-
The Journal of Dermatology Dec 2023Fusarium species (spp.) is frequently found in soil and plant residues and on plant bodies in all climatic zones worldwide. Although there have been few reports of... (Review)
Review
Fusarium species (spp.) is frequently found in soil and plant residues and on plant bodies in all climatic zones worldwide. Although there have been few reports of onychomycosis caused by Fusarium spp., it is characterized by drug sensitivity and other characteristics. Here, we report what may be the first case of onychomycosis caused by Fusarium lactis. We analyzed the mycology and characterized previously reported cases of onychomycosis caused by Fusarium spp. A 73-year-old otherwise healthy woman presented with discoloration and thickening of her right thumbnail with paronychia. Direct microscopy revealed unevenly swollen hyphae, and a Grocott-stained nail specimen showed septate hyphae. Based on the morphological features and gene analysis of fungus isolated from the nail, we diagnosed onychomycosis caused by F. lactis belonging to Fusarium fujikuroi species complex. Partial nail removal and topical application of 1% luliconazole solution resolved the condition in 6 months. Minimum inhibitory concentrations for isolated F. lactis showed high sensitivity to luliconazole but not itraconazole or terbinafine. The isolated F. lactis was temperature-sensitive. A search of the literature revealed 57 cases of onychomycosis caused by Fusarium spp. with delineated clinical characteristics. Since those cases were investigated using morphological and/or molecular methods, we analyzed them by species complex as well as species. Onychomycosis caused by Fusarium spp. is predominantly found on the big toe, with Fusarium solani species complex and Fusarium oxysporum species complex accounting for over 70% of cases. Infection of only one digit with paronychia is a characteristic clinical manifestation of onychomycosis caused by Fusarium spp. Since there has been an increase in instances of molecular determination of Fusarium spp., it is deemed necessary to clarify its clinical and fungal nature. Due to its characteristic drug sensitivity and temperature-sensitive nature, new treatments are expected to be developed.
Topics: Aged; Female; Humans; Antifungal Agents; Fusarium; Naphthalenes; Onychomycosis; Paronychia
PubMed: 37622410
DOI: 10.1111/1346-8138.16931 -
Journal of Veterinary Dentistry Dec 2023Patellar fracture and dental anomaly syndrome (PADS) is a congenital bone disease of cats that is characterized by atraumatic bone fractures (most commonly the patella),...
Patellar fracture and dental anomaly syndrome (PADS) is a congenital bone disease of cats that is characterized by atraumatic bone fractures (most commonly the patella), the persistence of deciduous teeth, and impaction of permanent teeth. Jaw swelling due to osteomyelitis is often the reason that cats with PADS are presented for veterinary dental care. The clinical history, oral examination findings, dental radiological findings, and histopathology were evaluated for 13 cats with dental and skeletal pathology consistent with PADS, including 9 with osteomyelitis. Cats in this study were predominantly domestic shorthair (12 of 13 cats), and there was no apparent sex predilection. All cats had multiple persistent deciduous teeth and multiple impacted permanent teeth, although the number of persistent and impacted teeth varied. Osteomyelitis of the jaw typically occurred within the first 4 years of life. Osteomyelitis of the mandible was 4 times more common than osteomyelitis of the maxilla. Histologically, osteomyelitis was chronic, neutrophilic, and osteoproliferative. Necrotic bone was confirmed in 67% of osteomyelitis lesions. Histological evaluation of jaws without inflammation demonstrated abnormal amounts of unmodeled bone, abnormally dense bone, and retention of cartilage in the caudal mandible. Three cats in the study had mandibular distoclusion and 2 had concurrent paronychia. To obtain a favorable clinical outcome in PADS cats with jaw swelling, prompt and aggressive surgical treatment of osteomyelitis is required. Extraction of persistent deciduous teeth and impacted permanent teeth is recommended when there is associated periodontitis or osteomyelitis.
Topics: Cats; Animals; Pathology, Oral; Fractures, Bone; Tooth, Impacted; Maxilla; Osteomyelitis; Cat Diseases
PubMed: 37248965
DOI: 10.1177/08987564231175594 -
Cancer Medicine Apr 2024Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of...
BACKGROUND
Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild-type metastatic colorectal cancer (mCRC).
METHODS
Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS-negative patients switched to FOLFIRI plus bevacizumab, whereas ETS-positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression-free survival.
