Pembrolizumab is an immune checkpoint inhibitor that selectively blocks the programmed cell death (PD)-1 receptor. Although it has a dramatic effect on the treatment of advanced malignancies, instability of immune tolerance may cause immune-related adverse events in the skin. A 62-year-old male with a history of metastatic urothelial carcinoma was referred to the dermatology department and presented with a widespread mucocutaneous rash. Itching appeared 7 days after the first administration of pembrolizumab, and on the third day after the second administration, an erythematous maculopapular rash that coalesced into large flaccid bullae on the whole body with a positive Nikolsky’s sign developed. A biopsy revealed a subepidermal bulla with basal keratinocyte necrosis. Pembrolizumab was discontinued due to the diagnosis of toxic epidermal necrolysis (TEN), and intravenous methylprednisolone was started. Herein, we report a case of TEN induced by pembrolizumab to highlight immune-related cutaneous adverse events in patients receiving anti-PD-1 therapy.

Background: Neuroinflammation plays an important role in cognitive decline and memory impairment in neurodegenerative disorders. Previously, we demonstrated that Humulus japonicus (HJ) has anti-inflammatory effects in rodent models of Alzheimer’s disease and Parkinson’s disease. The present study aimed to examine the protective potential of HJ extracts against lipopolysaccharide (LPS)-induced cognitive impairment and scopolamine-induced amnesia in mouse models. Cognitive improvement of mice was investigated by novel object recognition test. For analyzing effects on neuroinflammation, immunohistochemistry and quantitative real-time polymerase chain reaction (qRTPCR) assays were performed. Results: We found that the oral administration of HJ significantly improved cognitive dysfunction induced by LPS in a novel object recognition test. The LPS-induced activation of microglia was notably decreased by HJ treatment in the cortex and hippocampus. HJ administration with LPS also significantly increased the mRNA expression of interleukin (IL)-10 and decreased the mRNA expression of IL-12 in the parietal cortex of mice. The increased expression of LPS-induced complement C1q B chain (C1bq) and triggering receptor expressed on myeloid cells 2 (Trem2) genes was significantly suppressed by HJ treatment. In addition, HJ administration significantly improved novel object recognition in a scopolamine-induced amnesia mouse model. Conclusions These findings revealed that HJ has a beneficial effect on cognitive impairment and neuroinflammation induced by systemic inflammation and on amnesia induced by scopolamine in mice.

Background: Patients with stable psoriasis showing clearear-clear response can consider extending the dosing interval of biologics. However, few studies have reported the treatment outcomes following irregular dosing intervals of biologics in patients with psoriasis. Objective: We compared treatment outcomes after regular and irregular dosing intervals of biologics in patients with psoriasis. Methods: This single-center, retrospective observational study included patients who received biologics for treatment of plaque psoriasis between January 1, 2014 and December 31, 2019. We compared patient demographics, clinical characteristics, biologics administered, and treatment outcomes based on the regularity of the dosing interval. Results: Among 95 patients investigated, 63 (66.3%) received biologics at regular dosing intervals. We observed no significant intergroup differences in the final Psoriasis Area Severity Index (PASI) scores (1.2 vs. 1.8, p=0.16) and in the percentage improvement in PASI scores from baseline levels (−89.8% vs. −90.8%, p=0.68). The rate at which biologics were switched was higher in the irregular-dosing group than in the regular-dosing group; however, the difference was statistically nonsignificant (28.1% vs. 12.7%, p=0.06). We observed a significant intergroup difference in patients who were administered guselkumab at baseline (12 [21.8%] vs. 0 [0.0%], p=0.01). Conclusion This study showed that compared with regular dosing intervals, irregular dosing intervals of biologics were associated with high rates of switching of these agents, although we observed no statistically significant differences with regard to PASI scores. Therefore, it is important to adhere to the standard dosing schedule prescribed for biologics, and guselkumab may improve patient compliance.

