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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 -
Vaccines Jun 2024Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens...
Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens and mainly house dust mite allergens. This complex dermatological pathology involves Interleukin 31 (IL-31) as a central itch mediator. One of the most effective CAD treatments is a caninized monoclonal antibody (mAb) called Lokivetmab. It is produced in CHO cells and targets specifically canine IL-31 (cIL-31) and blocks its cellular messaging. This treatment has undoubtedly contributed to a breakthrough in dermatitis-related pruritus. However, its production in mammalian cells requires time-consuming procedures, high production costs, and investment. Plants are considered an emerging protein production platform for recombinant biopharmaceuticals due to their cost-effectiveness and rapidity for production. Here, we use transient expression in plants to produce recombinant canine Interleukin 31 (cIL-31) and an anti-IL-31 monoclonal antibody (M1). First, we describe the production and characterization of M1 and then its activity on an IL-31-induced pruritic model in dogs compared to its commercial homolog. Dogs treated with the plant-made M1 mAb have shown similar improvements to Lokivetmab-treated ones after different challenges using canine IL-31. Furthermore, M1 injections were not associated with any side effects. These results demonstrate the safety and efficacy of this plant-made Lokivetmab biosimilar to control dogs' pruritus in a well-established model. Finally, this study shows that the plant-production platform can be utilized to produce rapidly functional mAbs and bring hope to the immunotherapy field of veterinary medicine.
PubMed: 38932349
DOI: 10.3390/vaccines12060620 -
Pharmaceutics Jun 2024Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to...
Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.
Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.
PubMed: 38931936
DOI: 10.3390/pharmaceutics16060815 -
Medicina (Kaunas, Lithuania) Jun 2024Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic... (Review)
Review
Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic and recreational use of cannabis-based products. Sensitization possibly leading to allergy symptoms can occur not only through the smoking of cannabis, but also through ingestion, the inhalation of pollen, or direct contact. The severity of symptoms varies from benign pruritus to anaphylaxis. There is scant information available to support clinicians throughout the entire therapeutic process, starting from diagnosis and ending in treatment. In this review, we present six cases of patients in whom molecular in vitro testing revealed sensitization to cannabis extract and/or cannabis-derived nsLTP molecules (Can s 3). Based on these cases, we raise important questions regarding this topic. The article discusses current proposals and highlights the importance of further research not only on cannabis allergy but also on asymptomatic sensitization to cannabis allergens, which may be ascertained in some percentage of the population.
Topics: Humans; Cannabis; Adult; Immunoglobulin E; Male; Female; Allergens; Middle Aged; Hypersensitivity
PubMed: 38929571
DOI: 10.3390/medicina60060954 -
Antioxidants (Basel, Switzerland) Jun 2024Semaphorin 3A (SEMA3A), a nerve-repellent factor produced by keratinocytes, has an inhibitory effect on nerve extension to the epidermis. Epidermal innervation is...
Semaphorin 3A (SEMA3A), a nerve-repellent factor produced by keratinocytes, has an inhibitory effect on nerve extension to the epidermis. Epidermal innervation is involved in pruritus in inflammatory skin diseases such as atopic dermatitis (AD) and dry skin. We previously reported that tapinarof, a stilbene molecule, upregulates SEMA3A in human keratinocytes. We also showed that this mechanism is mediated via the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, and the nuclear factor erythroid 2-related factor 2 (NRF2) axis. Since some stilbenes activate AHR and NRF2, we attempted to identify other stilbenes that upregulate SEMA3A. We analyzed normal human epidermal keratinocytes (NHEKs) treated with 11 types of stilbenes and examined SEMA3A expression. We found that resveratrol and pinostilbene, antioxidant polyphenols, upregulated SEMA3A and increased nuclear AHR and NRF2 expression. In addition, AHR knockdown by small interfering RNA (siRNA) transfection abolished the NRF2 nuclear expression. Furthermore, AHR and NRF2 knockdown by siRNA transfection abrogated resveratrol- and pinostilbene-induced SEMA3A upregulation. Finally, we confirmed that resveratrol and pinostilbene increased SEMA3A promoter activity through NRF2 binding using ChIP-qPCR analysis. These results suggest that resveratrol and pinostilbene upregulate SEMA3A via the AHR-NRF2 axis in human keratinocytes.
PubMed: 38929171
DOI: 10.3390/antiox13060732 -
Veterinary Sciences Jun 2024Ischemic teat necrosis (ITN) is a growing problem in the dairy industry characterized by teat lesions, necrosis, pruritus and automutilation. Despite the economic and...
Ischemic teat necrosis (ITN) is a growing problem in the dairy industry characterized by teat lesions, necrosis, pruritus and automutilation. Despite the economic and welfare consequences, there is no treatment, and the etiology of the disease remains poorly understood. The aim of this study was to investigate ITN by analyzing its clinical presentation, potential risk factors and microbial involvement. Methods included collection of milk and swab samples from affected cows over a period of one-and-a-half years and completion of questionnaires by veterinarians and farmers. Microbial testing included PCR testing for spp. and cultural testing by anaerobic and aerobic incubation on blood agar. The results showed a high and significant prevalence of spp. and in affected teats compared to non-ITN-affected control teats, indicating their potential role in the development of ITN. Other factors such as edema and milking practices also appear to contribute to the tissue damage. First-lactation and early-lactation heifers are particularly at risk. In conclusion, ITN appears to have a multifactorial etiology with both infectious and non-infectious factors playing a role. Further research is needed to better understand the complex interplay of these factors and to develop effective prevention and management strategies.
