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Abstract Background Fluoropyrimidines, including 5-fluorouracil and capecitabine, are the most common chemotherapeutic agents for colorectal carcinoma. Although previous studies have suggested varying degrees of cardiotoxicity with these drugs, there is a notable lack of large-scale investigations with appropriate control groups. This study aimed to evaluate cardiovascular outcome among colorectal carcinoma patients treated with fluoropyrimidines. Methods A retrospective propensity score- matched cohort study was conducted in patients diagnosed with colorectal carcinoma between January 1, 1993 and December 31, 2021 at public hospitals in Hong Kong. Cardiovascular outcomes in patients prescribed fluoropyrimidines were compared with controls. Further analyses to compare 5-fluroracil and capecitabine were performed. Results A total of 51,888 colorectal carcinoma patients were identified. After 1:1 propensity score matching, 21,216 patients were included in the final analysis, with 10,608 patients in each group. 1.06% patients experienced a major adverse cardiovascular event (MACE) at 1 year. There was no significant difference in MACE risk between the two groups (HR 0.91, 95% confidence interval (95%CI): 0.70–1.18, p = 0.46). Risk of cardiovascular death was similar between the two groups (HR 1.05, 95%CI: 0.69–1.60, p = 0.82). Subgroup analysis did not demonstrate a statistically significant elevated risk of MACE during fluoropyrimidine use in high-risk patient groups. Further comparison of 5-fluorouracil and capecitabine did not reveal a difference in MACE (0.80% vs. 0.98%; HR 1.09, 95%CI: 0.64–1.85, p

Abstract Background Amiodarone is one of the most commonly used anti-arrhythmic agents. Amiodarone pulmonary toxicity is a potentially fatal adverse effect associated with amiodarone use. Previous studies on the epidemiology and risk factors for amiodarone pulmonary toxicity showed diverse results. Methods A multicenter retrospective cohort study was conducted to identify clinic-epidemiologic markers associated with amiodarone pulmonary toxicity for development of a prediction rule. Patients taking amiodarone who were managed in 3 centres in Hong Kong from 2005 to 2015 were included in this study. Penalized logistic regression was used to model the outcome as it is rare. Results A total of 34 cases with amiodarone pulmonary toxicity were identified among 1786 patients taking amiodarone for at least 90 days from 2005 to 2015. The incidence of amiodarone pulmonary toxicity was estimated to be 1.9%. The risk factors for amiodarone pulmonary toxicity included advanced age (OR 1.047, 95% CI 1.010–1.085, p = 0.013), ventricular arrhythmia (OR 2.703, 95% CI 1.053–6.935, p = 0.039), underlying lung disease (OR 2.511, 95% CI 1.146–5.501, p = 0.021) and cumulative dose of amiodarone (OR 4.762, 95% CI 1.310–17.309 p = 0.018). Conclusions The incidence of amiodarone pulmonary toxicity in Chinese patients in Hong Kong is estimated to be 1.9% in this study. Age, underlying lung disease, ventricular arrhythmia and cumulative dose of amiodarone are associated with the development of amiodarone pulmonary toxicity. A prediction rule was developed to inform the risk of developing amiodarone pulmonary toxicity.

Abstract Background Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease. Objective To apply a metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration to investigate the effect of border restriction as a public health measure to limit outbreak of coronavirus disease 2019. Methods We apply a modified metapopulation SEIR model with inspected migration with simulating population migration, and incorporating parameters such as efficiency of custom inspection in blocking infected travelers in the model. The population sizes were retrieved from government reports, while the number of COVID-19 patients were retrieved from Hong Kong Department of Health and China Centre for Disease Control (CDC) data. The R 0 was obtained from previous clinical studies. Results Complete border closure can help to reduce the cumulative COVID-19 case number and mortality in Hong Kong by 13.99% and 13.98% respectively. To prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R 0 to below 1.6 was necessary, apart from having complete border closure. Conclusions Early complete travel restriction is effective in reducing cumulative cases and mortality. However, additional anti-COVID-19 measures to reduce local R 0 to below 1.6 are necessary to prevent COVID-19 cases from overwhelming hospital isolation facilities.

