5, and L5-S1. The fluoroscopy times in the Interlaminar group were smaller than that of the Transforaminal group. We found no obvious significances between the Transforaminal and Interlaminar groups regarding operation time, incision length, postoperative landing time, hospitalization, and incision healing time. Postoperative VAS and ODI scores notably improved at follow-up. Besides, almost 90% LDH patients achieved excellent/good outcomes. Conclusion: The full-endoscopic visualization technique via interlaminar and transforaminal approaches safely and effectively treat LDH. Level of Evidence III, Retrospective Study.

RESUMO Um estudo anterior relatou os efeitos terapêuticos das abordagens interlaminar/transforaminal sob visualização totalmente endoscópica para tratar a hérnia de disco lombar (HDL) L5-S1. No entanto, a comparação das abordagens interlaminar/transforaminal para o tratamento de outros segmentos de HDL permanece pouco clara. Objetivo: Avaliar a eficácia clínica da discectomia lombar interlaminar e transforaminal totalmente endoscópica no tratamento da HDL. Métodos: Foram recolhidos retrospetivamente 93 pacientes com HDL submetidos a discectomia lombar interlaminar/transforaminal totalmente endoscópica. Os pacientes foram divididos em um grupo transforaminal (n=41) e um grupo interlaminar (n=52). A eficácia clínica foi avaliada através da escala visual analógica (EVA), do índice Oswestry de incapacidade (ODI) e do sistema de pontuação de MacNab modificado. Resultados: Dos 93 pacientes, os segmentos envolvidos na HDL referiam-se a L3-4, L4-5 e L5-S1. Os tempos de fluoroscopia no grupo Interlaminar foram menores do que no grupo Transforaminal. Não encontramos significâncias óbvias entre os grupos Transforaminal e Interlaminar em relação ao tempo de operação, comprimento da incisão, tempo de pós-operatório, hospitalização e tempo de cicatrização da incisão. As pontuações EVA e ODI pós-operatórias melhoraram notavelmente no acompanhamento. Além disso, quase 90% dos pacientes com HDL obtiveram resultados excelentes/bons. Conclusão: A técnica de visualização totalmente endoscópica através de abordagens interlaminar e transforaminal trata a HDL de forma segura e eficaz. Nível de Evidência III, Estudo Retrospectivo.

Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study.

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

Coexistence of low levels of HBsAg and high levels of anti-HBs may increase risk of hepatocellular carcinoma in chronic hepatitis B patients with high HBV load.

OBJECTIVE: The clinical significance of coexistence of HBsAg/anti-HBs in chronic hepatitis B (CHB) patients remains controversial. This study was aimed to assess the association of this serological pattern with hepatocellular carcinoma (HCC) in patients with CHB. METHODS: In this cross-section study, 206 CHB patients with coexistence of HBsAg/anti-HBs and 206 CHB patients with HBsAg alone were included to evaluate the risk of HCC development by logistic regression analysis. In addition, a retrospective cohort of 260 patients with CHB was recruited to estimate the cumulative incidence of HCC by Kaplan-Meier analysis. RESULTS: The serological pattern of coexistence of HBsAg/anti-HBs, with high levels of ("High") HBsAg/low levels of ("Low") anti-HBs, were considered as independent risk factors for HCC. In particular, patients with "High" HBsAg/"High" anti-HBs [odds ratio (OR), 4.295; 95% confidence interval (CI), 1.104-16.699; p = 0.035] and "Low" HBsAg/ "High" anti-HBs (OR, 3.207; 95%CI, 1.299-7.919; p = 0.012) exhibited significantly higher risk for HCC development. However, only "Low" HBsAg /"High" anti-HBs might increase risk of HCC in CHB patients with high HBV load (logrank p < 0.001) in our cohort study. CONCLUSION: The coexistence of "Low" HBsAg /"High" anti-HBs might increase the risk of HCC development in CHB patients with high HBV load, which reflected that the long-term interaction between immune response and virus might lead to the development of HCC. The identification of the patients with poor prognosis will help clinicians to refine the therapeutic decisions and individualize follow-up strategies.

Effect of Artemisia apiacea Hance on growth performance, cecal opportunistic bacteria, and microbicidal peptides in rabbits

This study aimed to investigate the effect of Artemisia apiacea Hance supplementation on growth performance, cecal opportunistic bacteria, and antimicrobial defense using 120 rabbits. There were four experimental diets containing a control and A. apiacea Hance added at doses of 25, 50, and 75 g kg−1 of feed. The trial lasted for 70 days. The results showed that diets supplemented with A. apiacea Hance improved feed intake, body weight gain, and feed efficiency. Linear and quadratic responses were found between feed intake and herbal meal doses. For cecal opportunistic pathogenic bacteria, compared with the control treatment, the herb decreased cecal C. perfringens, Gram-negative bacteria, and Salmonella spp. by 9.5 to 56.8%. Linear responses of herb doses were found on the four bacteria and a quadratic response on Salmonella spp. In addition, the herb increased the mRNA levels by 12.6 to 57.8% of cecal defensive peptides, including neutrophil peptide defensing-3a, regenerating family member-3 gamma defensin beta-1, and galectin-4. These genes linearly responded to the herb doses. The obtained data suggest that A. apiacea Hance is effective to improve animal growth by beneficially regulating gut opportunistic bacteria and microbicidal peptide activity.(AU)

Silencing of the integrin-linked kinase gene suppresses the proliferation, migration and invasion of pancreatic cancer cells (Panc-1).

Integrin-linked kinase (ILK) is an ankyrin repeat-containing serine-threonine protein kinase that is involved in the regulation of integrin-mediated processes such as cancer cell proliferation, migration and invasion. In this study, we examined the effect of a lentivirus-mediated knockdown of ILK on the proliferation, migration and invasion of pancreatic cancer (Panc-1) cells. Immunohistochemical staining showed that ILK expression was enhanced in pancreatic cancer tissue. The silencing of ILK in human Panc-1 cells led to cell cycle arrest in the G0/G1 phase and delayed cell proliferation, in addition to down-regulating cell migration and invasion. The latter effects were mediated by up-regulating the expression of E-cadherin, a key protein in cell adhesion. These findings indicate that ILK may be a new diagnostic marker for pancreatic cancer and that silencing ILK could be a potentially useful therapeutic approach for treating pancreatic cancer.