Immune-related adverse events caused by combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab for lung cancer

It has been less than a decade since immune checkpoint inhibitors became the mainstay of lung cancer treatment, and 2020 saw the advent of the era of complex immune checkpoint inhibitors. Although clinical trials have shown that the therapeutic effects of complex immune checkpoint inhibitors are favorable, they are associated with an increase in adverse events. The use of combined immune checkpoint inhibitors in clinical practice has progressed slowly, and the frequency and types of adverse events they cause remain unclear. Here we report the adverse events of six patients with lung cancer treated with regimens containing nivolumab and ipilimumab in 2021. Four of the six patients had grade 3 or higher adverse events, including one patient with lung injury and one patient with skin injury, both of whom died. The timing and nature of the adverse events were difficult to predict.

The clinical application of an innovative tracheotomy fixation belt in critically ill patients

BACKGROUND: Tracheotomy is one of the first-aid measures for rescuing critically ill patients. OBJECTIVE: This study was designed to observe the clinical effect of using an innovative tracheotomy fixation belt in critically ill patients and to explore the feasibility of using this fixation method. METHODS: Eighty critically ill patients requiring a tracheotomy in Putuo District Central Hospital of Shanghai were enrolled in this study and divided into the observation group and control group (n= 40, each). In the control group, fixation was performed with conventional cotton twill tape, while in the observation group the fixation was carried out using a tracheotomy fixation belt. The differences in neck skin injury, the occurrence of eczema, and the rate of detachment of the tracheotomy tube in the two groups were compared. RESULTS: The rate of neck skin injury was 7.5% lower in the observation group than in the control group (30%), and the difference was statistically significant (p< 0.05). The incidence of skin eczema was 5% lower in the observation group than in the control group (22.5%), and the difference was statistically significant (p< 0.05). The detachment rate of the tracheotomy tube was 5% lower in the observation group than in the control group (20%), and the difference was statistically significant (p< 0.05). CONCLUSION: The use of an innovative tracheotomy fixation belt can effectively reduce skin damage to the patient’s neck, the incidence of eczema, and the incidence of detachment of the tracheotomy tube.

Compound Kushen Injection Protects Skin From Radiation Injury via Regulating Bim

Background: Radiation-induced skin injury is a major side-effect observed in cancer patients who received radiotherapy. Thus identifying new radioprotective drugs for prevention or treatment of post-irradiation skin injury should be prompted. A large number of clinical studies have confirmed that Compound Kushen injection (CKI) can enhance efficacy and reduce toxicity of radiotherapy. The aim of this study is to confirm the effect of CKI in alleviating radiotherapy injury in the skin and explore the exact mechanism.Methods: 60 patients who met the inclusion/exclusion criteria were allocated to treatment group (CKI before radiotherapy) or control group (normal saline before radiotherapy) randomly. MTT assay, flow cytometry, Western Blot, and transient transfection were performed to detect the cell viability, cell apoptosis and Bim expression after treatment with CKI or/and radiotherapy.Results: CKI had the effect of alleviating skin injury in cancer patients who received radiotherapy in clinic. CKI induced cancer cell apoptosis when combined with irradiation (IR), while it reversed the induction of cell apoptosis by IR in human skin fibroblast (HSF) cells. And Bim, as a tumor suppressor, was induced in cancer cells but had no change in HSF cells when treated with CKI. Moreover, the above effect could be attenuated when Bim was silenced by siRNA.Conclusion: We conclude that CKI represents a promising radio-protective agent with a potential differential beneficial effect on both cancer cells (inducing apoptosis) and HSF cells (providing radio-protection via inhibiting IR-induced apoptosis), via regulating Bim. Our study uncovers a novel mechanism by which CKI inhibits human cancer cell while protects skin from radiotherapy, indicating CKI might be a promising radio-protective drug.Clinical Trial Registration: Chinese Clinical Trial Registry (www.chictr.org.cn), identifier ChiCTR2100049164.

Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome

This article mainly observed the protective effect of sulforaphane (SFN) on radiation-induced skin injury (RISI). In addition, we will discuss the mechanism of SFN’s protection on RISI. The RISI model was established by the irradiation of the left thigh under intravenous anesthesia. Thirty-two C57/BL6 mice were randomly divided into control group (CON), SFN group, irradiation (IR) group, and IR plus SFN (IR/SFN) group. At eight weeks after irradiation, the morphological changes of mouse skin tissues were detected by H&E staining. Then, the oxidative stress and inflammatory response indexes in mouse skin tissues, as well as the expression of Nrf2 and its downstream antioxidant genes, were evaluated by ELISA, real-time PCR, and Western blotting. The H&E staining showed the hyperplasia of fibrous tissue in the mouse dermis and hypodermis of the IR group. Western blotting and ELISA results showed that the inflammasome of NLRP3, caspase-1, and IL-1β, as well as oxidative stress damage indicators ROS, 4-HNE, and 3-NT, in the skin tissues of mice in the IR group were significantly higher than those in the control group (p < 0.05). However, the above pathological changes declined sharply after SFN treatment (p < 0.05). In addition, the expressions of Nrf2 and its regulated antioxidant enzymes, including CAT and HO-1, were higher in the skin tissues of SFN and IR/SFN groups, but lower in the control and IR groups (p < 0.05). SFN may be able to suppress the oxidative stress by upregulating the expression and function of Nrf2, and subsequently inhibiting the activation of NLRP3 inflammasome and DNA damage, so as to prevent and alleviate the RISI.

