Journal of the Chinese Medical Association : JCMA最新文献

Background: Achalasia is a rare disease of gastrointestinal motility characterized by impaired esophageal peristalsis and reduced esophageal sphincter relaxation. However, data on its epidemiology and outcomes in Taiwan are limited. This study aimed to assess the incidence, characteristics, and clinical management of achalasia in Taiwan.

Methods: Patients who were newly diagnosed with achalasia between 2001 and 2013 were recruited from the Taiwan National Health Insurance Research Database. The study obtained data on the age, sex, urbanization, socioeconomic status, area of residence, diagnostic methods, and interventional management of the patients. Incidence, diagnostic modalities, treatment methods, malignancy, and mortality outcomes were analyzed.

Results: In total, 206 new achalasia cases were identified. The mean annual incidence in Taiwan was 1.64 (95% confidence interval 1.22-2.05) per 100,000 persons. The mean age of the patients at diagnosis was 51.8 years. The age-specific incidence of achalasia peaked in patients aged between 70-80 years and above 80 years. For achalasia diagnosis, endoscopy, computed tomography (CT), barium studies, and manometry were performed in 123 (59.71%), 97 (47.09%), 49 (23.79%), and 11 patients (5.34 %), respectively. During long-term follow-up, seven patients (3.39%) developed esophageal cancer, and 39 patients (18.93%) died. The median survival was 10.65 years after achalasia diagnosis, with a 10-year survival rate of 76.22%.

Conclusion: This is the first population-based epidemiological study on achalasia in Taiwan, revealing the incidence of achalasia before the era of high-resolution manometry. Clinicians should be vigilant about the development of esophageal cancer and mortality during long-term follow-ups. There is also room to enhance the utilization of various diagnostic tools for achalasia.

Background: Limited information is available regarding the clinical features and outcomes of advanced human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) in Taiwan, despite expanding treatment options for this distinct subtype. The present study explored the clinical features and outcomes of HER2-mutant NSCLC in a real-world setting.

Methods: Relevant data were collected from patients with advanced or recurrent HER2-mutant NSCLC who received systemic therapy between 2011 and 2021 and were followed up until 2022 at two medical centers in Taiwan. Clinical features, treatment responses, and survival-associated factors were analyzed.

Results: This study included 45 patients (median age: 59.7 [range: 41.3-78.7] years). A775_G776insYVMA was the most common NSCLC subtype (57.8%), followed by G778_P780dup (11.1%). Approximately 53.3% of the patients received first-line platinum-based chemotherapy (PC) alone, whereas 13.3% received PC combined with an immune checkpoint inhibitor (ICI). The median overall survival (OS) and progression-free survival (PFS) after first-line therapy were 25.8 and 4.4 months, respectively. The objective response rate was generally higher in patients receiving first-line PC + ICI than in those receiving PC alone (33.3% vs. 12.5%; p = 0.269). Furthermore, patients receiving PC + ICI had longer PFS than did those receiving PC alone (9.5 vs. 4.4 months; p = 0.131) and those receiving tyrosine kinase inhibitor/ICI monotherapy (9.5 vs. 0.5 months; p = 0.015). Compared with patients having other NSCLC subtypes, those carrying HER2 exon 20 insertion mutations had shorter median PFS (17.3 vs. 2.9 months; p = 0.043) and OS (not reached vs. 19 months; p = 0.031).

Conclusion: This study highlights the clinical features and outcomes of advanced HER2-mutant NSCLC in Taiwan. PC + ICI may be more effective than other regimens as first-line therapy. The prognostic role of HER2 exon 20 insertion mutations warrants further investigation.

Background: ABO-incompatible liver transplantation (ABOi LT) can now be successfully performed with standard pretransplant induction therapy. For patients with chronic end-stage liver disease (ESLD), ABOi LT can achieve long-term outcomes comparable to those of blood type-compatible (ABOc) LT. Outcomes of patients with acute liver failure (ALF) who undergo urgent transplantation surgery with a limited induction period should be further investigated.

