Relationship between palliative care consultation service and end-of-life outcomes.

PURPOSE: Palliative care consultation service (PCCS) is currently utilized to provide care to terminal patients in Taiwan. However, there is little research on the relationship between PCCS and end-of-life outcomes. This study aimed to elucidate the association between PCCS and end-of-life outcomes in terminal cancer patients. METHODS: Retrospective chart reviews of terminal cancer patients who consulted the PCCS of a medical center in Taiwan from January 2007 to December 2012 were performed. Data on 1369 patients were recorded, which included details of outcomes such as discharge from hospital, transfer to hospice ward, and death after PCCS termination. Other variables such as demographics, disease-related information, symptoms, and psychosocial needs were also evaluated. Logistic regression models were employed to estimate the adjusted odds ratios and related 95% confidence intervals. RESULTS: The Eastern Cooperative Oncology Group performance status, timing of do-not-resuscitate (DNR) signature, constipation, and spiritual problems experienced by the patients were important predictors for terminal cancer patients who were discharged from the hospital or had expired at the time of PCCS termination. Age, gender, primary cancer diagnosis, timing of DNR signature, constipation, and other physical symptoms were the key predictors for patients who were transferred to the hospice ward or had expired. CONCLUSIONS: This study confirms the outcomes of PCCS and highlights the important predictors for patients at PCCS termination. These factors can be targeted to improve and enhance the quality of PCCS rendered in the future.

Association between pneumococcal pneumonia and venous thromboembolism in hospitalized patients: A nationwide population-based study.

BACKGROUND AND OBJECTIVES: This was a nationwide population-based retrospective cohort study to investigate the risk of developing deep-vein thrombosis (DVT) and pulmonary embolism (PE) in patients with a pneumococcal pneumonia. METHODS: We analysed data from 1998 to 2010 from the Taiwan National Health Insurance Database. The follow-up period was extended to the end of 2011. We identified patients with pneumococcal pneumonia and selected a comparison cohort matched for age, sex and diagnosis year at a ratio of one pneumococcal pneumonia patient to four control patients. We analysed the risks of DVT and PE by using Cox proportional hazards regression models, including gender, age and comorbidities. RESULTS: In total, 18,928 pneumococcal pneumonia patients and 75,712 controls were included in the study. The risks of developing DVT and PE were 1.78-fold (95% CI: 1.39-2.28) and 1.97-fold (95% CI: 1.43-2.72), respectively, in patients with pneumococcal pneumonia compared to the control cohort after adjusting for age, gender and comorbidities. The increased risks of DVT and PE were significant in patients who exhibited any comorbidity. The incidences of DVT and PE were highest in the first 4 weeks after pneumonia and remained slightly elevated from 13 weeks to 2 years after acute infection. CONCLUSION: Pneumococcal pneumonia should be considered a risk factor for DVT and PE, even after the patient has recovered from the acute infection.

LUBAC enables tumor-promoting LTß receptor signaling by activating canonical NF-κB.

Lymphotoxin ß receptor (LTßR), a member of the TNF receptor superfamily (TNFR-SF), is essential for development and maturation of lymphoid organs. In addition, LTßR activation promotes carcinogenesis by inducing a proinflammatory secretome. Yet, we currently lack a detailed understanding of LTßR signaling. In this study we discovered the linear ubiquitin chain assembly complex (LUBAC) as a previously unrecognized and functionally crucial component of the native LTßR signaling complex (LTßR-SC). Mechanistically, LUBAC-generated linear ubiquitin chains enable recruitment of NEMO, OPTN and A20 to the LTßR-SC, where they act coordinately to regulate the balance between canonical and non-canonical NF-κB pathways. Thus, different from death receptor signaling, where LUBAC prevents inflammation through inhibition of cell death, in LTßR signaling LUBAC is required for inflammatory signaling by enabling canonical and interfering with non-canonical NF-κB activation. This results in a LUBAC-dependent LTßR-driven inflammatory, protumorigenic secretome. Intriguingly, in liver cancer patients with high LTßR expression, high expression of LUBAC correlates with poor prognosis, providing clinical relevance for LUBAC-mediated inflammatory LTßR signaling.

The feasibility of targeted axillary dissection for breast cancer axillary surgery de-escalation after neoadjuvant therapy: A prospective cohort study.

