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Chin-Yi Yang,1,2,&ast; Ya-Ching Chang,2,&ast; Hao-Chih Tai,3 Yi-Hua Liao,4 Yu-Huei Huang,2 Rosaline Chung-Yee Hui,2 Yuan-Sung Kuo,3 Shyue-Yih Horng,3 Yi-Shuan Sheen,4 Tim-Mo Chen,5 Yuan-Sheng Tzeng,5 Chih-Hsin Wang,5 Shou-Cheng Teng,5 Chun-Kai Oscar Chang,5 Chang-Yi Chou5 1Department of Dermatology, New Taipei Municipal TuCheng Hospital, New Taipei City, 236, Taiwan; 2Department of Dermatology, Linkou Chang-Gung Memorial Hospital, Taoyuan, 333, Taiwan; 3Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 100, Taiwan; 4Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 100, Taiwan; 5Division of Plastic Surgery, Tri-Service General Hospital, Taipei, 100, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hao-Chih Tai, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Road, Zhongzheng Dist, Taipei, 100225, Taiwan, Tel +886 2 2312-3456&num;65062 65520, Email taihc1@gmail.com; taihc@ntu.edu.tw Yi-Hua Liao, Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Road, Zhongzheng Dist, Taipei, 100225, Taiwan, Tel +886 2 2312-3456&num; 265317, Email yihualiao@ntu.edu.twPurpose: Porcine-based dermal injectable collagen is effective for nasolabial fold correction. In the present study, a new dermal injectable collagen, incorporating a novel cross-linking technology and premixed with lidocaine, was introduced. The study aimed to determine the efficacy of the new dermal injectable collagen in improving bilateral nasolabial fold wrinkles, and reducing pain during injection.Patients and Methods: This prospective, double-blind, multicenter, parallel-group, randomized trial enrolled participants with moderate-to-severe bilateral nasolabial fold wrinkles from February 2019 to March 2021. Participants were randomly assigned to the test group (new dermal injectable collagen with lidocaine featuring a novel cross-linking technology) or control group (traditionally cross-linked dermal injectable collagen with lidocaine). Participants were monitored for adverse events (AEs), and for pain using the Thermometer Pain Scale (TPS) and a visual analog scale (VAS). Efficacy was measured using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS).Results: On the poor or better sides, the 2 groups exhibited a significant decrease in WSRS scores at 4, 12, 24, and 36 weeks after treatment, compared to baseline WSRS scores (all, p < 0.05). Compared to the control group, the test group had a greater decrease in WSRS score (poor or better sides) at 12, 24, 36, and 52 weeks after treatment (all, p < 0.05). A similar observation was also found in the WSRS response rate and GAIS score of the 2 groups. VAS and TPS scores were not significantly different between the 2 groups (p > 0.05), indicating that pain reduction was similar in the 2 groups. All AEs were anticipated AEs associated with facial aesthetic injections, and most recovered within 0 to 30 days without sequelae. There were no differences in AEs between the 2 groups (all, p > 0.05).Conclusion: The new dermal injectable collagen with lidocaine exhibited better efficacy for correcting nasolabial fold wrinkles compared to the control group. Both relieved pain and produced only transient and tolerable AEs.Keywords: adverse event, bilateral nasolabial folds, dermal filler, pain, porcine collagen, wrinkles

Rationale and Objectives: Application of a previously developed model-based algorithm on hyperpolarized (HP) (3)He magnetic resonance (MR) dynamic projection images of phantoms was extended to investigate the utility of HP (3)He MR imaging (MRI) in quantifying airway caliber changes associated with asthma.Materials and Methods: Airways of seven volunteers were imaged and measured using HP (3)He MRI and multidetector-row computed tomography (MDCT) before and after a methacholine (MCh) challenge. MDCT data were obtained at functional residual capacity and 1 L above functional residual capacity.Results: Comparison of the resultant data showed that HP (3)He MRI did not match MDCT in measuring the ratios of airway calibers before and after the MCh challenge in 37% to 43% of the airways from the first six generations at the two lung volumes tested. However, MDCT did yield the observation that 49% to 69% of these airways displayed bronchodilation following MCh challenge.Conclusion: The current implementation of HP (3)He MRI did not match the MCh-induced postchallenge-to-prechallenge airway caliber ratios as measured with MDCT. Elevated parenchymal tethering due to bronchoconstriction-induced hyperinflation was proposed as a possible explanation for this airway dilation. [ABSTRACT FROM AUTHOR]

The experience of pain is complex, involving both sensory and affective components, yet the underlying neural mechanisms remain elusive. Here, we show that formalin-induced pain behaviors coincide with increased responses in glutamatergic neurons within the anterior paraventricular nucleus of the thalamus (PVA). Furthermore, we describe non-overlapping subpopulations of PVAVgluT2 neurons involved in sensory and affective pain processing, whose activity varies across different pain states. Activating PVA glutamatergic neurons is sufficient to induce mechanical hypersensitivity and aversion behaviors, whereas suppression ameliorates formalin-induced pain. Furthermore, we identify the segregation of PVA VgluT2 projections to the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc), each influencing specific aspects of pain-like behavior. This finding provides an important insight into the mechanism of distinct components of pain, highlighting the pivotal role of PVA in mediating different aspects of pain-like behavior with distinct circuits., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To share our 20-year experience in major burn management and the impact of a newly implemented burn protocol since 2015 at Tri-Service General Hospital (TSGH)., Materials and Methods: We performed a retrospective cohort study of severely burned patients who were admitted to the intensive care unit (ICU) at TSGH from January 2003 to September 2023. Data regarding demographics, complications, and mortality were collected and analyzed. We compared the patient data before (pre-implementation) and after 2015 (post-implementation), when the new major burn management protocol was introduced., Results: No statistically significant differences were observed in the mean total body surface area of the burns between the groups. The post-implementation group had younger age (34.62 vs 45.06, P < 0.001) and lower rate of inhalation injury (60.8 % vs 82.5 %, P = 0.005). No statistically significant difference was observed in the ICU stays between the groups. The post-implementation group had a statistically significant lower all-cause mortality (8.1 % vs 47.6 %, P < 0.0001) and lower rate of renal replacement therapy (RRT) (20.3 % vs 42.9 %, P = 0.004) but earlier initiation of RRT., Conclusion: The new TSGH Burns Protocol revolutionized the care of major burns by introducing tailored, multidisciplinary burn management and improved patient outcomes., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interests for this article., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Background: Hypersensitivity to the new dermal injectable porcine-based collagen with lidocaine featuring a novel cross-linking technology (test filler) for nasolabial fold correction was compared to the commercially available traditional cross-linked dermal injectable porcine-based collagen with lidocaine (control filler). Methods: Recruited participants (n = 279) received a single 0.1 mL intradermal injection of either test filler or control filler in the left forearm as a screening skin allergy test. Injection sites were assessed clinically at 24 h post-implant. Treatment was given to 252 successfully screened participants, and injection sites were monitored for 21 days. Immunological examinations were performed at screening and then at 4 and 24 weeks post-treatment. Observations for adverse events continued until the 52nd week. Results: Intradermal allergy testing results were negative for all the test recipients (0/124) and positive for two control recipients (2/132, 1.5%). Most of the participants exhibited no changes in serum immunoglobulin (IgG, IgM) and complement (C3, C4) levels. No serious adverse events related to the device were recorded. Most adverse events were common complications of dermal filler treatment and were related to the injection site. Most adverse effects were resolved or under control by 52 weeks. Conclusions: Hypersensitivity reactions with the test filler were lower than those with the control filler, validating the safe use of test filler for nasolabial fold correction without the need for pretreatment skin testing.

