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SUMMARY OBJECTIVE: This study aimed to evaluate the relationship between the toxicity of cyclin-dependent kinase 4/6 inhibitors and body mass index and body surface area. METHODS: A total of 83 patients were included in the study. Patients were divided into 4 groups as 18-24.9, 25-29.9, 30-39.9, and >40 kg/m2 according to body mass index and into two groups as below and above 1.77 according to body surface area. The relationship between body mass index and body surface area and side effects was evaluated. RESULTS: No statistically significant difference was found between body mass index groups and side effects. Grade 3 neutropenia was more common in patients on palbociclib with a body surface area≤1.77. In our study, it was revealed that less hematological side effects can be encountered when body surface area is taken into account.
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Drugs have both therapeutic and toxic side effects. How to quickly determine the toxicity of the test substance is very important for drug development. In vitro cytotoxicity testing compensates for the shortcomings of using animal models for toxicity evaluation. Its role in toxicity evaluation is increasingly important. The development of computer technology and in-depth research in proteomics, genomics, and metabolomics provide a method for in vitro cytotoxicity evaluation towards a faster and more accurate direction. This paper reviews the commonly used cells, evaluation indicators, and detection techniques for in vitro cytotoxicity evaluation, in order to provide some reference for related research.
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Objective:To explore the correlation of the dose of capecitabine with the efficacy and cardiotoxicity in patient-derived tumor xenograft (PDX) model of mice with colorectal cancer.Methods:The fresh cancer tissues of 1 colorectal cancer patient were transplanted into the bilateral axillary subcutaneous of immunodeficient NOG mice to establish PDX model and passage stably. And then the morphology of tumor cells in primary generation and the second-generation tumor tissues was observed by using HE staining. The expression of tumor markers was detected by using immunohistochemistry method, and the model was evaluated. Mice were intragastrically infused with 200, 300 and 400 mg/kg capecitabine once a day, which were treated as low, middle and high dose groups respectively, 5 rats in each group; in the control group, 0.9% NaCl solution was perfused into the stomach; 14 d in total, use stop for 7 d, consecutively administered in this way. The body weight was measured every day and the tumor volume was measured every 3 days. After 100 days of observation, the mice were killed, and the tumor tissue was taken to measure the tumor weight and then the tumor volume, tumor volume inhibition rate and tumor inhibition rate were calculated. The morphology of tumor tissues was observed by using HE staining. The protein levels of anti-tumor effect indexes like rasP21, cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), cardiac troponin Ⅰ (cTn-Ⅰ) and brain natriuretic peptide (BNP) in serum of mice were detected by using enzyme linked immunosorbent assay (ELISA).Results:PDX model of mice with colorectal cancer was successfully constructed, and the histological characteristics of the primary tumor in the model were well preserved. During administration, 1 mouse died in the capecitabine high dose group; a slow down in tumor volume growth could be found with the increased dose of capecitabine. There was no statistically significant difference in body weight among 4 groups until all mice were killed ( P > 0.05). The tumor volume and tumor weight in the low, middle and high dose groups were lower than those in the control group (all P < 0.05), and the tumor volume and tumor weight showed an obvious decrease with the increase in dose. The tumor volume inhibition rates of low, middle and high dose groups were 42.61%, 67.61% and 77.27%, respectively, and the tumor inhibition rates were 35.53%, 67.77% and 75.09%, respectively. The serum anti-tumor effect indexes rasP21, COX2 and PGE2 in the middle and high dose groups were decreased compared with those in the control group (all P < 0.05), while cTn-Ⅰ and BNP levels were increased compared with those in the control group (all P < 0.05). Conclusions:The established PDX model of mice with colorectal cancer can better retain the histological characteristics of the original tumor. After treatment of middle and high dose of capecitabine, the tumor inhibition effect is obvious, but the risk of myocardial damage should be noticed.
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Hydroxychloroquine is widely used in a variety of autoimmune diseases. However, long-term use of hydroxychloroquine can cause severe retinopathy, which has a complex pathogenic mechanism and diverse clinical manifestations, mainly manifested as photoreceptor and retinal pigment epithelial damage and irreversible vision loss. Identifying damage before retinitis pigment epithelium lesions preserve central vision, so early detection is crucial to slow disease progression and reduce vision loss. The development of multimodal imaging technology and the issuance of the latest treatment guidelines provide a powerful tool for the early screening and treatment of hydroxychloroquine retinopathy. Proficient in the latest guidelines for the treatment of hydroxychloroquine can better guide clinicians to do a good job in disease screening and management, recommend risks, safe dosages and appropriate screening procedures to patients and strengthen the prevention of hydroxychloroquine retinopathy, which will help save the vision of more patients and reduce the waste of medical resources.
