Temporal trends of food consumption patterns in Tuvalu under the context of climate change: COMmunity-based Behavior and Attitude survey in Tuvalu (COMBAT) since 2020.

AIM: The aim of this study was to analyze temporal trends of food consumption patterns, attitudes, and health-related knowledge in Tuvalu, a small Pacific Island country facing the triple threat of obesity, climate change, and food insecurity. METHODS: Two waves of the COMmunity-based Behavior and Attitude (COMBAT) survey were conducted in 2020 and 2022. Descriptive characteristics of changes in obesity proportion, food intake, and sociodemographic factors were assessed. Additionally, this study also integrates individual climate data utilizing satellite-based prediction models, and estimates historical temperature, precipitation, and sea level trends among all islands in Tuvalu. RESULTS: The study revealed a high obesity proportion among adults (69.5% in 2020, 73.2% in 2022) and an increase in the percentage of adolescents with a high waist circumference. Variations in food intake were also observed between the two waves of the survey. CONCLUSIONS: The data collected in the COMBAT study provides valuable insights for future epidemiological research to elucidate the associations and causal relationships between climate change, food security, and non-communicable diseases in Tuvalu.

Clinical outcomes of cetuximab-based treatment for distant metastatic head and neck squamous cell carcinoma: A real-world study using Taiwan Head Neck Society registry database.

BACKGROUND: For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear. METHODS: From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab-based frontline therapy were collected for analysis. RESULTS: Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non-DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME-like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme-like regimen. CONCLUSION: DM coexisted with poorer prognosis in certain groups. LDH-associated biomarkers may aid treatment options for DM patients.

Higher Imported Food Patterns Are Associated with Obesity and Severe Obesity in Tuvalu: A Latent Class Analysis.

Background: Tuvalu is a Pacific Island country within the small island developing states that has observed a significant and alarming increase in obesity rates over the past 40 years, affecting ∼60 %-70 % of the current population. Objectives: This study aimed to investigate the association between food patterns and the proportion of obesity in a Pacific Island country. Methods: The 2022 COMmunity-based Behavior and Attitude survey in Tuvalu (COMBAT) included 985 adults with complete data on sociodemographic information and the frequency of consumption of 25 common foods. A latent class analysis determined 4 food patterns. Bayesian multilevel logistic and linear regression models estimated the association between food patterns and the proportion of obesity [body mass index (BMI) ≥30 kg/m2], severe obesity (BMI ≥40 kg/m2), and weight (kg), adjusting for potential confounders and accounting for clustering by region. Results: The latent class analysis revealed 4 food patterns with an entropy of 0.94 and an average posterior probability of class assignment for each individual of 0.97, described as follows: 1) local: locally produced foods with moderate food diversity (proportion of individuals = 28 %); 2) diverse-local: local with greater food diversity (17 %); 3) restricted-imported: more imported with restricted diversity (29 %); and 4) imported: heavily imported with high diversity (26 %). Compared to those following the diverse-local pattern, the odds of having obesity were greater for those classified with the imported pattern [odds ratio (OR): 2.52; 95 % credible interval (CrI): 1.59, 3.99], restricted-imported pattern (OR: 1.89; 95 % CrI: 1.59, 3.99), and local pattern (OR: 1.54; 95 % CrI: 0.94, 2.50). Similar trends were observed for severe obesity while body weight was positively associated with both restricted-imported and imported food patterns. Conclusions: The high consumption of imported foods, together with the low consumption of plant-based foods and protein-rich foods, could be a relevant modifiable lifestyle factor explaining the high levels of obesity and severe obesity in Tuvalu, a Pacific Island country.

Dispatchers trained in persuasive communication techniques improved the effectiveness of dispatcher-assisted cardiopulmonary resuscitation.

