Extent of Specific to Nonspecific Resistance in Mice: Parenteral Versus Aerosol Challenge

1970 ◽  
Vol 1 (3) ◽  
pp. 274-278
Author(s):  
Roberta J. Hackett ◽  
Stanley Marcus
Keyword(s):  
Klebsiella Pneumoniae ◽  
Salmonella Typhimurium ◽  
Survival Time ◽  
Intraperitoneal Injection ◽  
Quantitative Data ◽  
Control Group ◽  
Type I ◽  
Nonspecific Resistance ◽  
Significant Prolongation

Quantitative data were gathered concerning the extent of resistance induced in mice immunized by specific and nonspecific means and subsequently challenged both parenterally and by aerosol. Animals were immunized specifically by subcutaneous or intraperitoneal injection of Formalin-killed Klebsiella pneumoniae type I, which was also employed as a challenge organism. The intraperitoneal ld 50 was 30 bacilli. Nonspecific resistance was induced by injection of a Boivin preparation of Salmonella typhimurium endotoxin. Nonspecific resistance was highest 24 hr after injection of 10 μg of endotoxin. At this time, more than half of the mice survived challenge with 10 2 but not with 10 3 ld 50 . Specifically immunized mice were resistant to as much as 10 5 ld 50 , depending upon the route of immunization. Potency ratios for parenteral challenge were: nonspecific to normal, 100; specific to normal, 10 4 to 10 5 ; specific to nonspecific, 10 2 to 10 3 . Employing aerosol challenge, specific immunization protected in the ld 100 range; nonspecifically immunized animals showed significant prolongation of survival time, but the 30-day mortality was similar to the control group.

Protective effect of aldehyde dehydrogenase 2 against rat corneal dysfunction caused by streptozotocin-induced type I diabetes

2021 ◽  
pp. 153537022110133
Author(s):  
Pan Long ◽  
Mengshan He ◽  
Xi Zhang ◽  
Tao Luo ◽  
Yang Shen ◽  
...  
Keyword(s):  
Cell Death ◽  
Aldehyde Dehydrogenase ◽  
Intraperitoneal Injection ◽  
Corneal Edema ◽  
Inflammatory Factors ◽  
Corneal Epithelial Cell ◽  
Control Group ◽  
Type I ◽  
Aldehyde Dehydrogenase 2 ◽  
Corneal Cell

Aldehyde dehydrogenase 2 plays a pivotal role in detoxifying aldehydes, and our previous study revealed that aldehyde dehydrogenase 2 could alleviate diabetic retinopathy-associated damage. We aimed to characterize the potential role of aldehyde dehydrogenase 2 in diabetic keratopathy. Twenty-four rats with streptozotocin-induced (60 mg/kg, single intraperitoneal injection) type 1 diabetes mellitus (T1DM) were divided the T1DM group and the T1DM + Alda1 (an activator of aldehyde dehydrogenase 2) group (5 mg/kg/d, intraperitoneal injection, 1/2/3 months), while an additional 12 healthy rats served as the control group. Corneal morphology was examined in vivo and in vitro at one, two, and three months after T1DM induction. Additionally, serum inflammatory factors were measured by ELISA, and the expression of corneal vascular endothelial growth factor A (VEGF-A) and aldehyde dehydrogenase 2 was measured by immunofluorescence staining. Corneal cell death was evaluated by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Slit lamp analysis showed that the area of corneal epithelial cell injury in the T1DM + Alda1 group was significantly smaller than that in the T1DM group at one and two months after T1DM induction (all P <  0.05). OCT analysis and HE staining showed that the central corneal thickness (indication of corneal edema) and the epithelial keratinization level in the T1DM + Alda1 group was evidently decreased compared with those in the T1DM group (all P <  0.05). The serum inflammatory factors interleukin-1 and interleukin-6 were significantly upregulated in the T1DM group compared with the T1DM + Alda1 group at three months after T1DM induction (all P <  0.05), while there were no differences in SOD or TNF-α levels among all groups. Furthermore, corneal VEGF-A expression and corneal cell death in the T1DM + Alda1 group were dramatically reduced compared to those in the T1DM group (all P <  0.05). In conclusion, the aldehyde dehydrogenase 2 agonist Alda1 attenuated rat corneal dysfunction induced by T1DM by alleviating corneal edema, decreasing corneal cell death, and downregulating corneal VEGF-A expression.

scholarly journals Biliary Self-expandable Metallic Stent Combined with Iodine-125 Seeds in the Treatment of Malignant Biliary Obstruction (Bismuth type I or II)

