Anesth Pain Med (Seoul). 2023 Jan;18(1):11-20. doi: 10.17085/apm.22259. Epub 2023 Jan 25.

ABSTRACT

Due to unknown safety concerns, sugammadex should not be administered to patients withend-stage renal disease (ESRD). However, because the supply of benzylisoquinolinium-typeneuromuscular blocking agents (NMBAs) has been discontinued, rocuronium is the onlynon-depolarizing NMBA that can be used in clinical settings in some countries, includingSouth Korea. The administration of sugammadex cannot be avoided to achieve rapid andcomplete neuromuscular recovery in patients with ESRD or renal transplantation after rocuronium administration. Although there has been a limited number of clinical studies involving the use of sugammadex in patients with ESRD, studies have shown that sugammadexcan effectively and safely reverse rocuronium-induced neuromuscular blockade (NMB) inpatients with ESRD, however recovery of neuromuscular function in patients with ESRD isslower than in patients with normal renal function. Nonetheless, safety-concerns are yet tobe addressed. Considering the small number of clinical studies, high heterogeneity amongstudies, and insufficient safety information, more extensive data on the efficacy and safetyof sugammadex in patients with ESRD are needed. In particular, it is important to securedata on safety, including residual NMB after surgery, recurarization and cardiorespiratorycomplications, anaphylactic reactions, and long-term morbidity and mortality. Furthermore,anesthesiologists should remember that performing proper quantitative neuromuscularmonitoring and neuromuscular management based on the monitoring signs are the mostessential requirements when using sugammadex in patients with ESRD.

PMID:36746897 | DOI:10.17085/apm.22259

J Clin Aesthet Dermatol. 2023 Jan;16(1):14-17.

ABSTRACT

OBJECTIVE: We sought to describe skin injuries associated with unapproved topical mole and skin tag removers containing concentrated salicylic acid, Sanguinaria canadensis, or other caustic agents.

METHODS: We identified skin injuries associated with unapproved non-device topical mole and skin tag removers reported to the US Food and Drug Administration (FDA) through October 30, 2021 or described in Amazon consumer product reviews between 2019 and 2021.

RESULTS: We identified 38 cases, including 30 from Amazon consumer product reviews and eight reported to the FDA. Twenty-eight were from 2021. The most common reason for use was for mole and/or skin tag removal. Listed ingredients included salicylic acid, Sanguinaria canadensis, botanicals (includes homeopathic products), and calcium oxide. Seven cases involved products without ingredients listed. Adverse events included burns, pain, and ulceration, some resulting in permanent scarring and disfigurement. There were 14 facial injuries, including four adjacent to the eye. Reported treatments included antibiotics, hospital care, wound care, and dermatology advice to have a skin graft.

LIMITATIONS: Limitations include underreporting of adverse events to the FDA, limited clinical details and potential bias in consumer reviews, and poor replicability of review searches due to the dynamic nature of the Amazon website.

CONCLUSION: Unapproved, non-device topical mole and skin tag removers are associated with serious skin injuries. We found Amazon consumer reviews to be a novel and useful data source for safety surveillance of these types of skin products. When dermatologists are consulted about skin injuries, exposure to these products should be considered in the differential diagnosis.

PMID:36743972 | PMC:PMC9891211

Lancet. 2023 Feb 4;401(10374):347-356. doi: 10.1016/S0140-6736(22)01841-4.

ABSTRACT

BACKGROUND: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene-drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed.

METHODS: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug-gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug-gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug-gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants.

FINDINGS: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54-0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61-0·79]; p <0·0001).

INTERPRETATION: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe.

FUNDING: European Union Horizon 2020.

PMID:36739136 | DOI:10.1016/S0140-6736(22)01841-4

Br J Community Nurs. 2023 Feb 2;28(2):74-76. doi: 10.12968/bjcn.2023.28.2.74.

ABSTRACT

Adverse cutaneous drug reactions (ACDR) are relatively common, especially in multimorbid populations who take a range of medications. Francesca Ramadan provides an overview of several common types of ACDR and their most frequently associated drugs, alongside some options for diagnosis and management.

