Effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy.

Objective: To find out the effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy. Methods: This was a retrospective study. Sixty six patients with nasopharyngeal carcinoma who received radiotherapy in the Affiliated Hospital of Hebei University from March 2021 to March 2022 were included and randomly divided into the observation group and the control group, with 33 cases in each group. Patients in the control group were given conventional care measures, while those in the observation group were given psychological support intervention on top of conventional care measures. The nursing effects between the two groups were compared. Results: After the intervention, the psychological resilience score of the observation group was significantly higher than that of the control group, with a statistically significant difference (P<0.05). The psychological resilience scores after the intervention were significantly higher in the observation group than before the intervention, and those in the control group were higher than before the intervention, with a statistically significant difference(P<0.05). The overall health score of quality of life in the observation group was significantly higher than that in the control group after the intervention, with a statistically significant difference(P<0.05). Moreover, the skin reaction in the observation group after radiotherapy was significantly better than that of the control group (P<0.01). Conclusion: Psychological support intervention is an effective means to treat patients with nasopharyngeal carcinoma, which results in various benefits such as improving patients' mental resilience and quality of life and reducing the incidence of adverse reactions after radiotherapy.

Therapeutic Effect of Anti-Inflammatory Tripeptide Cream in Hand-Foot Syndrome/Skin Reaction Related to Anticancer Drugs: a Randomized, Double-Blind, Placebo-Controlled Pilot Trial.

Purpose: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are relatively common toxicities that interfere with the quality of life (QoL) of patients with cancer. Anti-inflammatory tripeptide cream (ATPC) is a complex formulation of anti-inflammatory tripeptides, the CD99-agonist BinterinTM and the Wnt-antagonist WinhibinTM. The present study aimed to assess the therapeutic effects of ATPC in HFS/HFSR associated with anticancer drugs. Materials and Methods: This was a single-center, randomized, double-blind, placebo-controlled trial. Patients who developed grade 1 HFS/HFSR after systemic anticancer treatments were enrolled, and randomly assigned to receive either ATPC or placebo cream (PC) and followed up at 3-week intervals for up to nine weeks. Primary endpoint was the development of grade ≥ 2 HFS/HFSR. Results: Between April 2019 and July 2022, 60 patients (31 in the ATPC and 29 in the PC group) completed the study. The incidence of grade ≥ 2 HFS/HFSR was significantly lower in the ATPC than in the PC group (25.8% vs. 51.7%, p=0.039). The ATPC showed trends towards a better QoL score, assessed by a HFSR and QoL questionnaire at 9 weeks (26.0 vs. 29.9, p=0.574), and a lower frequency of discontinuation, interruption, or dose reduction of anticancer drugs (51.6% vs. 58.6%, p=0.586) than the PC group over 9 weeks, though without statistical significance. Conclusion: Our results showed that ATPC significantly decreased the development of grade ≥ 2 HFS/HFSR in patients already with HFS/HFSR. Therefore, ATPC may be an effective treatment for HFS/HFSR associated with anticancer drugs.

A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Effect of Topical Urea for Secondary Prophylaxis of Hand Foot Skin Reaction in Renal Cell Cancer Patients on Sunitinib Therapy.

INTRODUCTION: Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. OBJECTIVE: In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. METHODS: Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. RESULTS: The results showed that urea-based cream was not superior to placebo (P = .075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. CONCLUSION: The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib.

Identification of Keratinocyte Cytoprotectants against Toxicity by the Multikinase Inhibitor Sorafenib Using Drug Repositioning.

Hand-foot skin reaction is the most common adverse event of multikinase inhibitors, such as sorafenib. Although hand-foot skin reaction is not life threatening, severe cases impair quality of life because of pain and reduced activities of daily living. However, the pathological mechanisms of hand-foot skin reaction have not yet been elucidated in detail, and there is currently no effective treatment. We aimed to identify keratinocyte cytoprotectants against sorafenib toxicity. The screening of cytoprotectants against sorafenib toxicity was performed using cultured normal human epidermal keratinocytes or a reconstructed human epidermis model and off-patent approved drugs in the Prestwick Chemical library. Among 1273 drugs in the chemical library, 8 dose-dependently increased cell viability by >200% in the presence of sorafenib. In the presence of sorafenib, the number of proliferating cell nuclear antigen-positive cells was significantly higher in clofazimine-, cyclosporin A-, and itraconazole-treated reconstructed human epidermis models than in sorafenib-treated models, and candidate drugs suppressed sorafenib-induced apoptosis in normal human epidermal keratinocytes. In addition, clofazimine, itraconazole, and pyrvinium pamoate significantly recovered the phosphorylation of extracellular signal-regulated kinase 1/2 in the presence of sorafenib. Collectively, hit drugs promoted cell viability and normalized keratinocyte proliferation in the presence of sorafenib. These candidate drugs have potential as treatments for multikinase inhibitor-induced hand-foot skin reaction.