RESULTS
This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS-negative and 22 were ETS-positive. Two ETS-negative patients and 17 ETS-positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression-free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients.
CONCLUSIONS
Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.
Topics: Humans; Bevacizumab; Cetuximab; Colorectal Neoplasms; Camptothecin; Fluorouracil; Colonic Neoplasms; Rectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Leucovorin
PubMed: 38591098
DOI: 10.1002/cam4.7107 -
Journal of Pediatric OrthopedicsDistinguishing the severity of the diagnosis and an appropriate treatment plan in pediatric hand infections can be complex due to the variable amount of information...
INTRODUCTION
Distinguishing the severity of the diagnosis and an appropriate treatment plan in pediatric hand infections can be complex due to the variable amount of information available at the presentation. Inflammatory blood markers, including white blood cell count, erythrocyte sedimentation rate, and C-reactive protein are reported to aid in determining the severity of infection and response to treatment in adult hand infections. The purpose of this study was to identify the relevance of inflammatory marker levels in pediatric patients with hand and wrist infections and to determine their utility in diagnosis and treatment.
METHODS
This multicenter, retrospective, cohort study included patients aged 0 to 18 who received treatment for an acute hand or wrist infection between 2009 and 2020. Data collected included demographics, time to presentation, diagnosis, inflammatory markers, culture results, antibiotic treatment, and surgical treatment. Infections were categorized as deep (osteomyelitis, tenosynovitis, abscess) and superficial (paronychia, felon, cellulitis). Exclusion criteria included: patients above 18 years of age, chronic infection, open fractures, and absence of any documented inflammatory markers. Statistically, t tests were used to compare mean differences in inflammatory markers between patients who did and did not receive pretreatment antibiotics and between patients who had superficial versus deep hand infections.
RESULTS
A total of 123 patients met the inclusion criteria. Pretreatment with antibiotics before definitive management was not significantly associated with differences in laboratory markers compared with patients not pretreated with antibiotics. Deep hand infections had inflammatory markers similar to superficial infections. Patients with deep hand infections required a bedside or operative procedure 78.9% of the time compared with superficial infections (21.2%) ( P <0.001). Patients with an isolated methicillin-resistant Staphylococcus aureus infection had inflammatory marker values that were not significantly different from patients infected with all other microbes.
CONCLUSIONS
Inflammatory markers were not significantly different between patients who received pretreatment with antibiotics and those who did not. While deep infections were often treated with bedside or surgical procedures, the inflammatory marker values were similar to those of superficial infections. The same held true for patients infected with culture-positive, isolated methicillin-resistant Staphylococcus aureus bacteria. Consequently, inflammatory markers may be useful to identify the presence of infection and monitor the response to treatment, they did not aid in determining the specific type of infection or selection of a treatment plan.
LEVEL OF EVIDENCE
Level III-retrospective comparative study.
Topics: Adult; Humans; Child; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Cohort Studies; Staphylococcal Infections; Infections; Abscess; Anti-Bacterial Agents
PubMed: 37678156
DOI: 10.1097/BPO.0000000000002508 -
BMC Cancer Feb 2024The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR... (Observational Study)
Observational Study
The difference between dacomitinib and afatinib in effectiveness and safety in first-line treatment of patients with advanced EGFR-mutant non-small cell lung cancer: a real-world observational study.
OBJECTIVES
The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and dacomitinib in this setting.
MATERIALS AND METHODS
Between September 2020 and March 2023, we retrospectively recruited patients diagnosed with advanced-stage EGFR-mutant NSCLC who were treated with first-line irreversible EGFR-TKIs. The enrolled patients were assigned to two groups based on whether they received afatinib or dacomitinib.
RESULTS
A total of 101 patients were enrolled in the study (70 to afatinib and 31 to dacomitinib). The partial response rates (PR) for first-line treatment with afatinib and dacomitinib were 85.7 and 80.6% (p = 0.522). The median progression-free survival (PFS) (18.9 vs. 16.3 months, p = 0.975) and time to treatment failure (TTF) (22.7 vs. 15.9 months, p = 0.324) in patients with afatinib and dacomitinib treatment were similar. There was no significant difference observed in the median PFS (16.1 vs. 18.9 months, p = 0.361) and TTF (32.5 vs. 19.6 months, p = 0.182) between patients receiving the standard dose and those receiving the reduced dose. In terms of side effects, the incidence of diarrhea was higher in the afatinib group (75.8% vs. 35.5%, p < 0.001), while the incidence of paronychia was higher in the dacomitinib group (58.1% vs. 31.4%, p = 0.004). The PFS (17.6 vs. 24.9 months, p = 0.663) and TTF (21.3 vs. 25.1 months, p = 0.152) were similar between patients younger than 75 years and those older than 75 years.