PURPOSE: Targeted axillary dissection (TAD) after neoadjuvant therapy (NAT) includes removing of marked and sentinel lymph nodes (SLNs). The aim was to investigate the optimization of TAD localization techniques after NAT among breast cancer patients. METHODS: From November 2020 to 2022, we prospectively enrolled 107 lymph node-positive breast cancer patients in XX Hospital and received complete cycles of NAT. Patients were randomly divided into the following 3 groups before treatment: group A, marked node with clip (n=34); group B, marked node with 125I seed (n=32); and group C, marked node with clip and 125I seed (n=41). Dual tracers were used to search for SLNs after NAT. The main endpoint was the detection rate of marked nodes and false-negative rate (FNR). RESULTS: The detection rates using the TAD localization technique were 82.6% (28/34), 100% (32/32), and 100% (41/41) for groups A, B, and C, respectively (P>0.05). The FNR rates were 15.8%, 5.9%, and 5.6% among group A, B, and C, respectively (P>0.05). The FNR rates in cN1 patients were 5.1%, 2.7%, and 2.6%, among these three groups, respectively (P>0.05). The change in distance between 125I seeds and clips in axillary lymph nodes was <3 mm. The FNR rates of TAD guided by dye tracer, radiolabeled tracer, and dual tracers were 5.4%, 5.2%, and 3.4%, respectively (P>0.05). The negative predictive values were 93.0%, 93.0%, and 95.2%, respectively (P>0.05). CONCLUSION: Considering inexpensive and detect rate of 125I seeds, it is recommended that placement of 125I seeds to localize metastatic nodes in neoadjuvant setting. The TAD guided by dye tracer is also feasible for axillary de-escalation surgery after NAT in countries or regions without radiolabeled colloid.

Thromboembolic events following a pit viper bite from Protobothrops mucrosquamatus (Taiwan Habu): A report of two cases.

Protobothrops mucrosquamatus, also known as the Taiwan Habu, is a venomous snake prevalent in Taiwan. It is accountable for most snakebites in the region. The toxin of the Taiwan Habu has significant hemorrhagic potential. However, patients bitten by this snake often suffer more local injuries than systemic ones. This report presents two cases of individuals bitten by the Taiwan Habu who subsequently experienced thromboembolism. In the first case, an 88-year-old male, bitten on his fourth toe, suffered a cerebral infarction 32 hours post-bite. In the second case, an 82-year-old female, bitten on her ankle, experienced cardiac arrest 19 hours later. Both patients promptly received antivenom and showed no signs of coagulopathy either before or after the snakebite. However, elevated coagulation factor VIII levels were observed in the first case. Our aim is to understand the mechanism behind these thromboembolic events. This report emphasizes the unusually high level of coagulation factor VIIIa and highlights the need for further investigation into the mechanisms involved. Consequently, physicians should assess the risk of thromboembolic events in snakebite patients by evaluating coagulation factors during treatment.

Development and validation of a nomogram for predicting internal mammary sentinel node metastasis in breast cancer patients.

OBJECTIVE: Internal mammary nodes are important in breast cancer prognosis, but their diagnosis is often missed in clinical practice, leading to inaccurate staging and treatment. We developed a validated nomogram to predict the presence of internal mammary sentinel nodes (IMSN) metastasis. METHODS: A total of 864 sequential IMSN biopsy procedures from a prospective studies database of 1505 cases were used for model development and validation. Multivariable logistic regression was performed on 519 sequential IMSN biopsy procedures from multi-center data between August 2018 and July 2022 to predict the presence of IMSN metastasis. A nomogram was developed based on the logistic regression model and subsequently applied to 345 sequential IMSN biopsy procedures from single-center data between November 2011 and July 2018. The model's discrimination was assessed using the area under the receiver operating characteristic curve. RESULTS: The overall frequency of IMSN metastasis was 17.0% in our study. A predictive model for IMSN metastasis was constructed using tumor size, tumor location, lymphovascular invasion, the number of positive axillary nodes (P < 0.05 for all variables in multivariate analysis), and histological grade (P < 0.05 only in univariate analysis). The nomogram was accurate, with a concordance index of 0.84 in the bootstrapping analysis and an area under the receiver operating characteristic curve of 0.80 in the validation population. CONCLUSION: Our nomogram provides an accurate and validated multivariable predictive model for estimating the individual likelihood of having IMSN metastasis. This may be useful for personalized treatment decisions regarding internal mammary radiotherapy in breast cancer patients.

Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia.

