The radiologist's role in detecting systemic anticancer therapy-related interstitial lung disease: an educational review.

Systemic anticancer therapies (SACTs) are the leading cause of drug-induced interstitial lung disease (ILD). As more novel SACTs become approved, the incidence of this potentially life-threatening adverse event (AE) may increase. Early detection of SACT-related ILD allows for prompt implementation of drug-specific management recommendations, improving the likelihood of AE resolution and, in some instances, widening the patient's eligibility for future cancer treatment options. ILD requires a diagnosis of exclusion through collaboration with the patient's multidisciplinary team to rule out other possible etiologies of new or worsening respiratory signs and symptoms. At Grade 1, ILD is asymptomatic, and thus the radiologist is key to detecting the AE prior to the disease severity worsening. Planned computed tomography scans should be reviewed for the presence of ILD in addition to being assessed for tumor response to treatment, and when ILD is suspected, a high-resolution computed tomography (HRCT) scan should be requested immediately. An HRCT scan, with < 2-mm slice thickness, is the most appropriate method for detecting ILD. Multiple patterns of ILD exist, which can impact patient prognosis. The four main patterns include acute interstitial pneumonia / acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, and non-specific interstitial pneumonia; their distinct radiological features, along with rarer patterns, are discussed here. Furthermore, HRCT is essential for following the course of ILD and might help to determine the intensity of AE management and the appropriateness of re-challenging with SACT, where indicated by drug-specific prescribing information. ILD events should be monitored closely until complete resolution. CRITICAL RELEVANCE STATEMENT: The incidence of potentially treatment-limiting and life-threatening systemic anticancer therapy-related interstitial lung disease (SACT-related ILD) events is likely increasing as more novel regimens become approved. This review provides best-practice recommendations for the early detection of SACT-related ILD by radiologists. KEY POINTS: Radiologists are crucial in detecting asymptomatic (Grade 1) ILD before severity/prognosis worsens. High-resolution computed tomography is the most appropriate method for detecting ILD. Drug-induced ILD is a diagnosis of exclusion, involving a multidisciplinary team. Familiarity with common HRCT patterns, described here, is key for prompt detection. Physicians should highlight systemic anticancer therapies (SACTs) with a known risk for interstitial lung diseases (ILD) on scan requisitions.

Antifungal prophylaxis against invasive Candida and Aspergillus infection in adult heart transplant recipients: protocol for a systematic review and meta-analysis.

INTRODUCTION: Invasive fungal infections (IFI) can contribute to increased mortality and morbidity rates after heart transplant in adults. The most common causes are Aspergillus and Candida species. There is uncertainty on how effective antifungal prophylaxis is against Candida spp infections and limited guidance on the prevention of Aspergillus spp infections. This systematic review and meta-analysis will assess the literature to see if antifungal prophylaxis reduces the incidence of IFI after heart transplant in adults. METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic reviews and Meta Analysis guidelines. A systematic search of the Cochrane Library, Web of Science, Scopus, Embase, MEDLINE, and Proquest databases will be undertaken. Reference lists of retrieved publications and conference abstracts will also be searched. Title, abstract and full-text screening will be undertaken by two reviewers. Discrepancies will be resolved by a third reviewer. Studies with paediatric patients, multi-organ transplants, or patients with a second heart transplant will be excluded, along with those who do not have clear definitions and diagnostic criteria for IFI. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool and the Risk of Bias in Non-randomised Studies of Interventions tool. A meta-analysis will be carried out, but if studies are not deemed to be sufficiently similar, only a narrative synthesis will be undertaken. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review as primary data will not be collected. The results of the review will be disseminated through publication in an academic journal and scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42024516588.

Therapeutic effect of epidural dexamethasone palmitate in a rat model of lumbar spinal stenosis.