CONCLUSION
This study showed that afatinib and dacomitinib had similar effectiveness and safety profiles. However, they have slightly different side effects. Afatinib and dacomitinib can be safely administered to patients across different age groups with appropriate dose reductions.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Afatinib; Lung Neoplasms; Retrospective Studies; Protein Kinase Inhibitors; Treatment Outcome; ErbB Receptors; Mutation; Quinazolinones
PubMed: 38373960
DOI: 10.1186/s12885-024-11956-w -
Skin Appendage Disorders Feb 2024Nail unit infestation by scabies mites (ungual scabies) is uncommon. It usually presents with distal subungual lesions, leading to recurrent and persistent disease by...
INTRODUCTION
Nail unit infestation by scabies mites (ungual scabies) is uncommon. It usually presents with distal subungual lesions, leading to recurrent and persistent disease by acting as a reservoir of infection. Periungual involvement in scabies with nail loss is rare and may lead to severe nail damage.
CASE PRESENTATION
We report a 14-year-old boy on chemotherapy for acute lymphocytic leukemia (ALL) who presented with extensive scaling and crusted plaques of scabies. Nail unit revealed periungual crusted plaques with paronychia and onychomadesis involving five digits. It was associated with partial to complete nail loss. Dermoscopy of periungual crusted plaques showed greyish-white scales with brown dots and globules. A sinuous burrow with a brown-triangular structure was visualized in the web space. KOH mount from skin scrapings showed the scabies mites. Treatment of scabies led to a marked improvement.
CONCLUSION
Though ungual scabies is generally a benign disease, proximal periungual involvement with damage to nail matrix is possible, leading to nail loss. We review manifestations of nail unit scabies reported in literature. Treatment options used and outcomes are also analyzed. The importance of nail-directed therapy in preventing relapses of scabies cannot be undermined.
PubMed: 38318430
DOI: 10.1159/000533881 -
Cancer Research and Treatment Apr 2024GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase...
PURPOSE
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
MATERIALS AND METHODS
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
RESULTS
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
CONCLUSION
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.
Topics: Humans; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; ErbB Receptors; Fluorouracil; Irinotecan; Leucovorin; Neoplasm Recurrence, Local; Rectal Neoplasms
PubMed: 38062706
DOI: 10.4143/crt.2023.1117 -
Oncology Letters Aug 2023The current treatment options for epidermal growth factor receptor (EGFR) mutation-positive lung cancer in the elderly with tyrosine kinase inhibitor (TKI) resistance...
The current treatment options for epidermal growth factor receptor (EGFR) mutation-positive lung cancer in the elderly with tyrosine kinase inhibitor (TKI) resistance are limited. Although chemotherapy combined with vascular endothelial growth factor inhibitors significantly improves progression-free survival (PFS) in TKI-resistant patients, it often cannot be tolerated in elderly patients, leading to treatment failure. Anlotinib is a small molecule inhibitor made in China. The application of low-dose anlotinib in elderly patients with TKI-resistant lung cancer deserves further investigation. A total of 48 elderly patients with non-small cell lung cancer (NSCLC) were enrolled to evaluate the efficacy of anlotinib combined with continuous EGFR-TKI vs. anlotinib monotherapy in patients with acquired EGFR-TKI resistance. Anlotinib was administered at a dose of 6-8 mg per day, lower than the normal dose and known as a low dose, which is well tolerated in elderly patients. There were 25 cases in the combination group and 23 cases in the anlotinib monotherapy group. The primary endpoint of the present study was PFS, and the secondary endpoints were overall survival (OS), response rate and toxicity. The median PFS (mPFS) was significantly longer in the combination group than that in the anlotinib monotherapy group: 6.0 months [95% confidence interval (CI), 4.35-7.65] compared with 4.0 months (95% CI, 3.38-4.62) (P=0.002). Analysis of the subgroups showed similar trends in results. The median OS was 32 months (95% CI, 22.04-41.96) in the combination group and 28 months (95% CI, 27.13-28.87) in the anlotinib monotherapy group (P=0.217). According to stratification analysis, second-line treatment with anlotinib combined with EGFR-TKI resulted in a better mPFS than third-line treatment (7.5 vs. 3.7 months, HR=3.477; 95% CI, 1.117-10.820; P=0.031). In the combination group, patients with gradual/local progression after EGFR-TKI failure had a longer mPFS than those with dramatic progression (7.5 vs. 6.0 months, HR=5.875; 95% CI, 1.414-10.460; P=0.015). Multivariate analyses showed that continuous EGFR-TKI combined with anlotinib after EGFR-TKI resistance was associated with longer PFS (P=0.019), whereas dramatic progression (P=0.014) had a detrimental effect on follow-up treatment. Grade 2 adverse events (AEs) were reported in four patients (17.39%) in the anlotinib monotherapy group and eight patients (32.00%) in the combination group. Of these, the most common grade 2 AEs were hypertension, fatigue, diarrhea, paronychia, mucositis and transaminase elevation. There were no grade 3/4/5 AEs. In conclusion, the present study demonstrated that low-dose anlotinib combined with EGFR-TKI is superior to anlotinib alone following EGFR-TKI failure, making it the preferred regimen for elderly patients with acquired EGFR-TKI resistance.