2021 ◽  
Author(s):  
Kai-cai Liu ◽  
Wei-fu Lv ◽  
Dong Lu ◽  
Xing-ming Zhang ◽  
Jing-kun Xiao ◽  
...  
Keyword(s):  
Survival Time ◽  
Biliary Obstruction ◽  
Malignant Biliary Obstruction ◽  
Combination Group ◽  
Control Group ◽  
Type I ◽  
Metallic Stent ◽  
Expandable Metallic Stent ◽  
Significant Difference ◽  
Iodine 125

Abstract Background:Biliary self-expandable metallic stent(SEMS) combined with iodine-125(125I) seeds are increasingly used in patients with malignant biliary obstruction (MBO), The purpose of this study was to evaluate the safety and efficacy of SEMS combined with 125I seeds in the treatment of Bismuth type I or II MBO.Methods:The clinical data of 74 cases of MBO treated with percutaneous SEMS combined with 125I seeds (combination group) and 81 cases of MBO treated with SEMS implantation alone (control group) in our hospital from January 2015 to December 2019 were retrospectively analyzed.Results:The surgical success rate of the two groups was 100%, and no surgery-related deaths occurred. The liver function of each group was significantly improved after 1 week and 1 month of follow-up. There was no significant difference in short-term efficacy or complications between the two groups (P> 0.05). The average biliary opening times of the combined group and control group were 9.01±4.38 months and 6.79±3.13 months, respectively (P <0.001). The average postoperative survival time was 12.08±5.38 months and 9.10±4.16 months, respectively (P <0.001). Univariate and multivariate analyses showed that the type of biliary stent and liver metastasis were independent factors affecting survival.Conclusions: SEMS combined with 125I seeds is a safe, effective and feasible palliative treatment for patients with Bismuth type I or II MBO, as it can delay the recurrence of jaundice and prolong the survival time of patients.

Liver, Kidney Function Tests and Oxidative Damage During and after Treatment of Salmonella typhimurium Infection in Experimental Local Rabbits

2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Mustafa Salah Hasan ◽  
Ayman Barzan Abdulgafor ◽  
Maher Saber Owain ◽  
Mohammed Ali Hussein ◽  
Qusay Mohammed Aboud ◽  
...  
Keyword(s):  
Single Dose ◽  
Oxidative Damage ◽  
Salmonella Typhimurium ◽  
Infected Group ◽  
Post Treatment ◽  
Kidney Damage ◽  
Control Group ◽  
Post Inoculation ◽  
Group 5 ◽  
Group 2

This study aimed to evaluate the liver, kidney damage caused by S. typhimurium and to estimate the oxidative damage in association with this bacteria. A highly virulent isolates of S. typhimurium were obtained from the department of internal and preventive medicine/ College of Veterinary Medicine/ University of Baghdad. A twenty five local rabbits of both genders with age range (2-4 months) weeks old were used for this study, the rabbits were divided randomly into five groups each group contains 5 rabbits :- group 1: drenched orally with 5 ml of normal saline and consider as control group, group 2: were drenched orally with (5 ml) suspension which contain (5��109 CFU) of Salmonella typhimurium and regarded as infected group, group 3 were drenched orally with (5 ml) suspension which have (5��109 CFU) of Salmonella typhimurium then treated with a single dose of gentamicin alone at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation), group 4 were drenched (5 ml) suspension having (5��109 CFU) of Salmonella typhimurium then treated with a single dose of Ca-EDTA alone at 40mg/kg orally after presence of signs (after 24hrs. post inoculation) and group 5 were drenched (5 ml) suspension that contain (5��109 CFU) of Salmonella typhimurium then treated with a single dose of combined gentamicin at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation) and Ca-EDTA 40mg/kg after presence of signs (after 24hrs. post inoculation).The results of biochemical profile showed a significant increase (p less than 0.05) in ALT, creatinine and urea levels in infected group as compared with control group, while, the treated groups especially group 5 showed a significant improvement in ALT, Urea and creatinine levels which returned to relative normal levels as compared with infected group after 96hrs. post treatment. Also, the results of oxidative stress showed a significant increase in the levels of MDA in G2, G3, G4 and G5 after 48 hrs. post treatment, while the level of GSH showed a significant decrease in the level at 48hrs., both were returned to relative normal levels after 96hrs.post treatment especially in group 5.In conclusion, S. typhimurium can causing liver and kidney damage which is manifested by increase ALT, Urea and Creatinine. Also, MDA and GSH is increased due to salmonellosis.