PMID:36735364 | DOI:10.12968/bjcn.2023.28.2.74

Med Oncol. 2023 Feb 3;40(3):88. doi: 10.1007/s12032-023-01954-6.

ABSTRACT

Chemotherapy is one of the widely used anticancer treatments that involves the use of powerful cytotoxic drugs to stop tumor growth by targeting rapidly dividing cells through various mechanisms, which will be elucidated in this review. Introduced during the early twentieth century, chemotherapy has since lengthened the longevity of innumerable cancer patients. However, the increase in lifespan is at the expense of quality of life as patients are at risk of developing short-term and long-term side effects following chemotherapy, such as alopecia (hair loss), chemotherapy-induced peripheral neuropathy, chemotherapy-induced nausea and vomiting, cardiotoxicity, diarrhea, infertility, and chemo brain. Currently, a number of these chemotherapy-induced adverse effects are managed through supportive care and approved treatments, while the rest of the side effects are unavoidable. Hence, chemotherapeutic drugs associated with inevitable side effects are only administered when their therapeutic role outweighs their chemotoxicity, thus severely limiting the potency of chemotherapy in treating malignancy. Therein, the potential approaches to alleviating side effects of chemotherapy ranging from pharmaceutical drugs to alternative therapies will be discussed in this review in hopes of increasing the tolerance and effectiveness of future chemotherapeutic treatments.

PMID:36735206 | DOI:10.1007/s12032-023-01954-6

Eur J Hosp Pharm. 2023 Feb 3:ejhpharm-2023-003701. doi: 10.1136/ejhpharm-2023-003701. Online ahead of print.

NO ABSTRACT

PMID:36737228 | DOI:10.1136/ejhpharm-2023-003701

J Environ Pathol Toxicol Oncol. 2023;42(1):1-16. doi: 10.1615/JEnvironPatholToxicolOncol.2022042088.

ABSTRACT

Melatonin is a serotonin-derived pineal gland hormone with many biological functions like regulating the sleep-wake cycle, circadian rhythm, menstrual cycle, aging, immunity, and antioxidants. Melatonin synthesis and release are more pronounced during the night, whereas exposure to light decreases it. Evidence is mounting in favor of the therapeutic effects of melatonin in cancer prevention, treatment and delayed onset in various cancer subtypes. Melatonin exerts its anticancer effect through modification of its receptors such as melatonin 1 (MT1), melatonin 2 (MT2), and inhibition of cancer cell proliferation, epigenetic alterations (DNA methylation/demethylation, histone acetylation/deacetylation), metastasis, angiogenesis, altered cellular energetics, and immune evasion. Melatonin performs a significant function in immune modulation and enhances innate and cellular immunity. In addition, melatonin has a remarkable impact on epigenetic modulation of gene expression and alters the transcription of genes. As an adjuvant to cancer therapies, it acts by decreasing the side effects and boosting the therapeutic effects of chemotherapy. Since current treatments produce drug-induced unwanted toxicities and side effects, they require alternate therapies. A recent review article attempts to summarize the mechanistic perspective of melatonin in different cancer subtypes like skin cancer, breast cancer, hepatic cancer, renal cell cancer, non-small cell lung cancer (NSCLC), colon oral, neck, and head cancer. The various studies described in this review will give a firm basis for the future evolution of anticancer drugs.

PMID:36734949 | DOI:10.1615/JEnvironPatholToxicolOncol.2022042088

Pharmacol Res Perspect. 2023 Feb;11(1):e01040. doi: 10.1002/prp2.1040.