BACKGROUND: Early recognition of cardiac arrest and early initiation of bystander cardiopulmonary resuscitation can increase the survival of patients with out-of-hospital cardiac arrest (OHCA). We compared dispatcher-assisted cardiopulmonary resuscitation (DACPR) effectiveness before and after using different communication models in the dispatching center. METHOD: We analyzed dispatch recordings of non-trauma origin OHCA cases received by the Taichung dispatch center between May 1 to September 30, 2021, and November 1, 2021, to March 31, 2022. The dispatchers underwent an 8-hour training intervention consisting of targeted education using a new communication model for DACPR. Several outcome measures were evaluated, including the sustained return of spontaneous circulation and the time to first chest compression. RESULTS: We included 640 cases in the preintervention group and 580 cases in the postintervention group. The return of spontaneous circulation (ROSC) rate, the time to first chest compression, and good neurological outcome were significantly improved in the postintervention group (20.9% vs. 31.0%, p < 0.001;168 seconds vs. 151 seconds, p = 0.004; 2.8% vs. 5.3%, p = 0.024, respectively). In subgroup analyses, the intervention was related to a statistical improvement in ROSC rate among patients whose caller was a family member (18.7% vs. 31.4%, p < 0.001). Among patients whose caller was female, both ROSC and good neurological outcome significantly improved after the intervention (19.8% vs. 36.6%, p < 0.001; 2.7% vs. 7.5%, p = 0.006, respectively). There was a statistical difference between the pre-intervention and post-intervention group with respect to ROSC rate among patients whose caller was family (the adjusted odds ratio:1.78, 95% CI: 0.59-1.25], p < 0.001.) or female (the adjusted odds ratio:3.18,95% CI: 1.77-5.70], p = 0.008.) in the multivariable regression model. CONCLUSION: The new communication model has enhanced the effectiveness of DACPR in terms of the ROSC rate, particularly when the caller was a family member or female, leading to improved rates of ROSC and favorable neurological outcomes.

Cetuximab Treatment beyond Progression in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Nationwide Population-Based Study (THNS-2021-08).

BACKGROUND: Little is known regarding the association of cetuximab treatment beyond progression (TBP) with survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Although immune checkpoint inhibitors (ICIs) are now considered as first-line treatment, not all patients are suitable for ICIs. OBJECTIVE: We conducted a multicenter, retrospective study to evaluate the role of cetuximab TBP in patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. PATIENTS AND METHODS: Patients with R/M HNSCC who had tumor progression after first-line cetuximab-containing chemotherapy were included into our study. Oncologic outcomes were estimated including time to cetuximab treatment discontinuation (TTD), progression-free survival 2 (PFS2), overall survival (OS), overall response rate (ORR), and disease control rate (DCR). Multivariate cox regression analysis with survival were conducted. Subgroup analysis with P16 and programmed death ligand 1 expression were performed. RESULTS: A total of 498 patients were eligible with 259 patients in the TBP group and 239 patients in the non-TBP group. The most common first-line chemotherapy was the EXTREME regimen in both groups. As for second-line treatment, the most common regimen were TPEx in the TBP group and taxane-based chemotherapy in the non-TBP group. Median TTD was 8.7 months in TBP and 5.5 months in non-TBP (p < 0.001). In terms of survival, median OS1 was significant longer in the TBP group than in the non-TBP group [14.1 months versus 10.9 months (p = 0.016)]. Multivariate analysis demonstrated cetuximab TBP was a factor independently associated with OS. CONCLUSIONS: Our retrospective study suggests cetuximab TBP to be effective and to provide better survival for patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. Further prospective studies are warranted to validate the role of cetuximab TBP in R/M HNSCC.

Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells.