CARDIOVASCULAR RISK FACTORS PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH MYOCARDIAL INFARCTION AND CHRONIC INFLAMMATORY LUNG DISEASES

2020 ◽  
pp. 21-25
Author(s):  
Tupitsyn V.V. ◽  
Bataev Kh.M. ◽  
Men’shikova A.N. ◽  
Godina Z.N.
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Heart Disease ◽  
Cardiovascular Risk ◽  
Digestive System ◽  
Control Group ◽  
Study Group ◽  
Type I ◽  
Internal Organs ◽  
History Of

Relevance. Information about the cardiovascular diseases risk factors (CVD RF) for in men with chronic lung inflam-matory pathology (CLID) is contradictory and requires clarification. Aim. To evaluate the peculiarities of CVD RF in men under 60 years of age with CLID in myocardial infarction (MI) to improve prevention. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with CLID - 142 patients; II - control, without it - 424 patients. A comparative analysis of the frequency of observation of the main and additional cardiovascular risk fac-tors in groups was performed. Results. In patients of the study group, more often than in the control group we observed: hereditary burden of is-chemic heart disease (40.8 and 31.6%, respectively; p = 0.0461) and arterial hypertension (54.2 and 44.6%; p = 0.0461), frequent colds (24.6 and 12.0%; p = 0.0003), a history of extrasystoles (19.7 and 12.7%; p = 0.04); chronic foci of infections of internal organs (75.4 and 29.5%; p˂0.0001), non-ulcer lesions of the digestive system (26.1 and 14.6%; p = 0.007), smoking (95.1 and 66.3%; p˂0.0001), MI in winter (40.8 and 25.9%; p = 0.006). Less commonly were observed: oral cavity infections (9.2 and 23.6%; p˂0.0001); hypodynamia (74.5 and 82.5%; p = 0.0358), over-weight (44.4 and 55.2%; p = 0.0136), a subjective relationship between the worsening of the course of coronary heart disease and the season of the year (43.7 and 55.2%; p = 0.0173) and MI - in the autumn (14.1 and 21.9%; p = 0.006) period. Conclusions. The structure of CVD RF in men under 60 years of age with CLID with MI is characterized by the pre-dominance of smoking, non-ulcer pathology of the digestive system, frequent pro-student diseases, meteorological dependence, a history of cardiac arrhythmias and foci of internal organ infections. It is advisable to use the listed factors when planning preventive measures in such patients.

PENGARUH PEMBERIAN KOMBINASI EKSTRAK BUAH MENGKUDU (Morinda citrifolia L.) DAN KUNYIT (Curcuma longa) TERHADAP HISTOPATOLOGI GINJAL TIKUS WISTAR YANG DIINDUKSI ALLOXAN

2020 ◽  
Vol 5 (2) ◽  
pp. 319-327
Author(s):  
Pelastri Rahayu ◽  
◽  
Retno Hestiningsih ◽  
Martini Martini ◽  
Dwi Sutiningsih ◽  
...  
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Curcuma Longa ◽  
Morinda Citrifolia ◽  
Control Group ◽  
Type I ◽  
Turmeric Extract ◽  
Measurement Results ◽  
Diabetes Nephropathy

The prevalence of DM in Riskesdas in 2018 according to the Perkeni consensus in 2015 is higher than according to the Perkeni consensus in 2011, the prevalence was10.9%. The disease can develop into diabetes nephropathy, Increased prevalence of diabetic nephropathy directly proportional with an increase in diabetes prevalence. Diabetic nephropathy is a microvascular complication in diabetics that develops around 30% in patients with type I DM and about 40% in patients with type II DM. Turmeric extract has antioxidant and anti-inflammatory effects to prevent the bad development of diabetes nephropathy. This study looked at the effect of giving a combination of noni and turmeric extract on histopathology of alloxan-induced renal rats. A total of 25 mice were divided into 5 treatment groups, namely the PI group (250 mg / kgBB extract dose), PII group (500 mg / kgBB extract dose), PIII group (750 mg / kgBB extract dose), positive control group (glibenklamid) and negative control group (without extract and glibenklamid). The study used Post Test Only Group. The highest percentage decrease in blood glucose in the PI group was 56.11% and the lowest decrease in the PIII group was 24.12% with p = 0.012. The results of the study were not based on the number of extract doses. The measurement results of rat body weight and glomerular diameter were not affected by blood glucose level with p = 0.700 for body weight and p = 0.187 for glomerular measurement results.