Background: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF., Methods: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan. Clinical manifestations were retrieved from electronic medical records, and findings on ophthalmologic examination and magnetic resonance images (MRIs) were reviewed., Results: A total of 102 patients (71 F/31 M, mean age 33.4 ± 12.2 years, mean CSF pressure 282.5 ± 74.5 mm CSF) were identified, including 46 (45.1%) with obesity (body-mass index ≥ 27.5), and 57 (62.6%) with papilledema. Overall, 80 (78.4%), 55 (53.9%), 51 (50.0%), and 58 (56.9%) patients met the Second and Third Edition of International Classification of Headache Disorders, Friedman, and Korsbæk criteria, respectively. Patients in the 200-250 mm CSF group (n = 40) were less likely to have papilledema (48.5% vs. 70.7%, p = 0.035), transient visual obscuration (12.5% vs. 33.9%, p = 0.005), and horizontal diplopia (10.0% vs. 30.6%, p = 0.006), and had fewer signs on MRIs (2.2 ± 1.3 vs. 2.8 ± 1.0, p = 0.021) when compared with those with CSF pressures > 250 mm CSF (n = 62). However, the percentages of patients with headache (95.0% vs. 87.1%, p = 0.109) at baseline, chronic migraine at six months (31.6% vs. 25.0%, p = 0.578), and visual field defect (86.7% vs. 90.3%, p = 0.709) were similar., Conclusions: It was found that obesity and papilledema were less common in Asian IIH patients when compared with Caucasian patients. Although patients with CSF pressures of 200-250 mm CSF had a less severe phenotype, the risks of having headache or visual loss were comparable to those in the > 250 mm CSF group. It is possible that a diagnostic cutoff of > 200 mm CSF could be more suitable for Asians, although further studies are still needed., (© 2024. The Author(s).)

Objective: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients., Methods: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS)., Results: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs., Conclusions: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The Taiwan Society of Cardiology (TSOC) and Taiwan Society of Plastic Surgery (TSPS) have collaborated to develop a joint consensus for the management of patients with advanced vascular wounds. The taskforce comprises experts including preventive cardiologists, interventionists, and cardiovascular and plastic surgeons. The consensus focuses on addressing the challenges in diagnosing, treating, and managing complex wounds; incorporates the perfusion evaluation and the advanced vascular wound care team; and highlights the importance of cross-disciplinary teamwork. The aim of this joint consensus is to manage patients with advanced vascular wounds and encourage the adoption of these guidelines by healthcare professionals to improve patient care and outcomes. The guidelines encompass a range of topics, including the definition of advanced vascular wounds, increased awareness, team structure, epidemiology, clinical presentation, medical treatment, endovascular intervention, vascular surgery, infection control, advanced wound management, and evaluation of treatment results. It also outlines a detailed protocol for assessing patients with lower leg wounds, provides guidance on consultation and referral processes, and offers recommendations for various wound care devices, dressings, and products. The 2024 TSOC/TSPS consensus for the management of patients with advanced vascular wounds serves as a catalyst for international collaboration, promoting knowledge exchange and facilitating advancements in the field of advanced vascular wound management. By providing a comprehensive and evidence-based approach, this consensus aims to contribute to improved patient care and outcomes globally., Competing Interests: All the authors declare no conflict of interest.

Introduction: The injectable skin fillers available for soft tissue augmentation are constantly growing, providing esthetic surgeons with more options in the treatment of scars, lines, and wrinkles. Hyaluronic acid (HA)-derived injectable fillers are ideal to reduce the appearance of nasolabial folding. This study investigated the efficacy and safety of the commercially available HA filler from Maxigen Biotech Inc. (MBI-FD) in the treatment of nasolabial folds (NLFs)., Methods: We analyzed 1,4-butanediol diglycidyl ether (BDDE) residues and injection force test and observed the protein content in MBI-FD, and then was cultured in fibroblast L929 cells and examined for cytotoxicity. Finally, 95 healthy participants underwent dermal filler injection therapy to evaluate the efficacy and safety for 24 and 52 weeks, respectively., Results: BDDE residues in MBI-FD was <0.125 µg/mL. MBI-FD was fitted using 27- and 30-G injection needles with an average pushing force of 14.30 ± 2.07 and 36.43 ± 3.11 N, respectively. Sodium hyaluronate protein in MBI-FD was 7.19 µg/g. The cell viabilities of 1× and 0.5× MBI-FD were 83.25% ± 3.58% and 82.23% ± 1.85%, respectively, indicating MBI-FD had no cytotoxicity, and decreased NLF wrinkles with no serious adverse events., Conclusion: MBI-FD is an effective filler for tissue augmentation of the NLFs and may be a suitable candidate as an injectable dermal filler for tissue augmentation in humans in the future.

Dacarbazine (DTIC) is the primary first-line treatment for advanced-stage metastatic melanoma; thus, DTIC resistance is poses a major challenge. Therefore, investigating the mechanism underlying DTIC resistance must be investigated. Dicer, a type III cytoplasmic endoribonuclease, plays a pivotal role in the maturation of miRNAs. Aberrant Dicer expression may contribute to tumor progression, clinical aggressiveness, and poor prognosis in various tumors. Dicer inhibition led to a reduction in DTIC sensitivity and an augmentation in stemness in melanoma cells. Clinical analyses indicated a low Dicer expression level as a predictor of poor prognosis factor. Metabolic alterations in tumor cells may interfere with drug response. Adenylosuccinate lyase (ADSL) is a crucial enzyme in the purine metabolism pathway. An imbalance in ADSL may interfere with the therapeutic efficacy of drugs. We discovered that DTIC treatment enhanced ADSL expression and that Dicer silencing significantly reduced ADSL expression in melanoma cells. Furthermore, ADSL overexpression reversed Dicer silencing induced DTIC resistance and cancer stemness. These findings indicate that Dicer-mediated ADSL regulation influences DTIC sensitivity and stemness in melanoma cells.

Objective: The present study aimed to compare sex differences in the clinical manifestations related to dependence behaviors in medication-overuse headache (MOH)., Methods: Consecutive patients with newly diagnosed chronic migraine (CM) with and without MOH based on the Third Edition of International Classification of Headache Disorders (ICHD-3) were enrolled prospectively from the headache clinic of a tertiary medical center. Demographics and clinical profiles were collected by using a questionnaire, which included current use of tobacco, alcohol, and caffeinated beverages, the Leeds Dependence Questionnaire (LDQ), the Severity of Dependence Scale (SDS), the Headache Impact Test-6 (HIT-6), and the Pittsburgh Sleep Quality Index (PSQI)., Results: In total, 1419 CM patients (1135F/284 M, mean age 41.7 ± 13.9 years) were recruited, including 799 with MOH (640F/159 M, mean age 42.5 ± 13.2 years) (56.3%). Smoking was associated with an increased risk for MOH in men (odds ratio [OR] = 3.60 [95% confidence interval = 1.73-7.50], p = 0.001), but not in women (OR = 1.34 [0.88-2.04], p = 0.171) (p = 0.021 for interaction). Hypnotic use ≥ 3 days/week was a risk factor for MOH (OR = 2.55 [95% confidence interval = 2.00-3.24], p < 0.001), regardless of sex. By using receiver operating characteristics (ROC) curves, the cutoff scores of the LDQ for MOH were determined at 7 for women and 6 for men, and those for the SDS were 5 and 4, respectively (area under curve all ≥ 0.83). Among patients with MOH, the male sex was associated with a shorter latency between migraine onset and CM onset (12.9 ± 11.1 vs. 15.4 ± 11.5 years, p = 0.008), despite less average headache intensity (6.7 ± 1.9 vs. 7.2 ± 1.9, p = 0.005), functional impacts (HIT-6: 63.4 ± 8.3 vs. 65.1 ± 8.0, p = 0.009), and sleep disturbances (PSQI: 10.9 ± 4.4 vs. 12.2 ± 4.3, p = 0.001)., Conclusions: The current study identified an association between smoking and MOH in men, as well as sex-specific cutoffs of the LDQ and the SDS, for MOH. MOH was characterized by a shorter latency between migraine onset and CM onset in men and a more severe phenotype in women. Sex should be considered as an important factor in the evaluation of MOH., (© 2023. The Author(s).)