ABSTRACT

This study assessed the safety, tolerability, and pharmacokinetics of single and multiple oral doses of DA-8010, a muscarinic M3 receptor antagonist, in healthy subjects. This was a randomized, double-blind, placebo-controlled, ascending single (Part A: 1, 2.5, 5, 20, and 40 mg QD fasted and 10 mg QD fasted and fed) and multiple doses (Part B: 5, 10, and 20 mg QD from Days 1 to 7 fasted), sequential-group study. Safety data were analyzed descriptively, time to maximum plasma concentration (tmax ) nonparametrically, and pharmacokinetic parameters using power and mixed models and ANOVA. Of 109 subjects randomized (Part A = 69 and Part B = 40; each part consisted a female group), 31 (44.9%) in Part A and 29 (72.5%) in Part B experienced treatment-emergent adverse events (TEAEs) in a dose-related manner. Common drug-related TEAEs in Part A and B were dizziness (8.7% and 15.0%), headache (5.8% and 12.5%) and blurred vision (8.7% and 20%). One male (20 mg) and one female (10 mg) from Part B discontinued the study due to a confusional state, and nausea and vomiting. Irrespective of sex, DA-8010 was steadily absorbed following single and multiple doses in the fasted state with increased systemic exposure in a dose-proportional manner with maximum plasma concentration occurring at a median tmax between 4.0 and 6.0 h. A high-fat meal increased systemic exposure. DA-8010 was safe, well tolerated, and well absorbed at lower doses and moderately tolerated at higher doses without any notable effects of food and sex.

PMID:36734627 | DOI:10.1002/prp2.1040

Med J Aust. 2023 Feb 2. doi: 10.5694/mja2.51841. Online ahead of print.

NO ABSTRACT

PMID:36733993 | DOI:10.5694/mja2.51841

Eur J Hosp Pharm. 2023 Feb 2:ejhpharm-2022-003453. doi: 10.1136/ejhpharm-2022-003453. Online ahead of print.

ABSTRACT

A female patient in her early 30s was treated with imatinib and high-dose methotrexate (HD-MTX) for Philadelphia chromosome-positive acute lymphoblastic leukaemia. The patient developed delayed MTX clearance and grade 3 acute kidney injury characterised by elevated creatinine (114% increase from baseline). After intensified calcium folinate rescue therapy and hydration, the MTX serum level was appropriately decreased 72 hours after the start of MTX infusion, and renal function returned to normal. Medication analysis by a clinical pharmacist suggested that the concomitant treatment with imatinib likely contributed to the delayed MTX clearance and caused the acute kidney injury.

PMID:36732034 | DOI:10.1136/ejhpharm-2022-003453

Anticancer Drugs. 2022 Nov 21. doi: 10.1097/CAD.0000000000001456. Online ahead of print.

ABSTRACT

SHR-A1201 is an antibody-drug conjugate (ADC) that combines trastuzumab with DM1 (a chemotherapeutic agent) using a chemical connector. This phase I study investigated the safety, tolerability and pharmacokinetics of SHR-A1201 in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. This phase I study enrolled patients in a traditional 3 + 3 dose-escalation design to receive a single dose of SHR-A1201 (1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg or 4.8 mg/kg). The observation period of dose-limiting toxicity (DLT) was 21 days. A total of 12 patients were enrolled and received SHR-A1201. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with elevated aspartate aminotransferase (75%), thrombocytopenia (75%), and nausea (66.7%) being reported most frequently. The common grade 3 TEAEs were thrombocytopenia and decreased lymphocyte count, and there were no grade 4 or above TEAEs. There were no serious adverse events or drug-related deaths. One DLT occurred in one patient treated with SHR-A1201 4.8 mg/kg (asymptomatic grade 3 increased γ-glutamyltransferase). The maximum tolerated dose of SHR-A1201 was not lower than that of T-DM1 (3.6 mg/kg). A total of 8.3% (1/12) of patients had ADA-positive reactions 504 h after administration, but no differences were observed in the type, incidence, or severity of TEAEs between patients with and without ADA. SHR-A1201 exhibited the pharmacokinetics characteristics of typical ADCs. An encouraging antitumor effect was observed in the 4.8 mg/kg dose group. SHR-A1201 was well tolerated and safe in patients with advanced HER2-positive breast cancer. The pharmacokinetics parameters showed a linear trend, and the immunogenicity results met the clinical expectations.

PMID:36730296 | DOI:10.1097/CAD.0000000000001456

J Cancer Surviv. 2023 Feb 2. doi: 10.1007/s11764-022-01316-7. Online ahead of print.

