Causative Drug Research Articles

Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management.

Drug-induced thrombotic microangiopathy (DITMA) represents 10%-13% of all thrombotic microangiopathy (TMA) cases and about 20%-30% of secondary TMAs, just behind pregnancy-related and infection-related forms. Although the list of drugs potentially involved as causative for TMA are rapidly increasing, the scientific literature on DITMA is quite scarce (mostly as individual case reports or little case series), leading to poor knowledge of pathophysiological mechanisms and clinical management. In this review, we focused on these critical aspects regarding DITMA. We provided an updated list of TMA-associated drugs that we selected from a scientific literature review, including only those drugs with a definite or probable causal association with TMA. The list of drugs is heterogeneous and could help physicians from several different areas to be familiar with DITMA. We describe the clinical features of DITMA, presenting the full spectrum of clinical manifestations, from systemic to kidney-limited forms. We also analyze the association between signs/symptoms (i.e., malignant hypertension, thrombocytopenia) and specific DITMA causative drugs (i.e., interferon, ticlopidine). We highlighted their multiple different pathophysiological mechanisms, being frequently classified as immune-mediated (idiosyncratic) and dose-related/toxic. In particular, to clarify the role of the complement system and genetic deregulation of the related genes, we conducted a revision of the scientific literature searching for DITMA cases who underwent renal biopsy and/or genetic analysis for complement genes. We identified a complement deposition in renal biopsies in half of the patients (37/66; 57%), with some drugs associated with major deposits (i.e., gemcitabine and ramucirumab), particularly in capillary vessels (24/27; 88%), and other with absent deposits (tyrosine kinase inhibitors and intraocular anti-VEGF). We also found out that, differently from other secondary TMAs (such as pregnancy-related-TMA and malignant hypertension TMA), complement genetic pathological mutations are rarely involved in DITMA (2/122, 1.6%). These data suggest a variable non-genetic complement hyperactivation in DITMA, which probably depends on the causative drug involved. Finally, based on recent literature data, we proposed a treatment approach for DITMA, highlighting the importance of drug withdrawal and the role of therapeutic plasma-exchange (TPE), rituximab, and anti-complementary therapy.

Trimethoprim-sulfamethoxazole induced aseptic meningitis case report

Drug-induced aseptic meningitis (DIAM) is an uncommon meningitis and trimethoprim with or without sulfamethoxazole is the most involved antibiotic. Although DIAM is easily treated with the discontinuation of the causative drug, the diagnosis is a big challenge for physicians, as it remains a diagnosis of exclusion. Here, we present a case report of trimethoprim-sulfamethoxazole induced aseptic meningitis in a woman with acute osteomyelitis. A 52-year-old woman was admitted to the hospital for septic shock and acute osteomyelitis of the right homerus. She was started on antibiotic therapy with oxacillin and daptomycin, then oxacillin was replaced with cotrimoxazole, due to its excellent tissue penetration, including bone tissue. During cotrimoxazole therapy, the patient developed a fluent aphasia with ideomotor apraxia and muscle hypertonus. Having excluded infectious, epileptic and vascular causes of the acute neurologic syndrome of our patient, given the improvement and full recovery after discontinuation of cotrimoxazole, we hypothesized a DIAM. After discontinuation of cotrimoxazole, in 48 hours the patient had a full recovery. Although DIAM can be easily managed with the withdrawal of the causative drug, it can be difficult to recognize if it is not included in the differential diagnosis. An antimicrobial stewardship program with a strict monitoring of patients by infectious disease specialists is essential, not only to optimize the appropriate use of antimicrobials, but also to improve patient outcomes and reduce the likelihood of adverse events.

DRESS syndrome with carbamazepine and Epstein–Barr virus reactivation

DRESS syndrome is a serious toxidermia, most often caused by anticonvulsants, including carbamazepine, which is responsible for a formidable clinical picture and which may be accompanied by viral reactivations, in particular of the herpes group. Herein, we report the case of a young girl affected by DRESS syndrome with the reactivation of EBV, in whom the evolution was favorable. Recurrent EBV infection is demonstrated by the presence of IgM antibodies to anti-EBV early antigen and IgG antibodies to anti-EBV nuclear antigen. Its pathogenesis suggests that viral reactivation is the consequence of a T-immune response directed against the causative drug in some patients. It is an unpredictable entity requiring immediate treatment, namely stopping the drug in question, monitoring the patient, searching for viral reactivation and notifying pharmacovigilance. Key words: Dress syndrom; carbamazepine; EBV; rash; reactivation

