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International Journal of Infectious... Sep 2023We evaluated the burden of noninvasive group A Streptococcus (GAS) infections in ambulatory pediatrics before and during the COVID-19 pandemic in France.
Surveillance of noninvasive group A Streptococcus infections in French ambulatory pediatrics before and during the COVID-19 pandemic: a prospective multicenter study from 2018-2022.
OBJECTIVES
We evaluated the burden of noninvasive group A Streptococcus (GAS) infections in ambulatory pediatrics before and during the COVID-19 pandemic in France.
METHODS
We analyzed data from a national network of ambulatory pediatricians between 2018 and 2022. Clinicians evaluating children ≤15 years old for tonsillopharyngitis, perianal infections, paronychia/blistering dactylitis, and scarlet fever were invited to perform a rapid antigen detection test (RADT) for GAS. Monthly incidence of noninvasive GAS infections per 10,000 visits was modeled using time series analysis, considering two breakpoints: March 2020 (first national lockdown) and March 2022 (end of mandatory mask-wearing in schools).
RESULTS
Over the study period, 125 pediatricians recorded 271,084 infectious episodes. GAS-related illnesses represented 4.3% of all infections. In March 2020, the incidence of GAS diseases decreased by 84.5% (P <0.001), with no significant trend until March 2022. After March 2022, the incidence significantly increased (+23.8% per month, P <0.001), with similar patterns across all monitored GAS-related diseases.
CONCLUSION
By using routine clinical data and RADTs, we have monitored changes in the incidence of noninvasive GAS infections in ambulatory pediatrics. COVID-19 mitigation measures have had a major impact on the epidemiology of noninvasive GAS infections, but their relaxation was followed by a surge above baseline levels.
Topics: Child; Humans; Adolescent; Streptococcus pyogenes; Prospective Studies; Pandemics; COVID-19; Communicable Disease Control; Streptococcal Infections; Pediatrics
PubMed: 37290573
DOI: 10.1016/j.ijid.2023.06.003 -
Clinical and Experimental Dermatology Oct 2023Epidermal growth factor receptor inhibitors (EGFRIs) are widely used to treat various types of malignancies. One of the common adverse reactions is cutaneous toxicity,...
Epidermal growth factor receptor inhibitors (EGFRIs) are widely used to treat various types of malignancies. One of the common adverse reactions is cutaneous toxicity, mostly presenting as acneiform eruptions, paronychia and xerosis. Erosive pustular dermatosis of the scalp (EPDS) is a rare cutaneous adverse reaction that develops during treatment with EGFRIs. The pathogenesis of EGFRI-induced EPDS is poorly understood. Here we present three cases of EPDS induced by EGFRIs. The proteins LTA4H (leukotriene A-4 hydrolase), METAP1 (methionine aminopeptidase 1), BID (BH3-interacting domain death agonist), SMAD1 (mothers against decapentaplegic homologue), PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A), YES1 (tyrosine-protein kinase Yes) and EGFL7 (epidermal growth factor-like protein 7) were significantly upregulated in EGFRI-stimulated peripheral blood mononuclear cell cultures, and validated in the lesions. All of the proteins colocalized with CD4+ and CD8+ T-cell expression. Next-generation-based human leucocyte antigen (HLA) typing showed all patients carried HLA-C*15:02, and modelling studies showed that afatinib and erlotinib bound well within the E/F binding pockets of HLA-C*15:02. Moreover, T cells were preferentially activated by EGFRIs in individuals carrying HLA-C*15:02. The case series revealed that EGFRI-induced EPDS may be mediated by drug-specific T cells.
Topics: Humans; Scalp; HLA-C Antigens; Leukocytes, Mononuclear; Skin Diseases; Exanthema; ErbB Receptors; Aminopeptidases; Calcium-Binding Proteins; EGF Family of Proteins
PubMed: 37710038
DOI: 10.1093/ced/llad282 -
The Journal of Foot and Ankle Surgery :... 2023To study the clinical effects of Ω toenail correction in the treatment of paronychia. One hundred thirty-six cases of 130 patients during the period from August 2018 to...