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Introducción: múltiples agentes quimioterapéuticos que se usan comúnmente pueden causar síndrome de Fanconi (SF) completo o parcial. El SF es una tubulopatía proximal que produce alteraciones electrolíticas y ácido-básicas, donde se evidencia pérdida de glucosa, aminoácidos, calcio, fósforo, potasio, ácido úrico y se produce acidosis metabólica por pérdida de bicarbonato. El SF usualmente no es reportado y muchas veces no se realiza el diagnóstico. Objetivo: resaltar la importancia del monitoreo urinario y sérico en pacientes que estén sometidos a quimioterapia, así como describir la literatura reciente acerca de la asociación entre agentes quimioterapéuticos y síndrome de Fanconi parcial o completo. Presentación de los casos: se presenta una serie de casos de pacientes pediátricos oncológicos con función renal preservada, donde se produjeron diferentes manifestaciones de nefrotoxicidad tubular proximal secundaria a agentes quimioterapéuticos como antimetabolitos, agentes alquilantes y antraciclinas. Discusión y conclusión: el espectro del SF puede ir de una tubulopatía proximal generalizada o completa a alteraciones parciales en la reabsorción de electrolitos. Se debe reconocer la importancia del monitoreo sérico y urinario en pacientes con lesiones tumorales que van a ser sometidos a quimioterapias con agentes potencialmente nefrotóxicos; asimismo, tener en cuenta la dosis, la frecuencia y la combinación de agentes quimioterapéuticos, con el fin de prevenir y tratar complicaciones de toxicidad renal, incluyendo SF completo o parcial.
Introduction: Several commonly used chemotherapeutic agents can cause complete or partial Fanconi syndrome (FS). FS is a proximal tubulopathy that produces electrolyte and acid base disorders where there is loss of glucose, amino acids, calcium, phosphorus, potassium, uric acid and metabolic acidosis occurs due to loss of bicarbonate. FS is not usually reported, and the diagnosis is often misled. Purpose: To highlight the importance of urinary and serum monitoring in patients undergoing chemotherapy, as well as describe the recent literature about the association between chemotherapeutic agents and partial or complete Fanconi syndrome. Case presentation: A series of cases of pediatric oncology patients with preserved renal function is presented in which different manifestations of proximal tubular nephrotoxicity occurred secondary to chemotherapeutic agents such as antimetabolites, alkylating agents, and anthracyclines. Discussion and conclusion: The spectrum of FS can range from a generalized or complete proximal tubulopathy to partial alterations in electrolyte reabsorption. The importance of serum and urinary monitoring should be recognized in patients with tumor lesions who will undergo chemotherapies with potentially nephrotoxic agents; the dosage, frequency and combination of chemotherapeutic agents should be taken into account, in order to prevent and treat the complications of renal toxicity including complete or partial SF.
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Introduction: Sudden death is unexpected death within 24 hours from the onset of symptoms with or without known preexisting conditions. Respiratory pathologies are the second most common cause of such deaths. Brief History of Case: 39 years old male patient with a history of mental illness for the last 10 years and on regular treatment with antipsychotic medications, suffered sudden deterioration of higher functions and was admitted to the Medical College, and Hospital, Kolkata with a provisional diagnosis of drug toxicity. He succumbed to his condition within 24 hours of admission and the dead body was referred to Kolkata Police Morgue for a medicolegal autopsy. Gross autopsy findings: Shows multi-system involvement in the form of Pulmonary Oedema, consolidation, broncho-pneumonic changes and subpleural petechiae, Cardiomegaly due to biventricular hypertrophy, Cerebral Oedema, Enlarged kidneys with loss of cortico-medullary differentiation and streaky cortico-medullary haemorrhages. Stomach findings were unremarkable. Salient findings in ancillary investigations: 1) Toxicological Examination of blood, bile, vitreous and routine viscera was negative for any poison or pharmacological agents. 2) Histopathological examination with routine H&E staining showed Pulmonary oedema with lymphocytic infiltration and the presence of fat and hematopoietic precursor cells in pulmonary vessels, Interstitial Oedema and focal glomerulosclerosis and Periportal inflammation in the liver.
