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Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Nutrients Jun 2024Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved... (Randomized Controlled Trial)
Randomized Controlled Trial
Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved by the European Commission (EFSA), dried miracle berries (DMB), contains the natural taste-modifying protein miraculin. DMB, also available as a supplement, has emerged as a possible alternative treatment for TDs. The present study aimed to evaluate the efficacy and safety of habitual DMB consumption in malnourished cancer patients undergoing active treatment. An exploratory clinical trial was carried out in which 31 cancer patients were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed a DMB tablet or placebo daily before each main meal (breakfast, lunch, and dinner). Throughout the five main visits, electrochemical taste perception, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes were evaluated. Patients consuming a standard dose of DMB exhibited improved taste acuity over time (% change right/left side: -52.8 ± 38.5/-58.7 ± 69.2%) and salty taste perception (2.29 ± 1.25 vs. high dose: 2.17 ± 1.84 vs. placebo: 1.57 ± 1.51 points, < 0.05). They also had higher energy intake ( = 0.075) and covered better energy expenditure (107 ± 19%). The quality of life evaluated by symptom scales improved in patients receiving the standard dose of DMB (constipation, = 0.048). The levels of arachidonic (13.1 ± 1.8; 14.0 ± 2.8, 12.0 ± 2.0%; = 0.004) and docosahexaenoic (4.4 ± 1.7; 4.1 ± 1.0; 3.9 ± 1.6%; = 0.014) acids in erythrocytes increased over time after DMB intake. The standard dose of DMB increased fat-free mass vs. placebo (47.4 ± 9.3 vs. 44.1 ± 4.7 kg, = 0.007). Importantly, habitual patients with DMB did not experience any adverse events, and metabolic parameters remained stable and within normal ranges. In conclusion, habitual consumption of a standard 150 mg dose of DMB improves electrochemical food perception, nutritional status (energy intake, fat quantity and quality, fat-free mass), and quality of life in malnourished cancer patients receiving antineoplastic treatment. Additionally, DMB consumption appears to be safe, with no changes in major biochemical parameters associated with health status. Clinical trial registered (NCT05486260).
Topics: Humans; Male; Female; Pilot Projects; Neoplasms; Middle Aged; Malnutrition; Dietary Supplements; Quality of Life; Aged; Nutritional Status; Treatment Outcome; Taste Perception; Adult
PubMed: 38931260
DOI: 10.3390/nu16121905 -
Biomedicines May 2024The SARS-CoV-2 virus has spread rapidly despite implementing strategies to reduce its transmission. The disease caused by this virus has been associated with a diverse... (Review)
Review
The SARS-CoV-2 virus has spread rapidly despite implementing strategies to reduce its transmission. The disease caused by this virus has been associated with a diverse range of symptoms, including common neurological manifestations such as dysgeusia, anosmia, and myalgias. Additionally, numerous cases of severe neurological complications associated with this disease have been reported, including encephalitis, stroke, seizures, and Guillain-Barré syndrome, among others. Given the high prevalence of neurological manifestations in this disease, the objective of this review is to analyze the mechanisms by which this virus can affect the nervous system, from its direct invasion to aberrant activation of the immune system and other mechanisms involved in the symptoms, including neuropsychiatric manifestations, to gain a better understanding of the disease and thus facilitate the search for effective therapeutic strategies.
PubMed: 38927354
DOI: 10.3390/biomedicines12061147 -
International Journal of Surgery Case... Jun 2024Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia,...
INTRODUCTION AND IMPORTANCE
Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia, burning sensations, and pruritus. These oral signs can serve as early indicators of systemic conditions such pernicious anemia.