Recurrence of pressure ulcers following reconstructive surgery occurs frequently, causing a significant burden on the patient and the public health care system. We assessed risk factors for the recurrence of pressure ulcers based on the experience of a single surgeon at our medical centre. We retrospectively analysed patients admitted to our medical centre with stage III and IV pressure ulcers who underwent reconstructive surgery. The hospital database was searched for patients diagnosed with pressure ulcers who underwent reconstructive surgery. Patient characteristics analysed included age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, duration of hospital stay, and wound complications. Recurrence and mortality rates were retrospectively examined. One hundred and eighty-nine patients were enrolled, and 166 patients with 176 pressure ulcers met our inclusion criteria. All 14 recurrences (7.95%) were followed for at least 1 year. Logistic regression analysis indicated that recurrence was associated with albumin levels (P = 0.001) and wound size (P = 0.043); however, no association was found for body mass index, bacterial profile, comorbidities, localisation, previous surgery, operation time, or time to admission for reconstruction. In conclusion, higher albumin levels were associated with lower recurrence rates in patients who underwent reconstructive surgery., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: This study evaluated tissue adhesives in comparison to sutures for treating facial lacerations in children., Methods: We retrospectively analyzed data from September 2017 to August 2022 involving pediatric facial lacerations managed with either tissue adhesives or sutures., Results: Among 50 children, 20 received tissue adhesives, and 30 received sutures. Both methods showed comparable outcomes in terms of wound complications such as dehiscence (adjusted odds ratio = 1.56, 95% CI = 0.08-31.25) and infection (adjusted odds ratio = 2.17, 95% CI = 0.08-58.80). The cosmetic outcomes, assessed using the Hollander Wound Evaluation Score, were also consistent between groups (adjusted beta = -0.55, 95% CI = -1.15-0.05). Notably, those treated with tissue adhesives reported greater satisfaction (adjusted beta = 1.13, 95% CI = 0.63 -1.63) and experienced significantly less pain (adjusted beta = -3.03, 95% CI = -4.15--1.90)., Conclusions: Both techniques displayed similar rates of infection, dehiscence, and cosmetic outcomes. However, tissue adhesives were associated with increased patient comfort, especially in terms of reduced pain and greater satisfaction.

Necrotizing fasciitis is a surgically diagnosed infection of the deep soft tissues that results in high mortality. It is usually caused by aerobic and anaerobic bacteria and group A Streptococcus . Metallosis is characterized by the deposition of metal debris in the blood that causes metal poisoning and tissue damage. The abrasion of metal components that occurs after joint replacements causes metallosis, which may lead to severe complications. We report a rare case of metallosis-induced necrotizing fasciitis of the right thigh. Metallosis should be considered as a cause of necrotizing fasciitis if the patient has had a joint replacement surgery.

The reconstruction of defects of the lateral malleolus involving the exposed fibular bone or tendon is challenging. This study aimed to evaluate the clinical application of the peroneal artery perforator flap with or without split-thickness skin grafting for soft tissue reconstruction of the bony defect of the lateral malleolus of the ankle joints. Reconstruction using a peroneal artery perforator flap with or without split-thickness skin grafting was performed for 15 patients (10 men, 5 women) between January 2007 and December 2018. The mean age was 53.7 years, and the mean size of the flaps was 40 cm 2 . The flaps were elevated in the form of a perforator flap, and split-thickness skin grafting was performed over the flaps and adjoining raw areas. The flaps survived in all cases; however, partial necrosis was observed in 3 cases. In cases of small-sized defects of the lateral malleolus of the ankle joints where a flap is required for the exposed bone or tendon, reconstruction using the peroneal artery perforator flap is advantageous, since the morbidity rate of the donor site is low and soft tissue is reconstructed.

Full-thickness skin grafting plays an important role in facial reconstruction for excessive skin defects or possible eye, nose, or lip distortion after a malignant tumor excision. For esthetic consideration, full-thickness skin grafts of the retroauricular region can be used, but the amount of skin is limited. The skin of the submental triangle has similar cutaneous features and provides a large graft. We aimed to evaluate the feasibility of using full-thickness skin grafts harvested from the submental triangle to reconstruct facial skin defects. We retrospectively analyzed 14 cases treated at a single institution to evaluate the clinical and esthetic outcomes, and patients' satisfaction. During 6-24 months of follow-up, the wounds healed with well-matched color, texture, and contour. No obvious hypertrophies or distortions were observed. Additionally, the removal of redundant submental triangle skin resulted in the secondary gain of double chin reduction. All patients were satisfied with the appearance of both donor and recipient sites. In conclusion, the submental triangle is a good possible option for full-thickness skin grafts used to resurface facial skin defects. Using this approach, both donor and recipient sites can achieve satisfactory esthetic outcomes.

Patients bitten by Protobothrops mucrosquamatus typically experience significant pain, substantial swelling, and potentially blister formation. The appropriate dosage and efficacy of FHAV for alleviating local tissue injury remain uncertain. Between 2017 and 2022, 29 snakebite patients were identified as being bitten by P. mucrosquamatus . These patients underwent point-of-care ultrasound (POCUS) assessments at hourly intervals to measure the extent of edema and evaluate the rate of proximal progression (RPP, cm/hour). Based on Blaylock's classification, seven patients (24%) were classified as Group I (minimal), while 22 (76%) were classified as Group II (mild to severe). In comparison to Group I patients, Group II patients received more FHAV (median of 9.5 vials vs. two vials, p -value < 0.0001) and experienced longer median complete remission times (10 days vs. 2 days, p -value < 0.001). We divided the Group II patients into two subgroups based on their clinical management. Clinicians opted not to administer antivenom treatment to patients in Group IIA if their RPP decelerated. In contrast, for patients in Group IIB, clinicians increased the volume of antivenom in the hope of reducing the severity of swelling or blister formation. Patients in Group IIB received a significantly higher median volume of antivenom (12 vials vs. six vials; p -value < 0.001) than those in Group IIA. However, there was no significant difference in outcomes (disposition, wound necrosis, and complete remission times) between subgroups IIA and IIB. Our study found that FHAV does not appear to prevent local tissue injuries, such as swelling progression and blister formation, immediately after administration. When administering FHAV to patients bitten by P. mucrosquamatus , the deceleration of RPP may serve as an objective parameter to help clinicians decide whether to withhold FHAV administration.

Dependence behaviors are common in patients with medication-overuse headache (MOH). This prospective study aimed to characterize dependence behaviors in MOH by using Leeds dependence questionnaire (LDQ), and to determine the clinical utility of LDQ in the diagnosis of MOH. In total, 563 consecutive chronic migraine (CM) patients (451F/112M, mean age 41.7 ± 12.0 years) were recruited, including 320 with MOH (56.8%) (254F/66M, mean age 42.3 ± 11.6 years). LDQ scores were positively correlated with the monthly frequency of acute medication use (Spearman's rho = 0.680, p < 0.001). When compared with patients without, those with MOH scored higher on LDQ (13.0 ± 7.6 vs. 3.9 ± 5.1, p < 0.001). By using a receiver operating characteristics curve, the cutoff value of LDQ was determined at 7 (sensitivity = 77.5%, specificity = 77.4%, area under curve = 0.85) for a diagnosis of MOH. An LDQ score of ≥7 was predictive of MOH (odds ratio = 11.80, 95% confidence interval = 7.87-17.67, p < 0.001). In conclusion, the presence of MOH in patients with CM is associated with more severe dependence behaviors. An LDQ score of ≥7 is useful in the detection of MOH in CM patients.