To study the clinical effects of Ω toenail correction in the treatment of paronychia. One hundred thirty-six cases of 130 patients during the period from August 2018 to August 2021 were treated with Ω toenail correction according to clinical stages, the clinical therapeutic effects of which were evaluated in terms of the operation time, the time to resume movement, treatment cycle, 1-y recurrence rate, and visual analogue scale (VAS) scores before and after treatment. The clinical efficacy was analyzed and compared of Ω toenail correction in treating paronychia of different clinical stages. It has been demonstrated that there was no significant difference in operation time, time to resume movement, treatment cycle and recurrence rate among different stages of paronychia, while there existed the significant difference (p < .05) in VAS score of resting-state pain before and after correction which stood at 6.43 ± 0.29 points with the after-treatment VAS scores at 1.10 ± 0.22. There is a statistical difference (p < .05) in VAS score of movement-evoked pain between before and after treatment. The VAS scores of movement-evoked pain stood at 7.55 ± 0.42, which is in contrast with the after-treatment VAS at 1.74 ± 0.93. It has been concluded that Ω toenail correction characterized by easy operation can relieve the pain immediately, which can achieve satisfactory clinical efficacy for treating paronychia of different stages.
Topics: Humans; Female; Male; Middle Aged; Paronychia; Adult; Treatment Outcome; Nails; Pain Measurement; Aged; Retrospective Studies; Operative Time
PubMed: 37580011
DOI: 10.1053/j.jfas.2023.05.010 -
Hand Surgery & Rehabilitation Apr 2024The nail unit is the most commonly affected area in hand infections, which can be primary infection or superinfection complicating other nail or skin disorders. Trauma,... (Review)
Review
The nail unit is the most commonly affected area in hand infections, which can be primary infection or superinfection complicating other nail or skin disorders. Trauma, mechanical or chemical, is usually the trigger enabling infiltration of infectious organisms. Artificial nails and nail polish are also a possible cause of bacterial infection, harboring microorganisms. In severe acute bacterial infection, surgical intervention is often needed to prevent morbidity and disability. Abscess should always be drained, but viral infection such as herpetic whitlow, may mimic an abscess and, in contrast, requires non-operative treatment; to prevent sequelae. A more conservative approach is also generally advisable in less severe bacterial infection, other viral infections and in subacute or chronic nail infection. The present review deals with acute, subacute and chronic bacterial and viral infections of the nail unit, with a focus on diagnostic and treatment options. LEVEL OF EVIDENCE: III, systematic review of level III studies.
Topics: Humans; Nail Diseases; Virus Diseases; Anti-Bacterial Agents; Bacterial Infections
PubMed: 36427761
DOI: 10.1016/j.hansur.2022.11.006 -
Dermatology (Basel, Switzerland) May 2024Introduction MEK inhibitors are in use for several indications for adults and children. Cutaneous toxicities are among the most common adverse effects. We aimed to...
Introduction MEK inhibitors are in use for several indications for adults and children. Cutaneous toxicities are among the most common adverse effects. We aimed to describe the spectrum of cutaneous adverse events, its frequency and severity in a cohort of pediatric patients. Methods We reviewed all records of patients in our tertiary treatment center treated with MEK inhibitors between January 2016 and January 2023 for all indications. Results Among 33 patients, 76% reported cutaneous adverse effects. The highest prevalence was in the group of patients treated with trametinib (90%), followed by the group treated with selumetinib (50%) and the group treated with combination of trametinib and BRAF inhibitor (dabrafenib, 34%). Xerosis, dermatitis, paronychia and hair heterochromia were most frequently reported. Severity was graded 1 or 2 for most adverse events, and 237 visits to the dermatology clinic related to these adverse events were recorded. Conclusions Cutaneous adverse events are common in the pediatric population as in adults, but the clinical spectrum is different. Although considered as mild, multiple dermatological consultations reflect the distress caused by these events. Dermatologists have a central role in the multidisciplinary care of pediatric patients receiving these agents.