CASE PRESENTATION
A 67 year old northern African female presented at the oral surgery service with complaints of a sore mouth and difficulty eating certain types of food. Her medical history revealed hypothyroidism and no history of gastrectomy. She was diagnosed with pernicious anemia in 2014 and is under hydroxocobalamin injection 5000μg/month since then. Dental history indicated extraction of all teeth, and in 2014, the patient was diagnosed with oral lichen planus. There were no contributory oral habits. Intraoral examination revealed a band like erythematous lesion on the palate with two superficial ulcerations, diagnosed as related to her pernicious anemia. The patient was prescribed a mouthwash containing sodium bicarbonate and corticosteroid to reduce inflammation and alleviate pain. A low level laser therapy was also considered to reduce the burning sensations.
CLINICAL DISCUSSION
Pernicious anemia (PA) is an autoimmune disease characterized by the gradual atrophy of the gastric mucosa, predominantly affecting the body and fundus of the stomach, leading to vitamin B12 deficiency. Its insidious onset often masks its presence. Patients have no anemic symptoms. However, they can present with oral manifestations related to vitamin B12 deficiency. Those oral signs can precede hematological symptoms helping in early diagnosis of PA.
CONCLUSION
Dentists and other oral health care providers must be aware of this condition and its oral manifestations. Investigating vitamin B12 levels should be considered in patients presenting with oral ulcers, oral erythema or burning sensations without an apparent origin.
PubMed: 38917702
DOI: 10.1016/j.ijscr.2024.109931 -
Clinical Nutrition ESPEN Jun 2024Among the side effects of chemotherapy, there is dysgeusia, which is an alteration or damage to the taste perception that negatively impacts the biopsychosocial sphere...
BACKGROUND/OBJECTIVE
Among the side effects of chemotherapy, there is dysgeusia, which is an alteration or damage to the taste perception that negatively impacts the biopsychosocial sphere of the patient. Therefore, it is important to recognize and manage it appropriately. The objective of this study is to identify clinical pharmacological strategies to reduce dysgeusia in chemotherapy patients.
METHODS
A systematic literature review was conducted following the PRISMA guidelines between February and May 2023, utilizing PubMed, Embase, Cochrane Library, CINAHL, and the British Nursing Database. Methodological quality and bias risk assessment were performed using the JBI framework, while evidence certainty was evaluated using the Oxford OCEBM methodology.
RESULTS
Out of 1225 consulted records, 12 articles were included. The results underscore the efficacy of diverse pharmacological interventions in mitigating dysgeusia among chemotherapy patients. These include zinc supplementation with a daily dosage ranging between 50 and 220 mg (p ≤ 0.005), lactoferrin at 250 mg thrice daily (p < 0.001), delta-9-tetrahydrocannabinol at 2 mg per day (p < 0.05), and cannabidiol at 150 mg per day (p = 0.04). All studies analysed showed a low risk of bias. The zinc and Delta-9-Tetrahydrocannabinoid treatment proved particularly promising, compared to the other treatments considered, where sample sizes were smaller and the placebo effect was not always clear.
CONCLUSION
Among the various pharmacological strategies identified, those that appear most promising concern the integration of zinc and Delta-9-Tetrahydrocannabinoid. Future studies should further explore the treatments identified in this review to expand the evidence base in this relatively underexplored field.
PubMed: 38900642
DOI: 10.1016/j.clnesp.2024.05.026 -
Cancers May 2024Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing... (Review)
Review
Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy's potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.
PubMed: 38893068
DOI: 10.3390/cancers16111947 -
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 -
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 -
Cureus Apr 2024We use vernakalant, an intravenous anti-arrhythmic, to cardiovert paroxysmal atrial fibrillation (AF) into sinus rhythm. It is a relatively atrium-selective,...
BACKGROUND
We use vernakalant, an intravenous anti-arrhythmic, to cardiovert paroxysmal atrial fibrillation (AF) into sinus rhythm. It is a relatively atrium-selective, early-activating potassium and frequency-dependent sodium channel blocker with a half-life of 2 to 3 hours. Due to concerns regarding its safety profile, it is not Food and Drug Administration (FDA)-approved.
OBJECTIVE
This study aims to assess the efficacy of intravenous vernakalant in cardioversion of paroxysmal AF and the safety of its use.