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Cardiotoxicity induced by anticancer drug; doxorubicin (DOX) is a limiting factor for its prolonged use in chemotherapy. No effective drug is currently available to prevent DOX induced cardiomyopathy. Ganoderma lucidum is highly valued medicinal mushroom used in traditional medicine. Mycelia biomasses are considered as alternate sources of mushroom bioactive compounds. We examined the effect of bioactive extract of G. lucidum mycelia biomass (GLME) to prevent cardiotoxicity induced by DOX in rats using a cumulative dose 18 mg/kg body wt. GLME was administered to animals at doses of 250 and 500 mg/kg body wt. once daily for five days prior to DOX administration and continued for three more days. Animals were sacrificed 24 h after the last dose of drug. Activities of creatine kinase (CK), lactate dehydrogenase (LDH), endogenous antioxidant status, oxidative stress markers, electrocardiograph (ECG) and haematological parameters were evaluated. DOX administration drastically elevated CK, LDH, myocardial peroxidation and oxidative stress and significantly lowered endogenous antioxidant activity. GLME administration attenuated elevated levels of CK, LDH and oxidative stress and also ameliorated alterations in haematological and ECG parameters. Results revealed that bioactive extract of G. lucidum mycelia imparted significant protection against DOX induced cardiomyopathy suggesting the potential therapeutic significance of G. lucidum mycelia bioactives to alleviate DOX induced cardiomyopathy.
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ABSTRACT Introduction: Methotrexate is a drug with chemotherapeutic properties frequently used for the treatment of certain types of cancer. The following is a clinical case which, to the best of the authors' knowledge, is the first report in Colombia on nephrotoxicity caused by this drug and describes the consequences as well as the treatment provided at a quaternary care hospital. Case report: A 71-year-old patient with a diagnosis of non-Hodgkin's lymphoma with normal renal function underwent chemotherapy (high-dose methotrexate intravenously) and developed stage 3 acute renal failure according to the KDIGO guidelines, which was most likely related to methotrexate intake. The patient received treatment with intravenous fluids and sodium bicarbonate as promoters of urine excretion of the toxin, and oral calcium folinate following the institutional protocol. The patient was discharged with recovery of kidney function and improved creatinine and urea nitrogen levels. Conclusion: The treatment given to the patient in this case report shows that although methotrexate nephrotoxicity is a potentially serious entity, it can have a good prognosis if treated promptly.
RESUMEN Introducción. El metotrexato es un fármaco con propiedades quimioterapéuticas usado de forma frecuente para el tratamiento de ciertos tipos de cáncer. A continuación, se presenta un caso clínico que, a conocimiento de los autores, es el primer reporte en Colombia sobre nefrotoxicidad por este medicamento, así como sus consecuencias y el manejo que se le dio en un hospital de cuarto nivel. Presentación del caso. Hombre de 71 años con diagnóstico de linfoma no Hodgkin y función renal normal, quien se sometió a tratamiento quimioterapéutico (metotrexato a altas dosis por vía endovenosa) y desarrolló insuficiencia renal aguda estadio 3 según las guías KDIGO, la cual muy probablemente se relacionaba al consumo de metotrexato. El paciente recibió manejo con líquidos endovenosos y bicarbonato de sodio como promotores de la eliminación renal del tóxico, así como folinato cálcico oral, según el protocolo institucional, con lo cual se logró la recuperación de su función renal y que los niveles de niveles de creatinina y nitrógeno ureico mejoraran. Conclusiones. El manejo del paciente reportado demuestra que aunque la nefrotoxicidad por metotrexato es una entidad potencialmente grave, puede tener un buen pronóstico si se maneja oportunamente.