Injection lipolysis or mesotherapy gained popularity for local fat dissolve as an alternative to surgical liposuction. Phosphatidylcholine (PPC) and aminophylline (AMPL) are commonly used compounds for mesotherapy, but their efficacy and safety as lipolytic agents have been controversial. Glycerophosphocholine (GPC) is a choline precursor structurally similar to PPC, and thus introduced in aesthetics as an alternative for PPC. This study aimed to evaluate the effects of GPC on adipocytes differentiation and lipolysis and compared those effects with PPC and AMPL using in vitro and in vivo models. Adipogenesis in 3T3-L1 was measured by Oil Red O staining. Lipolysis was assessed by measuring the amount of glycerol released in the culture media. To evaluate the lipolytic activity of GPC on a physiological condition, GPC was subcutaneously injected to one side of inguinal fat pads for 3 days. Lipolytic activity of GPC was assessed by hematoxylin and eosin staining in adipose tissue. GPC significantly suppressed adipocyte differentiation of 3T3-L1 in a concentration-dependent manner (22.3% inhibition at 4 mM of GPC compared to control). Moreover, when lipolysis was assessed by glycerol release in 3T3-L1 adipocytes, 6 mM of GPC stimulated glycerol release by two-fold over control. Subcutaneous injection of GPC into the inguinal fat pad of mice significantly reduced the mass of fat pad and the size of adipocytes of injected site, and these effects of GPC were more prominent over PPC and AMPL. Taken together, these results suggest that GPC is the potential therapeutic agent as a local fat reducer.

Injection lipolysis or mesotherapy gained popularity for local fat dissolve as an alternative to surgical liposuction. Phosphatidylcholine (PPC) and aminophylline (AMPL) are commonly used compounds for mesotherapy, but their efficacy and safety as lipolytic agents have been controversial. Glycerophosphocholine (GPC) is a choline precursor structurally similar to PPC, and thus introduced in aesthetics as an alternative for PPC. This study aimed to evaluate the effects of GPC on adipocytes differentiation and lipolysis and compared those effects with PPC and AMPL using in vitro and in vivo models. Adipogenesis in 3T3-L1 was measured by Oil Red O staining. Lipolysis was assessed by measuring the amount of glycerol released in the culture media. To evaluate the lipolytic activity of GPC on a physiological condition, GPC was subcutaneously injected to one side of inguinal fat pads for 3 days. Lipolytic activity of GPC was assessed by hematoxylin and eosin staining in adipose tissue. GPC significantly suppressed adipocyte differentiation of 3T3-L1 in a concentration-dependent manner (22.3% inhibition at 4 mM of GPC compared to control). Moreover, when lipolysis was assessed by glycerol release in 3T3-L1 adipocytes, 6 mM of GPC stimulated glycerol release by two-fold over control. Subcutaneous injection of GPC into the inguinal fat pad of mice significantly reduced the mass of fat pad and the size of adipocytes of injected site, and these effects of GPC were more prominent over PPC and AMPL. Taken together, these results suggest that GPC is the potential therapeutic agent as a local fat reducer.

Background: Patients with stable psoriasis showing clearear-clear response can consider extending the dosing interval of biologics. However, few studies have reported the treatment outcomes following irregular dosing intervals of biologics in patients with psoriasis. Objective: We compared treatment outcomes after regular and irregular dosing intervals of biologics in patients with psoriasis. Methods: This single-center, retrospective observational study included patients who received biologics for treatment of plaque psoriasis between January 1, 2014 and December 31, 2019. We compared patient demographics, clinical characteristics, biologics administered, and treatment outcomes based on the regularity of the dosing interval. Results: Among 95 patients investigated, 63 (66.3%) received biologics at regular dosing intervals. We observed no significant intergroup differences in the final Psoriasis Area Severity Index (PASI) scores (1.2 vs. 1.8, p=0.16) and in the percentage improvement in PASI scores from baseline levels (−89.8% vs. −90.8%, p=0.68). The rate at which biologics were switched was higher in the irregular-dosing group than in the regular-dosing group; however, the difference was statistically nonsignificant (28.1% vs. 12.7%, p=0.06). We observed a significant intergroup difference in patients who were administered guselkumab at baseline (12 [21.8%] vs. 0 [0.0%], p=0.01). Conclusion This study showed that compared with regular dosing intervals, irregular dosing intervals of biologics were associated with high rates of switching of these agents, although we observed no statistically significant differences with regard to PASI scores. Therefore, it is important to adhere to the standard dosing schedule prescribed for biologics, and guselkumab may improve patient compliance.