A retrospective study of adverse drug reactions reported in a tertiary care hospital

Background: Adverse drug reactions (ADRs) are defined as noxious changes due to a drug, which can occur at doses normally used in humans that require treatment or dose reduction, and also indicate that caution should be exercised with future use of the same drug. Periodic monitoring of ADRs in hospitals can motivate health-care professionals to realize their role and responsibility in the detection, management, and reporting of suspected ADRs and also make them learn how to make sure patients stay safe and healthy. The current study is expected to raise awareness among health-care professionals on the importance of ADR reporting. Aims and Objectives: The objective of the study was to analyze the incidence and pattern of ADRs with assessing the severity and causality of ADRs reported in the hospital. Materials and Methods: All ADR cases which were reported to the pharmacovigilance unit between January 2022 and December 2022 have been evaluated. A total of 220 ADR cases were reported during the study. The demography of patients, causative drugs, reactions, causality assessment, and severity have been analyzed. Causality assessment using the WHO-Uppsala Monitoring Center Scale and severity analysis using the modified Hartwig and Siegel Scale have been done. Results: A total of 220 ADR cases have been evaluated. The main age group affected in our study was 31–45 years with male preponderance. Maximum cases were reported from the dermatology department. The most commonly affected organ was the skin. Antibiotics like cephalosporins caused most of the ADRs. After causality assessment, the maximum cases were probable type (60%), and severity assessment revealed that most of the cases were moderate in severity (64%). Conclusion: ADRs are one of the growing causes of morbidity and mortality worldwide. Underreporting of ADRs may result in a loss of clinical information that could prevent significant harm to patients. The need of the hour is to encourage health-care professionals to report any suspected ADR and also keep accurate records to analyze, process, and draw conclusions from data to ensure patient safety.

Clinical features and prognostic factors of severe cutaneous adverse drug reactions: A single-center retrospective study of 209 cases in China.

Severe cutaneous adverse drug reactions (SCAR) are life-threatening and contain drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). We aimed to evaluate clinical features and prognostic factors for SCAR patients. From January 2010 to April 2022, 209 patients with SCAR (DRESS, n=46, SJS/TEN, n=128, AGEP, n=35) were included in this study. Clinical symptoms, laboratory tests, causative drugs, disease courses, treatments, and outcomes were investigated. Antibiotics ranked first (35.9%) followed by traditional Chinese medicine (15.8%) and antiepileptic drugs (14.8%) among causative drugs of SCAR. One patient (2.2%) with DRESS and seven patients (5.5%) with SJS/TEN died in the hospital, while there was no AGEP-related mortality. The multivariate logistic regression analysis showed that high Registry of Severe Cutaneous Adverse Reactions score (OR=2.340, 95% CI=1.192-4.591) and hemoglobin<100g/L (OR=0.126, 95% CI=0.016-0.983) were independent risk factors of DRESS. Anemia (OR=0.191, 95% CI=0.037-0.984) and body surface area detached involved at day 1 (OR=2.749, 95% CI=1.115-6.778) were independent risk factors of SJS/TEN for severe acute complications and hospital death (P<0.05). Lymphocytopenia (OR=0.004, 95% CI=0.000-0.553) was a risk factor of AGEP for acute complications (P=0.028). This study reveals the clinical features and independent prognostic factors for SCAR, which may be helpful in the clinical management for SCAR patients.