Background: Both inhalation injury and acute respiratory distress syndrome (ARDS) are risk factors that predict mortality in severely burned patients. Extracorporeal life support (ECLS) is widely used to rescue these patients; however, its efficacy and safety in this critical population have not been well defined. We report our experience of using ECLS for the treatment of severely burned patients with concurrent inhalation injury and ARDS., Methods: This was a retrospective analysis of 14 patients collected from a single medical burn center from 2012 to 2019. All patients suffered from major burns with inhalation injury and ARDS, and were treated with ECLS., Results: The median total body surface area of deep dermal or full thickness burns was 94.5%, ranging 47.7-99.0 %. The median revised Baux score was 122.0, ranging 90.0-155.0. All patients developed ARDS with a median partial pressure of arterial oxygen to a fraction of inspired oxygen ratio of 61.5, ranging 49.0-99.0. Indications for ECLS included sustained hypoxemia and unstable hemodynamics. The median interval for initiating ECLS was 2.5 days, ranging 1.0-156.0 days. The median duration of ECLS was 2.9 days, ranging 0.3-16.7 days. The overall survival to discharge was 42.8%. Causes of death included sepsis and multiple organ failure. ECLS-related complications included cannulation bleeding, catheter-related infection, and hemolysis. The incidence of risk factors reported in literature were higher in non-survivors, including Baux>120, albumin < 3.0 g/dL, and lactate > 8 mmol/L., Conclusions: For severely burned patients with concurrent inhalation injury and ARDS, ECLS could be a salvage treatment to improve sustained hypoxemia. However, the efficacy of hemodynamic support was limited. Identifying definite ECLS indications and rigorous patient selection would contribute to better clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

In the past decade, single-cell technologies have revealed the heterogeneity of the tumor-immune microenvironment at the genomic, transcriptomic, and proteomic levels and have furthered our understanding of the mechanisms of tumor development. Single-cell technologies have also been used to identify potential biomarkers. However, spatial information about the tumor-immune microenvironment such as cell locations and cell-cell interactomes is lost in these approaches. Recently, spatial multi-omics technologies have been used to study transcriptomes, proteomes, and metabolomes of tumor-immune microenvironments in several types of cancer, and the data obtained from these methods has been combined with immunohistochemistry and multiparameter analysis to yield markers of cancer progression. Here, we review numerous cutting-edge spatial 'omics techniques, their application to study of the tumor-immune microenvironment, and remaining technical challenges., (© 2022. The Author(s).)

The development of targeted therapy has improved treatment outcomes for patients with non-small cell lung cancer (NSCLC). However, paronychia, a common adverse effect of targeted therapy, remains burdensome. Although conservative treatments for paronychia have been well reported in the literature, studies on the efficacy of surgical partial matricectomy for paronychia, are scarce. This study aimed to evaluate the effect of surgical partial matricectomy in targeted therapy-induced paronychia in patients with NSCLC. This retrospective cohort study included 11 patients with a total of 18 lesions on the big toes. Data on lung cancer stages, types and duration of targeted therapy, onset of paronychia, pain scale scores, conservative treatments, course of matricectomy, paronychia-free interval after matricectomy, and wound condition were collected from medical records. The Wilcoxon signed-rank test was used for analysis. The mean pain scale score after matricectomy was significantly lower than that after conservative treatments (1.00 ± 0.00 vs 2.94 ± 0.87; P < .001) and before treatment (1.00 ± 0.00 vs 3.06 ± 0.80; P < .001). The mean duration of matricectomy was significantly shorter than that of conservative treatments (3.22 ± 1.00 vs 56.56 ± 52.29 weeks; P < .001). Surgical partial matricectomy is an effective and enduring intervention for targeted therapy-related paronychia. It provides a shorter course of treatment, reduced pain, and improved appearance of the healed wound. Furthermore, surgical partial matricectomy could result in a better quality of life during targeted therapy than that of conservative treatments., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives . Lymph node status is the most important prognostic factor in cutaneous melanoma patients. Recent studies showed that indocyanine green (ICG) fluorescence lymphography helps locating sentinel nodes better. Sometimes, flap reconstruction is needed after wide excision of tumor. Indocyanine green fluorescence also simplifies the intraoperative design of flaps. This study investigates the use of ICG fluorescence in patients with cutaneous melanoma during operation. Methods . We performed a single-center, retrospective study of subjects with cutaneous melanoma using ICG lymphograhy and/or angiography during wide excision of tumor between 2015 and 2019. Patients received a dermal injection of ICG and patent blue (PB) dye. The positive node was excised. Indocyanine green angiography was utilized to visualize better skin paddle during flap reconstruction if needed. Results . A total of 37 sentinel lymph nodes (SLNs) were removed in 12 patients. Indocyanine green successful localization was found in 10 of the 12 patients (83%). Three patients were found with 6 metastatic nodes on final pathology. 100% of these 6 nodes were identified by ICG, while 83% (5/6) were positive PB. Three of the 12 patients received flap reconstruction after operation, and no major complications occurred. Conclusions . ICG dye lymphangiography is a good alternative for locating SLNs in patients with melanoma. It could also visualize well perfusion skin paddle during reconstruction. We reported a reproducible and simple method to utilize ICG fluorescence in cutaneous melanoma patients.

Diabetes-related lower extremity amputations are an enormous burden on global health care and social resources because of the rapid worldwide growth of the diabetic population. This research aimed to determine risk factors that predict major amputation and analyse the time interval from first hospitalisation to amputation by using standard management protocols and Kaplan-Meier survival curves. Data from 246 patients with diabetes mellitus and diabetic foot ulcers from the Division of Plastic and Reconstructive Surgery of the Department of Surgery at XXX Hospital between January 2016 and May 2020 were analysed. Univariate and multivariate analyses of 44 potential risk factors, including invasive ulcer depth and C-reactive protein levels, showed statistically significant differences for those at increased risk for major amputation. The median time from hospitalisation to lower extremity amputation was approximately 35 days. Most patients with abnormal C-reactive protein levels and approximately 70% of patients with ulcers invading the bone were at risk for lower extremity amputations within 35 days. Therefore, invasive ulcer depth and C-reactive protein levels are significant risk factors. Other potential risk factors for major amputation and the time intervals from first hospitalisation to amputation should be analysed to establish further prediction strategies., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Background: The role of the NOTCH3 p.R544C variant, the predominant variant of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in multiple East Asian regions, in migraine is unknown., Methods: Migraine patients (n = 2,884) (2,279F/605M, mean age 38.8 ± 11.7 years), including 324 (11.2%) with migraine with aura, were prospectively enrolled by headache specialists according to the International Classification of Headache Disorders criteria. These patients and 3,502 population controls free of stroke, dementia, and headache were genotyped for NOTCH3 p.R544C by TaqMan genotyping assay or Axiom Genome-Wide TWB 2.0 Array. Clinical manifestations and brain magnetic resonance images were examined and compared between migraine patients with and without NOTCH3 p.R544C., Results: Thirty-two migraine patients (1.1%) and 36 controls (1.0%) harbored the p.R544C variant, and the percentages were comparable among migraine patients without and with aura, and controls (1.2%, vs. 0.6% vs. 1.0%, p = 0.625). Overall, migraine patients with and without the p.R544C variant had similar percentages of migraine with aura, headache characteristics, frequencies and disabilities. However, those with p.R544C were less likely to have pulsatile headaches (50.0% vs. 68.2%, p = 0.028), and more likely to have moderate to severe white matter hyperintensities in the external capsule (18.8% vs. 1.2%, p = 0.006) and anterior temporal lobe (12.5% vs. 0%, p = 0.008)., Conclusions: Our findings suggest that NOTCH3 p.R544C does not increase the risk of migraine with aura, or migraine as a whole, and generally does not alter clinical manifestations of migraine. The role of NOTCH3 variants, as well as potential influences from ethnicity or modifier genes, in migraine needs to be further clarified.