Unilateral Nevoid Telangectasia Syndrome (UNTS) is characterized by superficial telangiectasias in a unilateral distribution. Vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of UNTS in patients with underlying hepatic disease.  We report a case of a patient with UNTS accompanied by chronic hepatitis C virus infection, with a normal serum estrogen profile and strong positive immunohistochemical staining of lesional skin with VEGF.

Based upon regulatory and food industry–driven food safety standards, there is a need for rapid, accurate methods for assessing sanitary conditions. A commonly used assay is based on the assessment of the biochemical molecule adenosine triphosphate (ATP). A more recent assay, the total adenylate homologue–based (AXP) assay, targets the cumulative presence of ATP and its dephosphorylated homologues, adenosine diphosphate and adenosine monophosphate. Yet there is little information that compares the practical performance of these two assays. This work examined these two assay types with a comparative study in a grade A dairy foods processing plant and a licensed and inspected meat processing facility. A total of 1,920 concomitant analyses were conducted with main variables of assay type, processing facility type, and hygiene zone category. Statistical process control methodology was used to calculate 95% confidence control limits; data beyond those limits were considered contamination events. Results demonstrated that overall, the AXP assay detected contamination events approximately two times more often than the assay based on ATP only. This increase in the rate of contamination event detection was especially prevalent in the meat processing facility, where across all hygienic zones, there were 38 versus 85 contaminations events detected for the ATP and AXP assays, respectively. Across hygiene zones, the AXP data displayed either an equal or an increased incidence of soil detection compared with data from the ATP assay. This study provides applied evidence that assays solely dependent on ATP concentrations are less able to detect soil contaminants under conditions that favor ATP dephosphorylation reactions. [ABSTRACT FROM AUTHOR]

Rationale: Patients with asthma were advised to avoid coronavirus disease (COVID-19) and comply with medication during the COVID-19 pandemic. Respiratory tract infection is a common cause of asthma exacerbations. There has not been evidence suggesting the link between COVID-19 and asthma exacerbation, especially in places with dramatic responses in infection control with universal masking and aggressive social distancing. Objectives: To assess the number for admissions of asthma exacerbations in January to April 2020 in Hong Kong with reference to admission in the past 5 years. Methods: Admission records of asthma exacerbations were retrieved from the Clinical Data Analysis and Reporting System. Patients aged 18 years or older with a known history of asthma admitted for asthma exacerbation were included. Log-linear was used to model count, with year and masking used as covariate and further analysis on ambient temperature and length of hospital stays. Fisher's exact test was used to compare the mortality rate and mechanical ventilation between the periods. Admissions for myocardial infarction, ischemic stroke, and gastric ulcer were included as controls. Results: The number of admissions for asthma exacerbations significantly decreased by 53.2% (95% confidence interval [CI], 50.4-55.8%) in 2020 compared with monthly average admission in 2015-2019, with a higher magnitude of decrease compared with control diagnoses. Admissions for asthma exacerbations decreased by 2.0% (95% CI, 1.8-2.2%) with every 1°C (1.8°F) increase in temperature and by 0.8% with every 1% increase in masking (95% CI, 0.8-0.9%). Conclusions: Hospitalization number for asthma exacerbations significantly decreased in early 2020, with similar length of stay. This was observed with concomitant practice of universal masking and social distancing during the COVID-19 pandemic in Hong Kong. We proposed that universal masking and social distancing reduced respiratory viral infection, leading to fewer hospital admissions for asthma exacerbations. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic has disrupted tuberculosis (TB) services in many countries, but the impacts on sites of involvement, drug susceptibility, smear positivity and clinical outcomes, and clinical outcomes of co-infection with influenza and COVID-19 remain unclear. Descriptive epidemiological study using episode-based and patient unique data of tuberculosis from Hospital Authority's territory-wide electronic medical record database, comparing baseline (January 2015-December 2019) and COVID-19 period (January 2020-December 2022), followed by univariate and multivariate analyses. Effects of co-infection with influenza and COVID-19 were investigated. The study included 10,473 episodes of laboratory-confirmed TB, with 6818 in baseline period and 3655 during COVID-19 period. During COVID-19 period, TB patients had a lower proportion of smear positivity (49.2 % vs 54.7 %, P < 0.001), and fewer cases of extrapulmonary TB (7.0 % vs 8.0 %, P = 0.078) and multidrug resistant TB (1.0 % vs 1.6 %, P = 0.020). Mortality was higher in TB patients with COVID-19 coinfection (OR 1.7, P = 0.003) and influenza coinfection (OR 2.6, P = 0.004). During COVID-19 period, there were higher rates of treatment delay (20.5 % vs 15.5 %, P < 0.001) and episodic death (15.1 % vs 13.3 %, P = 0.006). Factors associated with higher mortality included age ≥ 70 years (OR 7.24), treatment delay (OR 2.16), extrapulmonary TB (OR 2.13). smear positivity (OR 1.71) and Charlson comorbidity index score ≥ 3 (OR 1.37). Higher mortality was observed with co-infection by influenza (OR 1.18) and COVID-19 (OR 1.7). The epidemiology and outcomes of TB were changed during COVID-19 period. Mortality was higher during COVID-19 period and with co-infection by influenza and COVID-19. [ABSTRACT FROM AUTHOR]