URTICARIAL ADVERSE DRUG REACTIONS TO ACE INHIBITORS AND BETA-BLOCKERS

PURPOSE. To evaluate the incidence of urticarial adverse drug reactions (ADRs) to ACE inhibitors and beta-blockers, patient demographics, drug causality, and treatment outcome. METHODS. An epidemiological study including 154 patients with urticarial ADRs, out of a total of 3554 hospitalized patients in the Clinic of Dermatology and Venereology, for a 7-year period. ADRs were defined according to the WHO and the Naranjo algorithm was used for case drug causality assessment. RESULTS. Urticarial ADRs were found in 4,1% of the study population (≥ 18 years), the average age was 50,2 years, and female prevalence was established. Concomitant cardiovascular diseases were found in 45,2% of the patients and 30,1% declared using ACE inhibitors and/or beta-blockers. The suspected drug was withdrawn, and alternative therapy was recommended by a cardiologist. The Naranjo algorithm showed 4.5% “definitive”, 45,5% “possible”, and 50% “probable” urticarial ADRs. Systemic antihistamines were administered to all patients and single short corticosteroid courses were added in 81,8%. Clinical recovery was achieved in 59% of the patients and improvement in 41%. CONCLUSIONS. The need for drug therapy and hospitalization in severe cases of urticarial ADRs to ACE inhibitors and beta-blockers are factors contributing to the overall socio-economic burden of ADRs.

Serum Level of Granulocyte-macrophage Colony-stimulating Factor in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Activated T-cells secrete high amounts of cytokines that increase the expression and activity of keratinocytes, including granulocyte-macrophage colony-stimulating factor (GM-CSF). AIMS: The aims of this study were to evaluate the serum level of GM-CSF in SJS and TEN as well as the relationship between it and the progress of SJS and TEN. METHODS: This was a sectional descriptive study conducted at the National Hospital of Dermatology and Venereology, in Hanoi, Vietnam, from October 2017 to September 2019. Forty-eight SJS/TEN patients, 43 erythema multiforme (EM) patients, and 20 healthy controls (HCs) participated. GM-CSF levels were measured using the fluorescence covalent microbead immunosorbent assay (ProcartaPlex Immunoassay Panels kit, Thermo Fisher Scientific, USA). The Mann–Whitney U-test was used to compare serum SJS/TEN levels of the two groups. The Wilcoxon tests were used to compare quantitative variables before and after the treatment. Differences were considered to be statistically significant at p &lt; 0.05. RESULTS: There were 19 SJS patients (39.5%) and 29 TEN patients (60.5%). The mean age was 49.3 years, range of 19–77 years. The male patients were 47.9%. The most common causative drugs were traditional medicine (29.1%), followed by carbamazepine (12.5%), and allopurinol (12.5%). On the day of hospitalization, the mean serum level of GM-CSF in the SJS/TEN group was 10.6 pg/mL, which was significantly higher than that of the EM group (p &lt; 0.05) but not higher than that of the HCs group and was higher than that on the day of re-epithelialization (3.6 pg/mL) and the difference was statistically significant with p &lt; 0.05. CONCLUSION: Serum GM-CSF level can be a good biomarker to evaluate the progress of SJS/TEN.

Raynaud's Phenomenon: A Brush Up!

Raynaud's Phenomenon: A Brush Up!

Ceftazidime-induced immune hemolytic anemia: a case report

Drug-induced immune hemolytic anemia (DIIHA) is considered a rare condition. Nonsteroidal anti-inflammatory drugs and antineoplastic drugs are the main causes of DIIHA. An 86-year-old male patient with pulmonary infection was admitted to the 960^th Hospital of the PLA Joint Logistics Support Force. The patient was treated with ceftazidime in addition to supportive treatment. A history of antibiotics intake and clinical and laboratory hemolysis features were considered to be key bases for DIIHA diagnosis. Clinicians need to be aware of and accurately diagnose this rare complication caused by commonly prescribed drugs to stop the use of causative drugs in time, and therefore, to prevent serious and sometimes fatal consequences.

Clinicoetiological Study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Spectrum and the Correlation of SCORTEN with Prognosis.

Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe cutaneous adverse reactions of major concern because of its high mortality. The prognosis of SJS and TEN is widely assessed with SCORTEN (SCORe of TEN). Although, it is a largely useful scale, the predictive ability is still variable. This study was conducted to assess the clinicoetiological profile and outcome of SJS and TEN and to evaluate the validity of SCORTEN in assessing the prognosis in South Indian population. This prospective observational study was conducted in the Department of Dermatology, Venereology and Leprosy in a Tertiary care hospital from January 2016 to June 2017. Detailed history, examination findings, treatment and SCORTEN scores were recorded. SCORTEN's accuracy in predicting the mortality was assessed on day 1, 3 and 5 of admission. The incidence of SJS/TEN among other drug reactions was 29.5%. The most common age group affected was 30-49years (41.1%), with male preponderance (76.5%). The age range of patients was 6 and 67 years. TEN (64.7%) was the predominant spectrum followed by SJS and SJS-TEN overlap in 17.6% each. Anticonvulsants (47%) were the commonest causative drug, followed by analgesics (35%) and antibiotics (11%). The validity of SCORTEN was the same on days 1, 3, and 5. There was good agreement between the actual and predicted mortality on all three days. A mortality of 17.6% (3 cases) was recorded in this study. Three patients (17.6%) died in our study. All survivors had a score of 4 or less. The predicted mortalities were 0.417, 1.836, and 2.574 and the observed mortalities were 0, 2, and 1 in SJS, SJS-TEN overlap, and TEN respectively. Analysis of SCORTEN on a single day, either day 1, 3, or 5 was found to be as useful as the serial analysis. SCORTEN gave a significant estimation of mortality in SJS-TEN overlap patients, whereas it overestimated mortality in TEN patients. An increase in individual scores for the elevation of blood urea nitrogen (BUN) in existing SCORTEN and the inclusion of new parameters like raised liver enzymes, thrombocytopenia, and pulmonary infiltrates aided in proposing a modified SCORTEN for the South Indian population. Further studies on a larger scale, are needed to validate the modified SCORTEN proposed by us.

Drug Safety Alerts Issued by the National Coordination Centre for Pharmacovigilance Programme of India

Background: Adverse drug reactions (ADRs) due to drug therapy are inevitable and prior knowledge of their causative agents can avoid unnecessary economic burden on patients as well as on the health-care system. Objectives: To create awareness among health-care professionals about the drug safety alerts (DSAs) issued by the National Coordination Centre for Pharmacovigilance Programme of India (NCC-PvPI) till December 2022 and to reiterate the importance of spontaneous reporting of adverse events for better patient care. Methodology: A retrospective analysis of 141 DSAs issued from March 2016 to December 2022 was done. The ADRs were analyzed for the type of reactions, system organ class, and according to drug class. Microsoft Office 2007 was used to formulate the data and presented it in a descriptive manner using numbers and percentages. Results: Out of 141 DSAs under analysis, 101 individual drugs, 2 drug classes, and 7 drug combinations have developed 144 ADRs. These ADRs were compressed into 86 different types as similar ADRs were caused by more than one drug. Drug Reaction with Eosinophilia and Systemic Symptoms is the most common ADR noticed, followed by skin manifestations such as toxic epidermal necrolysis, acute generalized exanthematous pustulosis, skin hyperpigmentation, fixed drug eruption, symmetrical drug-related intertriginous and flexural exanthema, and photosensitivity reaction. The most common causative drugs for ADRs were antimicrobial agents, cephalosporins being the most commonly implicated medication class. Conclusions: Most of the ADRs advised to closely monitor by the NCC-PvPI through DSAs were treatable by early and appropriate management. Due to the high number of skin manifestations observed in the analysis, the role of dermatologists in taking detailed drug history is critical when making a differential diagnosis of skin lesions. Motivation and creating awareness among health-care professionals and patients to spontaneously report adverse events can only strengthen the pharmacovigilance system in India.

Evaluation of Adverse Drug Reactions Due to Fixed-dose Combinations at a Tertiary Care Hospital: An Observational Retrospective Study

Introduction: The mushrooming of Fixed-dose Combinations (FDCs) has been observed in the past decade in the Indian market. The majority of these FDCs are irrational and put patient safety at risk. Aim: To evaluate Adverse Drug Reactions (ADRs) due to rational as well as irrational FDCs available in India. Materials and Methods: This was an observational, retrospective study where recorded data of ADRs reported over a period of 10 years (January 2011-December 2021) at the Regional Training Centre and ADR Monitoring Centre (B.J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India) was analysed. The data evaluation was carried out from May 1, 2022, to December 15, 2022. Any ADR where FDC(s) was the suspected causal drug was included in the analysis. Out of a total of 8,218 reported ADRs in the ten-year duration, 1,575 ADRs were reported to have occurred due to FDCs. The data were analysed for age, gender, System Organ Class (SOC), suspected drug, seriousness of the ADRs, causality assessment, and outcome of ADRs, and presented in terms of numbers or percentages. Results: A total of 1,575 ADRs occurred due to 1,649 FDC(s). The most common SOC class of ADRs was Gastrointestinal (GI) disorders in 359 (23%) cases, followed by skin and subcutaneous disorders in 317 (20%). The common suspected groups were Anti-Retroviral (ARV) drugs in 787 (50%) ADRs, followed by antitubercular drugs in 298 (19%). Out of a total of 1,649 FDCs as the suspected drug, 1,551 (94%) were rational, and 98 (6%) were irrational. A total of 169 (11%) serious ADRs were reported, of which seven ADRs were due to irrational FDCs (prescribed for cold and cough). Causality assessment using the World Health Organisation-Upsala Monitoring Centre (WHO UMC) classification showed a possible causal association with the suspect FDCs for 1,385 (84%) ADRs. Conclusion: FDCs contribute to a significant proportion of ADRs, which could be prevented by avoiding the use of irrational FDCs and monitoring the patients for the possible development of ADRs.