Mutations in the tumor suppressor TP53 cause cancer and impart poor chemotherapeutic responses, reportedly through loss-of-function, dominant-negative effects and gain-of-function (GOF) activities. The relative contributions of these attributes is unknown. We found that removal of 12 different TP53 mutants with reported GOFs by CRISPR/Cas9 did not impact proliferation and response to chemotherapeutics of 15 human cancer cell lines and colon cancer-derived organoids in culture. Moreover, removal of mutant TP53/TRP53 did not impair growth or metastasis of human cancers in immune-deficient mice or growth of murine cancers in immune-competent mice. DepMap mining revealed that removal of 158 different TP53 mutants had no impact on the growth of 391 human cancer cell lines. In contrast, CRISPR-mediated restoration of wild-type TP53 extinguished the growth of human cancer cells in vitro. These findings demonstrate that LOF but not GOF effects of mutant TP53/TRP53 are critical to sustain expansion of many tumor types. SIGNIFICANCE: This study provides evidence that removal of mutant TP53, thereby deleting its reported GOF activities, does not impact the survival, proliferation, metastasis, or chemotherapy responses of cancer cells. Thus, approaches that abrogate expression of mutant TP53 or target its reported GOF activities are unlikely to exert therapeutic impact in cancer. See related commentary by Lane, p. 211 . This article is featured in Selected Articles from This Issue, p. 201.

Pediatric neuroimaging findings and clinical presentations of COVID-19: A systematic review.

OBJECTIVES: Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children. METHODS: A literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients. RESULTS: A total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis. CONCLUSION: Radiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.

Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses.

Whole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that impact responses of malignant cells to anti-cancer agents. Applying this methodology to lymphoma cells, we conducted a genome-wide screen to identify novel inhibitors of tumour expansion that are induced by the tumour suppressor TRP53. We discovered that the absence of Arrestin domain containing 3 (ARRDC3) increases the survival and long-term competitiveness of MYC-driven lymphoma cells when treated with anti-cancer agents that activate TRP53. Deleting Arrdc3 in mice caused perinatal lethality due to various developmental abnormalities, including cardiac defects. Notably, the absence of ARRDC3 markedly accelerated MYC-driven lymphoma development. Thus, ARRDC3 is a new mediator of TRP53-mediated suppression of tumour expansion, and this discovery may open new avenues to harness this process for cancer therapy.

Emergency Medical Services in Taiwan: Past, Present, and Future.

This review assessed the development of Taiwan's emergency medical services (EMS) and focused on the optimizing initiatives of the EMS systems, the current state of Taiwan's EMS system, EMS benchmarks in different regions of Taiwan, EMS response during the coronavirus disease 2019 (COVID-19) pandemic, and future design. In the past decade, there has been a noticeable increase in prehospital services, numerous optimizing initiatives to improve patient prognosis, and the medical oversight model. Taiwan's current EMS system, including the dispatch system, out-of-hospital cardiac arrest (OHCA) patient management, time-sensitive critical illness in prehospital settings, and disaster response, has undergone significant improvements. These improvements have been demonstrated to have a measurable impact on patient outcomes, as supported by medical literature. Each region in Taiwan has developed a unique EMS system with local characteristics, such as the implementation of the Global Resuscitation Alliance 10 steps for OHCA-related quality control, hearing automated external defibrillator program, a five-level prehospital triage system, an island-hopping strategy for patients with major trauma, dispatcher-assisted teamwork for OHCA resuscitation, and optimized prehospital care for acute coronary syndrome patients. In response to the COVID-19 pandemic from 2019 to 2023, Taiwan's EMS implemented measures to combat the outbreak such as interagency collaboration to obtain patient's personal information, to optimize prehospital management initiatives, and to provide financial compensation and personal insurance for emergency medical technicians. The areas that need focus include integrating prehospital and in-hospital information to build a national-level database (One-Stop Emergency Management), increasing public awareness of first responders and emergency casualty care, and evolving the EMS system by incorporating private EMS system, initiating school-based education of paramedicine, and legally recognizing paramedics as medical and health care personnel. By improving these areas, we can better prepare for the future and ensure that Taiwan's EMS system continues to provide high-quality care to those in need.

Exploring the link between home garden use and severe obesity: Insights from a nationwide survey in Tuvalu.