This paper develops a composite likelihood-based approach for multiple changepoint estimation in multivariate time series.We derive a criterion based on pairwise likelihood and minimum description length for estimating the number and locations of changepoints and for performing model selection in each segment. The number and locations of the changepoints can be consistently estimated under mild conditions and the computation can be conducted efficiently with a pruned dynamic programming algorithm. Simulation studies and real data examples demonstrate the statistical and computational efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

Abstract Background Sinew acupuncture is a new modality of acupuncture in which needles are inserted into acupoints, ashi points or spasm points of sinew and muscles along the meridian sinew pathway. A previous observational study revealed that sinew acupuncture has immediate analgesic effects on various soft tissue injuries, including knee injuries. However, no rigorous trials have been conducted. This study aims to examine whether sinew acupuncture can safely relieve pain and symptoms of knee osteoarthritis (KOA) and improve patients’ functional movement and quality of life. Methods/design A randomized, sham-controlled, patient- and assessor-blinded trial will be conducted to compare the efficacy of sinew acupuncture and sham acupuncture. Subjects will be assessed by the physician and acupuncturists. A sample of eighty-six eligible subjects will be randomized into either the sinew acupuncture group or the sham acupuncture group. The intervention will be performed in the Hong Kong Tuberculosis Association Chinese Medicine Clinic cum Training Centre of the University of Hong Kong by acupuncturists with over 3 years of acupuncture experience. Subjects will receive 10 sessions of interventions for 4 weeks, followed by a 6-week follow-up. The visual analogue scale (VAS) score at week 4 will be the primary outcome. The Western Ontario and McMasters University Osteoarthritis Index (WOMAC), Timed Up & Go Test (TUG), 8-step Stair Climb Test (SCT) and the 36-Item Short Form Survey (SF-36) will be secondary outcomes. Discussion Sinew acupuncture is a potential alternative non-pharmacological therapy for KOA. This rigorous trial will expand our knowledge of whether sinew acupuncture reduces pain intensity and improves symptoms, functional movements, and quality of life of KOA patients. Trial registration The study was registered at ClinicalTrials.gov (Identifier: NCT03099317) in March 2017.