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Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:An ambispective study was conducted on 123 AD patients treated with dupilumab in Department of Dermatology, the Second Xiangya Hospital of Central South University from July 2020 to March 2022, clinical data were collected, and efficacy and safety of dupilumab were evaluated. Primary outcomes included scores of eczema area and severity index (EASI) , patient-oriented eczema measure (POEM) , peak pruritus numerical rating scale (NRS) and dermatology life quality index (DLQI) before and after 4-, 8-, 12- and 16-week treatment, and adverse reactions and events were recorded. Comparison of scores before and after treatment was performed using paired t test or repeated measures analysis of variance, Mann-Whitney U test was used for the comparison of efficacy among patients with different types of skin lesions or different IgE levels, and multiple regression model based on robust standard errors was used to analyze factors influencing the efficacy. Results:Among the 123 AD patients, 107 were enolled into the efficacy analysis, and 85 (79.44%) completed at least 4 weeks of treatment, including 6 (7.06%) achieving EASI75 and 23 (27.06%) achieving EASI50, and the EASI, NRS, POEM, DLQI scores (10.41 ± 6.72, 4.12 ± 1.74, 8.60 ± 4.29, 7.81 ± 4.38, respectively) significantly decreased compared with those before treatment (18.08 ± 10.69, 7.21 ± 2.01, 16.88 ± 5.74, 12.95 ± 5.95, respectively; all P < 0.001) in the 85 patients. Among the 107 patients, 47 (43.93%) completed at least 16 weeks of treatment. Among the 47 patients, 23 (82.14%) of 28 adults and 17 (89.47%) of 19 adolescents and children achieved 75% or greater improvement in EASI score; the EASI, NRS, POEM and DLQI scores before the treatment all significantly differred from those 4, 8, 12, 16 weeks after the treatment (all P < 0.001) , and all the scores were significantly lower at weeks 4, 8, 12 and 16 than at the previous adjacent time points (all P < 0.05) . At week 4 during the treatment, the EASI improvement rate was significantly lower in the AD patients with prurigo nodularis than in those without ( U = 151.00, P = 0.006) , while there was no significant difference in the EASI improvement rate between the AD patients with xeroderma and those without ( P > 0.05) ; at week 16 during the treatment, there was no significant difference in the EASI improvement rate between patients with prurigo nodularis or xeroderma and those without (both P > 0.05) . Multiple regression analysis based on robust standard errors at week 16 showed that the improvement degree in the EASI score was not correlated with the type of skin lesions ( β = 3.20, P = 0.075) , but correlated with age ( β = -0.22, P = 0.030) , whether patients were in adulthood ( β = 9.54, P = 0.049) , immediate family history ( β = 7.46, P = 0.017) ; the improvement degree in the NRS score was correlated with the type of skin lesions ( β = 0.55, P = 0.032) , age ( β = -0.04, P = 0.033) , weight ( β = -0.05, P = 0.020) , whether patients were in adulthood ( β = 2.06, P = 0.003) and whether patients received combined treatment with antihistamines ( β = -1.91, P = 0.001) . Adverse reactions: among the 123 patients, 6 (4.88%) developed conjunctivitis, and 2 (1.63%) developed facial erythema. Adverse events: vitiligo-like changes occurred on the right forehead of 1 patient, and 3 patients discontinued the treatment with dupilumab due to Henoch-Sch?nlein purpura, distal axonal damage in peripheral nerves in both upper limbs, and epilepsy, respectively. The causal relationship between these adverse events and dupilumab was unclear. Conclusion:Dupilumab is effective in the treatment of AD with high overall safety, and can serve as a new treatment option for AD patients with an unsatisfactory response to traditional treatment.
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Objective:To evaluate efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:A retrospective study was conducted among patients with AD who showed poor response to topical agents and then received standardized injections of dupilumab for 16 weeks in Department of Dermatology, Peking University First Hospital from June 1, 2020 to September 1, 2021. Basic information on the patients was collected, so were the Investigator′s Global Assessment (IGA), Eczema Area and Severity Index (EASI), Itch Numeric Rating Scale (NRS), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM) scores recorded before and at weeks 2, 4, 8, 12, and 16 during treatment. Adverse reactions were recorded during treatment. Wilcoxon rank sum test was used to compare the scores of all patients at the end of follow-up with those before treatment.Results:A total of 57 patients were enrolled in the study, and all completed 16-week injections and follow-up. At week 16, the patients′ IGA, EASI, NRS, DLQI, and POEM scores significantly decreased from 4.0 (4.0, 5.0), 30.0 (17.2, 36.0), 9.0 (7.0, 10.0), 15.0 (11.5, 20.5), and 19.0 (15.5, 23.0) points respectively at baseline to 1.0 (1.0, 1.0), 4.0 (1.6, 7.3), 1.0 (0.0, 1.0), 3.0 (1.0, 4.0), and 4.0 (2.0, 4.0) points respectively ( Z = 6.65, 6.57, 6.59, 6.57, and 6.57 respectively, all P < 0.001). All the 5 scale scores showed a continuous downward trend within 16 weeks after the start of dupilumab treatment. During the follow-up period, no serious adverse reaction was observed, and only two patients developed conjunctivitis. Conclusion:Dupilumab shows marked efficacy in the treatment of AD, with favorable safety.
