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Photobiomodulation, Photomedicine, and... Jun 2024
Randomized Controlled Trial
Topics: Humans; COVID-19; Dysgeusia; Single-Blind Method; Low-Level Light Therapy; Male; Female; Middle Aged; SARS-CoV-2; Aged
PubMed: 38888186
DOI: 10.1089/pho.2024.0045 -
Clinical Cancer Research : An Official... Jun 2024On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro®, Bristol Myers Squibb Corporation), for the...
On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro®, Bristol Myers Squibb Corporation), for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The approval was based on TRIDENT-1, a single arm trial with multiple cohorts of patients with ROS1 fusion-positive (hereafter "ROS1-positive") NSCLC, (NCT03093116), who were either treatment naïve or had received prior ROS1 TKI and/or platinum-based chemotherapy. The primary efficacy outcome measure is objective response rate (ORR) assessed by blinded independent central review (BICR) using response evaluation criteria in solid tumors (RECIST) version 1.1. ORR was assessed in 71 patients who were ROS1 TKI naïve and 56 patients who had received a prior ROS1 TKI. Among 71 patients who were ROS1 TKI naïve, the ORR was 79% (95% CI 68, 88); median duration of response was 34.1 months (95% CI 26, NE). In patients who had received a prior ROS1 TKI and no prior chemotherapy, the ORR was 38% (95% CI 25, 52). The median duration of response was 14.8 months (95% CI 7.6, NE) BICR-assessed responses were observed in CNS metastases in patients in both cohorts, and in patients who developed resistance mutations following prior TKI therapy. The most common (> 20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs.
PubMed: 38875108
DOI: 10.1158/1078-0432.CCR-24-0949 -
Turkish Neurosurgery Aug 2023Taste consists of perception and sensation. Specific neural structures transmit a stimulus from the taste buds to the gustatory cortex to generate taste sensation. Any...
Taste consists of perception and sensation. Specific neural structures transmit a stimulus from the taste buds to the gustatory cortex to generate taste sensation. Any disruption of this pathway, whether it affects sensation or perception, can result in taste disorders. Stereotactic procedures involving the thalamus may result in gustatory complications. A 41-year-old female patient who underwent stereotactic drainage of a thalamic cyst suffered transient ageusia. Subsequently, she developed metallic taste perception. When her stereotactic plan was re-evaluated, it was noted that the posteromedial ventral thalamus nucleus was in the path of the needle tract and the needle had passed through it. Follow-up was recommended and her symptoms completely resolved within 2 months following surgery. Modern imaging techniques allow for the visualization of neural structures related to the sense of taste. Additionally, care must be taken when planning stereotactic procedures for such lesions.
PubMed: 38874247
DOI: 10.5137/1019-5149.JTN.43601-23.3 -
Clinical Lymphoma, Myeloma & Leukemia May 2024Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2...
BACKGROUND
Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were > 71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection-associated AEs. Management strategies for talquetamab-associated AEs are described.
DISCUSSION
GPRC5D-associated AEs included dermatologic (rash, nonrash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies.
CONCLUSION
Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence.
PubMed: 38871558
DOI: 10.1016/j.clml.2024.05.003 -
World Journal of Otorhinolaryngology -... Jun 2024This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China.
Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.
OBJECTIVE
This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China.
METHODS
This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders.
RESULTS
Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms.
CONCLUSIONS
The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.
PubMed: 38855290
DOI: 10.1002/wjo2.167 -
Stereotactic and Functional Neurosurgery Jun 2024Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for drug-resistant tremor. The most frequent side effects are ataxia, gait...
INTRODUCTION
Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for drug-resistant tremor. The most frequent side effects are ataxia, gait disturbance, paresthesias, dysgeusia, and hemiparesis. Here, we report the first case of thalamic hand dystonia rapidly occurring after MRgFUS thalamotomy of the ventral intermediate nucleus (V.im).
CASE PRESENTATION
MRgFUS thalamotomy was performed in a 60-year-old left-handed patient for his disabling medically refractory essential tremor. The intervention resulted in a marked reduction of his action tremor. However, the patient developed an unvoluntary abnormal posture in his left hand a few days after the procedure with difficulty holding a cigarette between his fingers. Brain MRI revealed the expected MRgFUS lesion within the right V.im as well as an extension of the lesion anteriorly to the V.im in the ventro-oralis nucleus. Tractography showed that the lesion disrupted the dentato-rubro-thalamic tract as expected with a lesion suppressing tremor. However, the lesion also was interrupted fibers connecting to the superior frontal and pre-central cortices (primary motor cortex, premotor cortex, and supplementary area). We hypothesized that the interventional MRgFUS thalamotomy was slightly off target, which induced a dysfunction within the cortico-striato-thalamo-cortical network and the cerebello-thalamo-cortical pathway reaching a sufficient threshold of basal ganglia/cerebellum circuitry interference to induce dystonia.
CONCLUSION
This rare side effect emphasizes the risk of imbalance within the dystonia network (i.e., basal ganglia-cerebello-thalamo-cortical circuit) secondary to V.im thalamotomy.
PubMed: 38834047
DOI: 10.1159/000538931 -
Nature Medicine Jun 2024Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER) breast cancer preclinical models....
Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER human epidermal growth factor receptor-negative (HER2) metastatic breast cancer (mBC). The primary objectives of assessing the safety and tolerability and determining the recommended dose for expansion of PF-07248144, as monotherapy and in combination with fulvestrant, were met. Secondary endpoints included characterization of PK and evaluation of antitumor activity, including objective response rate (ORR) and progression-free survival (PFS). Common treatment-related adverse events (any grade; grades 3-4) included dysgeusia (83.2%, 0%), neutropenia (59.8%, 35.5%) and anemia (48.6%, 13.1%). Exposure was approximately dose proportional. Antitumor activity was observed as monotherapy. For the PF-07248144-fulvestrant combination (n = 43), the ORR (95% confidence interval (CI)) was 30.2% (95% CI = 17.2-46.1%) and the median PFS was 10.7 (5.3-not evaluable) months. PF-07248144 demonstrated a tolerable safety profile and durable antitumor activity in heavily pretreated ERHER2 mBC. These findings establish KAT6A and KAT6B as druggable cancer targets, provide clinical proof of concept and reveal a potential avenue to treat mBC. clinicaltrial.gov registration: NCT04606446 .
PubMed: 38824244
DOI: 10.1038/s41591-024-03060-0 -
Journal of Clinical Oncology : Official... Jun 2024Taletrectinib, a highly potent, CNS-active, tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate...
PURPOSE
Taletrectinib, a highly potent, CNS-active, tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) of taletrectinib for non-small cell lung cancer in China.
METHODS
TRUST-I evaluated TKI-naїve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety.
RESULTS
As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n = 106; crizotinib pretreated: n = 67). In TKI-naїve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naїve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low.
CONCLUSION
Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.
PubMed: 38822758
DOI: 10.1200/JCO.24.00731 -
Current Drug Safety May 2024Some drugs cause tongue disorders as adverse effects. Most of the druginduced tongue disorders are benign and will resolve after drug discontinuation. However, the...
BACKGROUND
Some drugs cause tongue disorders as adverse effects. Most of the druginduced tongue disorders are benign and will resolve after drug discontinuation. However, the changes in the color or appearance of the tongue may frighten patients and decrease compliance with drug therapy.
OBJECTIVE
To review the literature to find all reports of drug-induced tongue disorders, their presentation, management, and outcome of patients Methods: The search was conducted in Google Scholar and PubMed using key words "ageusia," "burning tongue," "coated tongue," "drug-induced taste disturbances," "dysgeusia," "glossitis," "glossodynia," "hairy tongue," "hypogeusia," "stomatodynia," "stomatopyrosis," "swollen tongue" "tongue discoloration," "tongue irritation," "tongue numbness, "tongue oedema," and "tongue ulcer. All reports that were published from 1980 to 2022 in the English language were included in the study. Reports that were not in English language but had English abstracts with adequate data for extraction were also included.
RESULTS
A total of 208 case reports and case series were included. The most reported drug classes were antineoplastic and immunomodulating agents and anti-infectives for systemic use, and the most common tongue disorders were tongue discoloration and black hairy tongue. Having good oral hygiene and discontinuing the offending drug could manage and resolve the problem.
CONCLUSION
Drug-induced tongue disorders are not rare adverse drug reactions. They are benign in most cases, and withholding offending agents results in significant improvement or complete resolution of tongue lesions.
PubMed: 38797908
DOI: 10.2174/0115748863299971240513061630 -
Reviews in Medical Virology May 2024COVID-19 as a pan-epidemic is waning but there it is imperative to understand virus interaction with oral tissues and oral inflammatory diseases. We review periodontal... (Review)
Review
COVID-19 as a pan-epidemic is waning but there it is imperative to understand virus interaction with oral tissues and oral inflammatory diseases. We review periodontal disease (PD), a common inflammatory oral disease, as a driver of COVID-19 and oral post-acute-sequelae conditions (PASC). Oral PASC identifies with PD, loss of teeth, dysgeusia, xerostomia, sialolitis-sialolith, and mucositis. We contend that PD-associated oral microbial dysbiosis involving higher burden of periodontopathic bacteria provide an optimal microenvironment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These pathogens interact with oral epithelial cells activate molecular or biochemical pathways that promote viral adherence, entry, and persistence in the oral cavity. A repertoire of diverse molecules identifies this relationship including lipids, carbohydrates and enzymes. The S protein of SARS-CoV-2 binds to the ACE2 receptor and is activated by protease activity of host furin or TRMPSS2 that cleave S protein subunits to promote viral entry. However, PD pathogens provide additional enzymatic assistance mimicking furin and augment SARS-CoV-2 adherence by inducing viral entry receptors ACE2/TRMPSS, which are poorly expressed on oral epithelial cells. We discuss the mechanisms involving periodontopathogens and host factors that facilitate SARS-CoV-2 infection and immune resistance resulting in incomplete clearance and risk for 'long-haul' oral health issues characterising PASC. Finally, we suggest potential diagnostic markers and treatment avenues to mitigate oral PASC.
Topics: Humans; Angiotensin-Converting Enzyme 2; COVID-19; Dysbiosis; Host-Pathogen Interactions; Mouth; Periodontal Diseases; Post-Acute COVID-19 Syndrome; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Internalization
PubMed: 38782605
DOI: 10.1002/rmv.2543