Background: Diabetic foot and leg ulcers are a major cause of disability among patients with diabetes mellitus. A topical gel called ENERGI-F703, applied twice daily and with adenine as its active pharmaceutical ingredient, accelerated wound healing in diabetic mice. The current study evaluated the safety and efficacy of ENERGI-F703 for patients with diabetic foot and leg ulcers., Methods: This randomized, double-blind, multicenter, phase II trial recruited patients from eight medical centers in Taiwan. Patients with intractable diabetic foot and leg ulcers (Wagner Grade 1-3 without active osteomyelitis) were randomly assigned (2:1) to receive topical ENERGI-F703 gel or vehicle gel twice daily for 12 weeks or until complete ulcer closure. The investigator, enrolled patients and site personnel were masked to treatment allocation. Intention to treat (ITT) population and safety population were patient to primary analyses and safety analyses, respectively. Primary outcome was complete ulcer closure rate at the end of treatment. This trial is registered with ClinicalTrials.gov, number NCT02672436., Findings: Starting from March 15 th , 2017 to December 26 th , 2019, 141 patients were enrolled as safety population and randomized into ENERGI-F703 gel (n = 95) group or vehicle gel (n = 46) group. In ITT population, ENERGI-F703 (n = 90) and vehicle group showed ulcer closure rates of 36.7% (95% CI = 26.75% - 47.49%) and 26.2% (95% CI = 13.86% - 42.04%) with difference of 9.74 % (95 % CI = -6.74% - 26.23%) and 25% quartiles of the time to complete ulcer closure of 69 days and 84 days, respectively. There were 25 (26.3%) patients in ENERGI-F703 group and 11 (23.9%) patients in vehicle group experiencing serious adverse events and five deaths occurred during the study period, none of them related to the treatment., Interpretation: Our study suggests that ENERGI-F703 gel is a safe and well-tolerated treatment for chronic diabetic foot and leg ulcers. Further studies are needed to corroborate our findings in light of limitations., Funding: Energenesis Biomedical Co., Ltd., Competing Interests: This project was sponsored by Energenesis Biomedical Co. Ltd. Han-Min Chen, Jiun-Tsai Lin, Yi-Fang Cheng, Guang-Huar Young, Chun-Fang Huang, Ya-Chun Kuo are current employees of Energenesis Biomedical Co., Ltd. All other authors have no conflicts of interest to declare., (© 2022 The Authors.)

Objective: To investigate the distribution, clinical associations, and treatment responses for the most bothersome symptoms of migraine in a large sample of patients with migraine in Taiwan., Background: The most bothersome symptom is recently recommended as a co-primary endpoint in clinical trials of acute treatment of migraine. However, most clinical trials and observational studies have been conducted in the United States and Europe, with photophobia representing the most common most bothersome symptom., Methods: Patients who were newly diagnosed with migraine by headache specialists in Taipei Veterans General Hospital were recruited. All participants completed a questionnaire for headache profile, including the most bothersome symptom. Clinical associations of the most bothersome symptoms and response rates to previous acute treatments were analyzed., Results: Among the recruited 1188 patients with migraine (female 79.4%, mean age 39.0 ± 12.1 years) in this cross-sectional study, nausea (n = 729/1188, 61.4%) was the most common symptom that was most bothersome, followed by phonophobia (n = 280/1188, 23.6%), and photophobia (n = 122/1188, 10.3%). The frequency ranking was the same regardless of sex and age. Compared to migraine without aura, migraine with aura was associated with photophobia (adjusted odds ratio [OR] = 2.97, 95% confidence interval [CI] 1.76-5.0, p < 0.001). Chronic migraine was associated with phonophobia (adjusted OR = 1.51, 95% CI 1.13-2.01, p = 0.005), but there was a lower chance for nausea (adjusted OR = 0.68, 95% CI 0.53-0.88, p = 0.004), as the most bothersome symptom. Patients with different most-bothersome symptoms responded similarly to previous acute treatments, with an overall response rate of 52.2% (n = 550/1053)., Conclusion: Patients with migraine in Taiwan reported a distinct ranking of the most bothersome symptom. However, the response rates of the most bothersome symptom and headache were similar, which supports the most bothersome symptom as an outcome measure for acute treatment of migraine. Further studies recruiting different populations are required to investigate regional differences in most bothersome symptoms., (© 2022 American Headache Society.)

This was the first study to analyse patients who sustained severe self-induced burns from this common Asian practice. There is a need to raise public awareness and physician attention about the consequences of preventable burn injuries and the importance of first aid in patients with diabetic neuropathy. Retrospective data on 16 consecutive patients who had diabetes and neuropathy admitted to the plastic surgery ward at the Tri-Service General Hospital from January 1, 2015, to February 2, 2021 with burn injuries because of heat applications were collected and analysed for this study. Age, gender, season, first aid adequacy, comorbidity, interventions, total body surface area (TBSA), degree of burn, aetiology, length of stay (LOS), and status at discharge were reviewed. The mean age of the 16 patients was 65.13 years. The most common burn aetiology was contact (50%), followed by scald (37.5%) and radiation burns (12.5%). TBSA burn averaged ± standard deviation 1.54 ± 1.22. Seven patients (44%) had wound infections, and three patients underwent amputations. The average LOS was 28.2 days. Asian practice of heat application is the common aetiology of severe and preventable burn injuries. Education about neuropathy and the consequences of a burn injury should be provided to patients with diabetes., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Background: In the management of major burn wounds, allogeneic skin transplantation is a critical procedure to improve wound repair. Our previous works found that intermittent exposure to carbon dioxide leads to permissive hypercapnia (HCA) and prolongs skin allograft survival. However, the modulatory effects of HCA exposure on the immune system are not well understood., Objectives: Our purpose was to investigate how intermittent exposure to HCA can effectively reduce the immune reaction to allogeneic skin graft rejection., Methods: A fully major histocompatibility complex-incompatible skin transplant from BALB/c to C57BL/6 mice model was utilized. Immune cells from splenic and draining lymph nodes were analyzed by flow cytometry. Serum proinflammatory cytokines were analyzed by ELISA., Results: Serum levels of IFN-γ, IL-2, IL-6, and TNF-α were significantly decreased in the HCA group. Additionally, the percentage of CD8+ cells in draining lymph nodes was significantly lower in HCA than in the control group. Moreover, the generation rate of FoxP3+ regulatory T cells (Tregs) from spleen naïve CD4+ T cells was increased by intermittent exposure to carbon dioxide. The infiltrated neutrophils were also eliminated by HCA. Taken together, we concluded that intermittent hypercapnia exposure could effectively suppress skin rejection by stimulating Treg cell generation and suppressing immune reactions.

Introduction: Fluoroquinolone exposure is reportedly associated with a higher risk of tendon disorders, tendonitis, or tendon rupture. However, studies in East Asian populations have not confirmed these risks in patients with comorbidities or concomitant medication use. This cohort study was designed to investigate the associations among fluoroquinolone exposure, comorbidities, medication use, and tendon disorders in Taiwan. Materials and Methods: This population-based, nationwide, observational, cohort study used data from the National Health Insurance Research database in Taiwan, a nationwide claims database that covers more than 99% of the Taiwanese population. The study period was from January 2000 to December 2015, and the median follow-up time was 11.05 ± 10.91 years. Patients who were exposed to fluoroquinolones for more than three consecutive days were enrolled, and patients without fluoroquinolone exposure who were matched by age, sex, and index year were enrolled as controls. The associations of comorbidities and concomitant medication use with tendon disorder occurrence were analyzed using Cox regression models. Results: The incidence of tendon disorders were 6.61 and 3.34 per 10 5 person-years in patients with and without fluoroquinolone exposure, respectively (adjusted hazard ratio, 1.423; 95% confidence interval [1.02,1.87]; p = 0.021). Sensitivity analyses yielded similar results. Patients under 18 and over 60 years with fluoroquinolone exposure; those with chronic kidney disease, diabetes, rheumatologic disease, cardiac disease, lipid disorder, or obesity; and those who concomitantly used statins, aromatase inhibitors, or glucocorticoids, had a significantly higher risk of tendon disorders. Conclusion: The long-term risk of tendon disorders was higher in patients with fluoroquinolone exposure than in those without fluoroquinolone exposure. Clinicians should assess the benefits and risks of fluoroquinolone use in patients at high risk of tendon disorders who require fluoroquinolone administration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chang, Chien, Hsu, Chiao, Chung, Tzeng, Huang, Ou, Wang, Chen and Wang.)