PubMed: 38772345
DOI: 10.1159/000539374 -
Journal of Neuro-oncology May 2024Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder which commonly causes neoplasms leading to disfigurement or dysfunction. Mitogen-activated protein...
PURPOSE
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder which commonly causes neoplasms leading to disfigurement or dysfunction. Mitogen-activated protein kinase inhibitors (MEKi) are generally well-tolerated treatments which target neural tumor progression in patients with NF1. However, cutaneous adverse events (CAEs) are common and may hinder patients' abilities to remain on treatment, particularly in children. We aim to characterize CAEs secondary to MEKi treatment in pediatric and young adult patients with NF1.
METHODS
We reviewed institutional medical records of patients under 30 years with a diagnosis of "NF1," "NF2," or "other neurofibromatoses" on MEKi therapy between January 1, 2019 and June 1, 2022. We recorded the time-to-onset, type, and distribution of CAEs, non-cutaneous adverse events (AEs), AE management, and tumor response.
RESULTS
Our cohort consisted of 40 patients with NF1 (median age, 14 years). Tumor types included low-grade gliomas (51%) and plexiform neurofibromas (38%). MEKi used included selumetinib (69%), trametinib (25%), and mirdametinib (6%). A total of 74 CAEs occurred, with 28 cases of acneiform rash (38%). Other common CAEs were paronychia, seborrheic dermatitis, eczema, xerosis, and oral mucositis. The most common treatments included oral antibiotics and topical corticosteroids. Most patients had clinical (stable or improved) tumor response (71%) while 29% had tumor progression while on a MEKi. There was no significant association between CAE presence and tumor response (p = 0.39).
CONCLUSIONS
Improvement in characterization of MEKi toxicities and their management is important to develop treatment guidelines for pediatric and young adult patients with NF1 on MEKi therapy.
Topics: Humans; Neurofibromatosis 1; Female; Male; Adolescent; Child; Young Adult; Adult; Protein Kinase Inhibitors; Retrospective Studies; Child, Preschool; Neurofibroma, Plexiform; Follow-Up Studies; Drug Eruptions; Prognosis
PubMed: 38443692
DOI: 10.1007/s11060-024-04617-2 -
Cancer NursingMost advanced non-small-cell lung cancer (NSCLC) patients received targeted therapies of epidermal growth factor receptor tyrosine kinase inhibitors. However, few...
BACKGROUND
Most advanced non-small-cell lung cancer (NSCLC) patients received targeted therapies of epidermal growth factor receptor tyrosine kinase inhibitors. However, few studies reported the relationships between adverse events (AEs) and psychological distress.
OBJECTIVES
The aims of this study were to (1) examine the differences in the incidence of AEs, fear of progression (FoP), anxiety, and depression among 3 generations of epidermal growth factor receptor tyrosine kinase inhibitors (first, gefitinib and erlotinib; second, afatinib; third, osimertinib) and (2) examine the difference in levels of FoP, anxiety, and depression between the presence and absence of AEs in NSCLC patients.
METHODS
This study used a cross-sectional study design. Patients with NSCLC (N = 120) were recruited from a medical center in northern Taiwan. Adverse events, FoP, anxiety, and depression were assessed by questionnaires.
RESULTS
The incidence rates of photosensitivity, mouth and throat sores, and diarrhea were significantly high in the gefitinib, erlotinib, and afatinib groups, respectively. A lesser proportion of patients experienced AEs in the osimertinib group, compared with those in the gefitinib and erlotinib, and afatinib groups. The incidence rates of FoP, anxiety, and depression were 13.8% to 26.0%, 24.1% to 40.4%, and 17.6% to 40.0%, respectively. Patients with photosensitivity, paronychia, and alopecia had significantly higher levels of FoP, anxiety, and depression.