ABSTRACT

PURPOSE: Platinum-based chemotherapies used to treat many types of cancers are ototoxic. Ototoxicity management (OtoM) to mitigate the ototoxic outcomes of cancer survivors is recommended practice yet it is not a standard part of oncologic care. Although more than 10,000 patients each year are treated with platinum-based chemotherapies at the US Veterans Health Administration (VA), the current state of OtoM in VA is not well-defined. This study reports on a national survey of VA audiologists' perceptions regarding OtoM in cancer patients.

METHODS: A 26-item online survey was administered to VA audiologists and service chiefs across the VA's 18 regional systems of care. Descriptive statistics and deductive thematic analysis were used to analyze the data.

RESULTS: The 61 respondents included at least one from each VA region. All reported they felt some form of OtoM was necessary for at-risk cancer patients. A pre-treatment baseline, the ability to detect ototoxicity early, and management of ototoxic effects both during and after treatment were considered high value objectives of OtoM by respondents. Roughly half reported routinely providing these services for patients receiving cisplatin and carboplatin. Respondents disagreed regarding appropriate hearing testing schedules and how to co-manage OtoM responsibilities with oncology. They identified barriers to care that conformed to three themes: care and referral coordination with oncology, audiology workload, and lack of protocols.

CONCLUSIONS: Although VA audiologists value providing OtoM for cancer patients, only about half perform OtoM for highly ototoxic treatment regimens. The OtoMIC survey provides clinician perspectives to benchmark and address OtoM care gaps.

IMPLICATIONS FOR CANCER SURVIVORS: Collaboration between oncology and audiology is needed to improve current OtoM processes, so that cancer survivors can have more control over their long term hearing health.

PMID:36729345 | DOI:10.1007/s11764-022-01316-7

Clin Ophthalmol. 2023 Jan 26;17:385-390. doi: 10.2147/OPTH.S393519. eCollection 2023.

ABSTRACT

PURPOSE: To determine the reported rates of intraocular inflammation (IOI) in patients treated with intravitreal aflibercept (IVT-AFL) 2 mg in routine clinical practice (ie, outside interventional studies), across all indications and within all countries (excluding the United States), with access to either the vial presentation or pre-filled syringe (PFS).

PATIENTS AND METHODS: A search was conducted using the Bayer EYLEA® Global Safety Pharmacovigilance Database for reported cases of IOI and IVT-AFL use between October 2012 and March 31, 2022.

RESULTS: With more than 10 years of post-marketing experience with the IVT-AFL vial presentation (>25 million sold units), and over 2 years of experience with the PFS of IVT-AFL (>6.7 million sold units) the rate of any IOI, including endophthalmitis, outside the United States was 0.3 events per 10,000 units for the PFS and 1.2 events per 10,000 units for the vial presentation. The event rates specifically for endophthalmitis were 0.1 per 10,000 units for the IVT-AFL PFS and 0.6 per 10,000 units for the IVT-AFL vial presentation.

CONCLUSION: In patients with retinal diseases treated in routine clinical practice with IVT-AFL either from a vial or the PFS, medically important adverse events of IOI, and in particular, endophthalmitis, are infrequently reported events. Numerically, reported rates of IOI and endophthalmitis are low for the vial presentation and even lower for the PFS.

PMID:36726365 | PMC:PMC9886133 | DOI:10.2147/OPTH.S393519

Cutis. 2023 Feb;111(2):80-81. doi: 10.12788/cutis.0700.

NO ABSTRACT

PMID:37075187 | DOI:10.12788/cutis.0700

Indian J Pharmacol. 2022 Nov-Dec;54(6):417-422. doi: 10.4103/ijp.ijp_474_22.

ABSTRACT

BACKGROUND: Mucormycosis is a rare but serious fungal infection which has dramatically increased in post-COVID patients. There is a paucity of safety data on amphotericin B (amphoB) used for mucormycosis treatment.

OBJECTIVES: The objective of this prospective, observational, active safety surveillance study was to evaluate the safety profile of amphoB in a cohort of hospitalized patients who were on the drug for suspected mucormycosis.