BACKGROUND: Dexamethasone palmitate (DEP), a prodrug of dexamethasone (DEX), is a synthetic corticosteroid medication distinguished by the inclusion of a fatty acid component known as palmitate. This study introduces DEP as a novel therapeutic option for spinal epidural injection, aiming to provide safer and longer-lasting pain relief as an alternative to for patients with spinal stenosis. METHODS: 40 rats were randomly divided into four groups: those receiving epidural administration of normal saline (NS), and DEP in the lumbar spinal stenosis (LSS) model, and non-model rats receiving epidural NS administration. Paw withdrawal thresholds to mechanical stimulation and motor function (neurogenic intermittent claudication) were observed for up to 21 days. Hematology and blood chemistry analyses were performed 1 week after drug therapy. Tissue samples were collected for steroid pathology examination to evaluate adhesion degree, perineural area inflammation, and chromatolysis in the dorsal root ganglion (DRG), and adrenal gland. RESULTS: The DEX and DEP groups demonstrated significant recovery from mechanical allodynia and motor dysfunction after 2 weeks of drug therapy (p<0.001). However, by the third week, the effect of DEX started to diminish while the effect of DEP persisted. Furthermore, the DEP group exhibited reduced fibrosis and less chromatolysis than the NS group. No steroid overdose or toxin was observed in any group. CONCLUSION: The epidural administration of DEP demonstrated therapeutic efficacy in reducing allodynia and hyperalgesia resulting from chronic DRG compression, thus offering prolonged pain relief. These findings underscore the potential of DEP as a promising treatment alternative for pain associated with LSS, serving as a viable substitute for .

Efficacy and safety of dose-dense gemcitabine plus cisplatin as neoadjuvant chemotherapy for muscle-invasive bladder cancer.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of dose-dense gemcitabine and cisplatin (ddGC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). METHODS: Patients with locally advanced MIBC (cT2aN0M0-cT4N1M0) who received ddGC between December 2017 and December 2023 were included. Regimens of ddGC with pegfilgrastim were administered every 2 weeks for 4 cycles, followed by radical cystectomy. The pathological complete response (CR) (pT0N0) and objective response (OR) (

Clopidogrel-induced thrombotic microangiopathy: a case report.

Thrombotic microangiopathy is a serious condition that can be precipitated by exposure to certain medications. Although rare, it is life threatening and requires a high index of clinical suspicion, appropriate laboratory testing and immediate cessation of the offending agent. We present a case of a 75-year-old man with a history of ischaemic heart disease treated with clopidogrel and aspirin. One month after initiating the treatment he developed microangiopathic haemolytic anaemia and thrombocytopenia. Extensive clinical and laboratory investigations suggested thrombotic microangiopathy secondary to clopidogrel. The drug was immediately discontinued and treatment with intravenous corticosteroids was started. Within a week the patient's laboratory parameters normalised, indicating successful recovery. This case highlights the role of early detection and immediate discontinuation of suspected medication in the effective management of clopidogrel-induced thrombotic microangiopathy. Healthcare professionals should consider drug-induced thrombotic microangiopathy as a possible diagnosis in patients receiving clopidogrel who present with thrombocytopenia and microangiopathic haemolytic anaemia.

Cost-effectiveness of preoperative pharmaceutical care consultations: a 5-year analysis.