Methods: Between 2004 and 2023, adult patients who underwent living donor liver transplantation (LDLT) at Taipei Veterans General Hospital were enrolled. Based on the chronicity of liver disease and the transplant type, patients were divided into 4 groups for outcome analysis: ALF patients who received ABOi LDLT, ALF patients who received ABOc LDLT, ESLD patients who received ABOi LDLT, and ESLD patients who received ABOc LDLT.

Results: Four instances of diffuse intrahepatic cholangiopathy (DIC) occurred in the ABOi LDLT group (n=3, 27.3% in group 1 and n=1, 2.6% in group 3, p=0.03). In ABOi LDLT patients, rituximab was administered closer to LT in group 1 (5 [3~6] days before LDLT) than that in group 3 (15 [14~22] days before LDLT) (p<0.01). Univariate analysis revealed that ALF, small graft-to-recipient weight ratio (GRWR), low rituximab dose (<210 mg/m 2) and postoperative rebound of isoagglutinin immunoglobulin M (IgM) antibody titers were factors contributing to an increased risk of DIC. Allograft loss eventually occurred in 3 of the 4 patients with DIC. Overall, ABOi LDLT showed inferior long-term outcomes for ALF (5-year patient survival: 62.3%/73.6%/74.1%/76.7% in groups 1/2/3/4, respectively, p=0.25).

Conclusion: ABOi LDLT achieved outcomes comparable to those of ABOc LDLT among ESLD patients but not among ALF patients. DIC results in a high risk of allograft loss; however, the combination of potent immunosuppressive agents and early recognition of antibody rebound and the initiation of salvage treatment may improve long-term outcomes among these patients.

Background: Noninfectious anterior uveitis shares genetic factors, including HLA-B27, with ankylosing spondylitis (AS). The aim of this study was to identify significant single nucleotide polymorphisms (SNPs) associated with noninfectious anterior uveitis in AS patients, which could help predict the risk of developing this condition and provide deeper insights into its genetic underpinnings.

Methods: A genome-wide association study (GWAS) was conducted utilizing the genomic data of 468 AS patients, including 90 with noninfectious anterior uveitis and 378 without it, from the Taiwan Precision Medicine Initiative. This study identified associated genes via SnpXplorer and developed a polygenic risk score (PRS) model to identify AS patients with increased risk of noninfectious anterior uveitis. Biological pathways were analyzed via Enrichr-KG and various databases.

Results: GWAS revealed two novel SNPs, rs1736952 and rs17354984, with p values < 5x10-8, and seventy-four SNPs with p values < 1x10-4. The associated genes were involved mainly in antigen presentation, interferon signaling, immune regulation pathways, ciliary movement, and neurodegeneration. An optimal PRS model was built using nineteen SNPs with an area under the curve of 0.907.

Conclusion: Our results revealed that two novel and significant SNP loci, rs1736952 and rs17354984, are strongly associated with noninfectious anterior uveitis in patients with ankylosing spondylitis. However, their roles in uveitis and other immune disorders warrant further investigation.

Background: Unlike conventional photon radiotherapy, particle therapy has the advantage of dose distribution. Carbon-ion radiotherapy is also advantageous in terms of biological effectiveness and other radiobiological aspects. These benefits lead to a higher response probability for previously known radioresistant tumor types. Therefore, Taipei Veterans General Hospital, which is located in the northern district of Taipei, built the first carbon-ion irradiation facility in Taiwan.

Methods: Taipei Veterans General Hospital completed a phase 1 trial to evaluate the safety of carbon-ion radiotherapy. Six patients (4 males and 2 females with prostate adenocarcinoma, sacral chordoma, hepatocellular carcinoma, lung adenocarcinoma, or parotid high-grade carcinoma) were enrolled in this study. The mean age of the patients was 62.7 years. The mean dose was 57.3 Gy(RBE) (fraction range, 4-16 Gy(RBE)).