METHODS
Patients with paroxysmal AF who presented to the American University of Beirut Medical Center (AUBMC) between 2015 and 2020 and received vernakalant for cardioversion were included. Patients did not receive vernakalant if they had any of the following: QTc > 440 ms, heart rate < 50 bpm, acute coronary syndrome within the last 30 days, second- and third-degree atrioventricular (AV) block in the absence of a pacemaker, severe aortic stenosis (AS), use of intravenous antiarrhythmics (class I and class III) within four hours of vernakalant infusion, systolic blood pressure <100 mmHg, and heart failure (New York Heart Association (NYHA) III or NYHA IV class). The primary endpoint is conversion to sinus rhythm for at least one minute within 90 minutes of the start of the vernakalant infusion. The secondary endpoint included the presence of these side effects: bradycardia, QTc prolongation, AV block, ventricular arrhythmias, hypotension, taste alteration/dysgeusia, sneezing, nausea, vomiting, paresthesia, cardiogenic shock, or death.
RESULTS
The study included 23 patients with paroxysmal AF (15 men, mean age 54 ± 14 years). Fourteen patients (61%) cardioverted to sinus rhythm within 90 minutes of the start of the Vernakalant infusion. Seven patients (30%) reverted to sinus rhythm within 15 minutes after the first infusion. After treatment with vernakalant, four patients (17%) developed sinus bradycardia, and four patients (17%) developed first-degree AV block. No patient had a QTc greater than 460 ms. None of the patients experienced sinus pauses, high-grade AV block, ventricular arrhythmias, hypotension, dysgeusia, sneezing, nausea, vomiting, paresthesia, cardiogenic shock, or death.
CONCLUSION
Vernakalant had 61% efficacy in the rapid cardioversion of paroxysmal AF to sinus rhythm, was well tolerated, and had a low rate of adverse events in our study population.
PubMed: 38770450
DOI: 10.7759/cureus.58616 -
MedRxiv : the Preprint Server For... May 2024Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of...
BACKGROUND
Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of taste and smell, and impaired daily functioning.
RESEARCH QUESTION
This study aims to better understand the chronology of long-COVID symptoms.
STUDY DESIGN AND METHODS
We prospectively enrolled 403 adults from the University of Iowa long-COVID clinic (June 2020 to February 2022). Participants provided symptom data during acute illness, symptom progression, and other clinical characteristics. Patients in this registry received a survey containing questions including current symptoms and status since long-COVID diagnosis (sliding status scale, PHQ2, GAD2, MMRC). Those >12 months since acute-COVID diagnosis had chart review done to track their symptomology.
RESULTS
Of 403 participants contacted, 129 (32%) responded. The mean age (in years) was 50.17 +/-14.28, with 31.8% male and 68.2% female. Severity of acute covid treatment was stratified by treatment in the outpatient (70.5%), inpatient (16.3%), or ICU (13.2%) settings. 51.2% reported subjective improvement (sliding scale scores of 67-100) since long-COVID onset. Ages 18-29 reported significantly higher subjective status scores. Subjective status scores were unaffected by severity. 102 respondents were >12 months from their initial COVID-19 diagnosis and were tracked for longitudinal symptom persistence. All symptoms tracked had variance (mean fraction 0.58, range 0.34-0.75) in the reported symptoms at the time of long-COVID presentation when compared with patient survey report. 48 reported persistent dyspnea, 23 (48%) had resolved it at time of survey. For fatigue, 44 had persistence, 12 (27%) resolved.
INTERPRETATION
Overall, 51.2% respondents improved since their long-COVID began. Pulmonary symptoms were more persistent than neuromuscular symptoms (anosmia, dysgeusia, myalgias). Gender, time since acute COVID infection, and its severity didn't affect subjective status or symptoms. This study highlights recall bias that may be prevalent in other long-COVID research reliant on participant memory.
PubMed: 38746213
DOI: 10.1101/2024.04.30.24306497