OBJECTIVES: Preoperative medication errors can be prevented by screening patients through a preoperative pharmaceutical care consultation. The aim of this study was to analyse the cost-effectiveness of implementing such a consultation and to determine which patients would benefit most. METHODS: A retrospective study was conducted that included all patients who underwent a preoperative pharmacy consultation between 2016 and 2020. During this consultation, two part-time pharmacists reviewed patients' appropriate preoperative chronic medication management. All prevented errors were collected and classified by therapeutic group and type of error. A team of pharmacists and anaesthetists assigned to each prevented medication error a probability of causing an adverse event 'p', following the methodology of Nesbit et al by establishing five different 'p' values: 0, 0.01, 0.1, 0.4, and 0.6. 'p' = 1 was not considered. The cost of an adverse event was determined to be between €4124 and €6946 according to current literature, and a sensitivity analysis was performed by increasing the interval by 20% above and below. The cost of employing two part-time specialist pharmacists was estimated to be €59 142. Savings per medication error prevented were calculated as (€4124 OR €6946) × 'p'. Total savings were the sum of all costs associated with prevented medication errors. Patients on chronic medications who were in therapeutic groups with a 0.6 probability of an adverse event or who were in therapeutic groups responsible for 50% of the prevented adverse events were considered prioritisable. RESULTS: 3105 patients attended the consultation and 1179 medication errors were prevented, corresponding to 300 adverse events. 42.2% of the errors had a 'p' of 0.4. The costs avoided by this consultation ranged from €1 237 200 to €2 083 800, while the cost of its implementation was €295 710. The cost-effectiveness ratio was between €4.2 and €7.0 saved per euro invested. In the sensitivity analysis, the ratios ranged from €3.3 to €8.5 per euro invested. Fifteen different therapeutic groups accounted for 90% of the medication errors prevented. The therapeutic groups 'Agents acting on the renin-angiotensin system', 'Antidiabetics, non-insulin (excluding SGLT2)' and 'Antithrombotics: low molecular weight heparins' were responsible for 56% of the prevented adverse events. The therapeutic groups 'Antidiabetics: rapid-acting insulin' and 'Antithrombotic agents: vitamin K antagonists, low-molecular-weight heparins, or direct oral anticoagulants' had a 'p' of 0.6. Therefore, patients in six therapeutic groups should be prioritised for preoperative pharmacy counselling. CONCLUSIONS: The implementation of preoperative pharmaceutical care consultations in Spain has proven to be cost-effective. Incorporating the probability of a medication error causing an adverse event allowed the prioritisation of patients for these consultations. Patients taking anticoagulants, oral antidiabetics, rapid-acting insulins, and agents acting on the renin-angiotensin system benefited the most. This study could serve as a basis for implementing such consultations in other hospitals, as they are effective in reducing the cost of medication errors in surgical patients.

Top 10 Signs and Symptoms of Psychotropic Adverse Drug Events to Monitor in Residents of Long-Term Care Facilities.

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants. DESIGN: A 3-round Delphi study. SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries. METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms. RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth. CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

Anticholinergic burden and health-related quality of life among adult patients in a resource-limited setting: a cross-sectional study.

BACKGROUND: Anticholinergic medications are now widely acknowledged for their unfavorable risk-to-benefit profile owing to their adverse effects. Health-related quality of life (HRQoL) is commonly regarded as a crucial person-centered outcome. AIM: This study aimed to investigate the association between anticholinergic burden and HRQoL in hospitalized and ambulatory patients seen in Ethiopia. METHOD: This cross-sectional study utilized a questionnaire and medical records to collect data from a convenience sample of adult patients attending both inpatient wards and ambulatory clinic of University of Gondar Comprehensive Specialized Hospital between April and September 2022. Anticholinergic burden was measured by anticholinergic cognitive burdens scale (ACBS), while HRQoL was measured using EQ5D-index (Euroqol-5 dimensions-5-Levels index) and EQ5D-VAS (visual analogue scale). Linear regression was used to assess the influence of high anticholinergic burden (ACBS score ≥ 3) on EQ5D-index and EQ5D-VAS, with adjustments made for sociodemographic and clinical confounders. RESULTS: A total of 828 patients participated in this study (median (IQR) age was 45.0 (30, 60) and 55.9% were female). On multiple linear regression analysis, high anticholinergic burden was associated with a statistically significant decline in HRQoL, as evidenced by reductions in both EQ5D index (- 0.174 (- 0.250, - 0.098)) and EQ5D-VAS scores (- 9.4 (- 13.3, - 5.2)). CONCLUSION: A significant association between high anticholinergic burden and diminished HRQoL was found among a relatively younger cohort in a resource-limited setting, even after adjustment for important confounding variables. Clinicians should be cognizant of the cumulative impact of anticholinergic burden on HRQoL outcomes and strive to minimize anticholinergic burden.

The Occurrence of Etoricoxib-Induced Stevens-Johnson Syndrome With Oral Manifestations in a Female Patient: A Case Study.