Purpose: This study investigated the status of spontaneous otoacoustic emissions (SOAEs) on cochlear function in a cohort of male/female participants with a wide age range. It examined whether there was a correlation between the presence of SOAEs and measurements of transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), SOAEs and extended high-frequency (EHF) hearing thresholds. Methods: 463 participants (222 male, 241 female; age range 20–59 years) with pure-tone thresholds ≤25 dB HL for octave frequencies of 500–8000 Hz were included in the study, divided into three age groups (20–29, 30–39, and 40–59 years). Evaluations included EHF (9000–16,000 Hz) hearing thresholds and TEOAE, DPOAE and SOAE measures. Results: Multiple regression models showed that participants with SOAEs had larger expected amplitudes and signal-to-noise ratios (SNRs) for TEOAE and DPOAE responses than participants without SOAEs, holding gender and age variables constant. Spearman correlation tests identified deterioration in TEOAE and DPOAE amplitudes and SNRs, and EHF hearing thresholds with age in participants without SOAEs. Among participants with SOAEs, no significant decreases in TEOAE and DPOAE measures were shown in participants with older age. Nonetheless, as expected, EHF hearing thresholds did become worse with age, with or without SOAEs. Conclusions: Participants with identifiable SOAEs had greater TEOAE and DPOAE amplitudes and SNRs than participants without SOAEs. SOAEs appear to be a useful marker of cochlear health in adults.

Influenza is an important respiratory viral pathogen in adults, with secondary bacterial pneumonia being a common complication. While pneumococcal vaccines can prevent pneumococcal pneumonia and invasive pneumococcal disease, whether they can also prevent the severe in-hospital outcomes among patients hospitalized for influenza has not been examined. A territory-wide retrospective study was conducted in Hong Kong, which included all adult patients having chronic airway diseases (asthma, bronchiectasis, and chronic obstructive pulmonary disease) hospitalized for influenza and who had received seasonal influenza vaccine. The occurrence of secondary bacterial pneumonia, mortality, and other severe in-hospital outcomes were compared among subjects with or without pneumococcal vaccination. There was a total of 3066 eligible patients who were hospitalized for influenza in public hospitals in Hong Kong from 1 January 2016 to 30 June 2023. Completed pneumococcal vaccination with PSV23/PCV13 conferred protection against secondary bacterial pneumonia, all-cause mortality, and respiratory cause of mortality with adjusted odds ratios of 0.74 (95% CI = 0.57–0.95, p = 0.019), 0.12 (95% CI = 0.03–0.53, p = 0.005), and 0.04 (95% CI = 0.00–0.527, p = 0.0038), respectively.

The American Dream--the perception that upward social mobility depends on effort--is a central cultural ethos in the United States. The belief in upward social mobility is not unique to Americans, and cultural groups across the world endorse it to varying degrees. The current study aims to examine cross-cultural trends in perceived mobility and to test possible mechanisms that may explain changes in perceived mobility. Using a dataset of over 1.4 million participants across 167 countries from 2005 to 2019, we comprehensively document cultural variations in perceived mobility. Citizens in Bhutan, Qatar, and Uzbekistan reported the highest levels of perceived mobility, and the United States ranked 107. We further examined the trajectories of perceived mobility across a 15-year timespan and found rapid declines in perceived mobility in countries experiencing sociopolitical crises (e.g., in Syria and Hong Kong). Multilevel analyses revealed high-income individuals are 32% (95% confidence interval, CI [24%, 39%]) more likely to perceive mobility than low-income individuals, and the level of disparity did not decrease over time. Preregistered time-series analyses showed education privatization and economic condition Granger-cause perceived mobility, but these temporal associations showed heterogeneity across countries. Overall, we performed the world's largest global monitor of perceived mobility and discussed how the cultural value of perceived mobility unfolds in social, economic, and political contexts. [ABSTRACT FROM AUTHOR]

Abstract There are a range of approaches to compare differences between or among optimum nitrogen (N) fertilizer rates resulting from different management practices; however, this goal lacks statistical standardization. To provide the statistical rigor needed to give clear recommendations for greater or less N need based on specific management practices, we propose a bootstrapping approach that resamples residuals with replacement. While bootstrapping is not new to data processing in agronomic fields, we provide an example of how to conduct residual‐resampled bootstrapping with nonlinear regression to identify differences in response curves, optimum N rates, and maximum yields using the FertBoot package in R. Our example dataset provides clear evidence of the value of the bootstrapping approach, as it can aid in determining significant differences between even relatively small differences in optimum N rate. We encourage adoption of this approach as a way to accurately evaluate differences in optimum fertilizer levels between or among treatments to better inform future agronomic decision making.