Results: During this phase 1 trial, all patients were monitored for 3 months to evaluate acute toxicity and short-term outcomes after treatment with carbon irradiation. Only 2 patients experienced grade 2 toxicity, which resolved without medication 1 month after completing treatment. The tumor response demonstrated 1 complete response, 1 partial response, and 4 cases of stable disease.

Conclusion: Carbon-ion radiotherapy was determined to be an effective and safe treatment.

Background: Acute carbon monoxide poisoning (COP) has been a common cause of emergency hospital visits over the past decade. Besides the immediate symptoms of poisoning, carbon monoxide exposure can cause various long-term complications, especially delayed neurological sequelae (DNS) and myocardial injury (MI).

Methods: This study retrospectively enrolled 502 patients with COP, including complete collection data, from the Taiwan National Poison Control Center between January 1, 2000, and December 31, 2015. After collecting the relevant clinical and laboratory data, multivariate logistic regression analysis was performed to investigate the associations between potential predictors and risk factors, hazard ratio (HR), and confidence intervals (CI).

Results: The cumulative incidence rates were 12.0% and 19.7% for DNS and MI, respectively. A Glasgow Coma Scale (GCS) score of <9 (HR 2.55; 95% CI: 1.52-4.27) and rhabdomyolysis (HR 2.68; 95% CI: 1.59-4.53) were identified as individual indicators of DNS in patients with COP. However, a greater risk for MI was associated with a GCS score of <9 (HR 2.50; 95% CI: 1.67-3.74), rhabdomyolysis (HR 4.91; 95% CI: 3.28-7.35), acute renal impairment (HR 2.43; 95% CI: 1.59-3.71), and leukocytosis (HR 9.55; 95% CI: 3.88-23.50). Hyperbaric oxygen therapy for patients with COP was more beneficial for DNS (HR 0.64; 95% CI: 0.34-1.20) than for MI (HR 1.94; 95% CI: 0.94-4.01).

Conclusion: Early differentiation of risk factors between DNS and MI contributes to an effective evaluation of patients with acute COP and the provision of appropriate therapy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene. This review highlights the increasing recognition of intracerebral hemorrhage (ICH) as a significant manifestation of CADASIL, often predominantly characterized by ischemic strokes and vascular dementia. Recent studies indicate that the prevalence of ICH in CADASIL patients ranges from 0.5% to 33.3%, the variability of which is mainly influenced by ethnicity. In East Asian cohorts, where specific NOTCH3 mutations like p.R544C and p.R75P are more prevalent and have been associated with a higher rate of ICH, suggesting a link between these mutations and the hemorrhagic risk. Hypertension, as with other etiologies of ICH, is a key risk factor in CADASIL patients, with 40-90% of those who experience ICH also having a history of hypertension. The presence of cerebral microbleeds (CMBs) and a high CMBs load are strongly associated with increased risk of ICH. Neuroimaging studies show that ICH in CADASIL patients predominantly occurs in the thalamus and basal ganglia. There is a notable spatial correlation between CMBs and subsequent ICH, suggesting that CMBs may serve as markers of microangiopathy in regions prone to vascular injury. CADASIL patients with ICH experience greater morbidity, higher mortality rates, and increased annual stroke recurrence risk compared to those with ischemic events. In summary, this review emphasizes the need for tailored management strategies that prioritize rigorous blood pressure control and the careful use of antithrombotic agents in CADASIL patients with a high burden of CMBs. By advancing our understanding of ICH in CADASIL, we aim to improve diagnostic and therapeutic approaches, ultimately enhancing patient outcomes and quality of life in this high-risk population.