Stevens-Johnson Syndrome (SJS) constitutes a rather uncommon, and rarely fatal hypersensitivity reaction that primarily impacts the skin and mucous membranes and in certain cases may be attributed to drug administration. The aim of this article is to present a case of etoricoxib-induced SJS in a 46-year-old, female patient. The patient presented herself, as a medical emergency, to the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, reporting pain, especially acute pain while eating certain foods, discomfort, dysphagia, and a wound in the left half of the hard palate. The clinical examination revealed a broad ulcer, in the left half of the hard palate as well as multiple ulcerations and erosions in the upper and lower lip. Her medical history was clear; however, the patient mentioned to have received etoricoxib, due to severe back pain, one day prior to our clinical examination. The patient received methylprednisolone 16 mg, twice per day, for two days, followed by methylprednisolone 8 mg, twice per day, for two more days. Her symptoms resigned and since the connection between etoricoxib and SJS was established, the patient was advised to avoid etoricoxib and be wary of adverse effects, when taking drugs especially non-steroidal anti-inflammatory medication. This is one of the first case reports in the literature, linking etoricoxib administration with the emergence of SJS, highlighting the importance of pharmacovigilance. The up-to-date registration of drug-induced adverse effects is of immense importance to protect future patients. SJS does not have a defined treatment strategy. Therefore, most patients are given supportive care and symptomatic treatment, which most commonly involves corticosteroids and antivirals such as acyclovir.

Prediction of adverse drug reactions in geriatric patients admitted to intensive care units. / [Artículo traducido] Predicción de reacciones adversas a medicamentos en pacientes geriátricos ingresados en unidades de cuidados intensivos.

INTRODUCTION: Intensive Care Units (ICUs) pose challenges in managing critically-ill patients with polypharmacy, potentially leading to Adverse Drug Reactions (ADRs), particularly in the elderly. OBJECTIVE: To evaluate whether the severity and clinical prognosis scores used in ICUs correlate with the prediction of ADRs in aged patients admitted to an ICU. METHODS: A cohort study was conducted in a Brazilian University Hospital ICU. APACHE II and SAPS 3 assessed clinical prognosis, while GerontoNet ADR Risk Score and BADRI evaluated ADR risk at ICU admission. Severity of the patients' clinical conditions was evaluated daily based on the SOFA score. Adverse Drug Reaction (ADR) screening was performed daily through the identification of ADR triggers. RESULTS: 1295 triggers were identified (median 30 per patient, IQR = 28), with 15 suspected ADRs. No correlation was observed between patient severity and ADRs at admission (p=0.26), during hospitalization (p=0.91), or at follow-up (p=0.77). There was also no association between death and ADRs (p=0.28) or worse prognosis and ADRs (p>0.05). Higher BADRI scores correlated with more ADRs (p=0.001). CONCLUSIONS: The data suggest that employing the severity and clinical prognosis scores used in Intensive Care Units is not sufficient to direct active pharmacovigilance efforts, which are therefore indicated for critically ill patients.

[Low-dose methotrexate: Indications and side effects, particularly in cases of diffuse interstitial pneumonia]. / Méthotrexate à faible dose : indications et effets secondaires, en particulier en cas de pneumopathie interstitielle diffuse.

INTRODUCTION: Methotrexate (MTX) is a folate antagonist used as an immunosuppressant in a number of conditions, including rheumatoid arthritis (RA). Low-dose MTX (MTX-LD) is associated with a risk of haematological, hepatic, gastrointestinal and pulmonary toxicity, which may up until now have limited its use. STATE OF THE ART: In RA, data from retrospective cohorts have reported a possible excess risk of methotrexate toxicity in cases of underlying interstitial lung disease (ILD). However, recent prospective and retrospective multicentre studies have found no such increased risk, and have reassuringly concluded that MTX-LD can be prescribed in cases of RA-associated ILD (RA-ILD). PERSPECTIVES AND CONCLUSIONS: Current recommendations are not to delay the introduction of MTX in patients with RA at risk of developing ILD or in the presence of RA-ILD with mild to moderate respiratory impairment.

Management of hereditary hemorrhagic telangiectasia-like symptoms induced by trastuzumab emtansine in a breast cancer patient: case report.