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Objective:To investigate clinical characteristics of bullous pemphigoid (BP) developing after the treatment with dipeptidyl peptidase-Ⅳ inhibitors (DPP4i) in patients with diabetes mellitus.Methods:A total of 116 inpatients with BP complicated by diabetes mellitus were collected from the Seventh People′s Hospital of Shenyang between January 2014 and December 2020, and divided into 2 groups: DPP4i-BP group treated with DPP4i before the onset of BP, and general BP group receiving no treatment with DPP4i. General clinical data, skin lesion area, laboratory indicators, treatment regimens, and prognosis were analyzed and compared between the above 2 groups, the time interval from the administration of DPP4i to the diagnosis of BP was recorded in the DPP4i-BP group. One-way analysis of variance was used to compare measurement data among multiple groups, two-independent-sample t test was used for comparisons between two groups, and paired t-test for intra-group comparisons before and after treatment; chi-square test was used to compare enumeration data between groups. Results:There were 32 patients aged 77.17 ± 15.32 years in the DPP4i-BP group, with a male-to-female ratio being 15∶17; there were 84 patients aged 76.65 ± 19.32 years in the general BP group, with a male-to-female ratio being 43∶41. The time interval from the administration of DPP4i to the diagnosis of BP was 14.61 ± 3.93 months in the DPP4i-BP group. The time interval for vildagliptin was the shortest (5.42 ± 2.84 months) , and there was a significant difference in the time interval among vildagliptin, sitagliptin, linagliptin and saxagliptin ( F= 8.93, P < 0.001) . The proportion of patients with severe BP was significantly higher in the DPP4i-BP group (16 cases, 50%) than in the general BP group (25 cases, 29.76%; Z= 2.63, P= 0.008) . There was no significant difference in the positivity rate of anti-BP180 antibody between the two groups ( χ2= 0.03, P= 0.870) . However, the level of anti-BP180 antibody was significantly higher in the DPP4i-BP group than in the general BP group before and after treatment ( P= 0.015, < 0.001, respectively) , and the decrease in the level of anti-BP180 antibody was significantly less in the DPP4i-BP group than in the general BP group after treatment ( t= 5.11, P < 0.001) . There was no significant difference in the average effective dose of glucocorticoids required to control the disease between the two groups ( t= 1.00, P= 0.322) . However, the DPP4i-BP group showed a significant increase in the average time required to control the disease and in the proportion of patients requiring combined treatment with immunosuppressants or other drugs compared with the general BP group ( t= 6.72, 10.05, P < 0.001,= 0.002, respectively) . Within 6 months after the start of systemic treatment, the recurrence rate was significantly higher in the general BP group (17 cases, 27.86%) than in the DPP4i-BP group (2 cases, 7.69%; χ2= 4.35, P= 0.037) ; at 6 months, the average dose of glucocorticoids was also significantly higher in the general BP group than in the DPP4i-BP group ( t= 7.04, P < 0.001) . Conclusions:Among the DPP4i hypoglycemic drugs, vildagliptin was the most common drug administrated by patients before the onset of BP, with the shortest interval from the administration to the onset of BP. DPP4i-BP may be difficult to control at the early stage, but the prognosis is good.
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Objective:To analyze adverse drug reactions (ADR) and reasons for drug discontinuation during acitretin therapy in patients with psoriasis vulgaris.Methods:A total of 292 patients with psoriasis vulgaris treated with acitretin were collected from the First Affiliated Hospital of Guangxi Medical University from 2014 to 2019. According to the inclusion and exclusion criteria, 193 patients who received periodic follow-up were included in this study, clinical data were collected from these patients and retrospectively analyzed. ADRs occurring during the acitretin treatment and reasons for drug discontinuation were analyzed.Results:Totally, 519 cases of ADRs occurred in 171 of the 193 patients, with the incidence rate being 88.6%. Of these cases, 174 (33.5%) involved the epithelial tissues, 126 (24.3%) the endocrine system, 1 (0.2%) the reproductive system, 29 (5.6%) the motor system, 77 (14.8%) the circulatory system, 3 (0.6%) the nervous system, 71 (13.7%) the digestive system, and 38 (7.3%) involved the urinary system. Relatively common ADRs included dryness of skin and mucous membranes, as well as musculoskeletal pain, and common biochemical changes included dyslipidemia, elevated platelets, and abnormal aminotransferase levels. Most ADRs (81.6%) were reported within 1 month after the start of acitretin therapy. Rare ADRs included alopecia, tinnitus, paronychia, myasthenia, sensory abnormalities, headache, menstrual disorders and hyperbilirubinemia, which were mainly (70.6%) reported within 1 to 6 months after the start of therapy. Of the 519 cases of ADRs, 324 could be alleviated or subsided without drug intervention, 195 were alleviated or subsided after drug withdrawal and/or drug intervention, and there were no cases of serious illness or death. Among the 193 patients, 186 had discontinued acitretin therapy, of whom 116 (62.4%) discontinued due to improvement in disease condition, 35 (18.8%) discontinued due to ADR-induced poor medication compliance, 27 (14.5%) discontinued under the guidance of clinicians due to ADRs, and 8 (4.3%) discontinued due to poor disease control.Conclusion:The incidence of adverse reactions to acitretin is high in the treatment of psoriasis vulgaris, but most of them have a good prognosis.