Introduction: MicroRNAs may be implicated in the acquisition of drug resistance in chronic myeloid leukemia as they regulate the expression of not only BCR-ABL1 but also genes associated with the activation of drug transfer proteins or essential signaling pathways. Methods: To understand the impact of specifically expressed miRNAs in chronic myeloid leukemia and their target genes, we collected peripheral blood mononuclear cells (PBMC) from patients diagnosed with chronic myeloid leukemia (CML) and healthy donors to determine whole miRNA expression by small RNA sequencing and screened out 31 differentially expressed microRNAs (DE-miRNAs) with high expression. With the utilization of miRNA set enrichment analysis tools, we present here a comprehensive analysis of the relevance of DE-miRNAs to disease and biological function. Furthermore, the literature-based miRNA-target gene database was used to analyze the overall target genes of the DE-miRNAs and to define their associated biological responses. We further integrated DE-miRNA target genes to identify CML miRNA targeted gene signature singscore (CMTGSS) and used gene-set enrichment analysis (GSEA) to analyze the correlation between CMTGSS and Hallmark gene-sets in PBMC samples from clinical CML patients. Finally, the association of CMTGSS stratification with multiple CML cell lineage gene sets was validated in PBMC samples from CML patients using GSEA. Results: Although individual miRNAs have been reported to have varying degrees of impact on CML, overall, our results show that abnormally upregulated miRNAs are associated with apoptosis and aberrantly downregulated miRNAs are associated with cell cycle. The clinical database shows that our defined DE-miRNAs are associated with the prognosis of CML patients. CMTGSS-based stratification analysis presented a tendency for miRNAs to affect cell differentiation in the blood microenvironment. Conclusion: Collectively, this study defined differentially expressed miRNAs by miRNA sequencing from clinical samples and comprehensively analyzed the biological functions of the differential miRNAs in association with the target genes. The analysis of the enrichment of specific myeloid differentiated cells and immune cells also suggests the magnitude and potential targets of differentially expressed miRNAs in the clinical setting. It helps us to make links between the different results obtained from the multi-faceted studies to provide more potential research directions.

RNF128 regulates neutrophil infiltration and myeloperoxidase functions to prevent acute lung injury.

Acute lung injury (ALI) is characterised by severe pulmonary inflammation, alveolar-capillary barrier disruption, and pulmonary oedema. Therefore, establishing effective therapeutic targets for ALI prevention is crucial. The present study reports a novel function of RNF128 in regulating LPS-induced ALI. Severe lung damage and increased immune cell infiltration were detected in RNF128-deficient mice. In vitro experiments revealed that RNF128 inhibits neutrophil activation by binding to myeloperoxidase (MPO) and reducing its levels and activity. Moreover, RNF128 regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-κB activation, hence decreasing pro-inflammatory cytokines. Our results demonstrate for the first time that RNF128 is a negative regulator of MPO and TLR4 in neutrophils and alveolar macrophages, respectively. However, AAV9-mediated RNF128 overexpression alleviated lung tissue damage and reduced inflammatory cell infiltration. Thus, RNF128 is a promising therapeutic candidate for pharmacological interventions in ALI.

Platelet-lowering therapy with anagrelide as an adjuvant therapy for treatment of primary pulmonary neoplasm-associated extreme thrombocytosis.

Thrombocytosis is a common paraneoplastic syndrome in patients with lung cancer. However, complications associated with malignancy-related thrombocytosis, including thrombosis and hemorrhage, have rarely been reported. In this case, we describe a 57-year-old man with unresectable adenocarcinoma of the lung who presented with a platelet count over 100 × 10(4)/mm(3). In addition, deep venous thrombosis of the left femoral vein was found during admission. The circumference of the left lower leg and platelet count progressed during the period without chemotherapy and anticoagulants; however, with the addition of anagrelide they improved. We provided an adjuvant therapy with platelet-lowering therapy to treat cancer-induced thrombocytosis during the period without chemotherapy.

Hidden diagnosis of Tuberculous pleurisy masked by concomitant Pseudomonas oryzihabitans bacteremia.

The clinical presentations of tuberculous pleurisy are usually nonspecific and have an insidious course, thus resulting in diagnostic challenges. Pseudomonas oryzihabitans is a nonfermenting, oxidase-negative, catalase-positive, Gram-negative bacillus that has rarely been encountered as a human pathogen. We present the case of a 30-year-old male patient who exhibited intermittent fever despite antibiotic treatment for Pseudomonas oryzihabitans bacteremia for 6 days. Tuberculous pleurisy was finally diagnosed by histopathologic and microbiologic studies. He recovered after a 2-week antibiotic course and 6-month antituberculosis treatment.