Antidiabetic and Hypolipidemic Effects of Extracts of Gymnema Sylvestre in Streptozotocin Induced Type I Diabetes in Rats

2017 ◽  
Vol 12 (3) ◽  
Author(s):  
Nishtha R. Mahida ◽  
G. . Mandali ◽  
Vijaysinh V. Sindha ◽  
S. K. Raval
Keyword(s):  
Blood Glucose ◽  
Lipid Profile ◽  
Type I Diabetes ◽  
Histopathological Examination ◽  
Diabetic Control ◽  
Hypolipidemic Activity ◽  
Control Group ◽  
Type I ◽  
Gymnema Sylvestre ◽  
Altered Glucose

Gymnema sylvestre of the family Asclepiadaceae is one of the most important medicinal plants of the central eco-region. It is popularly known as Gurmar, which means “sugar killer”. Extract of leaves is reported to have tannins, gum, flavonoids, proteins and saponins. It has displayed a wide array of pharmacological activities. This study was aimed to investigate the antidiabetic and hypolipidemic effects of Gymnema sylvestre extract in experimentally induced diabetes in rats. Diabetes was produced in adult Wistar rats with single dose of streptozotocin (STZ) @ 60 mg/kg b.wt. intraperitoneally. After the confirmation of diabetes on 7th day (sugar >200 mg/dl), alcoholic and aqueous extracts of G. sylvestre (400 mg/kg) were administered orally to the experimental rats from 8th day and continued for 42 days thereafter. The antidiabetic and hypolipidemic activity was estimated by measuring blood glucose, lipid profile and histopathological examination of various tissues from all the groups. Administration of STZ resulted in a significant (p less than 0.01) increase in blood glucose and lipid profile and histopathological alterations in Diabetic control group as compared to healthy control group. Gymnema treatment demonstrated significant (p less than 0.01) antidiabetic effect indicated by restoration of blood glucose compared to STZ control group. The study concluded that extracts of Gymnema sylvestre improved the altered glucose and lipid profile in diabetic rats, suggesting that the Gymnema Sylvestre extracts exhibit the antidiabetic and hypolipidemic activity.

scholarly journals MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zheng Zheng ◽  
Yan Chen ◽  
Yinzhou Wang ◽  
Yongkun Li ◽  
Qiong Cheng
Keyword(s):  
Cell Death ◽  
Intracranial Aneurysm ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Control Group ◽  
Type I ◽  
Mrna Levels ◽  
Reporter Assay ◽  
Over Expression ◽  
Tnf Α

AbstractCollagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA.

scholarly journals POS0611 THE EFFECT OF RITUXIMAB BIOSIMILAR THERAPY ON THE EXPRESSION OF INTERFERON-STIMULATED GENES (“INTERFERON SIGNATURE”) IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 542.2-542
Author(s):  
A. Avdeeva ◽  
E. Tchetina ◽  
G. Markova ◽  
E. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Signature ◽  
Response To Therapy ◽  
Type I Interferons ◽  
Control Group ◽  
Type I ◽  
Acute Phase Reactants ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Healthy Donors

Background:Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including rheumatoid arthritis. IFN activity is usually quantified using expression of interferon-stimulated genes (ISGs) referred to as an IFN signature. Acellbia (BIOCAD) is the first Russian rituximab (RTX) biosimilar which was approved for medical use in rheumatoid arthritis (RA) patients in Russia and some CIS countries.Objectives:To evaluate the changes in expression of ISGs in patients (pts) with RA during RTX biosimilar therapyMethods:20 RA pts (18 woman, Me;IQR age 61.5(54-66.5) years, disease duration 39.5(20-84) months, mean DAS 28 5.6(4.9-6.8)) received two intravenous RTX biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and 24 weeks after the first infusion of RTX. 5 genes (IFI44L, MX1, IFIT 1, RSAD2, EPSTI1) were selected for evaluation of the “interferon signature” (Type I IFN gene signature – IFNGS). IFI44L and IFIT1 expression was undetectable, therefore the remaining three genes (MSX1, EPSTI1, RSAD2) were included into further analysis. IFNGS was calculated as the average expression values of the three selected genes. The control group included 20 age and gender matching healthy donors.Results:The baseline expression levels of MX1-11.48 (5.45-19.38), EPSTI1-12.83 (5.62-19.64), RSAD2-5.16 (2.73-10.4), and IFNGS-10.3 (5.18-17.12) in RA patients were significantly higher compared to healthy donors– 1,26 (0,73-1,6); 1,06 (0,81-1,48); 0,93 (0,72-1,19); 1,09 (0,92-1,42), (p<0.05, respectively). IFNGS was detected in 15 (75%) patients, and was not found in 5 (15%) patients. RTX induced reduction in disease activity, and the level of acute phase reactants (ESR, CRP) after 12 and 24 weeks of therapy, p<0.05 (fig.1). Increased RSAD 2 expression (p<0.05) and a trend to increasing IFNGS levels (p=0.06) were documented in the whole group, and also in patients with moderate treatment effects by week 24. Among patients with a good EULAR response to therapy, changes in expression were not significant (p> 0.05) (fig.1)Figure 1.Conclusion:Expression of IFN-stimulated genes was increased in RA patients compared to healthy donors. Increased RSAD2 and IFNGS expression was documented in patients with moderate effect of RTX therapy, therefore, these findings have important clinical relevance as predictors of RA clinical course which necessitates personified approach to treatment.Disclosure of Interests:None declared