Background: Obesity is prevalent and increasing but understudied across Pacific Islanders. Tuvalu is a South Pacific country with a high obesity rate and faces multiple threats of food insecurity. Home garden serves as a sustainable food source and can be a possible intervention for the obesity pandemic in Tuvalu. This study investigated Tuvaluans' home garden use and obesity, and explored factors associated with increased use of home gardens. Methods: We conducted a nationwide, cross-sectional study in Tuvalu during 2022. Structured questionnaires were administered during the in-person interviews, and trained interviewers measured the height and weight of each participant. The association between home garden use, obesity and severe obesity were tested with univariate and multivariable logistic regression. We also applied overlapping weights to balance the distribution of baseline demographic factors. Results: The average body mass index was 34.87 kilogrammes (kg) / square metre (m2) among the study population of 1024 adults (630 from Funafuti and 394 from other islands in Tuvalu). Overall, people having home gardens was associated lower odds for severe obesity compared to those without a home garden in overlap weighting models (odds ratio (OR) = 0.946, 95% CI = 0.897-0.997, P = 0.039) and the association was stronger in Funafuti (OR = 0.927, 95% CI = 0.866-0.991, P = 0.027) than in the outlying islands (OR = 0.967, 95% CI = 0.889-1.052, P = 0.435). Furthermore, increased age was positively associated with having a home garden in Funafuti, and smoking showed an inverse association. Conclusions: Having a home garden is associated with lower odds of severe obesity in Tuvalu, and the association is stronger in Funafuti. Smokers are less likely to have home gardens, and increased age is positively associated with having home gardens. These findings promote more home garden utilisation and provide evidence for targeted interventions in Tuvalu.

Prognostic utility of neutrophil-to-albumin ratio in surgically treated oral squamous cell carcinoma.

BACKGROUND: We aimed to evaluate the prognostic significance of preoperative neutrophil-to-albumin ratio (NAR) in oral squamous cell carcinoma (OSCC). METHODS: A total of 622 patients with surgically treated OSCC were enrolled. NAR was defined as the absolute neutrophil count divided by the serum albumin level in peripheral blood before the radical surgery. Cox proportional hazards model were used to discover survival outcome-associated factors. RESULTS: The optimal cut-off of NAR to predict overall survival (OS) was determined to be 0.1. In Cox model, high NAR was identified as an independent negative prognosticator of OS, cancer-specific survival, and recurrence-free survival (adjusted hazard ratio: 1.503, 1.958, and 1.727, respectively; all p < 0.05). The NAR-based nomogram accurately predicted OS (concordance index: 0.750). CONCLUSION: Our study suggests that preoperative NAR is a convenient and effective prognostic marker for OSCC and NAR-based nomogram can be a promising prognostic tool in clinical setting.

Evaluation of Sinonasal Outcome Test (SNOT-22) Domains in the Assessment of the Quality of Life in Patients with Nasopharyngeal Carcinoma.

Background: Few instruments are available for assessing the otorhinologic-related quality of life (QOL) in nasopharyngeal carcinoma (NPC) patients. Therefore, we evaluated whether the 22-item Sinonasal Outcome Test (SNOT-22) could be applied to these patients. Methods: Patients diagnosed with NPC, who had been treated with standard protocol and followed up in our institute between 2019 and 2022, were invited to join the cross-sectional study during their clinic visits. All participants completed the SNOT-22 and Eustachian Tube Dysfunction Questionnaire-7 once they were recruited. Confirmatory factor analysis (CFA) was performed to decide the most suitable model for the underlying SNOT-22 subdomains, along with various validity and reliability tests. Results: We identified a total of 275 patients, with 84 (30.5%) women and 191 (69.5%) men. The mean age was 54.1 years (standard deviation: 11.2). Among these patients, 171 (62.1%) were in late stages, and 260 (94.5%) received chemoradiotherapy as treatment. The median interval between primary RT treatment and questionnaire completion was 50 months (interquartile range: 29-93). CFA supported a five-factor model for the SNOT-22 for NPC patients, including nasal, ear/facial, sleep, function, and emotion domains. The internal consistency and test-retest reliability of the SNOT-22 domain score were good. In addition, known-group validity was good for the SNOT-22 total score and domain scores according to the disease recurrence status. Conclusion: Psychometric analyses supported the reliability and validity of a five-domain SNOT-22 for assessing otorhinologic-related QOL in NPC patients.