MATERIALS AND METHODS: All suspected adverse drug reactions (ADRs) in hospitalized mucormycosis patients who had received amphoB were analyzed. The nature, severity, outcome of the ADRs were recorded and analyzed.

RESULTS: Of the 77 patients enrolled, 70% had documented history of prior COVID-19 infection. 96% had comorbidities, the most common being diabetes. Majority received conventional amphotericin B deoxycholate formulation. 97% experienced at least one suspected ADR and the median ADR/patient was 3. Out of 214 ADRs, 91 were serious but there were no ADR-related deaths. The most common ADRs were hypokalemia (31.78%), infusion-related reactions (22.43%), and anemia (17.29%). Thirty-three patients had serum potassium <2.5 mEq/L, while 11 had serum magnesium <1.25 mg/dL. Doubling of pretreatment creatinine level was noted in 15 patients. Seventy percent ADRs were of "possible" category as per the World Health Organization Uppsala Monitoring Centre categorization.

CONCLUSION: AmphoB deoxycholate use in mucormycosis patients was associated with a high incidence of electrolyte abnormalities and infusion-related reactions. All ADRs subsided with medical management and none were fatal. The safety data generated from this study may be useful in resource-limited settings where the far more expensive liposomal formulation is not being used.

PMID:36722553 | DOI:10.4103/ijp.ijp_474_22

Longit Life Course Stud. 2022 Oct 11;14(1):22-47. doi: 10.1332/175795921X16615892091105.

ABSTRACT

Considerable evidence demonstrates that perceiving oneself as an object of discrimination has negative consequences for mental health. However, little is known about whether this experience is more or less harmful in distinct phases of the life course, consistent with the life course principle of timing; or whether, in accord with the principle of lifespan development, it has long-term implications. We draw on longitudinal data addressing perceived workplace discrimination based on race/ethnicity and gender from the prospective Youth Development Study, covering early adulthood to midlife. Hierarchical linear modelling of the effects of discrimination on depressed mood indicates that both forms of discrimination have short-term (within life stages) and long-term (across stages) adverse effects on adult mental health. The impacts of perceived discrimination within stages on depressed mood appear to be greatest in the mid-30s and to weaken by midlife. Lingering effects of discrimination are more pronounced early on. These patterns are observed with controls for key time-varying negative experiences at work and personal socio-economic status, as well as invariant background characteristics (gender, race and parental socio-economic status). We consider these findings in relation to the dynamics of personal change in the context of occupational careers.

PMID:36722305 | DOI:10.1332/175795921X16615892091105

Drug Ther Bull. 2023 Feb 1:dtb-2023-000005. doi: 10.1136/dtb.2023.000005. Online ahead of print.

ABSTRACT

Overview of: van Dyck CH, Swanson CJ, Aisen P, et al Lecanemab in Early Alzheimer's Disease. N Engl J Med 2023;388:9-21.

PMID:36725282 | DOI:10.1136/dtb.2023.000005

Sci Transl Med. 2023 Feb;15(681):eabq5241. doi: 10.1126/scitranslmed.abq5241. Epub 2023 Feb 1.

ABSTRACT

In October 2019, Novartis launched brolucizumab, a single-chain variable fragment molecule targeting vascular endothelial growth factor A, for the treatment of neovascular age-related macular degeneration. In 2020, rare cases of retinal vasculitis and/or retinal vascular occlusion (RV/RO) were reported, often during the first few months after treatment initiation, consistent with a possible immunologic pathobiology. This finding was inconsistent with preclinical studies in cynomolgus monkeys that demonstrated no drug-related intraocular inflammation, or RV/RO, despite the presence of preexisting and treatment-emergent antidrug antibodies (ADAs) in some animals. In this study, the immune response against brolucizumab in humans was assessed using samples from clinical trials and clinical practice. In the brolucizumab-naïve population, anti-brolucizumab ADA responses were detected before any treatment, which was supported by the finding that healthy donors can harbor brolucizumab-specific B cells. This suggested prior exposure of the immune system to proteins with structural similarity. Experiments on samples showed that naïve and brolucizumab-treated ADA-positive patients developed a class-switched, high-affinity immune response, with several linear epitopes being recognized by ADAs. Only patients with RV/RO showed a meaningful T cell response upon recall with brolucizumab. Further studies in cynomolgus monkeys preimmunized against brolucizumab with adjuvant followed by intravitreal brolucizumab challenge demonstrated that high ADA titers were required to generate ocular inflammation and vasculitis/vascular thrombosis, comparable to RV/RO in humans. Immunogenicity therefore seems to be a prerequisite to develop RV/RO. However, because only 2.1% of patients with ADA develop RV/RO, additional factors must play a role in the development of RV/RO.