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This review summarizes the contribution of interleukin-17 (IL-17) to the susceptibility to mucocutaneous fungal infections, and superficial fungal infections associated with IL-17-targeting biological agents, such as secukinumab, ixekizumab, brodalumab, bimekizumab and ustekinumab, in the treatment of psoriasis. The superficial fungal infections associated with the treatment with IL-17-related biological agents are usually mild or moderate, and most of them are limited, with a good response to anti-fungal therapy. In addition, this review introduces clinical evaluation, monitoring and treatment of related superficial fungal infections, and provides a basis for safe clinical use of IL-17-targeting biologics.
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Objective:To explore safe dosage of single intravitreal injection of ganciclovir (IVG) in healthy rabit eyes, and to explore retinal toxicity of different dosage of ganciclovir after continues intravitreal injection into the vitreous cavity of healthy albino rabbit eyes.Methods:Ten healthy New Zealand albino rabbits were divided into 5 groups with 2 rabbits in each group. Each group was injected with 1 mg/0.025 ml,2 mg/0.025 ml, 5 mg/0.025 ml, 10 mg/0.025 ml ganciclovir or 0.025 ml saline (control group). After 1 week of intervention, rabbits were examined by ultra-wide-angle fundus photography, optical coherence tomography (OCT) and full field electroretinogram (ERG). The maximum mixed response of rod and cone cells (Max-R) was measured under dark adaption conditions, cone response (Cone-R) and 30 Hz flicker response (30 Hz-R) were measured under light adaption conditions. Twenty-four healthy New Zealand albino rabbits were randomly divided into a low-dose experimental group, a low-dose control group, a high-dose experimental group, and a high-dose control group, with 6 rabbits in each group, with the right eye as the experimental eye. The rabbits in the high-dose experimental group were continuously injected with ganciclovir 2 mg/0.025 ml, once a week, for a total of 4 times. The rabbits in the low-dose experimental group were injected with 1 mg/0.025 ml ganciclovir, the induction period was 2 times/week, a total of 4 times; the maintenance period was 1 time/week, a total of 2 times. The rabbits in the high-dose control group and the low-dose control group were injected with 0.025 ml normal saline into the vitreous cavity respectively. Full-field ERG examination was performed 1 day before each injection and 1 week after the last injection. Max-R was measured under dark-adapted conditions, and Cone-R and 30 Hz-R were measured under light-adapted conditions. OCT was recorded before the first injection and one week after the last injection. One week after the last injection, the experimental rabbits in each group were sacrificed for hematoxylin-eosin staining, and the retinal structure was observed under a light microscope. The comparison of a-wave and b-wave amplitude of Max-R, Cone-R and 30 Hz-R amplitude at different time was performed by two independent sample nonparametric test.Results:There were no abnormal results of fundus photography, OCT and ERG after single intravitral injection of 1 mg or 2 mg ganciclovir. One week after single 5 mg IVG, fundus photography of rabbits showed vascular occlusion and preretinal hemorrhage and ERG showed slight decrease of amplitude of Max-R, Cone-R and 30 Hz-R. One week after single 10 mg IVG, retinal necrosis and exudative changes were also observed. OCT showed edema and unclear retinal structure in the necrotic area. ERG showed significant decrease of amplitude of Max-R, Cone-R and 30 Hz-R. After continuous IVG in high dose and low-dose experimental group, the amplitude of Max-R a wave ( Z=-0.160, 0.000) and b wave ( Z=-0.321, 0.000), Cone-R a wave ( Z=-0.641,-0.641) and b wave ( Z=-0.321, -0.160), and 30 Hz-R ( Z=-0.321,-0.160) showed no difference compared to control group. No histologic evidences of retinal microstructure abnormalities were found in both groups. OCT and fundus photography before and after the intervention did not show any difference, either. Conclusion:There was no retinal toxicity of continuous 1 mg or 2 mg IVG recorded in albino rabbits.