Factors Causing Drug Abuse in Rehabilitation Clients and Psychological Attendants

The dominant problem encountered is the rampant use of drugs in Payakumbuh City which makes the causative factor dari drug abuse rehabilitation. Seeing the increasing number of drug use in Indonesia, there is also more damage to the younger generation in Indonesia. The purpose of this study was to determine the factors causing drug abuse in rehabilitation clients in BNN Payakumbuh City. This research is descriptive qualitative research. The data collection was carried out by interviewing subjects totaling 4 victims of drug abuse who were undergoing rehabilitation. Based on the results of the study, it was found that the factors causing the actions of drug abusers in the National Narcotics Agency (BNN) of Payakumbuh City were individual and environmental factors (peers). The individual factor comes from having curiosity and wanting to try drugs. From family, factors do not affect the rehabilitation client on the cause of drug abuse in the rehabilitation client in BNN Payakumbuh City. Environmental factors influence on the rehabilitation client on the causes of drug abuse. Environmental factors (peers) found that the client was in drug abuse from his peers' problems which started from introducing drugs to informants as well as inviting informants to use drugs while gathering together. Meanwhile, from the information media factor, it was found that 2 clients did not get information about drugs from the information media but 2 rehabilitation clients got news about drugs while also looking for information about drugs in the information media but did not affect the client on the cause of drug abuse in rehabilitation clients in BNN Payakumbuh City

Immediate adverse reactions in the chemotherapy treatment of patients with cancer at an oncology day hospital.

A descriptive and cross-sectional study was performed to characterize the degree of immediate adverse reaction and the type of causative antineoplastic drug presented by 371 different patients treated for cancer at the oncology day hospital unit of the San Carlos Clinical Hospital (Madrid, Spain), during the period between January 2015 and December 2019. In the case series, 488 immediate adverse reactions secondary to chemotherapy toxicity were detected. The dominating factors were: Female sex, age from 51-70 years old, skin melanoma and the use of vinca alkaloids and analogs. Among the most frequent adverse reactions, the following stood out: Disorders of the nervous and musculoskeletal systems and of the connective tissue. There was a higher number of moderate adverse reactions (grade 2 according to the Common Terminology Criteria for Adverse Events Version 4.0) between the first and third chemotherapy cycles, with a latency period of between 6 and 15 min., generally lasting less than 30 min. Association with the degree of immediate adverse reaction (grade) has been observed in male subjects over 71 years of age, with soft tissue neoplasm type and monoclonal antibodies therapeutic group.

Ocular toxicity of investigational anti-cancer drugs in early phase clinical trials

SummaryOcular toxicities arising from anti-cancer drugs occur sporadically and are sometimes underestimated because they are not life-threatening. Reports focusing on ocular toxicities from cancer therapy are limited. We investigated the detailed progress of ocular toxicities of anti-cancer drugs including first-in-class ones. A retrospective review of medical records was conducted for patients who were involved in early phase clinical trials with scheduled ophthalmologic examinations according to their protocols between January 2014 and August 2021. Patients with ocular toxicity suspected to be related to the investigational drugs in the ophthalmic examination were investigated in detail. In total, 37 ocular toxicities related to investigational drugs occurred in 7.6% of patients (33/434). The median age of the 33 patients was 61 years (range, 33–76 years), and 20 were male. Causal drugs with a high incidence of ocular toxicities were HSP90 inhibitors and FGFR inhibitors. Retinopathy was most frequent, while conjunctivitis, dry eye, keratitis, keratopathy, and uveitis were also observed. Dim vision as a subjective finding was a unique adverse event. Most patients developed ocular toxicities even though their dose was below the drug’s maximum tolerated dose. Except for one case, all ocular toxicities occurred bilaterally. About 60% (22/37) of ocular toxicity cases needed a temporary hold of the drug. All except for three cases fully recovered. This study reported the risks and timing of the onset of a variety of ocular toxicities of anti-cancer drugs, which were fundamentally controllable. (Trial registration number. Retrospectively registered)

