Development and Application of Procedures for the Management of Skin Toxicity Related to Immune Checkpoint Inhibitors in Patients with Lung Cancer

Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the Oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in Ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.

The Construction of Integrated Nursing Model Prevention of Oxaliplatin Chemotherapy-Induced Peripheral Nerve Injury

Objective: To investigate the effect of the integrated nursing model in the prevention of chemotherapy-induced peripheral injury. Methods: A total of 60 tumor patients receiving oxaliplatin for 1 - 6 cycles of chemotherapy from January to September 2023 were selected. 30 patients were selected from January to March and divided into the control group, and 30 patients were selected from July to 9 as the experimental group. The control group received conventional chemotherapy nursing, while the experimental group received integrated nursing. Anxiety, peripheral nerve toxicity stage and quality of life score were compared between the two groups before and after intervention. Results: After intervention, the scores of the self-rating Anxiety Scale (SAS) and the total scores of the oxaliplatin Levi specific sensory neurotoxicity scale in the experimental group were significantly lower than those in the control group, and the differences were statistically significant (P< 0.05);The Quality of Life Scale (FACT-G) score of cancer patients was higher than that of control group, and the difference was statistically significant (P< 0.05). Conclusion: The integrated nursing model can effectively reduce the anxiety of patients, reduce the incidence of peripheral nerve injury and improve the quality of life of patients.

Psychotropic drugs and liver disease:A critical review of pharmacokinetics and liver toxicity

The liver is the organ by which the majority of sub-stances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first--pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity.

An investigation into the occupational protection status of clinical nursing staff exposed to anti-tumor drugs

Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocationally exposed to anti-tumor drugs.Results:Recognition of the need for protection and dependent occupational protection behaviors were very poor in clinical nursing staff vocationally exposed to anti-tumor drugs.The management of the occupational protection of clinical nursing staff vocationally exposed to anti-tumor drugs was also seriously underdeveloped.Conclusion:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to anti-tumor drugs in our hospital.The protection measures currently employed in medical practice are inadequate in virtually every aspect considered.It is recommended that all clinical nursing staff should receive full occupational protection training in these matters.The training must raise nursing staff's awareness of the need for occupational protection and standardize their occupational protection behaviors to conform to "best practice" models.These "best practice" models should be quickly established and all staff made cognizant of them forthwith.In addition,where occupational protection systems are already in place,they should be improved to come into line with the new "best practice" models instigated.

Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Body Composition as A Determinant of Pharmacokinetics and Toxicity of Anticancer Drugs

Chemotherapy-induced toxicity,resulting from inter-individual variability in pharmacokinetics is emerging as a highly active area of investigation.Body composition analysis,primarily concerning the amount of fat mass(FM)and lean body mass(LBM),has provided a proof-concept that the inter-individual variability in pharmacokinetics and toxicity profiles may be partially explained by the discrepancies of FM and LBM in patients.Recent research suggests a close relationship among body composition,pharmacokinetics and toxicity of anticancer drugs.Because LBM and FM,significantly influence the exposure to drugs,they are considered as the promising predictors of chemotherapy-induced toxicity and a potential basis for optimizing the dosing of oncology drugs and the outcomes.Our review summarizes the recent studies rendering the aforementioned correlations to highlight that a critical evaluation of body composition has initiated a new era for dose standardization.

Nursing Care of Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: Case Study of Dermatology Unit of Referral Hospital, Kenya

Introduction: Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are adverse reaction to drugs whose manifestation affect the skin and mucous membranes whose outcomes may be life threatening and fatal. Supportive management has been proven to be the mainstay with well executed nursing care resulting in quality clinical outcomes. The aim was to evaluate the nursing care interventions in management of patients with SJS/TEN in the dermatology unit. Methods: Qualitative design was used, data were collected through observation of nursing care activities, informant interviews and focus group discussion with the nurses. Qualitative data were recorded in audio tapes and transcribed. Qualitative content analysis was used for the analysis of the transcribed texts. Study was approved by KNH/ERC and informed written consent from participants. Funding was obtained from KNH through the Research and Programs department. Findings: 20 nurses participated in the study. The commonest nursing care interventions were described as routine tasks initiated at clinical diagnosis and routinely performed. They include aggressive skin care, wound care, mucosal and eye care, infection surveillance and prevention practices and general patient monitoring for complications. Skin and wound care were most challenging part of nursing care due to severe erosion or exfoliation. Nurses do not use any specific guidelines of care but consider their role a key in quality outcomes for patients with SJS/TEN in this hospital.