[Identification of the potential distribution area of Cunninghamia lanceolata in China under climate change based on the MaxEnt model]. / 基于MaxEnt模型预测气候变化下杉木在中国的潜在地理分布.

Based on the distribution records of Cunninghamia lanceolata, we used the maximum Entropy (MaxEnt) model and geographic information system (GIS) methods, combined with environmental factors such as climate and terrain, to predict the potential distribution areas suitable for C. lanceolata under current and future climate scenarios. The results showed that annual precipitation was the most important factor driving the distribution of C. lanceolata. Under the current climate scenario, the total area of suitable for C. lanceolata growth was about 3.28 million km2, accounting for about 34.5% of the total land area of China. Among all the suitable areas, the lowly, intermediately, and highly suitable areas accounted for 18.3%, 29.7% and 52.0% of the total, respectively. Under future climate scenarios, the suitable area of C. lanceolata would increase, showing a clear trend of northward expansion in China. A concentrated and contiguous distribution region highly suitable for C. lanceolata would appear in the humid subtropical areas of southern China. The model was tested by the receiver operating characteristic curve (ROC). The average area under the curve of ROC of the training set was 0.91, showing high reliability.

The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study.

BACKGROUND AND AIMS: Liver cancer is a detrimental complication in patients with chronic viral hepatitis and alcoholic or nonalcoholic fatty liver disease (NAFLD). However, metabolic risk factors underlying NAFLD usually cause substantial differences in their clinical outcomes. Recently, several studies have used a novel definition of metabolic dysfunction-associated fatty liver disease (MAFLD) to reassess patients with NAFLD and pointed out the importance of metabolic risk factors. Since patients with NAFLD, MAFLD, or metabolic syndrome (MetS) have different burden of metabolic risk factors, it is crucial to decipher the risk of developing hepatic complications in these populations. METHODS: Through a longitudinal nationwide cohort study, the risk of liver cancer was investigated in patients with MetS alone, NAFLD alone, overlap NAFLD/MAFLD, and coexisting MetS and NAFLD. The general characteristics, comorbidities, and incidence of liver cancer were also compared. RESULTS: Intriguingly, patients diagnosed with MetS alone did not have a significant risk of developing HCC compared to control individuals, while patients with NAFLD alone, NAFLD/MAFLD, and coexisting NAFLD and MetS exhibited 6.08-, 5.81-, and 15.33-fold risks of developing HCC, respectively. Apart from metabolic risk factors, renal function status and liver cirrhosis were the independent risk factors for the development of HCC among these groups. CONCLUSION: Our data emphasize that metabolic dysfunction has a significant impact on hepatocarcinogenesis in patients with NAFLD. Moreover, coexisting multiple metabolic risk factors would dampen the risk of developing HCC in patients with NAFLD. Closely tracing HCC formation through laboratory examination or imaging is crucial in these patients.

Perforated acute appendicitis resulting from appendiceal villous adenoma presenting with small bowel obstruction: a case report.

BACKGROUND: A villous adenoma is an extremely rare benign tumour in the appendix, in contrast to other benign appendiceal lesions. The clinical features are usually asymptomatic. Acute appendicitis is the most common complication with the lesion obstructing the orifice of the appendiceal lumen. Thus, a villous adenoma is usually found during surgical intervention for acute appendicitis. Mechanical obstruction induced by acute perforated appendicitis has been previously reported. Acute appendicitis caused by a villous adenoma presenting with acute intestinal obstruction has not been previously reported. CASE PRESENTATION: A 78-year-old woman presented to our Emergency Department with diffuse abdominal pain and tenderness. The abdominal plain film and computed tomography revealed an intestinal obstruction. After surgical intervention, the ruptured appendix was shown to be associated with intestinal obstruction. The post-operative pathologic diagnosis was an appendiceal villous adenoma. CONCLUSIONS: This is the first report describing an appendiceal villous adenoma, which is an occasional cause of perforated acute appendicitis, presenting as a complete intestinal obstruction. We emphasize that in elderly patients without a surgical history, the occult cause of complete intestinal obstruction must be determined. If an appendiceal tumour is diagnosed, an intra-operative frozen section is suggested prior to selecting a suitable method of surgical intervention.

Pulmonary cryptococcus infection after mono-chemotherapy with gemcitabine.