Analysis of burden and outcomes of anti-tuberculosis therapy-induced adverse drug effects at a tertiary care center

Background: Tuberculosis (TB), one of the most ancient diseases known to mankind, is one of the ten major causes of mortality worldwide. Combinations of antibiotics, called anti-TB therapy (ATT), are given for a period of six months or more as treatment. Aims and Objectives: The aim of this study was to assess the incidence of adverse drug reactions (ADRs), clinical profile, severity and causality among the admitted patients taking ATT in a tertiary care hospital. Materials and Methods: This was a hospital-based, prospective, observational and non-interventional cohort study undertaken in the General Medicine wards of the hospital. This study was conducted from June 2017 to December 2018. The Patients’ data was recorded using a structured ADR reporting form. The baseline parameters, medical history and details of underlying diseases, clinical data, characteristics of ADRs and details of medication responsible for ADRs as well as medication for treatment of ADRs were recorded. The data was analyzed using descriptive statistics with the Statistical Packages for the Social Sciences (SPSS) version 26.0 software. Results: Out of the 164 patients admitted due to ADRs within the study period, 45 (27.4%) developed ADRs due to anti-TB treatment. Most ATT-related ADRs involved the liver (n=39). The severity of ADR was found to be mild in two patients (4.4%), moderate in 28 patients (62.5%) and severe in 15 patients (33.3%). 16 patients (35.6%) completely recovered, 23 patients (51.1%) were still recovering (at the time of the analysis of the data), one patient (2.2%) did not recover and five patients (11.1%) had a fatal outcome. The presence of systemic comorbidities and polypharmacy was found to be a significant risk factor associated with ATT associated ADRs. Conclusion: ATT is not without its side effects. About 27.4% of the patients on ATT in our study developed ADRs, a few resulting in fatality. Educating the patients about possible ADRs associated with ATT at the time of prescription can improve patient compliance and strengthen the doctor-patient relationship. Early diagnosis and treatment of ADRs associated with ATT is paramount. This requires a better surveillance system, which India is in a dire need for.

Sex‐specific molecular profiling to understand pathology and identify causal genes and drug targets for Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is a highly heterogeneous multifactorial disease. Genetic influences on AD are strong as shown by several pathogenic genes and over 50 AD GWAS loci. There are also clear sex differences in AD risk and progression. Women are at a higher risk of developing AD and present faster progression. A recent GTEx study also highlights sex differences in the genetic regulation of gene expression. Despite these established sex differences, sex‐specific molecular findings in AD are still limited.MethodWe generated and performed analysis using 713 CSF proteomic data that passed QC obtained from Knight‐ADRC and DIAN samples. The sample includes 190 late onset clinical AD patients and 509 age‐ and gender‐matched cognitively healthy individuals. Age at lumbar puncture and surrogate variables (to account for unmeasured heterogeneity) were included as covariates. To evaluate sex‐specific molecular signatures, we performed sex‐stratified analysis by separately analyzing 333 males and 366 females.ResultIn male CSF tissues, 99 proteins significantly associated with late onset AD status (FDR P &lt; 0.05) and 131 proteins in female CSF tissues. Those proteins were enriched in pathways involved in the endolysosome and proteasome pathway including HSP70. We identified 44 proteins presenting a suggestive evidence of sex‐specific effects on AD status. In particular, several proteins that were previously reported to be associated with AD risk show sex‐specific effects. Downregulation of LRIG3 improves cognitive impairment and alleviate neuronal damage in hippocampus tissues in AD rats through modulating the PI3K/Akt pathway. We found that LRIG3 was associated in males only and would not have been identified through a combined analysis that simply included sex as a covariate (P = 3.4×10‐3 in males; P &gt; 0.5 in females; P = 0.067 in all).ConclusionThis study demonstrates that 800 proteins in 700 CSF tissues can provide a suggestive information on sex‐specific proteomic profiles. We will extend our sex‐specific analysis using our recently generated 7000 proteomic data to fully understand the biology of the disease and determine the role of sex in disease, create sex‐specific genes and prediction models. This will provides insights for clinically translatable interventions for prevention and treatment.