Amphotericin B release rate is the link between drug status in the liposomal bilayer and toxicity

Amphotericin B(AmB)is an amphiphilic drug commonly formulated in liposomes and administered intravenously to treat systemic fungal infections.Recent studies on the liposomal drug product have shed light on the AmB aggregation status in the bilayer,which heat treatment(curing)modifies.Although toxicity was found related to aggregation status-loose aggregates significantly more toxic than tight aggregates-the precise mechanism linking aggregation and toxicitywas notwell understood.This study directlymeasured drug release rate fromvarious AmB liposomal preparations made with modified curing protocols to evaluate correlations among drug aggregation state,drug release,and in vitro toxicity.UV–Vis spectroscopy of these products detected unique curing-induced changes in the UV spectral features:a∼25nm blue-shift of the main absorption peak(λ_(max))in aqueous buffer and a decrease in the OD_(346)/OD_(322) ratio upon thermal curing,reflecting tighter aggregation.In vitro release testing(IVRT)data showed,by applying and fitting first-order release kinetic models for one or two pools,that curing impacts two significant changes:a 3–5-fold drop in the overall drug release rate and a ten-fold decrease in the ratio between the loosely aggregated and the tightly aggregated,more thermodynamically stable drug pool.The kinetic data thus corroborated the trend independently deduced from the UV–Vis spectral data.The in vitro toxicity assay indicated a decreased toxicity with curing,as shown by the significantly increased concentration,causing half-maximal potassium release(TC50).The data suggest that the release of AmB requires dissociation of the tight complexes within the bilayer and that the reduced toxicity relates to this slower rate of dissociation.This study demonstrates the relationship between AmB aggregation status within the lipid bilayer and drug release(directly measured rate constants),providing a mechanistic link between aggregation status and in vitro toxicity in the liposomal formulations.

Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma

AIM:To study the relationship between adverse events(AEs),efficacy,and nursing intervention for sorafenibtherapy in patients with hepatocellular carcinoma(HCC).METHODS:We enrolled 37 consecutive patients withadvanced HCC who received sorafenib therapy.Relationships among baseline characteristics as well as AEoccurrence and tumor response,overall survival(OS),and treatment duration were analyzed.The nursingintervention program consisted of education regardingself-monitoring and AEs management,and telephoneRESULTS:A total of 37 patients were enrolled in the study,comprising 30 males(81%) with a median age of 71 years.The disease control rate at 3 mo was 41%,and the median OS and treatment duration were 259 and 108 d,respectively.Nursing intervention was given to 24 patients(65%).Every patient exhibited some kinds of AEs,but no patients experienced G4 AEs.Frequently observed AEs > G2 included anorexia(57%),skin toxicity(57%),and fatigue(54%).Factors significantly associated with longer OS in multivariate analysis demonstrated that age ≤ 70 years,presence of > G2 skin toxicity,and absence of > G2 hypoalbuminemia.The disease control rate in patients with > G2 skin toxicity was 13/20(65%),which was significantly higher compared with that in patients with no or G1 skin toxicity.Multivariate analysis revealed that nursing intervention and > G2 skin toxicity were independent significant predictors for longer treatment duration.CONCLUSION:Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC.Nursing intervention contributed to better adher-ence,which may improve the efficacy of sorafenib.

Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease

AIM: To evaluate the relationship between thiopu- rine S-methyltransferase (TPMT) polymorphisms and thiopurine-induced adverse drug reactions (ADRs) in inflammatory bowel disease (IBD). METHODS: Eligible articles that compared the frequency of TPMT polymorphisms among thiopurine-tolerant and-intolerant adult IBD patients were included. Statistical analysis was performed with Review Manager 5.0. Sub-analysis/sensitivity analysis was also performed. RESULTS: Nine studies that investigated a total of 1309 participants met our inclusion criteria. The inci- dence of TPMT gene mutation was increased 2.93-fold (95% CI: 1.68-5.09, P = 0.0001) and 5.93-fold (95% CI: 2.96-11.88, P < 0.00001), respectively, in IBD patients with thiopurine-induced overall ADRs and bone marrow toxicity (BMT), compared with controls. The OR for TPMT gene mutation in IBD patients withthiopurine-induced hepatotoxicity and pancreatitis was 1.51 (95% CI: 0.54-4.19, P = 0.43) and 1.02 (95% CI: 0.26-3.99, P = 0.98) vs controls, respectively. CONCLUSION: This meta-analysis suggests that the TPMT polymorphisms are associated with thiopurine-induced overall ADRs and BMT, but not with hepatotoxicity and pancreatitis.