PMID:36724238 | DOI:10.1126/scitranslmed.abq5241

Curr Opin Oncol. 2023 Mar 1;35(2):132-144. doi: 10.1097/CCO.0000000000000924. Epub 2022 Dec 28.

ABSTRACT

PURPOSE OF REVIEW: Because the high risk of death and poor prognosis of patients with refractory thyroid cancer (TC), studies related to tyrosine kinase inhibitors (TKIs) in treating different types of refractory TC have gradually attracted attention. Thus, we conducted a meta-analysis of published randomized controlled trials and single-arm trials to evaluate tyrosine kinase inhibitors' efficacy and safety profile treatment in TC patients.

RECENT FINDINGS: The studies of 29 in 287 met the criteria, 9 were randomized controlled trials and 20 were single-arm trials, involving 11 TKIs (Apatinib, Anlotinib, Cabozantinib, Imatinib, Lenvatinib, Motesanib, Pazopanib, Sorafenib, Sunitinib, Vandetanib, Vemurafenib). Treatment with TKIs significantly improved progression-free survival [hazard ratio [HR] 0.34 (95% confidence interval [CI]: 0.24, 0.48), P < 0.00001] and overall survival [OS] [HR 0.76, (95% CI: 0.64, 0.91), P = 0.003] in randomized controlled trials, but adverse events (AEs) were higher than those in the control group (P < 0.00001). The result of the objective response rate (ORR) in single-arm trials was statistically significant [odds ratio [OR] 0.49 (95% CI: 0.32, 0.75), P = 0.001].

SUMMARY: TKIs significantly prolonged progression-free survival and OS or improved ORR in patients with different types of TC (P < 0.01). Our recommendation is to select appropriate TKIs to treat different types of TC patients, and to prevent and manage drug-related AEs after using TKIs.

PMID:36721897 | DOI:10.1097/CCO.0000000000000924

Cureus. 2022 Dec 28;14(12):e33064. doi: 10.7759/cureus.33064. eCollection 2022 Dec.

ABSTRACT

Infliximab belongs to the family of tumor necrosis factor (TNF) alpha inhibitors and since its development, it has revolutionized treatment for both rheumatological diseases and inflammatory bowel disease (IBD). In IBD specifically, it has shown to result in symptomatic, endoscopic, and histological remission which is why it is one of the most widely used treatments for moderate to severe IBD. While common side effects include infections due to immunosuppression, cytopenias and hepatotoxicity, interstitial lung disease (ILD) has been infrequently reported to result from inflixiamb use. We present the case of a patient with ulcerative colitis (UC) who achieved remission with infliximab, however, after about two years of infusions, developed evidence of non-specific interstitial pneumonitis (NSIP). Extensive work up was done to rule out infections, mixed connective tissue disorders, and hypersensitivity pneumonitis. Although lung biopsy remains the gold standard for diagnosing NSIP; clinical, laboratory, and radiographic findings were sufficient in establishing this diagnosis. Initiation of empiric high dose steroids, and cessation of infliximab infusions showed improvement in respiratory status and resolution of lung findings. This case highlights the importance of recognizing adverse effects of infliximab on the pulmonary status of an IBD patient given that infliximab mediated ILD does not adhere to a specific timeline. Considering that respiratory function may be compromised post any number of infusions, it is imperative to acknowledge patients' respiratory complaints and initiate prompt investigation and evaluation for this rare complication.

PMID:36721597 | PMC:PMC9883057 | DOI:10.7759/cureus.33064