EVALUATION OF ANTIOXIDANT, ANTIMICROBIAL AND WOUND HEALING ACTIVITY OF POIKILOSPERMUM SUAVEOLENS

Poikilospermum suaveolens is a plant could grows in the limestone area in Maros, Indonesia. The leaves are generally widely used as traditional medicine for treatment of wounds by local communities. This study aims to examine the wound healing potential of P. suaveolens leaves extract as well as scientific clarify of the plant. The plant leaves were extracted by maceration. The measurement of antioxidant activity by the DPPH technique (1,1 diphenil-2-pikrilhidrazil) spectrophotometrically. The antimicrobial activity was evaluated by formation of the inhibition zone. The wound healing activity was performed the percentage of injury closure in rats skin injury. The antioxidant activity showed that 70% ethanol and ethyl acetate extracts were not significantly different, however, highly distinct to the positive control (Butylated Hidroxyanisole). The antimicrobial activity of extract showed 70% ethanol and ethyl acetate extracts were not significantly against Staphylococcus aureus and Candida albicans, but significantly against Pseudomonas aeruginosa. The evaluation of P. suaveolens extract on the rate of wound closure activity quickly, i.e., within 15 days the injury on the test animal was recovered. This study concludes that the P. suaveolens plant extracts are potential as a sources of active substances for wound healing.

Critical Review of Gaps in the Diagnosis and Management of Drug-Induced Liver Injury Associated with Severe Cutaneous Adverse Reactions

Drug-induced liver injury (DILI) encompasses the unexpected damage that drugs can cause to the liver. DILI may develop in the context of an immunoallergic syndrome with cutaneous manifestations, which are sometimes severe (SCARs). Nevirapine, allopurinol, anti-epileptics, sulfonamides, and antibiotics are the most frequent culprit drugs for DILI associated with SCARs. Interestingly, alleles HLA-B*58:01 and HLA-A*31:01 are associated with both adverse reactions. However, there is no consensus about the criteria used for the characterization of liver injury in this context, and the different thresholds for DILI definition make it difficult to gain insight into this complex disorder. Moreover, current limitations when evaluating causality in patients with DILI associated with SCARs are related to the plethora of causality assessment methods and the lack of consensual complementary tools. Finally, the management of this condition encompasses the treatment of liver and skin injury. Although the use of immunomodulant agents is accepted for SCARs, their role in treating liver injury remains controversial. Further randomized clinical trials are needed to test their efficacy and safety to address this complex entity. Therefore, this review aims to identify the current gaps in the definition, diagnosis, prognosis, and management of DILI associated with SCARs, proposing different strategies to fill in these gaps.

Pressure dressings versus nonpressure dressings after hemorrhoidectomy: study protocol for a randomized controlled trial

Background Pressure dressings have been used after open hemorrhoidectomy to protect surgical wounds and manage postoperative bleeding for many years. However, pressure dressings may increase the incidence of postoperative complications, such as urinary retention, medical adhesive-related skin injury, and pain. A previous controlled trial included 67 patients who underwent Milligan-Morgan hemorrhoidectomy. The data indicated that the use of a nonpressure dressing after hemorrhoidectomy reduces the incidence of urinary retention and catheterization. However, the incidence of severe postoperative bleeding and other postoperative complications was not assessed. There is no consensus on whether it is necessary and beneficial to use a nonpressure dressing after hemorrhoidectomy. The results of this randomized clinical study will help answer this question. Methods In this study, we plan to include 186 patients who have undergone modified Milligan-Morgan hemorrhoidectomy, which only sutured external hemorrhoids to reduce the risk of bleeding. The purpose is to determine whether the use of nonpressure dressings after open hemorrhoidectomy is inferior to the use of pressure dressings in terms of severe postoperative bleeding and postoperative complications. The primary endpoints of the trial are the incidence of urinary retention within 24 h after surgery and the incidence of severe postoperative bleeding 1 h after dressing removal, which requires revision surgery within 24 h after the surgery. The secondary endpoints of the study are the pain score, anal distension score, postoperative use of analgesics, and incidence of medical adhesive-related skin injury, all of which will be assessed before removing the dressings. The length of hospitalization in days and hospitalization expenses will be recorded. Safety will be assessed with consideration of all adverse and severe adverse events related to the study treatment. Discussion The study received full ethics committee approval. The first patient was enrolled on 27 November 2020. The results of this trial will finally answer the question of whether a nonpressure dressing after open hemorrhoidectomy is necessary and beneficial. Trial registration Chinese Clinical Trial Registry ChiCTR2000040283. Registered on 28 November 2020.