Neurotoxicity of intrathecal injections of dexmedetomidine into the rat spinal dorsal horn

To investigate the neurotoxicity of intrathecal injections of dexmedetomidine,Sprague-Dawley rats were intrathecally injected with dexmedetomidine at doses of 0.75,1.50 and 3.00μg/kg into the spinal dorsal horn.We found that c-Fos expression in the rat spinal dorsal horn peaked at 7 hours following the 3.00μg/kg dexmedetomidine injection,while the levels of c-Fos expression following 0.75 and 1.50μg/kg dexmedetomidine were similar to those in the spinal dorsal horn of normal rats. At 48 hours following administration,the level of c-Fos expression was similar to normal levels.In addition,the intrathecal injections of dexmedetomidine increased paw withdrawal mechanical thresholds and prolonged thermal tail flick latencies.These results indicate that dexmedetomidine has pronounced antinociceptive effects.However,dexmedetomidine appears to have neurotoxic effects in the spinal cord because it increased c-Fos expression in the spinal dorsal horn within 7 hours following administration.

Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients

AIM: To analyze the prevalence of thiopurine-methyltransferase (TPMT) genotypes and their association with drug toxicity in inflammatory bowel disease (IBD) patients from southeastern Brazil.

Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents

Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.

A review: Systematic research approach on toxicity model of liver and kidney in laboratory animals

Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.

Comparative study on pharmacokinetics and toxicity of intravitreal and sub-Tenon injection of triamcinolone acetonide in ocular tissues

AIM:To compare the differences in kinetics,distribution,and toxicity of triamcinolone acetonide(TA)between the injection methods,sub-Tenon and intravitreal injections in rabbit ocular tissues.METHODS:TA was injected into the vitreous or the sub-Tenon in rabbits.For pharmacokinetic study,rabbits were sacrificed periodically and then TA in blood and ocular tissues(retina/choroids,vitreous,and aqueous humor)were measured over 91 d.For toxicological study,clinical signs,slit-lamp microscopic examination,ophthalmological test were performed.The eyeballs and surrounding tissues were collected and fixed with glutaraldehyde-formalin solution,and then paraffin embedded for histological investigation.RESULTS:Higher levels of TA were distributed in the intraocular tissues when injected into the vitreous compared to the sub-Tenon.Conversely,TA level was remarkably lower in the rabbits which received intravitreal TA injections than those treated with sub-Tenon injection throughout the study period in plasma.Optical discharge probably caused by systemic circulation of TA was observed by receiving sub-Tenon TA injection.Meanwhile,technicassociated toxicological ocular symptoms and findings were more frequently observed in intravitreal injection than in sub-Tenon injection.CONCLUSION:There are significant differences in kinetics and distribution of TA in vitreous body,aqueous humor and plasma,between the two injection methods.Although further study is needed to explain the species difference between human and rabbit,it is assumed that the difference in the frequency of intraocular pressure elevation and cataract formation by TA between the two injection methods are directly related to the TA concentrations in aqueous humor and vitreous body in each injection methods.Systemic toxicity and technic-associated toxicity are also closely related to kinetics of TA in plasma and each injection method itself,respectively.

Prediction of nephrotoxicity induced by cisplatin combination chemotherapy in gastric cancer patients

AIM:To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.METHODS:We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008.We investigated patients who had shown acute renal failure(ARF),and examined their clinical characteristics,laboratory data,use of preventive measures,treatment cycles,the amount of cisplatin administered,recovery period,subsequent treatments,and renal status between the recovered and unrecovered groups.RESULTS:Forty-one of the 552 patients had serum creatinine(SCR)levels greater than 1.5 mg/dL.We found that pre-ARF SCR,ARF SCR,and ARF glomerular filtration rates were significantly associated with renal status postARF between the two groups(P=0.008,0.026,0.026,respectively).On the receiver operating characteristic curve of these values,a 1.75 mg/dL ARF SCR value had 87.5%sensitivity and 84.8%specificity(P=0.011).CONCLUSION:Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.