CONCLUSION
This study confirmed the priorities of care among 3 generations of epidermal growth factor receptor tyrosine kinase inhibitors in NSCLC patients, using both the Common Terminology Criteria for Adverse Events (CTCAE 4.03) and PRO-CTCAE 1.0. Photosensitivity, paronychia, and alopecia were associated with higher levels of FoP, anxiety, and depression. Therefore, these AEs require further management.
IMPLICATIONS FOR PRACTICE
Our study suggests a follow-up to address AEs and psychological distress.
PubMed: 36089694
DOI: 10.1097/NCC.0000000000001147 -
Cancers Nov 2023This study aimed to evaluate treatment outcomes and safety of afatinib in patients with squamous cell carcinoma of the lung (LSCC) who progressed after chemotherapy and...
Real-World Treatment Outcomes and Safety of Afatinib in Advanced Squamous Cell Lung Cancer Progressed after Platinum-Based Doublet Chemotherapy and Immunotherapy (SPACE Study).
This study aimed to evaluate treatment outcomes and safety of afatinib in patients with squamous cell carcinoma of the lung (LSCC) who progressed after chemotherapy and immunotherapy. We recruited patients both retrospectively and prospectively and collected the outcomes and safety data. Additionally, we performed next-generation sequencing using tumor tissue and/or plasma to explore potential molecular biomarkers. Altogether, 42 patients were included in the final analysis. The median number of prior treatments was three (range 1-8), and the median TTF was 2.1 months. Objective response rate and disease control rate were 16.2% and 59.5%, respectively, and median duration of response was 4.0 months among response evaluable patients ( = 37). Treatment-related adverse events (TRAEs, including diarrhea, stomatitis, and paronychia) occurred in 22 (52.3%) patients; however, most were grade 2 or lower, and only 5 cases were grade 3. TRAEs led to dose modification in 17 (40.5%) and discontinuation in 4 (9.5%) patients. The TTF in patients with mutations was significantly longer than that in patients without (6.8 vs. 2.1 months, = 0.045). Our results highlight that afatinib is a reasonable treatment option in terms of effectiveness and safety, and mutation can be used as a predictive biomarker in clinical settings.
PubMed: 38067272
DOI: 10.3390/cancers15235568 -
Cancer Mar 2024Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non-small cell lung cancer...
BACKGROUND
Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non-small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab.
METHODS
In this single-arm phase 2 trial, patients with advanced NSCLC harboring an EGFR ex20ins mutation were treated with afatinib 40 mg once daily in combination with cetuximab 500 mg/m every 2 weeks. The primary end point was disease control rate (DCR) at 18 weeks of treatment.
RESULTS
Thirty-seven patients started treatment, with a median age of 65 years (range, 40-80 years), 78% female, and 95% White. The study achieved its primary end point with a DCR of 54% at 18 weeks, an overall response rate (ORR) of 43%, and a 32% confirmed ORR. Best responses were partial (n = 16), stable (n = 16), progressive disease (n = 2), or not evaluable (n = 3). Median progression-free survival was 5.5 months (95% CI, 3.7-8.3 months) and median overall survival was 16.8 months (95% CI, 10.7-25.8 months). The most common treatment-related adverse events (TRAEs) were diarrhea (70%), rash (65%), dry skin (59%), paronychia (54%), and erythema (43%). Grade 3 TRAEs were reported in 54% of all patients.
CONCLUSIONS
Combination treatment with afatinib and cetuximab demonstrated antitumor activity with a DCR of 54% at 18 weeks and a 32% confirmed ORR. Toxicity was significant, although manageable, after dose reduction.
Topics: Humans; Female; Adult; Middle Aged; Aged; Aged, 80 and over; Male; Carcinoma, Non-Small-Cell Lung; Afatinib; Cetuximab; Lung Neoplasms; ErbB Receptors; Antineoplastic Combined Chemotherapy Protocols; Exons; Mutation; Protein Kinase Inhibitors
PubMed: 37905752
DOI: 10.1002/cncr.35090 -
Cancers Oct 2023Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second...
A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study).
Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44-3.12) years. The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.
PubMed: 37894366
DOI: 10.3390/cancers15204999