Tadalafil is a selective phosphodiesterase type 5 (PDE5) inhibitor commonly used for the treatment of erectile dysfunction and benign prostatic hyperplasia. Its mechanism of action involves the inhibition of PDE5, leading to increased levels of nitric oxide and cyclic guanosine monophosphate in the corpus cavernosum, which facilitates smooth muscle relaxation. This article reviews studies using tadalafil in the treatment of cardiovascular diseases and emphasizes its potential advantages in conditions such as pulmonary arterial hypertension, atherosclerosis, coronary artery disease, myocardial infarction, heart failure, stroke, diabetic ulcers, and cardiomyopathy. Although tadalafil shows potential efficacy in treating cardiovascular disease, further experimental studies are needed to clarify its pharmacological effects on cardiovascular protection beyond PDE5 inhibition.

Antrodia cinnamomea ( Ac ), also known as "Niu-Chang-Chih" in Chinese, is a valuable fungus that has been widely used as medicine and food among indigenous people in Taiwan. Ac is rich in polysaccharides ( Ac -PS), making it a promising candidate for adjunctive therapy in cancer and inflammation conditions. There are two types of Ac -PS: general (non-sulfated) PS ( Ac -GPS) and sulfated PS ( Ac -SPS). This review highlights that both Ac -GPS and Ac -SPS possess immunomodulatory, anti-inflammatory, and anticancer properties. Each type influences interleukin signaling pathways to exert its anti-inflammatory effects. Ac -GPS is particularly effective in alleviating inflammation in the brain and liver, while Ac -SPS shows its efficacy in macrophage models. Both Ac -GSP and Ac -SPS have demonstrated anticancer effects supported by in vitro and in vivo studies, primarily through inducing apoptosis in various cancer cell lines. They may also synergize with chemotherapy and exhibit antiangiogenic properties. Notably, Ac -SPS appears to have superior anticancer efficacy, potentially due to its sulfate groups. Furthermore, Ac -SPS has been more extensively studied in terms of its mechanisms and effects on lung cancer compared with Ac -GPS, highlighting its significance in cancer research. In addition, Ac -SPS is often reported for its ability to activate macrophage-mediated responses. Clinically, Ac -GPS has been used as an adjunctive therapy for advanced lung cancer, as noted in recent reports. However, given the numerous studies emphasizing its anticancer mechanisms, Ac -SPS may exhibit greater efficacy, warranting further investigation. This review concludes that Ac -derived Ac -GPS or Ac -SPS have the potential to be developed into functional health supplements or adjunctive therapies, providing dual benefits of anti-inflammatory and anticancer effects.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Critically ill patients with COPD exacerbations may require invasive mechanical ventilation (IMV). Ventilator-associated pneumonia (VAP) commonly occurs in the intensive care unit (ICU) and is usually associated with high mortality. Current studies on the association between COPD and VAP are limited. This work compared the causes and clinical outcomes of VAP in patients with and without COPD in Taiwan.

Methods: This retrospective observational study was conducted at the Chiayi Chang Gung Memorial Hospital. Patients diagnosed with VAP were enrolled between January 2015 and December 2019. The COPD diagnosis was based on postbronchodilator pulmonary function tests. We compared the bacterial cause, ICU and hospital stay length, IMV duration and mortality rates in patients with and without COPD.

Results: A total of 175 patients with VAP were enrolled, 44% of whom presented had preexisting COPD. The disease severity on the day of admission was similar in both groups. Microorganisms were identified in 83 (47%) patients, with Pseudomonas aeruginosa , Acinetobacter spp., and Klebsiella pneumoniae being the most common pathogens. The proportion of multidrug resistant isolates showed no significant differences between groups. Most patients underwent antibiotic treatment before VAP onset. The length of ICU and hospital stays and IMV duration after VAP onset were similar between the two groups, as well as ICU mortality, in-hospital mortality, and 14-day mortality.

Conclusion: Our study revealed that COPD was not associated with worse clinical outcomes in patients with VAP. No significant differences in bacterial cause were observed between the two groups.