Background: Cellular dermatofibromas (CDFs) are uncommon benign fibrous histiocytomas with histologic patterns resembling malignancies. Despite their benign nature, CDFs can recur and metastasize. Physicians are uncertain about the management of CDF, given its resemblance to dermatofibrosarcoma protuberans., Objective: This review aims to review CDF's clinical and histologic features, differentiate it from similar presenting malignancies, and discuss treatments and outcomes for better clinical management., Materials and Methods: In April 2024, a PubMed and Google Scholar search was completed using "cellular dermatofibroma" through the University of California Davis Medical School's library databases. The search included meta-analyses, randomized controlled trials, observational studies, reviews, and case studies published within the past 70 years. References from retrieved articles were utilized as additional resources., Results: Clinical signs of CDF include firm, skin-colored to hyperpigmented lesions usually larger than 2 cm, typically on extremities. Currently, there are no definitive indicators for CDF recurrence or metastasis. Diagnosis requires microscopic and histopathologic examination, with surgical excision as the preferred treatment. Recurrence is not uncommon, while metastasis is rare., Conclusion: CDFs often develop in young/middle-aged adults with a tendency to recur and in rare cases can metastasize. Future studies could explore lesion characteristics that are associated with potential for recurrence and metastasis., (Copyright © 2025 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Cutaneous melanoma can lead to metastasis, and it is associated with high mortality. Currently, there are no widely accepted immunohistochemistry markers for melanoma prognosis in routine staging. Preferentially expressed antigen in melanoma (PRAME) is a possible biomarker for prognosis in several noncutaneous neoplasms. Ki-67 is a cell proliferation marker correlated with poor outcomes in many cancers. This study assessed PRAME and Ki-67 as potential prognostic markers for sentinel lymph node outcomes and survival among melanoma patients. This is a retrospective study analyzing cutaneous melanoma cases from a Brazilian cancer center (2005-2021). All cases were tested using immunohistochemistry to evaluate PRAME expression and Ki-67 index. Descriptive analysis, Spearman correlations, means comparison, Kaplan-Meier analysis, χ 2 , and Cox models were performed. In univariate analysis of 123 cutaneous melanoma cases, high extent ( P = 0.0267) and elevated intensity ( P = 0.043) of PRAME were associated with decreased overall survival. The Ki-67 index was associated with overall survival ( P = 0.05) and sentinel lymph node status ( P = 0.0403), with a positive correlation between the markers ( P = 0.0004) and between Ki-67 and Breslow thickness ( P = 0.0001). However, in multivariate analysis, only Breslow thickness significantly influenced overall survival ( P = 0.0003). Then, the present results can suggest that elevated PRAME and Ki-67 expression are associated with poor overall survival in cutaneous melanoma; however, in multivariate analysis, only the Breslow thickness had a significant influence. These findings highlight the potential of PRAME and Ki-67 as prognostic markers, opening frontiers that could improve strategies for treating cutaneous melanoma., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Allergic contact dermatitis cannot be reliably differentiated from other forms of spongiotic/eczematous dermatitis by histology alone. Textbooks and recent studies have variably supported the specificity of dermal eosinophils, eosinophilic spongiosis, and Langerhans cell collections, among other features., Objective: To assess which histopathologic features favor a diagnosis of allergic contact dermatitis., Methods: In this case control study with prospective validation, patients were evaluated by patch testing and skin biopsy. Lesional histopathologic features were independently assessed., Results: One hundred seventy cases fulfilled inclusion criteria. Langerhans cell collections were more likely to be found in allergic contact dermatitis (29/111, 26%) (P = .03). Heavy dermal eosinophilic infiltration was associated with diagnoses other than allergic contact dermatitis. No significant differences were found for any other predictor variables., Limitations: Mostly retrospective