scholarly journals Salmonella Bacterin Vaccination Decreases Shedding and Colonization of Salmonella Typhimurium in Pigs

2021 ◽  
Vol 9 (6) ◽  
pp. 1163
Author(s):  
Eduarda Alexandra Gonçalves de Oliveira Moura ◽  
Daniela Gomes da Silva ◽  
Caio Henrique Turco ◽  
Thainara Vitoria Carnevalli Sanches ◽  
Gabriel Yuri Storino ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Blood Count ◽  
Control Strategies ◽  
Control Group ◽  
Blood Samples ◽  
Commercial Vaccine ◽  
Serum Igg ◽  
And Control ◽  
Experimental Group ◽  
Over Time

Since the occurrence of swine salmonellosis has increased over time and control strategies other than biosecurity are highly recommended, the present study aimed to evaluate the efficacy of vaccination with Salmonella Choleraesuis and Salmonella Typhimurium bacterins in pigs. Two experimental groups were formed: G1, animals immunized with two doses of a commercial vaccine (n = 20); G2, control group (n = 20). After vaccination, all pigs were orally challenged (D0) with 108 CFU of Salmonella Typhimurium and evaluated for 40 days. Every 10 days after D0, five piglets from each experimental group were euthanized and submitted to the necroscopic examination, when organ samples were collected. Blood samples and rectal swabs were collected before the first dose of the vaccine (D−42), before the second dose (D−21), before the challenge (D0), and thereafter, every three days until D39. Blood count, serum IgG measurement by ELISA, and the excretion of Salmonella Typhimurium in feces were evaluated. While the results from blood count and serum IgG concentration did not differ, the detection and excretion of Salmonella between G1 and G2 differed (p < 0.05). Therefore, it was observed that this vaccine partially protected the animals against experimental infection with Salmonella Typhimurium, reducing the excretion of bacteria in feces.

scholarly journals Effect of Systemic Corticosteroid Therapy on the Efficacy and Safety of Nivolumab in the Treatment of Non-Small-Cell Lung Cancer

2021 ◽  
Vol 28 ◽  
pp. 107327482098579
Author(s):  
Kengo Umehara ◽  
Kaori Yama ◽  
Keisuke Goto ◽  
Azusa Wakamoto ◽  
Tae Hatsuyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung ◽  
Corticosteroid Administration

Introduction: Corticosteroids are used to treat immune-related adverse events (irAEs) associated with nivolumab. However, patients with non-small-cell lung cancer who are administered corticosteroids before the initiation of nivolumab treatment are commonly excluded from clinical trials. The appropriate timing for corticosteroid administration in relation to nivolumab treatment, effects of corticosteroids on the efficacy of nivolumab, and resulting adverse events are not clearly understood. In this study, the effects of differences in the timing of corticosteroid administration on nivolumab efficacy and the resulting adverse events were examined. Methods: A retrospective study was conducted with 109 patients who were treated with nivolumab at Sapporo Minami-Sanjo Hospital between December 2015 and March 2018. Results: Of the 109 patients treated with nivolumab, 12 patients were administered corticosteroids before the first cycle of nivolumab (pre-CS), and 33 patients were administered corticosteroids after the first cycle of nivolumab (post-CS). These 2 groups were compared with the control group comprising 64 patients who were not administered corticosteroids (non-CS). The objective response rate in the post-CS group was significantly higher than that in the non-CS group, and the disease control rate in the pre-CS group was significantly lower than that in the non-CS group. The overall survival time and progression-free survival time in the pre-CS group were significantly shorter than those observed in the non-CS group; however, these did not differ from those in the post-CS group. Conclusions: These results suggest that corticosteroids administered to patients with non-small-cell lung cancer after initiation of nivolumab treatment did not affect the disease prognosis. Thus, corticosteroids can be administered immediately for rapid treatment of irAEs.

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