PubMed: 38922018
DOI: 10.3390/vetsci11060271 -
Veterinary Sciences May 2024(1) Background: Dysbiosis is frequently observed in Canine Atopic Dermatitis (CAD). Antimicrobial treatment may be necessary to treat flare ups and the use of topical...
(1) Background: Dysbiosis is frequently observed in Canine Atopic Dermatitis (CAD). Antimicrobial treatment may be necessary to treat flare ups and the use of topical treatments is beneficial to prevent the development of bacterial resistance. Wipes are an easy way to apply antiseptic agents on the skin. The aim of this study was to evaluate the benefits of 3% chlorhexidine impregnated wipes (Pyoskin wipes, MP Labo, France) on local areas of dysbiosis in dogs with CAD. (2) Methods: A total of 20 dogs suffering from CAD presented with localised areas of dysbiosis were included in this study. Affected areas were cleansed with the daily application of chlorhexidine wipes once a day for 14 days. Follow-up visits were scheduled after one and two weeks. Clinical signs (lesions and pruritus), dysbiosis scored by cytological counts (cocci and ) and investigator and owner global appreciation were evaluated. (3) Results: A statistically significant decrease in clinical scores and cytological counts were observed as soon as D7 and until D14. Both owner and investigator appreciation were considered high (4) Conclusions: The use of chlorhexidine impregnated wipes is a useful and easy way to manage localised dysbiosis in atopic dogs and allows limiting of systemic medication to prevent bacterial resistance.
PubMed: 38921987
DOI: 10.3390/vetsci11060240 -
Veterinary Sciences May 2024The present study aimed at evaluating the effect of a gentle shampoo and a mousse containing Adelmidrol, tapioca starch and a non-prescription antimicrobial complex on...
Effects of a Protocol Combining a Non-Irritating Shampoo and an Adelmidrol-Based Adsorbent Mousse on Seborrhoea and Other Signs and Symptoms Secondary to Canine Atopic Dermatitis: A Multicenter, Open-Label Uncontrolled Clinical Trial.
The present study aimed at evaluating the effect of a gentle shampoo and a mousse containing Adelmidrol, tapioca starch and a non-prescription antimicrobial complex on seborrhoea and other clinical signs secondary to canine atopic dermatitis (cAD). Forty-six dogs with cAD-associated seborrhoea and/or pruritus > 4 cm on the pruritus visual analogue scale (P-VAS) and/or bacterial/ overgrowth were enrolled. The mousse was applied twice daily, and dogs were evaluated at days (D)0, 7, 14 and optionally 28, by means of a skin seborrheic index (SSI), P-VAS, cAD lesion index (CADLI), and a semiquantitative cytological score. The mean SSI value improved during the first two weeks (4.1 ± 0.37 to 1.9 ± 0.30; < 0.0001). The mean P-VAS score (cm) decreased from 6.6 ± 0.19 at D0 to 3.8 ± 0.31 at D14 ( < 0.0001). The mean CADLI score dropped from 13.7 ± 1.24 to 8.5 ± 1.14 at D14 ( < 0.001). The cytological score for bacteria and decreased from 3.2 ± 0.10 and 3.2 ± 0.11, respectively, to 1.2 ± 0.19 and 1.2 ± 0.24 ( < 0.0001). All the investigated signs further improved at D28. Altogether, these observations suggest that the tested protocol might be useful in managing cAD-associated signs.
PubMed: 38921976
DOI: 10.3390/vetsci11060229 -
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 -
Acta Dermato-venereologica Jun 2024This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine... (Comparative Study)
Comparative Study
This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine cream, in reducing itch in patients with brachioradial pruritus at a tertiary care center. Electronic medical records of 64 brachioradial pruritus patients seen at the University of Miami Itch Center were analyzed. A significant reduction in itch scores was seen with both treatments, with no significant difference between the groups. A small number of patients experienced adverse effects, including drowsiness and weight gain with pregabalin and skin irritation with ketamine, amitriptyline, and lidocaine cream. Ultimately, our findings underscore the potential of utilizing combined therapy for difficult-to-treat brachioradial pruritus cases and implementing individualized approaches for managing neuropathic pruritus. Further controlled clinical trials are needed to establish optimal treatment protocols.
Topics: Humans; Retrospective Studies; Pruritus; Female; Male; Tertiary Care Centers; Middle Aged; Treatment Outcome; Amitriptyline; Lidocaine; Ketamine; Pregabalin; Aged; Drug Therapy, Combination; Adult; Antipruritics; Florida; Skin Cream; Administration, Cutaneous; Electronic Health Records
PubMed: 38916180
DOI: 10.2340/actadv.v104.40246