Association of VEGFA and CCL4L2 polymorphisms with hand-foot skin reaction and survival of regorafenib in Japanese patients with colorectal cancer.

PURPOSE: Treatment with regorafenib, which inhibits vascular endothelial growth factor (VEGF) receptor, frequently results in hand-foot skin reaction (HFSR), requiring treatment discontinuation or dose reduction. In our prospective study of regorafenib on patients with metastatic colorectal cancer, 17% of patients developed grade 3 HFSR. Herein, we retrospectively examined genetic polymorphisms associated with regorafenib-induced severe HFSR. METHODS: To identify associated polymorphisms, exploratory whole-exome sequencing focusing on factors related to VEGF-mediated signaling pathways was first performed in seven patients each, with grade 3 HFSR and without HFSR. The identified HFSR-associated polymorphisms were analyzed in all the 40 patients. RESULTS: The genotype frequency of rs3025009 G/A or A/A in the gene encoding VEGF-A (VEGFA) in patients with ≥ grade 2 HFSR was significantly higher than in other patients (P = 0.0257, Pc = 0.0771 [Bonferroni correction]). The frequency of C-C motif of chemokine ligand 4-like 2 (CCL4L2) rs3744596 A/T or T/T in patients with grade 3 HFSR was significantly lower than in others (P = 0.00894, Pc = 0.0268). The combination of the risk genotypes VEGFA rs3025009 G/A or A/A and CCL4L2 rs3744596 A/A was significantly associated with a higher incidence of grade 3 (P = 0.000614, Pc = 0.00246) and a longer median progression-free survival (P = 0.0234) than others. CONCLUSIONS: These VEGF-related polymorphisms were found to be associated with HFSR and the survival benefits of regorafenib treatment. TRIAL REGISTRATION NUMBER AND DATE: UMIN000013939, registered on May 12, 2014, when 6 months after the approval by the Institutional Review Board of Showa University.

Bone-anchored hearing aids: Percutaneous versus transcutaneous attachments - a health economics comparison in paediatric patients.

INTRODUCTION: Bone anchored hearing aids (BAHA) are a useful support when conventional hearing aids are not suitable. The two types of attachment of the aid are onto a percutaneous abutment or a transcutaneous magnet. Anecdotally, the abutment requires more care, revision procedures and causes more infections than magnet-based devices. METHODS: A multicentre, retrospective review was conducted of all patients that underwent a BAHA since our programme began, identified through a prospectively maintained database of patients. Patients' charts were audited for outpatient clinic visits, skin complications and revision surgeries. Developmental delay was also recorded. Patients were censored if the hearing aid was removed, replaced or the patient reached 16 years old. Bilateral or reimplanted patients were recorded as separate implants. Statistical analysis was performed using SAS version 9.4. RESULTS: 150 implants were assessed over 126 patients: 115 transcutaneous and 35 percutaneous. Percutaneous patients had significantly more outpatient clinic attendances (Least square mean 4.19 vs. 1.39 p = 0.00), skin complications (mean 4.82 v 0.11 p = 0.00) and theatre visits (mean 2.8 vs. 1.03 p = 0.00) compared to transcutaneous patients. 77 implants were in patients that had developmental delay; having same made no significant difference to above outcomes. CONCLUSION: There is a significant difference in healthcare burden between percutaneous and transcutaneous systems in a paediatric population. The increased cost of the percutaneous implant to the healthcare system and inconvenience to the patient is cause to consider a transcutaneous system in the first instance.

Periorbital Necrotizing Fasciitis: Case Presentation.

Necrotizing fasciitis (NF) is an aggressive and potentially life-threatening infection of the superficial fascia and surrounding skin, fat, fascia, muscle, and other soft tissue structures. Here, we outline the rare case of a 26-year-old man with a periorbital Streptococcus pyogenes A NF infection. Our case report underscores a unique instance of periorbital NF, distinctively presenting without any predisposing risk factors, shedding light on its presentation, treatment, and pathophysiology.