Background: Breast reconstruction is an integral part of breast cancer treatment, and implant-based breast reconstruction is the most commonly used method worldwide. However, there is still no technique that allows surgeons to predict the volume of the required implant. Although computed tomography and magnetic resonance imaging provide adequate representations of the breast, these procedures are time-consuming, expensive, and expose patients to radiation. Therefore, there is a need for safer, noninvasive alternatives for preoperative breast volume measurements., Patients and Methods: This study is a prospective review of 12 patients with early-stage breast cancer who underwent nipple-sparing mastectomy and immediate breast reconstruction with implants. Preoperatively, the Artec Eva 3D scanner was used to acquire volumetric measurements of the breasts. Intraoperatively, the volume of the mastectomy specimen was measured using the water displacement method. Correlations among the preoperative breast, mastectomy specimen, and estimated and final implant volumes were analyzed through Pearson correlation coefficient. A correction prediction factor of 85% was applied where necessary. Patient and physician satisfaction were evaluated 3 months postoperatively., Results: Our study found a statistically significant correlation between the preoperative breast volumes measured by the Artec Eva 3D scanner and intraoperative mastectomy specimen volumes (r = 0.6578). There was no correlation between the preoperative breast volumes and final implant volumes, mastectomy specimen volumes and final implant volumes, and estimated implant volumes and final implant volumes., Conclusions: Although the Artec Eva 3D scanner can offer relatively accurate measurement of breast volumes, multiple studies still need to be done to determine how these data can be applied to the mastectomy procedure and breast implant selection. It may be more applicable for preoperative planning in breast augmentation surgery. Future surgeons should also take into account that variabilities in natural breast size, tumor size, cancer stage, and in patient and physician preferences all influence the outcome of breast reconstruction surgery., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In this study, we aimed to analyze the clinical efficacy of closed-incision negative pressure wound therapy (CiNPWT) when combined with primary closure (PC) in a patient with pressure ulcers, based on one single surgeon's experience at our medical center., Methods: We retrospectively reviewed the data of patients with stage III or IV pressure ulcers who underwent reconstruction surgery. Patient characteristics, including age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, application of CiNPWT to reconstructed wounds, duration of hospital stay, and wound complications were analyzed., Results: Operation time (38.16 ± 14.02 vs. 84.73 ± 48.55 min) and duration of hospitalization (36.78 ± 26.92 vs. 56.70 ± 58.43 days) were shorter in the PC + CiNPWT group than in the traditional group. The frequency of debridement (2.13 ± 0.98 vs. 2.76 ± 2.20 times) was also lower in the PC + CiNPWT group than in the traditional group. The average reconstructed wound size did not significantly differ between the groups (63.47 ± 42.70 vs. 62.85 ± 49.94 cm 2 ), and there were no significant differences in wound healing (81.25% vs. 75.38%), minor complications (18.75% vs. 21.54%), major complications (0% vs. 3.85%), or mortality (6.25% vs. 10.00%) between the groups., Conclusions: Our findings indicate that PC combined with CiNPWT represents an alternative reconstruction option for patients with pressure ulcers, especially in those for whom prolonged anesthesia is unsuitable.

Aims: Pressure injury is a gradually increasing disease in the aging society. The reconstruction of a pressure ulcer requires a patient and surgical technique. The patients were exposed to the radiation risk under other ways of detection of perforators such as computed tomographic angiography and magnetic resonance angiography. Here, we compared two radiation-free methods of a superior gluteal artery perforator (SGAP), flap harvesting and anchoring. One is the traditional method of detecting only handheld acoustic Doppler sonography (ADS) (Group 1). The other involves the assistance of intraoperative indocyanine green fluorescent near-infrared angiography (ICGFA) and handheld ADS (Group 2)., Materials and Methods: This is a single-center, retrospective, observational study that included patients with sacral pressure injury grades III and IV, who had undergone reconstructive surgery with an SGAP flap between January 2019 and January 2021. Two detection methods were used intraoperatively. The main outcome measures included the operative time, estimated blood loss, major perforator detection numbers, wound condition, and incidence of complications., Results: Sixteen patients underwent an SGAP flap reconstruction. All patients were diagnosed with grade III to IV sacral pressure injury after a series of examinations. Group 1 included 8 patients with a mean operative time of 91 min, and the mean estimated blood loss was 50 mL. The mean number of perforators was 4. Postoperative complications included one wound infection in one case and wound edge dehiscence in one case. No mortality was associated with this procedure. The mean total hospital stay was 16 days. Group 2 included 8 patients with a mean operative time of 107.5 min, and the mean estimated blood loss was 50 mL. The mean number of perforators was 5. Postoperative complications included one wound infection. No mortality was associated with this procedure. The mean total hospital stay was 13 days., Conclusions: The combination of detection of the SGAP by ICGFA and handheld ADS for the reconstruction of a sacral pressure injury provides a more accurate method and provides the advantage of being radiation-free.

Necrotizing fasciitis is a severe deep soft tissue infection with poor disease prognosis. The Aeromonas species is characterized as gram-negative, facultative, anaerobic small bacilli that are ubiquitously distributed in aquatic environments. Necrotizing fasciitis caused by this species is rare but has an extremely high mortality rate, especially in immunocompromised individuals. This study presents the case of a 39-year-old man with alcoholic liver cirrhosis, Child-Pugh class B, with necrotizing fasciitis caused by Aeromonas hydrophila . Despite debridement and bilateral above-knee amputation performed immediately, rapid progression to bilateral upper limbs and trunk was noted in 24 hours. The patient expired from septic shock with multiple organ failure in less than 48 hours following initial presentation. Two similar cases with different medical intervention and results have been reported in the literature and are further discussed in the present study. This allows the authors to suggest potential solutions for an improved clinical outcome.

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.

Patients bitten by Naja atra who are treated with bivalent freeze-dried neurotoxic antivenom in Taiwan have an improved survival rate but develop necrotic wound changes. The World Health Organization (WHO) has suggested using the minimum necrotizing dose (MND) of venom as a method of evaluating the neutralization effect of antivenom. The aim of this study was to evaluate the effectiveness of antivenom for the prevention of necrosis based on the MND and clarify which component of the venom of N. atra induces necrosis. The neurotoxins (NTXs) were removed from the crude venom (deNTXs), and different concentrations of deNTXs were injected intradermally into the dorsal skin of mice. After three days, the necrotic lesion diameter was found to be approximately 5 mm, and the MND was calculated. A reduction in the necrotic diameter of 50% was used to identify the MND 50 . Furthermore, both phospholipase A 2 (PLA 2 ) and cytotoxins (CTXs) were separately removed from the deNTXs to identify the major necrosis-inducing factor, and the necrotic lesions were scored. All mice injected with deNTXs survived for three days and developed necrotic wounds. The MND of the deNTXs for mice was 0.494 ± 0.029 µg/g, that of the deNTXs-dePLA 2 (major component retained: CTXs) was 0.294 ± 0.05 µg/g, and that of the deNTX-deCTX (major component retained: PLA 2 ) venom was greater than 1.25 µg/g. These values show that CTX is the major factor inducing necrosis. These results suggest that the use of the deNTXs is necessary to enable the mice to survive long enough to develop venom-induced cytolytic effects. CTXs play a major role in N. atra -related necrosis. However, the MND 50 could not be identified in this study, which meant that the antivenom did not neutralize venom-induced necrosis.

Background: The incidence of acute compartment syndrome (ACS) following snakebite envenomation may be seriously overestimated in Taiwan. Snakebite-induced ACS is difficult to determine solely by clinical examination. Snakebite patients previously underwent surgical intervention based on speculation and general clinical examinations suggesting ACS presentations instead of direct intracompartmental pressure (IP) measurement prior to fasciotomy. Point-of-care ultrasound (POCUS) is a relatively widely available noninvasive tool. This study aimed to evaluate snakebite-envenomated patients for the presence of subcutaneous edema and diastolic retrograde arterial flow (DRAF)., Materials and Methods: Snakebite patients were prospectively recruited between 2017 and 2019. All patients were examined with POCUS to locate edema and directly visualize and measure the arterial flow in the compressed artery. The presence of DRAF in the compressed artery is suggestive of ACS development because when compartment space restriction occurs, increased retrograde arterial flow is observed in the artery., Results: Twenty-seven snakebite patients were analyzed. Seventeen patients (63%) were bitten by Crotalinae snakes, seven (26%) by Colubridae, one (4%) by Elapidae, and two (7%) had unidentified snakebites. All Crotalinae bit patients received antivenom, had subcutaneous edema and lacked DRAF in a POCUS examination series., Discussion: POCUS facilitates clinical decisions for snakebite envenomation. We also highlighted that the anatomic site of the snakebite is an important factor affecting the prognosis of the wounds. There were limitations of this study, including a small number of patients and no comparison with the generally accepted invasive evaluation for ACS., Conclusions: We are unable to state that POCUS is a valid surrogate measurement of ACS from this study but see this as a starting point to develop further research in this area. Further study will be needed to better define the utility of POCUS in patients envenomated by snakes throughout the world.