Trastuzumab emtansine (T-DM1) is a targeted therapy combining trastuzumab and emtansine for human epidermal growth factor receptor 2(HER2)-positive breast cancer, with common side effects including fatigue, nausea, pain, headache, low platelet count, and elevated liver enzymes. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by vascular malformations and telangiectasias in various organs. We present a case of a female patient with advanced breast cancer who developed HHT-like symptoms while on T-DM1 treatment. A 59-year-old woman treated with radiotherapy and T-DM1 every 21 days developed recurring nosebleeds and mucocutaneous and liver telangiectasias indistinguishable from HHT three months after receiving the first dose of T-DM1. Other organ vascular malformations were ruled out through screening protocols. The patient had no previous HHT symptoms or family history. Nasal care measures like lubrication and antifibrinolytics (tranexamic acid) were provided. In addition, propranolol was also prescribed due to its antiangiogenic and antitumoral properties, leading to significantly decreased epistaxis and telangiectasias. Microtubule disruptions caused by T-DM1, along with other angiogenic mechanisms may contribute to the development of telangiectasias resembling HHT. The use of propranolol, an initial approach for HHT, proved to be effective in this case. It is crucial for oncologists and HHT specialists to be aware of this rare adverse event associated with T-DM1 and to implement appropriate management strategies.

Evaluation of the associations of interlukin-7 genetic variants with toxicity and efficacy of immune checkpoint inhibitors: A replication study of a Japanese population, based on the findings of a European genome-wide association study.

AIM: Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population. METHODS: From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders. RESULTS: In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis. CONCLUSIONS: In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry with the number UMIN000043798.

Severe Bradycardia Associated with the Use of Terlipressin: A Case Report.

Introduction: Although terlipressin is known to cause bradycardia, this adverse effect is usually described in association with hypertension and is considered a benign compensatory response mediated by arterial baroreceptors. Cardiac monitoring for patients receiving terlipressin is not routinely recommended. Case Presentation: A 77-year-old female patient with no history of coronary artery disease and no other coexisting risk factors for cardiac arrhythmias or conduction disturbances was admitted to intensive care unit with severe cholangitis, complicated by variceal bleeding. She developed severe sinus bradycardia following the use of terlipressin, which was associated with significant hypotension that required the infusion of norepinephrine. The bradycardia occurred again when terlipressin therapy was reattempted. Conclusion: Vasopressin is known to sensitize baroreceptor reflexes by a central mechanism though its actions on V1a receptors in the area postrema, and we speculate that vasopressin analogues such as terlipressin may act in the same manner. That this effect is not widely described in terlipressin safety literature may be due to the overall younger age range of the trial population. This raises the possibility that cardiac monitoring may be warranted for elderly patients receiving terlipressin.

Patient reported medication-related problems, adherence and waste of oral anticancer medication over time.

OBJECTIVES: Patients on oral anticancer therapy regularly experience medication-related problems (MRPs), potentially leading to non-adherence and medication waste. Most studies reporting these experiences have cross-sectional designs. The aim of our study was to explore patient reported MRPs, adherence and waste of oral anticancer medication over time. METHODS: A prospective longitudinal quantitative interview study with 4 months follow-up was performed among patients on oral anticancer medication (mainly tyrosine kinase inhibitors, (anti)hormonal therapy, pyrimidine antagonists) using a semi-structured questionnaire. Patients from two Dutch university medical centres were included from March to December 2022 after informed consent was given. Four interviews were performed with 1 month in between. All interviews were audiotaped, after which the data were entered into an electronic case report form. The primary outcome was the mean number of MRPs per patient per interview round. Secondary outcomes were the proportion of patients with at least one MRP, types of MRPs, perceived non-adherence, medication waste (both in general and specifically for anticancer medication), costs of anticancer medication waste, and factors associated with medication waste as mentioned by the patient. Descriptive statistics were used to analyse the data. RESULTS: Forty patients were included with a mean (SD) age of 64 (9) years; 43% were male. The mean number of MRPs per patient was 2.1 in the first interview and 1.2, 1.0 and 0.9 in the second, third and fourth interviews, respectively. Adverse drug reactions were the most frequently reported type of MRPs (30 (75%) patients in the first interview and 19 (65%) in the last interview). Unintentional non-adherence was regularly reported, especially in the first interview. Medication changes were frequent and associated medication waste was mentioned in all interviews. CONCLUSIONS: Many patients using oral anticancer treatment report MRPs and this number remains substantial over time.