Lymph node ratio as a survival predictor for head and neck squamous cell carcinoma with multiple adverse pathological features.

BACKGROUND: The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features. METHODS: In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled. RESULTS: The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016). CONCLUSION: For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.

Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis.

Many lymphoid malignancies arise from deregulated c-MYC expression in cooperation with additional genetic lesions. While many of these cooperative genetic lesions have been discovered and their functions characterised, DNA sequence data of primary patient samples suggest that many more do exist. However, the nature of their contributions to c-MYC driven lymphomagenesis have not yet been investigated. We identified TFAP4 as a potent suppressor of c-MYC driven lymphoma development in a previous genome-wide CRISPR knockout screen in primary cells in vivo [1]. CRISPR deletion of TFAP4 in Eµ-MYC transgenic haematopoietic stem and progenitor cells (HSPCs) and transplantation of these manipulated HSPCs into lethally irradiated animals significantly accelerated c-MYC-driven lymphoma development. Interestingly, TFAP4 deficient Eµ-MYC lymphomas all arose at the pre-B cell stage of B cell development. This observation prompted us to characterise the transcriptional profile of pre-B cells from pre-leukaemic mice transplanted with Eµ-MYC/Cas9 HSPCs that had been transduced with sgRNAs targeting TFAP4. This analysis revealed that TFAP4 deletion reduced expression of several master regulators of B cell differentiation, such as Spi1, SpiB and Pax5, which are direct target genes of both TFAP4 and MYC. We therefore conclude that loss of TFAP4 leads to a block in differentiation during early B cell development, thereby accelerating c-MYC-driven lymphoma development.

Transdermal buprenorphine improves overall quality of life and symptom severity in cancer patients with pain.

AIM AND OBJECTIVES: This study explored the effect of transdermal buprenorphine on quality of life and six symptoms in cancer patients with pain. BACKGROUND: Transdermal opioids offer advantages over traditional routes of administration. The impact of transdermal buprenorphine on quality of life for patients with cancer in Asian populations is unknown. DESIGN: This study employed a single-arm observational repeated measures design. Cancer patients with pain were evaluated prior to treatment (baseline). Over a 4-week treatment period, quality of life and symptoms were assessed at 2 and 4 weeks. This study adhered to the recommendations of STROBE guidelines. METHODS: This multi-site study was conducted in six hospitals located across northern, middle and southern Taiwan. Adult cancer patients whose pain was previously stable with opioid analgesics and, based on clinical judgement, were able to convert to transdermal buprenorphine treatment were invited to participate. Quality of life was measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). RESULTS: Generalised estimating equations showed participants who completed at least one follow-up measurement (N = 80) over 4-weeks had a significant improvement in overall quality of life. Functional status only improved for social functioning. However, symptom severity decreased significantly for nausea/vomiting, pain, insomnia and constipation. CONCLUSIONS: The study provides initial evidence supporting transdermal buprenorphine for providing beneficial effects of improving quality of life and reducing severity of symptoms in Asian patients with cancer. RELEVANCE TO CLINICAL PRACTICE: The findings of this study can inform the clinical practice that the use of transdermal buprenorphine in cancer patients with pain may also reduce the severity of other symptoms and improve overall quality of life. TRIAL REGISTRATION DETAILS: This study was registered in ClinicalTrials.gov. Identifier: NCT04315831.

Safety and effectiveness of transdermal buprenorphine in cancer pain: An observational study in Taiwan (SOOTHE).