Mono-chemotherapy with gemcitabine (difluorodeoxycytidine) is an effective cancer chemotherapy, and is often used instead of a more effective but more toxic combination chemotherapy regimen. Infection associated with gemcitabine is very rare. We present a case of Cryptococcus neoformans pneumonia that developed after 5 courses of gemcitabine for advanced bladder carcinoma. Lung biopsy and antigens demonstrated C. neoformans. The pneumonia resolved after antifungal therapy.

E3 ubiquitin ligase Grail promotes hepatic steatosis through Sirt1 inhibition.

In obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.

Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome, and the current standard of care is the use of tyrosine kinase inhibitors (TKI). However, some patients will not achieve a molecular response and may progress to blast crisis, and the underlying mechanisms remain to be clarified. In this study, next-generation sequencing was used to explore endogenous miRNAs in CML patients versus healthy volunteers, and miR-342-5p was identified as the primary target. We found that miR-342-5p was downregulated in CML patients and had a significant inhibitory effect on cell proliferation in CML. Through a luciferase reporter system, miR-342-5p was reported to target the 3'-UTR domain of CCND1 and downregulated its expression. Furthermore, overexpression of miR-342-5p enhanced imatinib-induced DNA double-strand breaks and apoptosis. Finally, by analyzing clinical databases, we further confirmed that miR-342-5p was associated with predicted molecular responses in CML patients. In conclusion, we found that both in vivo and in vitro experiments and database cohorts showed that miR-342-5p plays a key role in CML patients, indicating that miR-342-5p may be a potential target for future CML treatment or prognostic evaluation.

Uracil-tegafur vs fluorouracil as postoperative adjuvant chemotherapy in Stage II and III colon cancer: A nationwide cohort study and meta-analysis.

ABSTRACT: We conducted a population-based cohort study enrolling patients with Stage II and III colon cancer receiving postoperative adjuvant chemotherapy with uracil and tegafur (UFT) or fluorouracil (5-FU) from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the current study were disease-free survival (DFS) and overall survival (OS). Hazard ratios (HRs) were calculated by multivariate Cox proportional hazard regression models. We compared our effectiveness results from the literature by meta-analysis, which provided the best evidence. Severe adverse events were compared in meta-analysis of reported clinical trials. In the nationwide cohort study, UFT (14,486 patients) showed DFS similar to postoperative adjuvant chemotherapy (adjusted HR 1.037; 95% confidence interval [CI] 0.954-1.126; P = .397) and OS (adjusted HR 0.964; 95% CI 0.891-1.041; P = .349) compared with the 5-FU (866 patients). Our meta-analysis confirmed the similarity of effectiveness and found the incidence of leucopaenia was statistically significantly reduced in UFT (risk ratio 0.12; 95% CI 0.02-0.67; I2 = 0%). Through our analysis, we have confirmed that UFT is a well-tolerated adjuvant therapy choice, and has similar treatment efficacy as 5-FU in terms of DFS and OS in patients with Stage II and III colon cancer.

[Evaluation of the role of combined TES-MEP and CSEP monitoring during the spinal surgery].

OBJECTIVE: To evaluate of the role of transcranial electrical stimulation motor evoked potential (TES-MEP) in combination with cortical somatosensory evoked potential (CSEP) monitoring during the spinal surgery. METHODS: TES-MEP on bilateral anterior tibial muscle and flexor hallucal brevis and CSEP on bilateral posterior tibial nerve were observed simultaneously on 293 patients during spinal surgery from July 2006 to April 2009. Intravenous anesthesia was employed in all the patients, a part of which were added low dose of sevoflurane or muscle relaxant. The results of TES-MEP, CSEP and combined monitoring were analyzed statistically. Pre-operative and post-operative motor and sensory functions of spinal cord were compared. RESULTS: Success rate of TES-MEP, CSEP and combined monitoring was 90.8%, 96.9% and 100% respectively. For the judgment of motor function of spinal cord, the sensitivity of TES-MEP and CSEP was 100% and 89.3% respectively and the specificity of 98.4% and 96.9%. The Youden index of the two methods was 0.984 and 0.862. For sensory function, the sensitivity of them was 76.7% and 93.3% respectively and the specificity of 98.7% and 98.0%. The Youden index was 0.754 and 0.913. The sensitivity of combined monitoring was 100%, with the specificity of 96.9%. The Youden index was 0.969. CONCLUSIONS: The precision of monitoring motor function of spinal cord with TES-MEP is higher than that with CSEP, however, for sensory function, CSEP is more precise. The sensitivity and precision of combined monitoring for spinal cord function were apparently better than that of unitary TES-MEP or CSEP. The combined TES-MEP and CSEP monitoring is a relatively ideal method.