Early excision and autografting have been the principles in managing acute burn wounds. Despite the known benefits of early autografting, there are situations in which the placement of autograft is unsafe or even unavailable. In these clinical situations, skin substitutes like artificial dressings and human skin allografts are considered as useful for temporary wound coverage. We present an immunosuppressed patient with deep lower limb burn wound who received human skin allograft for wound management. The applied human skin allograft persisted for a longer period without infection or rejection and successfully improved her wound healing. Large and well-designed prospective studies are needed to confirm the encouraging results of the present case report.

Abstract: Skin grafts are not suitable for closing tendon- or bone-exposing wounds, which require flap surgery. Dermal regeneration templates have value for closing such wounds, but the disadvantages of the technique include implantation failures because of infection, hematoma formation, or inappropriate immobilization. Negative-pressure wound therapy was reported to increase graft acceptance in difficult wounds.This retrospective case series of 65 patients evaluated negative-pressure therapy combined with artificial dermis for the treatment of acute or chronic tendon- or bone-exposing wounds. The artificial dermis was placed after adequate wound-bed preparation, with simultaneous application of a vacuum-assisted closure system. Split-thickness skin grafting was performed after the implanted artificial dermis had become established.The overall success rate was 88.1% (59/67): 88.6% (39/44) in the chronic wounds group and 87% (20/23) in the acute-trauma group separately. The overall mean survival time of artificial dermis in success cases was 13.24 ± 7.14 days. In separately, the survival time of artificial dermis had no statistically difference in chronic wound group (13.64 ± 7.53 vs 12.60 ± 5.86. P = .943), but had significant statistical difference in acute trauma group (12.45 ± 6.44 days vs 23.33 ± 4.04 days, P = .018). Also, comorbidity of PAOD was found a strong risk factor of failure in chronic wound group (100% vs 23.1%, P < 0.001).We concluded that artificial dermis combined with negative-pressure therapy followed by split-thickness skin grafting might be a reliable and effective option for surgical reconstruction of tendon- or bone-exposing wounds, and could decreasing waiting periods of autologous skin graft., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Preserving both esthetic and functional outcome remains challenging in facial burn injuries. The major issue is the initial treatment of injury. In this study, we focused on patients with partial-thickness facial burns admitted to the burn unit of Tri-Service General Hospital, Taipei, from November 2016 to November 2018. In 21 included patients, customized mask-style, transparent hydrogel-based dressing was applied to the burns. The mean age of included patients was 37.4 years. The mean area of burn injury was 11.9% of total body surface area, and the mean area of second-degree facial burns was 162.3 cm2. Full reepithelialization took, on average, 10.86 days. Scarring was acceptable in terms of texture and color, and no hypertrophic or keloidal scarring was noted. The mean Vancouver Scar Scale score was 2.07. Use of the hydrogel-based dressing masks seems to be a promising means of reducing pain, providing uninterrupted wound healing, facilitating observation, and positively affecting scarring in patients with second-degree facial burns., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Proper wound care along with the use of skin grafts over deep burn wounds has been the standard treatment. However, the goal in burn wound care has shifted from achieving a satisfactory survival rate to improving long-term form and function of the healed wound, which is sometimes hindered by scar contracture. This has prompted surgeons to find alternative ways to treat burn wounds without compromising function. Among burn cases, hand injuries are the most problematic when it comes to delicate function recovery., Methods: This study presents the results of conjunctive use of a bilayer artificial dermis, negative pressure wound therapy, and split-thickness skin grafts for grafting over acute burn wounds and scar-releasing defects after severe hand burns., Results: Three months after the operation, the scar was soft and pliable, the aesthetic outcome was good, and the patients gained much improvement in hand function and quality oflife., Conclusions: The combined technique achieved a good scar quality and aesthetic effect on burned hands as well as excellent functional outcome, which resulted in major improvements and an independent life for the patient., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

With aging, pressure ulcers become a common health problem causing significant morbidity and mortality for physically limited or bedridden elderly persons. Here, we present our strategy for such patients. Between August 2010 and March 2019, 117 patients were enrolled. Patient age, etiology, defect size and location, flap reconstruction, outcome, and follow-up period were reviewed. Of these patients, 64 were female and 53 were male, with an age range of 21 to 96 years (mean 75.6). The mean area of defect was 61.5 cm. The most common etiology was dementia (33.3%), and ulcers were most frequently caused by sacral pressure (70.3%). The commonest surgical treatment was a V-Y advancement flap (50%). The complication rate was 27.5%, including dehiscence and late recurrence. Negative pressure wound therapy could be used if the initial defect was large. V-Y advancement flap is the most frequent surgical treatment for sacral pressure ulcers because it is simple and available for most types of defect. Primary closure may be considered as the simplest method if the defective area is <16 cm. Intraoperative indocyanine green angiography can help avoid secondary flap revisions. Our protocol ensures a short surgery time, little bleeding, and a low complication rate.

Various animal studies have shown beneficial effects of hypercapnia in lung injury. However, in patients with acute respiratory distress syndrome (ARDS), there is controversial information regarding the effect of hypercapnia on outcomes. The duration of carbon dioxide inhalation may be the key to the protective effect of hypercapnia. We investigated the effect of pre-treatment with inhaled carbon dioxide on lipopolysaccharide (LPS)-induced lung injury in mice. C57BL/6 mice were randomly divided into a control group or an LPS group. Each LPS group received intratracheal LPS (2 mg/kg); the LPS groups were exposed to hypercapnia (5% carbon dioxide) for 10 min or 60 min before LPS. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. LPS significantly increased the ratio of lung weight to body weight; concentrations of BALF protein, tumor necrosis factor-α, and CXCL2; protein carbonyls; neutrophil infiltration; and lung injury score. LPS induced the degradation of the inhibitor of nuclear factor-κB-α (IκB-α) and nuclear translocation of NF-κB. LPS increased the surface protein expression of toll-like receptor 4 (TLR4). Pre-treatment with inhaled carbon dioxide for 10 min, but not for 60 min, inhibited LPS-induced pulmonary edema, inflammation, oxidative stress, lung injury, and TLR4 surface expression, and, accordingly, reduced NF-κB signaling. In summary, our data demonstrated that pre-treatment with 10-min carbon dioxide inhalation can ameliorate LPS-induced lung injury. The protective effect may be associated with down-regulation of the surface expression of TLR4 in the lungs.

Background: Diabetes is the most common comorbidity of necrotizing fasciitis (NF), but the effect of stress-induced hyperglycemia (SIH) on diabetic patients with NF has never been investigated. The aim of this study was to assess whether SIH, as determined by the glycemic gap between admission glucose levels and A1C-derived average glucose levels, predicts adverse outcomes in diabetic patients hospitalized with NF., Methods: We retrospectively reviewed the glycemic gap and clinical outcomes in 252 diabetic patients hospitalized due to NF from 2011 to 2018 in a single medical center in Taiwan. A receiver operating characteristic (ROC) curve was used to analyze the optimal cutoff values for predicting adverse outcomes. Univariate and multivariate logistic regression analyses were employed to identify significant predictors of adverse outcomes., Results: In total, 194 diabetic NF patients were enrolled. Compared with patients without adverse outcomes, patients with adverse outcomes had significantly higher glycemic gaps, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and C-reactive protein (CRP) levels; lower albumin and hemoglobin levels; greater incidence of limb loss; and longer hospital and intensive care unit stays. The glycemic gap positively correlates with the laboratory risk indicator for NF scores, APACHE II scores and CRP levels. A glycemic gap of 146 mg/dL was the optimal cutoff value for predicting adverse outcomes using the ROC curve. Compared with patients with glycemic gaps ≤146 mg/dL, those with glycemic gaps >146 mg/dL had higher APACHE II scores and incidence rates of adverse outcomes, especially bacteremia and acute kidney injury. Multivariate analysis revealed that a glycemic gap >146 mg/dL and APACHE II score >15 were independent predictors of adverse outcomes, while the presence of hyperglycemia at admission was not., Conclusions: An elevated glycemic gap was significantly independently associated with adverse outcomes in diabetic NF patients. Further prospective studies are warranted to validate the role of the glycemic gap in NF patients with diabetes., Competing Interests: The authors have declared that no competing interests exist.