AIM: Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real-world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population. METHODS: This is an open-labeled, multicenter, 4-week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI-SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs). RESULTS: A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p < .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug-related AEs in the Asian population with cancer pain. CONCLUSION: This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831).

Efficacy and safety of topical agents in the treatment of melasma: What's evidence? A systematic review and meta-analysis.

BACKGROUND: Various topical agents have been used to treat melasma; however, a large-scale evaluation among the currently available treatment is lacking. OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of topical agents for melasma. METHODS: The MEDLINE, Embase, Web of Science, Cochrane, and Alt-Healthwatch databases were searched in November 2021. Original studies that reported pre- and post-treatment Melasma Area Severity Index (MASI)/modified Melasma Area Severity Index (mMASI) scores and/or adverse effects (AEs) were eligible for inclusion. The main outcome was the efficacy analyzed by the changes in the pre- and post-treatment with standardized mean difference (SMD) of MASI/mMASI scores; the AEs were calculated with incidence proportion by the reported percentage of skin irritations. RESULTS: A total of 45 studies (2359 patients) and 55 studies (4539 patients) met the inclusion criteria for efficacy and AEs, respectively. Hydroquinone (HQ) monotherapy (SMD -1.3, 95% CI [-1.6 to -1.0]), HQ-containing combination therapy (-1.4, [-1.7 to -1.1]), cysteamine (-1.6, [-2.0 to -1.2]), tranexamic acid (-1.5, [-2.0 to -1.1]), azelaic acid (-1.3, [-1.7 to -1.0]), and kojic acid (-0.9, [-1.3 to -0.5]) demonstrated comparable efficacy, while zinc sulfate did not exhibit statistically significant improvement (-1.2, [-2.7 to 0.4]). HQ-containing combination therapy (50.9%) and cysteamine (42.2%) demonstrated the highest incidence of irritation, while azelaic acid (18.7%), kojic acid (5.3%), and tranexamic acid (0.8%) revealed a lower risk. CONCLUSIONS: In this meta-analysis, non-HQ agents except zinc sulfate may be considered as an alternative to HQ-containing agents. However, treatment should be guided by patient's tolerance, availability, and physicians' experience.

Acute radiation dermatitis among patients with nasopharyngeal carcinoma treated with proton beam therapy: Prognostic factors and treatment outcomes.

A high incidence of severe acute radiation dermatitis (ARD) has been reported for cancer patients treated by proton beam therapy (PBT). This observational study investigated the prognostic factors and treatment outcomes of ARD among patients with nasopharyngeal carcinoma (NPC) treated with PBT. Fifty-seven patients with newly diagnosed NPC and treated with PBT were enrolled. ARD was recorded weekly based on the criteria of Common Terminology Criteria for Adverse Events version 4.0 at treatment visits (1st to 7th weeks) and 1 week (8th week) and 1 month (11th week) after the completion of PBT. The maximum ARD grade was 1, 2, and 3 in 26 (45.6%), 24 (42.1%), and 7 (12.3%) of the patients, respectively. The peak incidence of grade 2 and 3 ARD was observed during the period of the 6th to 8th weeks. Treatment of ARD included topical corticosteroid alone in 24 (42.1%) patients, topical corticosteroid plus silver sulfadiazine in 33 (57.9%) patients, and non-adhering silicone dressing to cover severe skin wound area in 25 (43.8%) patients. In the 11th week, most grade 2 and 3 ARD had disappeared and 93.0% of the patients had ARD of grade 1 or lower. In the binary logistic regression model, we identified habitual smoking (odds ratio [OR]: 5.2, 95% confidence interval [CI]: 1.3-18.8, P = .012) and N2 to N3 nodal status (OR: 4.9, 95% CI: 1.6-15.4, P = .006) as independent predictors of grade 2 and 3 ARD. The results show ARD is a major concern for patients with NPC treated with PBT, especially those with habitual smoking or advanced nodal status. Topical corticosteroid, silver sulfadiazine, and non-adhering silicone dressing are effective for treating ARD induced by PBT.