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As a new type of anti-cancer drugs, immune checkpoint inhibitors have been widely used for the treatment of various tumors in recent years, but they have also caused a variety of immune-related adverse reactions, among which cutaneous adverse reactions are the most common. The onset of cutaneous adverse reactions is usually early, and most are mild, but some can also be life-threatening. This review summarizes recent advances in cutaneous immune-related adverse reactions induced by immune checkpoint inhibitors.
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Objective:To evaluate the efficacy and safety of dupilumab in the treatment of adult prurigo nodularis.Methods:A prospective study was conducted on patients with prurigo nodularis who received the treatment with dupilumab in Peking University People′s Hospital from January 2021 to November 2021. Efficacy was assessed using the Investigator′s Global Assessment (IGA) , Numerical Rating Scale (NRS) and Dermatology Life Quality Index (DLQI) at weeks 0, 4 and 16. Wilcoxon signed-rank test and paired t test were used to analyze changes in the above parameters before and after treatment. Results:A total of 17 patients were enrolled in this study, including 12 females and 5 males, aged 48.47 ± 16.26 years. After 16-week treatment with dupilumab, the pruritus NRS score decreased from 8.00 ± 1.50 at baseline to 1.29 ± 0.85 ( t = 6.98, P < 0.001) , the sleeplessness NRS score decreased from 5.18 ± 2.98 at baseline to 0.12 ± 0.49 ( t = 12.55, P < 0.001) , and the DLQI score declined from 13.29 ± 4.03 at baseline to 0.88 ± 0.70 ( t = 16.39, P < 0.001) ; at week 16, the IGA grade of all the 17 patients decreased from 3 - 4 at baseline to 0 - 2, 16 achieved IGA grades 0 - 1, and 12 achieved IGA grade 0. During the treatment, mild conjunctivitis occurred in 2 cases, local injection reaction occurred in 1, and both conditions were improved after short-term symptomatic treatment. Conclusion:Dupilumab is markedly effective and safe in the treatment of adult prurigo nodularis.
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Objective:To investigate the efficacy and nephrotoxicity of high-dosepolymyxin B (PMB) in treatment of patients with multidrug-resistant Gram-negative bacteria (MDR-GNB) infections.Methods:Clinical data of 90 patients with MDR-GNB infections who admitted to the Affiliated Huaian First People′s Hospital from January 2018 to December 2020 were retrospectively analyzed. Thirty one patients receivedhigh-dose PMB(≥25 000 U·kg?1·d?1) for treatment (high-dose group) and 59 patients received standard-dose PMB(<25 000 U·kg?1·d?1) for treatment (control group). The curative effect and renal function of the two groups were compared. The factors related toacute kidney injury (AKI) were analyzed with logistic regression.Results:The daily PMB dose and treatment course in high-dose group were (29 800±4 500) U/kg and (9.16±4.15) d, while those of the control group were (17 300±3 500)U/kg and (7.32±3.87) d ( P<0.01). The effective rate of the high-dose group was higher than that of control group (83.9% vs. 61.0%, χ2=4.95, P<0.05).The creatinine levels in high-dose group were increased significantly from 69.40(47.00, 94.70)μmol/L before treatment to 116.20(59.20, 213.20)μmol/L after treatment ( Z=-2.99, P<0.01); while there were no significant changesin control group before and after treatment [55.00(37.00, 92.47)μmol/L vs. 50.10(34.00, 156.00)μmol/L, Z=-1.78, P=0.78]. The 30-day mortality rate in the high-dose group was 32.3% (10/31), that in the standard-dose group was 49.2% (29/59)(χ2=2.36, P=0.12). The AKI incidence rate in high-dose group was higher than that in standard-dose group [ 67.7% (21/31) vs. 45.8% (27/59), χ2=3.94, P=0.04]. There were 4 and 10 deaths due to AKI in the high-dose and standard-dose groups, respectively (χ2=0.25, P=0.61). Logistic regression analysis showed that daily high-dose PMB was independently associated with AKI( OR=2.662, 95% CI:1.082-6.549, P=0.03). Conclusion:Thehigh-dose PMB is effective in treatment of patients with multidrug-resistant Gram-negative bacteriainfections, but the incidence of AKI is also significantly increased. Therefore, when using daily high-dose PMB, the pros and cons must be weighed to avoid increasing the risk of AKI.
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Imatinib mesylate is the first-line drug for the treatment of chronic myeloid leukemia and malignant gastrointestinal stromal tumors, and causes mucocutaneous adverse reactions at a high frequency. Based on Chinese and international literature, the authors comprehensively describe various mucocutaneous symptoms induced by imatinib mesylate, and summarize their pathogenesis and management strategies, aiming to help dermatologists improve their understanding of mucocutaneous adverse reactions to this drug, and provide timely diagnosis and treatment.