BACKGROUND AND OBJECTIVES: The effect of palliative injection laryngoplasty in cancer-related unilateral vocal cord paralysis patients on voice and swallowing function is uncertain and there are few previous studies of its suitability, benefits as a palliative treatment option. The purpose of this study is to confirm the objective results of voice and swallowing function after palliative office-based hyaluronic acid injection laryngoplasty in cancer-related unilateral vocal cord paralysis patients. MATERIALS AND METHOD: 36 patients who had unilateral vocal cord paralysis from non-thyroidal, extralaryngeal neoplasms were included in this study. To evaluate the clinical outcome, we analyzed perceptual GRBAS grading, acoustic analysis, aerodynamic study, Electroglottography (EGG), Voice Handicap Index (VHI-30) about voice function and disability rating scale (DRS), gastric tube dependency, aspiration pneumonia about swallowing function and 36-Item Short Form Survey version 2 (SF-36v2) about quality of life. RESULTS: In GRBAS scale, G (p < 0.001), R (p=0.004), B (p=0.001), A (p=0.011), and S (p=0.007) showed significant improvement. Jitter, shimmer, speaking fundamental frequency, maximal phonation time, VHI-30, DRS score, gastric tube dependency, aspiration pneumonia, and SF-36v2 were significantly improved after injection (p=0.016, p=0.011, p=0.045, p=0.005, p < 0.001, p < 0.001 p=0.003, p < 0.001, and p < 0.001 respectively). CONCLUSION: From this study we concluded office-based hyaluronic acid injection can be used as a useful palliative treatment option in cancer-related ill patients with unilateral vocal cord paralysis. Palliative hyaluronic acid injection laryngoplasty avoids the need for tube feeding, thus reducing the risk of aspiration pneumonia. These outcomes are accompanied by significant improvement in voice quality.
Acoustics ; Deglutition ; Enteral Nutrition ; Humans ; Hyaluronic Acid ; Laryngoplasty ; Methods ; Palliative Care ; Phonation ; Pneumonia, Aspiration ; Quality of Life ; Vocal Cord Paralysis ; Voice ; Voice Quality

BACKGROUND/AIMS: The use of extracorporeal membrane oxygenation (ECMO) is spreading rapidly, with successful procedures reported in the ECMO for Severe Adult Respiratory failure (CESAR) trial and treatment of the H1N1 pandemic. However, ECMO is associated with a high mortality rate. This study aimed to show that increased experience and improved teamwork through education may reduce the mortality rate associated with ECMO. METHODS: A retrospective study was performed. Data were collected from January 1, 2009, to December 31, 2011. The data were divided into two periods: 2009/2010 (period 1) and 2011 (period 2). The protocol and training program were applied during period 2. RESULTS: Seventy-six patients were included. The most common disease requiring ECMO support was pneumonia (43.4%). ECMO was applied within 7 days in 76.3% of patients. The primary outcomes, such as Intensive Care Unit (ICU) and hospital mortality rates, were higher during period 1 (91.3%) than period 2 (66.7%, p = 0.013). A multivariate analysis revealed that ECMO weaning failure was the only factor associated with ICU and hospital mortality (ICU mortality: hazard ratio [HR], 11.349; 95% confidence interval [CI], 1.281 to 100.505; p = 0.029; hospital mortality: HR, 17.976; 95% CI, 2.263 to 142.777; p = 0.006). CONCLUSIONS The mortality rate associated with the ECMO procedure decreased following the ECMO training program. However, applying the training program to ECMO management is not an independent factor for the mortality rate. Further studies should be performed to help reduce the mortality rate associated with ECMO.