PubMed: 37415629
DOI: 10.3892/ol.2023.13909 -
The Australasian Journal of Dermatology Aug 2023The cutaneous toxicity of MEK inhibitors may limit treatment adherence. The authors present a retrospective study of 41 paediatric patients with NF-1 undergoing therapy...
The cutaneous toxicity of MEK inhibitors may limit treatment adherence. The authors present a retrospective study of 41 paediatric patients with NF-1 undergoing therapy with selumetinib and propose a treatment algorithm.
Topics: Humans; Child; Retrospective Studies; Paronychia; Protein Kinase Inhibitors; Skin Diseases; Mitogen-Activated Protein Kinase Kinases
PubMed: 37224380
DOI: 10.1111/ajd.14079 -
Targeted Oncology Jun 2024Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer....
BACKGROUND
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer. An updated toxicity profile of EGFR-TKIs proves valuable in guiding clinical decision making.
OBJECTIVE
This study comprehensively assessed the risk of EGFR-TKI-related adverse events (AEs) involving different systems/organs.
METHODS
We systematically searched PubMed, Embase, Web of Science, and Cochrane library for phase III randomized controlled trials comparing EGFR-TKI monotherapy with placebo or chemotherapy in patients with non-small cell lung cancer. The odds ratio (OR) of all-grade and high-grade adverse events (AEs) including dermatologic, gastrointestinal, hematologic, hepatic, and respiratory events was pooled for a meta-analysis. Subgroup analyses based on the control arm (placebo or chemotherapy) and individual EGFR-TKIs (erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib) were conducted.
RESULTS
Thirty-four randomized controlled trials comprising 15,887 patients were included. The pooled OR showed EGFR-TKIs were associated with a significantly increased risk of all-grade dermatologic AEs including paronychia, pruritus, rash, skin exfoliation, and skin fissures, gastrointestinal AEs including abdominal pain, diarrhea, dyspepsia, mouth ulceration, and stomatitis, hepatic AEs including elevated alanine aminotransferase and aspartate aminotransferase, and respiratory AEs including epistaxis, interstitial lung disease and rhinorrhea. Furthermore, a significantly increased risk of high-grade rash (OR 7.83, 95% confidence interval [CI] 5.11, 12.00), diarrhea (OR 2.10, 95% CI 1.44, 3.05), elevated alanine aminotransferase (OR 3.93, 95% CI 1.71, 9.03), elevated aspartate aminotransferase (OR 3.22, 95% CI 1.05, 9.92) and interstitial lung disease (OR 2.35, 95% CI 1.38, 4.01) was observed in patients receiving EGFR-TKIs. When stratified by individual EGFR-TKIs, gefitinib showed a significant association with all-grade and high-grade hepatotoxicity and interstitial lung disease.
CONCLUSIONS
Epidermal growth factor receptor tyrosine kinase inhibitors were associated with a significantly increased risk of various types of AEs. Clinicians should be vigilant about the risks of these EGFR-TKI-related AEs, particularly for severe hepatotoxicity and interstitial lung disease, to facilitate early detection and proper management.
PubMed: 38824269
DOI: 10.1007/s11523-024-01073-w