Dermatologic adverse effect of subcutaneous furosemide administration in a cat.

Background: Furosemide is a mainstay of treatment in congestive heart failure (CHF) and is widely prescribed to dogs and cats by several formulations, including the subcutaneous one. In canine and human medicine, dermatologic adverse effects of subcutaneous furosemide (SF) have been documented; conversely, no prior case has been published describing skin reactions to this therapeutic protocol in cats. In this report, we describe, for the first time in feline medicine, a suspected dermatologic adverse effect after SF in a cat. Case Description: A 2-year-old domestic shorthair cat was presented for CHF associated with lung edema and pleural effusion. Echocardiography revealed asymmetric left ventricular myocardial thickening and severe left atrial dilation. The cat was hospitalized and initially treated with oxygen, intravenous furosemide, and clopidogrel. After discharge, the route of administration of furosemide was switched from intravenous to oral. Within the following 2 weeks, the cat experienced two relapses of lung edema despite the progressive increase of the furosemide dose, the addition of spironolactone and adherence to the therapeutic protocol by the owners. The dose of furosemide was further increased and its route of administration at home was switched from oral to parental. As the owner was not able to administrate intramuscular injections, SF was prescribed. This allowed the prevention of further episodes of lung edema. However, although the cat had never presented skin problems before, multiple well-defined circular, crusted ulcerative cutaneous lesions associated with alopecia developed at the sites of furosemide injections 2 weeks later. After ruling out several differential diagnoses for these lesions, a rare side effect of furosemide, not yet described in cats but already known in canine and human medicine, was strongly suspected as the possible cause. Therefore, the ongoing injectable formulation of furosemide was interrupted and substituted with an alternative brand, maintaining the same dose and route of administration. Thanks to this change, the dermal ulcerations disappeared within 1 month. Subsequently, the cat experienced neither further skin problems nor a recurrence of lung edema. Conclusion: Although SF is sometimes prescribed in small animal practice, it should be noticed that this may lead to dermatologic adverse reactions in the cat.

Stevens-Johnson Syndrome in Adult Patient Secondary to COVID-19 Infection: Case Report.

COVID-19 is a global pandemic caused by a novel zoonotic RNA virus named SARS-CoV-2. Various cutaneous manifestations associated with COVID-19 have been described, including urticarial rash, confluent erythematous rash, papulovesicular exanthem, chilblain-like acral pattern, livedo reticularis, and purpuric vasculitis pattern. Here, we are presenting a case of a 45-year-old male with mucocutaneous features of Stevens-Johnson syndrome.

[Lichenoid drug eruption with unfavorable evolution. Difficulties in diagnosis]. / Erupción liquenoide medicamentosa con evolución desfavorable. Dificultades en el diagnóstico.

We report the case of a woman who started with a lichenoid eruption, unfavorable evolution, for which a drug reaction was suspected. The final diagnosis was paraneoplastic pemphigus. Multidisciplinary care and evaluation by an Allergist is important in patients with severe skin reactions, suspected of drug reactions, due to the difficulty in establishing the diagnosis.

Se reporta el caso de una mujer que inició con erupción liquenoide, con evolución desfavorable, por lo que se sospechó una reacción medicamentosa. El diagnóstico final fue pénfigo paraneoplásico. Es importante la atención multidisciplinaria y la evaluación de un alergólogo en pacientes con reacciones cutáneas graves, por sospecha de reacciones farmacológicas, debido a la dificultad para establecer el diagnóstico.

Value of the Lymphocyte Transformation Test for the Diagnosis of Drug-Induced Hypersensitivity Reactions in Hospitalized Patients with Severe COVID-19.

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays for PBMCs. We included five nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT result for at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT result. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.

A Rare Case of Diltiazem-Induced Photosensitivity.