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Objective:To evaluate the clinical efficacy and safety of omalizumab in the treatment of chronic spontaneous urticaria (CSU) .Methods:Clinical data were collected from 60 patients, who were diagnosed with CSU and received subcutaneous injections of omalizumab at a dose of 300 mg once every 4 weeks for 3 sessions in Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College from March 2020 to September 2020, and retrospectively analyzed. At weeks 0, 2, 4, 6, 8, 10 and 12, urticaria activity score over 7 days (UAS7) and chronic urticaria quality of life (CU-Q2oL) score were used to evaluate clinical symptoms and quality of life of patients. Changes in the use of other drugs were evaluated before and after the treatment with omalizumab. Paired t test was used to compare UAS7 or CU-Q2oL score before and after treatment. Results:All the 60 CSU patients received 12 weeks of omalizumab treatment. The baseline UAS7 score was 22.37 ± 8.88 points; after one session of the treatment, the UAS7 score dropped to 2.01 ± 5.13 points, reaching the treatment plateau; at week 12, it dropped to 0.6 ± 2.63 points, and 0 point (complete control) in 93.3% of the patients, 1-6 points (favorable control) in 3.3%; the time required for UAS7 score to decrease to 0 point was 22.4 ± 3.2 days. The baseline CU-Q2oL score was 34.10 ± 15.01 points; after one session of the treatment, the CU-Q2oL score dropped to 2.41 ± 7.18 points, reaching the treatment plateau; at week 12, it was 0.56 ± 2.90 points; the time required for CU-Q2oL score to drop to 0 point was 21.15 ± 16.02 days. After the combination treatment with omalizumab, a gradual decrease in dosage or withdrawal of previous therapeutic drugs was realized. At week 12, 39 patients (65%) achieved complete control, and withdrew all therapeutic drugs except omalizumab. During the treatment and follow-up, omalizumab showed good safety, and no adverse reactions were observed.Conclusion:Omalizumab at a dose of 300 mg once every 4 weeks is markedly effective and safe for the treatment of CSU, providing a new treatment option for CSU patients with poor response to traditional therapy.
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Objective:To evaluate the mechanism of dexmedetomidine alleviating sevoflurane-induced neurotoxicity and the relationship with neuroglobin (Ngb) in neonatal rats.Methods:Eighty-four healthy male Sprague-Dawley rats, aged 7 days, weighing 12-16 g, were divided into 4 groups ( n=21 each) using a random number table method: control group (group C), sevoflurane group (group S), sevoflurane plus dexmedetomidine group (group SD), and sevoflurane plus dexmedetomidine and yohimbine group (group SDY). Sevoflurane anesthesia method: anesthesia was induced by inhaling 8% sevoflurane and then maintained by inhaling 3% sevoflurane for 4 h. At the end of anesthesia, dexmedetomidine 50 μg/kg was intraperitoneally injected in group SD, and 0.5 mg/kg yohimbine (α 2 adrenergic receptor antagonist) was intraperitoneally injected immediately after the end of intraperitoneal injection of dexmedetomidine 50 μg/kg in group SDY.Six rats were randomly selected from each group and sacrificed at 24 h after the end of anesthesia.The brain tissues were removed for determination of histopathologic changes in hippocampal CA1 region (using HE staining), the expression of Ngb in the area of the hippocampus (by immunofluorescence staining) and the expression of cytochrome C (Cyt c) and caspase-3 (by Western blot). The other rats were fed until 28 days old, and Morris water maze test was performed. Results:Compared with group C, the expression of Ngb, Cyt c and caspase-3 was significantly up-regulated ( P<0.05), histopathologic changes in hippocampal CA1 region were accentuated, and Ngb fluorescence intensity was increased in group S. Compared with group S, the expression of Ngb was significantly up-regulated, expression of Cyt c and caspase-3 was down-regulated, the escape latency was shortened ( P<0.05), histopathologic changes in hippocampal CA1 region were reduced, and Ngb fluorescence intensity was increased in group SD.Compared with group SD, the expression of Ngb was significantly down-regulated, expression of Cyt c and caspase-3 was up-regulated, the escape latency was prolonged ( P<0.05), histopathologic changes in hippocampal CA1 region were accentuated, and Ngb fluorescence intensity was decreased in group SDY. Conclusion:The mechanism by which dexmedetomidine reduces sevoflurane-induced neurotoxicity may be related to activating α 2 adrenergic receptors and up-regulating the expression of Ngb in neonatal rats.