Carbon nanotubes:A review on risks assessment,mechanism of toxicity and future directives to prevent health implication

Carbon nanotubes(CNTs)have tremendous applications in almost every walk of life;however,their harmful impacts on humans and the environment are not well addressed.CNTs have been used in various applications ranging from medical science to different engineering branches,to ease human life.Generally,the toxicological profile of CNTs under laboratory conditions cannot be assessed primarily in medical science due to the inconsistent availability of cytotoxic study data.CNT toxicity has been affected by many physicochemical properties(e.g.,size,type of functionalization),concentration,the extent of exposure,mode of exposure,and even the solvents/medium used to dissolve/disperse CNTs for their application.These inconsistencies arise due to the variation in synthesis methods as well as the mode of their human exposure.Besides their unlimited use in various fields,most of CNT toxicity aspects and mechanisms remain uncertain.Additionally,in-depth knowledge of CNTs toxicity is scarce,and the available literature shows dissimilarities in experimental data and exposure studies.To understand the toxicological issues,it is the need of the hour to provide insight into the published data,post-exposure studies,and various factors that may damage the cells due to CNTs toxicity.This review article analyses the hazardous potential through toxicological implications and summarizes the detailed mechanism(s)of CNTs studied on the different model organisms,including human cell lines.In this review article,we hypothesized that thorough knowledge of various aspects,as mentioned above,helps us design and develop possible strategies to reduce the toxicity of nanomaterial to make them safer and secure for humanity’s betterment.

Evaluation of Biotinylated PAMAM Dendrimer Toxicity in Models of the Blood Brain Barrier: A Biophysical and Cellular Approach

The interaction of biotinylated G4 poly(amidoamine) (PAMAM) dendrimer conjugates and G4 PAMAM dendrimers with in vitro models of the blood brain barrier (BBB) was evaluated using Langmuir Blodgett monolayer techniques, atomic force microscopy (AFM) and lactate dehydrogenase measures of cell membrane toxicity. Results indicate that both G4 and G4 biotinylated PAMAM dendrimers disrupt the composition of the liquid condensed (LC) and liquid expanded (LE) phases of the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayer. The disruption is concentration dependent and more marked for G4 biotinylated PAMAMs. Lactate dehydrogenase (LDH) assays using endothelial cell culture models of the BBB indicate that biotinylation results in higher levels of toxicity than non-biotinylation. This approach provides valuable information to assess nanoparticle toxicity for drug delivery to the brain.

Recent advances in the development of in vitro liver models for hepatotoxicity testing

Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical treatment.If not properly treated,patients with severe liver injury can suffer from acute liver failure or even death.Thus,utilization of the convenient in vitro hepatotoxicity assessment model for early detection of drug-induced hepatotoxicity is vital for drug development and safe personalized medication.Biomaterials(e.g.,hydrogels,nanofibers,decellularized liver matrix)and bioengineering technologies(e.g.,microarrays,micropatterns,3D printing,and microfluidics)have been applied for in vitro hepatotoxicity assessment models.This review summarizes the structure and functions of the liver as well as the components of in vitro hepatotoxicity assessment models.In addition,it highlights the latest advances in developing hepatotoxicity models with the ultimate goal of further clinical translation.

Comparative toxicity assessment between generic salbutamol sulphate inhaler containing hydrofluoroalkane and Ventolin Evohaler

Salbutamol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm such as asthma and chronic obstructive pulmonary disease (COPD). It is mostly taken through an inhaler device. The comparative toxicity assessment between two salbutamol sulfate preparations containing hydrofluoroalkane (HFA) metered dose inhalers with 100 μg per puff was evaluated in selected patients with asthma and COPD after prescribing. An open label, non-randomized, non-interventional observational study was designed. A large cohort of patients with asthma or related respiratory disorder of the general population from Dhaka and Chittagong of Bangladesh were recruited and treated with prescribed generic preparation Azmasol inhaler and brand preparation Ventolin Evohaler. Total 508 patients with asthma and minor obstructive airway disease were selected by the general medical practitioners in Bangladesh those who visited out patient consultation center in hospitals and physicians’ chambers and reported any adverse side effects of inhaled medications. There were no significant differences between the metered dose generic preparation Azmasol inhaler and Ventolon Evohaler among the patients treated with the medicines in asthma and related respiratory diseases in terms of adverse effects like immune system problem,dizziness,tremor,headache,nervousness,diarrhea,nausea,vomiting,heartburn,palpitation,skin rash,hypertension and taste feeling. It is concluded that Azmasol Inhaler, the generic salbutamol sulphate metered dose preparation containing HFA was as safe as the Ventolin Evohaler,a salbutamol sulfate brand preparation containing HFA when given to the patients in primary care after their physicians’ visits. Both the preparations have shown the similar safety profiles after regular use.