Photosensitivity is a condition of heightened skin sensitivity to sunlight or other forms of ultraviolet light. The case presented here highlights a rare occurrence of diltiazem-induced photosensitivity in an 87-year-old female patient with a history of atrial fibrillation and multiple comorbidities. The patient developed a distinctive erythematous rash limited to the sun-exposed area of the left side of her face during her hospital stay for respiratory failure and pneumonia. The localized distribution of the rash, along with its resolution upon reducing sun exposure, strongly suggested a photosensitivity reaction induced by diltiazem. Prompt discontinuation of the medication and transitioning to verapamil led to the resolution of the cutaneous manifestations. This case emphasizes the importance of recognizing and managing photosensitivity reactions as potential adverse effects of medications, such as diltiazem. Further research is needed to better understand the pathophysiology and risk factors associated with photosensitivity reactions to calcium channel blockers. Through this case report, we aim to contribute to the existing knowledge in this field and emphasize the significance of vigilance in clinical practice.

Clinical characteristics, treatment outcomes, and prognosis in patients with MKIs-associated hand-foot skin reaction: a retrospective study.

BACKGROUND: Multikinase inhibitors (MKIs) treatment has been proven as a powerful strategy in cancer therapy. However, it is greatly hampered by its common adverse effect known as hand-foot skin reaction (HFSR), especially in patients with moderate-to-severe HFSR. OBJECTIVE: To investigate the clinical characteristics, histopathological features, treatment response, and bio-indicators of HFSR. METHODS: We retrospectively reviewed the medical records of 102 patients with moderate-to-severe HFSR resulting from MKIs therapy. RESULTS: The median time to development of moderate-to-severe HFSR was 18 days, which would be significantly affected by the type of MKIs and the history of HFSR. Notably, we found that HFSR was classified into three consecutive stages: erythematous lesion, yellow hyperkeratotic lesion with surrounding erythema, and hyperkeratotic lesion. Inflammation was observed in the first two stages of HFSR, but disappeared in the third stage; in contrast, the hyperkeratosis gradually became thicker from stage one to stage three. Moreover, topical medications were demonstrated as an effective therapy for HFSR, among which, the topical steroids and urea ointment treatment response rate was 37.14%, the Shouzu Ning Decoction (SND) treatment response rate was 65%, and the SND in combination with urea ointment treatment response rate was 75%, meanwhile, systemic therapies did not improve the therapeutic efficacy of topical medications alone. In addition, the serum levels of HMGB1 were found to be a potential indicator for tracking the healing process as well as predicting the prognosis of HFSR. CONCLUSION: This study revealed the potential factors affecting the development of HFSR, evaluated the therapeutic response towards different strategies for treating HFSR, and identified a potential prognostic indicator of HFSR.

Skin Reactions Following Primary Total Knee Arthroplasty With an Adhesive Superficial Closure System: A Case Series.

BACKGROUND: We investigated a skin adhesive closure device consisting of a self-adhesive polyester mesh placed over the surgical incision, followed by a liquid adhesive that is spread over the mesh and surrounding the skin. It is intended to reduce wound closure times, scarring, and skin complications associated with traditional closure with sutures or staples. The aim of this study was to report on skin reactions in patients who underwent primary total knee arthroplasty (TKA) using the skin adhesive closure system. METHODS: A retrospective review of patients who underwent TKA using adhesive closure between 2016 to 2021 at a single institute was performed. A total of 1,719 cases were analyzed. Patient demographics were collected. The primary outcome was any postoperative skin reaction. Skin reactions were classified as allergic dermatitis, cellulitis, or other. Treatment(s), duration of symptoms, and surgical infections were also collected. RESULTS: A total of 5.0% (86) of patients were found to have any type of skin reaction following their TKA. Of these 86, 39 (2.3%) had symptoms of allergic dermatitis (AD), 23 (1.3%) had symptoms of cellulitis, and 24 (1.4%) had other symptoms. A total of 27 (69%) allergic dermatitis patients were treated with a topical corticosteroid cream only; their symptoms resolved within an average of 25 days. There was only 1 case of superficial infection (<0.001%). No prosthetic joint infections were observed. CONCLUSION: Despite skin reactions appearing in 5.0% of cases, the rate of infection was low. A patient-specific preoperative workup and effective treatment strategies can minimize complications associated with adhesive closure system and increase patient satisfaction following TKA.

SARS-CoV-2 and allergy - what have we learned after two and a half years?