study with small validation sample., Conclusion: This largest study to date is the first to independently confirm Langerhans cell collections as the single histopathologic feature most closely associated with allergic contact dermatitis., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Due to the immune-mediated nature of non-infectious cutaneous vasculitis, skin biopsy specimens are often submitted for direct immunofluorescence (DIF) testing when vasculitis is considered clinically. However, evidence regarding the clinical value of DIF has not been rigorously appraised., Objective: In this scoping review, we aimed to systematically evaluate the peer-reviewed literature on the utility of DIF in vasculitis to assist with the development of appropriate use criteria by the American Society of Dermatopathology., Methods: Two electronic databases were searched for articles on DIF and vasculitis (January 1975-October 2023). Relevant case series involving more than or equal to three patients, published in English, and with full-text availability were included. Additional articles were identified manually via reference review. Due to study heterogeneity, findings were analyzed descriptively., Results: Of 255 articles identified, 61 met the inclusion criteria. Cumulatively representing over 1000 DIF specimens, several studies estimated DIF sensitivity to be 75%. While vascular immunoglobulin A (IgA) deposits on DIF were associated with renal disease, other systemic associations were inconsistent. Vascular IgG deposition may be overrepresented in ANCA-associated vasculitis. Granular vascular and epidermal basement membrane zone Ig deposition differentiated hypocomplementemic from normocomplementemic urticarial vasculitis. Few studies have assessed the added value of DIF over routine microscopy alone in vasculitis., Conclusions: This scoping review discovered that DIF testing for vasculitis has been performed not only for diagnostic confirmation of vasculitis but also for disease subtype classification and prediction of systemic associations. Future studies on test sensitivity of DIF compared to that of histopathology are needed., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The diagnosis of cutaneous T-cell lymphoma (CTCL) remains challenging. Demonstration of a clonal T-cell population using T-cell receptor (TCR) gene rearrangement studies by next-generation sequencing (NGS) has been explored in several studies. This review summarizes the current literature on NGS-based sequencing methods for the assessment of TCR clonality in the evaluation of atypical cutaneous lymphoid infiltrates and CTCL on behalf of the American Society of Dermatopathology Appropriate Use Criteria Committee (lymphoproliferative subgroup). PubMed was searched for relevant articles, including CTCL and NGS, for clonality from 1967 to 2022. Thirteen studies were included in the analysis. The skin was the most commonly assayed compartment with TCR NGS. Sensitivity for TCR NGS in the skin ranged between 69% and 100%, compared to 44%-72% for polymerase chain reaction (PCR)-capillary electrophoresis. Specificity for TCR NGS in the skin ranged from 86% to 100%, compared to 77%-88% for PCR capillary electrophoresis. TCR NGS was also reported to have potential prognostic value in CTCL and can also be used to detect relapse and/or minimal residual disease after treatment., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The COVID-19 pandemic brought not only a huge healthcare challenge to the world but also introduced many questions of how the human immune system reacts to counter viral invasion, including vaccination. Unlike most vaccinations that are not usually linked to any specific skin eruptions, COVID-19 vaccination has been linked to a variety of skin lesions. In this paper, we present two patients who developed granulomatous skin lesions post-COVID-19 vaccination, one patient has generalised granuloma annulare (GA) and the other patient develops localised GA. Both patients have good responses to treatment regimens containing systemic corticosteroids. We review the literature pertaining to COVID-19-linked skin diseases, particularly granulomatous diseases and discuss the possible pathomechanism of granulomatous eruptions in relation to COVID-19 vaccination., Competing Interests: None to declare., (© 2024 The Author(s). Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Competing Interests: None dislosed.