Our previous study demonstrated that administration of NVP-BEZ235 (BEZ235), a dual PI3K/mTOR inhibitor, before radiotherapy (RT) enhanced the radiotherapeutic effect in colorectal cancer (CRC) cells both in vitro and in vivo. Here, we evaluated whether maintenance BEZ235 treatment, after combinatorial BEZ235 + RT therapy, prolonged the antitumor effect in CRC. K-RAS mutant CRC cells (HCT116 and SW480), wild-type CRC cells (HT29), and HCT116 xenograft tumors were separated into the following six study groups: (1) untreated (control); (2) RT alone; (3) BEZ235 alone; (4) RT + BEZ235; (5) maintenance BEZ235 following RT + BEZ235 (RT + BEZ235 + mBEZ235); and (6) maintenance BEZ235 following BEZ235 (BEZ235 + mBEZ235). RT + BEZ235 + mBEZ235 treatment significantly inhibited cell viability and increased apoptosis in three CRC cell lines compared to the other five treatments in vitro. In the HCT116 xenograft tumor model, RT + BEZ235 + mBEZ235 treatment significantly reduced the tumor size when compared to the other five treatments. Furthermore, the expression of mTOR signaling molecules (p-rpS6 and p-eIF4E), DNA double-strand break (DSB) repair-related molecules (p-ATM and p-DNA-PKcs), and angiogenesis-related molecules (VEGF-A and HIF-1α) was significantly downregulated after RT + BEZ235 + mBEZ235 treatment both in vitro and in vivo when compared to the RT + BEZ235, RT, BEZ235, BEZ235 + mBEZ235, and control treatments. Cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), 53BP1, and γ-H2AX expression in the HCT116 xenograft tissue and three CRC cell lines were significantly upregulated after RT + BEZ235 + mBEZ235 treatment. Maintenance BEZ235 treatment in CRC cells prolonged the inhibition of cell viability, enhancement of apoptosis, attenuation of mTOR signaling, impairment of the DNA-DSB repair mechanism, and downregulation of angiogenesis that occurred due to concurrent BEZ235 and RT treatment.

Rationale: The main cause of death in melanoma patients is widespread metastases as it can metastasize to almost every organ. However, melanoma skeletal muscle metastases (MSMM) are exceptional, and only a few cases of MSMM to the rectus abdominis muscles have been previously described. And our case maybe the first reported case in Asia region., Patient Concerns: A 45-year-old man with history of right scalp melanoma, pT3aN0M0, stage IIA status post wide excision with 2 cm safe margin and right neck lymph node dissection at 5 years before. He had an almost 5 years disease-free period but presented to our clinic due to intermittent abdominal sharp pain for 1 to 2 months, with a palpable soft tissue mass over his right abdomen. Metastatic melanoma to rectus abdominis muscles was highly suspected., Interventions: The patient subsequently underwent radical en-block extraperitoneal 15 cm segmental resection of the right rectus abdominis muscle including tumor mass. The resected tumor was a black-gray colored solid mass, and the final histologic study showed a metastasis of melanoma., Outcomes: Postoperative course of the patient was uneventful, and the right abdominal pain was improved. The patient was referred for further target therapy, but passed away half a year later due to multiple metastasis., Lessons: Scalp melanoma with isolated rectus muscle metastasis is extremely rare especially for a young aged patient who had an almost 5-year disease-free period. Surgery is a potentially curative therapy for patients with isolated metastatic melanoma. The goal is negative resection margins, in order to avoid local recurrences. Radical compartmental surgery should be considered for selected stage IV melanoma patients with sole rectus abdominis MSMM, whose disease could be amenable to complete resection, in preliminary procedure to prolong disease-free survival time. For oligometastatic disease, surgical resection is sometimes useful in carefully selected patients after systemic therapy; also, it could be performed as symptomatic treatment.

A mass casualty incident (MCI) can have an enormous impact on an already crowded emergency department (ED), affecting the quality of health care provided to non-MCI ED patients. On June 26, 2015, a burn MCI (BMCI) occurred due to a cornstarch explosion at a party at a water park. The competing needs of the BMCI patients might have crowded out the needs of the non-BMCI patients. Although crowd-out effects have been previously documented in a variety of health care situations, they have not been extensively evaluated during MCIs. We aimed to determine whether the outcomes of the non-MCI patients were compromised during this incident.We conducted a retrospective observational study comparing several health care parameters and outcomes between non-BMCI patients and historical controls during the designated period using institutional electronic records and the National Health Insurance Research Database.On the night of the incident, 53 patients were sent to our ED; most of them arrived within 3 hours after the BMCI. There was a significant increase in the wait time for ICU beds among non-BMCI patients compared to the wait times during the corresponding week of the previous year (8.09 ± 4.21 hours vs 3.77 ± 2.15 hours, P = .008). At the hospital level, there was a significantly increased length of hospital stay (LOS) in the ICU after the MCI compared with the LOS in the ICU in the same week of the preceding year (median days: 15 vs 8, P ≤ .001). At the regional level, there were no significant differences between the 2 periods in the LOS in acute care, LOS in the ICU or mortality rates at the involved medical centers.Crowd-out effects from the MCI occurred in the ED and at the institutional level. Although there was an increased wait time for admission to the ICU and a longer LOS in the ICU, the LOS in acute care beds, treatment of time-sensitive diseases, and mortality rates were not compromised by the current MCI protocol at either the institutional or regional levels.

Introduction: Ischial pressure ulcers are considered the most difficult type of pressure ulcers (PUs) to treat., Objective: The authors report the use of a pedicled anterolateral thigh (pALT) myocutaneous flap as an alternative for covering an ischial PU., Materials and Methods: The authors retrospectively collected the data of 21 patients with an indurated recurrent ischial ulcer or a fresh ischial ulcer. A pALT myocutaneous flap was harvested without intramuscular dissection and skeletonization of the perforators for the ischial defect reconstruction. Two modified flap-insetting techniques, an open-route method and a subcutaneous tunnel method, were used for the ischial defect reconstruction. The open-route flap-insetting was used for a recurrent ulcer status after other surgical procedures, and the subcutaneous tunnel method was used for fresh ulcers., Results: The mean follow-up period was 10 months (range, 4-14 months). During the postoperative follow-up, all open-route reconstructions resulted in flap take; however, poor healing with seroma was noted in 2 patients who had undergone pALT reconstruction with subcutaneous tunneling after other previous surgical reconstructions., Conclusions: In the authors' experience, because of constant blood supply, sufficient bulk, easy elevation, longer pedicle for the arc of rotation, primary closure of the donor site without morbidity, and a non-weightbearing flap donor site, the pALT myocutaneous flap for ischial ulcer reconstruction can serve as a primary treatment and secondary salvage.

Pressure sores remain a common health problem, particularly among the physically limited or bedridden elderly, and can cause significant morbidity and mortality. This study aimed to present our surgical treatment and strategy for patients with multiple pressure sores. Between January 2010 and December 2016, 18 patients were enrolled. After adequate debridement, pressure sores were managed based on our treatment protocol. Patients' age, aetiology, defect size and location, flap reconstruction, outcome, and follow-up period were reviewed. A total of 10 men and 8 women (average age, 82.3 years) with a mean follow-up period of 28.3 months (6-72 months) were included. The mean defect area was 63.7 cm 2 . The most common aetiology of the bedridden state was cerebrovascular accident (38.89%), and the most frequent sores were trochanteric pressure sores (53.57%). The average operative time and blood loss were 105.5 minutes and 100.8 mL, respectively. No haemodynamic variation or blood transfusion was noted during the surgery. The complication rate for each sore was 10.7%, including late recurrence. In conclusion, treating pressure ulcers requires careful patient education, intensive multidisciplinary optimisation, and meticulous wound care, and our treatment protocol ensures a shorter surgery time, less bleeding, and low complication rate., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)