BACKGROUND: Coronavirus disease-2019 (COVID-19) has significantly hampered the regular workflow for allergists and allergy departments. MATERIALS AND METHODS: The purpose of this review is to highlight our own experiences on SARS-CoV-2 and allergy as well as to discuss findings from the literature. RESULTS: Vaccination against SARS-CoV-2 is needed for protection against severe infection. Skin reactions may arise with SARS-CoV-2 infections. Short-term general immune reactions and skin reactions are also possible upon SARS-CoV-2 vaccination; however, they recur in only a proportion of patients during follow-up vaccinations. Initial reports of anaphylaxis after vaccination fueled public fear. On the other hand, more recent epidemiologic data do not show a substantially increased anaphylaxis risk compared with other vaccines. Fear-related reactions may be essential for many "anaphylaxis" reports. In Germany, the flow chart developed by Paul-Ehrlich-Institut (PEI) and Robert-Koch-Institut (RKI) together with the allergological societies helps to care for patients with suspected "allergy history" safely and effectively. Through this, patients with increased risk of anaphylaxis to SARS-CoV-2 vaccines and their ingredients (e.g., polyethylene glycol (PEG), polysorbate 80) are identified. However, since only small amounts of these excipients are contained in mRNA vaccines, even some PEG-allergic patients can tolerate the vaccination. In Germany, an allergy test-guided procedure is recommended for high-risk patients, including an allergy history, prick tests, intradermal and basophil activation tests, and, if necessary, provocation tests. This also appears effective for anxiety reduction in patients with vaccination skepticism. To date, all of our patients have been able to be vaccinated with SARS-CoV-2 vaccines without the occurrence of significant reactions. CONCLUSION: Many initial concerns about unexpected side effects of SARS-CoV-2 vaccination have not been confirmed. The flowchart and, in the case of suspicion of hypersensitivity, an allergy test-guided risk assessment helps to reduce patients' fear of vaccination and enables safe vaccination.

The Efficacy and Safety of the Shouzu Ning Decoction Treatment Versus Halometasone Plus Celecoxib Treatment in Patients With Grade 2 HFSR: A Randomized Clinical Trial.

OBJECTIVES: To compare the effects of the Shouzu Ning Decoction (SND) and Halometasone plus Celecoxib (Hal/Cxb) as therapy in patients with grade 2 hand-foot skin reaction (HFSR). MATERIALS AND METHODS: Fifty patients with grade 2 HFSR participated in a randomized, single-center, open-label study. Patients were randomly assigned in a 1:1 ratio to receive the SND or Hal/Cxb treatment, twice daily for 4 weeks, followed by 4 weeks of post-treatment follow-up. The primary endpoint was clinical remission of HFSR at the end of the fourth week (W4). The secondary endpoints were recurrence rate, quality of life (QoL), pain intensity, and safety. RESULTS: In this study, 46 patients successfully completed the study, and 4 patients were excluded. There was no statistically significant difference between the 2 groups on demographic and baseline clinical characteristics. In the SND group, 56.52% of patients showed clinical remission at W4, which was significantly superior to that achieved in the Hal/Cxb group (26.09%, P = .036). In addition, the HF-QoL score was statistically lower in the SND group compared to the Hal/Cxb group at W2 (P = .007), W3 (P = .005), and W4 (P = .005), respectively. In line with this, the inter-group difference in NRS score was statistically significant (P = .004). CONCLUSION: In the present study, SND treatment has been observed to be effective and well tolerated for patients with grade 2 HFSR. Thus, SND treatment could be considered a suitable option for HFSR patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027518. Registered on 17 Nov 2019.

A Potential Association of Zinc Deficiency and Tyrosine Kinase Inhibitor-Induced Hand-Foot Skin Reaction.

Hand-foot skin reaction (HFSR) is a common skin-related adverse event induced by multikinase inhibitors targeting both platelet-derived growth factor receptor and vascular endothelial growth factor receptor, possibly due to inadequate repair following frictional trauma. Zinc is a trace element and essential nutrient in humans that plays critical roles in the development and differentiation of skin cells. Zinc transporters (Zrt- and Irt-like proteins and Zn transporters) and metallothioneins are involved in zinc efflux, uptake, and homeostasis and have been reported to be involved in skin differentiation. The underlying mechanism of HFSR remains unclear, and the association between HFSR and zinc has not been previously studied. However, some case reports and case series provide potential evidence to suggest that zinc deficiency may be involved in HFSR development and zinc supplementation may relieve HFSR symptoms. However, no large-scale clinical studies have been conducted to examine this role. Therefore, this review summarizes the evidence supporting a possible link between HFSR development and zinc and proposes potential mechanisms underlying this association based on current evidence.