029 Possible plasticity of cytotoxic resident memory T cells in fixed drug eruption

Fixed drug eruption (FDE) repeats in the same sites and the lesions increase by repetitive exposure to the causative drug. Although FDE is regarded to be mediated by skin resident memory T cells (TRM), which are sessile and do not recirculate from skin, the clinical characteristics of FDE cannot be fully explained by the known functions of TRM in human. In order to elucidate the contribution of TRM in the FDE manifestation, skin T cells isolated from lesions of total five recurrent and four cured FDE subjects, and total seven controls from surgical discards were analyzed for the expression of cell-surface molecules representing the phenotypes of TRM and central memory T cells (TCM) by flow cytometry.

Identification and characterization of lysophosphatidylcholine 14:0 as a biomarker for drug-induced lung disease

Drug-induced interstitial lung disease (DILD) occurs when drug exposure causes inflammation of the lung interstitium. DILD can be caused by different types of drugs, and some DILD patterns results in a high mortality rate; hence, DILD poses a serious problem in clinical practice as well as drug development, and strategies to diagnose and distinguish DILD from other lung diseases are necessary. We aimed to identify novel biomarkers for DILD by performing lipidomics analysis on plasma samples from patients with acute and recovery phase DILD. Having identified lysophosphatidylcholines (LPCs) as candidate biomarkers for DILD, we determined their concentrations using validated liquid chromatography/mass spectrometry biomarker assays. In addition, we evaluated the ability of LPCs to discriminate patients with acute phase DILD from those with recovery phase DILD, DILD-tolerant, or other lung diseases, and characterized their association with clinical characteristics. Lipidomics analysis revealed a clear decrease in LPC concentrations in the plasma of patients with acute phase DILD. In particular, LPC(14:0) had the highest discriminative index against recovery phase and DILD-tolerant patients. LPC(14:0) displayed no clear association with causal drugs, or subjects’ backgrounds, but was associated with disease severity. Furthermore, LPC(14:0) was able to discriminate between patients with DILD and other lung diseases, including idiopathic interstitial pneumonia and lung disease associated with connective tissue disease. LPC(14:0) is a promising biomarker for DILD that could improve the diagnosis of DILD and help to differentiate DILD from other lung diseases, such as idiopathic interstitial pneumonia and connective tissue disease.

Comparative Evaluation Of Knowledge And Awareness About Mucormycosis In Dental And Medical Practitioners In Western Maharashtra

Introduction: The estimated mucormycosis mortality rate in India ranges from 28-52%. High morbidity and mortality have been linked to delayed diagnosis and treatment. Medical and dental practitioners play a crucial role in identifying the disease and formulating a treatment plan. Hence it is important for medical and dental practitioners have adequate knowledge about mucormycosis.Objective: To evaluate and compare knowledge and awareness about mucormycosis amongst dental and medical practitioners.Methods: This cross-sectional survey was conducted among Medical and Dental practitioners in Western Maharashtra. A specially designed prevalidated questionnaire was developed, consisting of 15 questions. It was distributed through electronic mode utilizing google form during July 1st, 2022 to August 31st, 2022. SPSS Version 21 software was used for statistical analysis. The data obtained was statistically analysed using paired T-test.Results: A total of 604 responses were obtained among which 266 (44.04%) were medical practitioners and 338 (54.96%) were dental practitioners. Variations in responses indicated that practitioners from both the groups were nescient regarding causative organisms, predisposing factors, and guidelines for drugs used in treatment of mucormycosis. There was no significant difference observed in the level of knowledge and awareness among both the groups.Conclusions: Majority of the dental and medical practitioners lacked adequate knowledge and awareness about causative agents, predisposing factors, clinical symptoms, and drug regimens used to treat mucormycosis. Periodic continuing professional education programs are required to impart updated knowledge about mucormycosis among these practitioners.