Clinical implications of hepatitis B virus core antigen-mediated immunopathologic T cell responses in chronic hepatitis B.

Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore -specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBVcore -specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD-1. Our parallel study showed HBV-specific CD8 T cells were more activated with greater PD-1 expression than CMV-specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD-1 fluctuation pattern of HBVcore -specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD-1 levels of HBVcore -specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.

Effectiveness of glutamine for the treatment of radiodermatitis in cancer patients: a meta-analysis of randomized controlled trials.

BACKGROUND: After receiving radiation therapy, 60%-95% of patients with cancer develop radiodermatitis, which causes pain, wound infection, and poor quality of life. Glutamine is a popular nutritional supplement for patients with cancer. Several studies examined the usefulness of glutamine for reducing radiodermatitis. However, there is still no consolidated evidence for clinical use. METHODS: We searched PubMed, Embase, Cochrane Library, CINAHL PLUS, and the China Knowledge Resource Integrated Database for the relevant literature published up to March 2023, without language restrictions. Two reviewers screened, filtered, and appraised these articles independently, and their data were pooled using a random-effects model. RESULTS: Five randomized controlled trials (RCTs) with 218 participants were analyzed. The incidence of radiodermatitis in the glutamine group (89/110) was significantly lower than in the placebo group (99/108; risk ratio [RR], 0.90; 95% CI, 0.81-1.00; p = 0.05; I2 = 7%). The incidence of moderate to severe radiodermatitis was significantly lower in the glutamine group than in the placebo group (RR, 0.49; 95% CI, 0.32-0.76; p = 0.001; I2 = 52%). Moreover, subgroup analysis demonstrated heterogeneity (I2 = 52%) for moderate to severe radiodermatitis, the risk of which might be significantly reduced by a glutamine dose of 20-30 g/day (RR, 0.60; 95% CI, 0.41-0.87; I2 = 0%). CONCLUSION: The meta-analysis indicate that glutamine might lead to a lower incidence of radiodermatitis, and that a glutamine dose of 20-30 g/day might decrease the incidence of moderate to severe dermatitis. Thus, the serious impact of radiodermatitis on treatment follow-up makes the clinical use of glutamine even more important. PROSPERO number: CRD42021254394.

Estimating Taiwan's QALY league table for catastrophic illnesses: Providing real-world evidence to integrate prevention with treatment for resources allocation.

BACKGROUND/PURPOSE: Curative technologies improve patient's survival and/or quality of life but increase financial burdens. Effective prevention benefits all three. We summarize estimation methods and provide examples of how much money is spent per quality-adjusted life year (QALY) or life year (LY) on treating a catastrophic illness under a lifetime horizon and how many QALYs/LYs and lifetime medical costs (LMC) could be potentially saved by prevention. METHODS: We established cohorts by interlinkages of Taiwan's nation-wide databases including National Health Insurance. We developed methods to estimate lifetime survival functions, which were multiplied with the medical costs and/or quality of life and summed up to estimate LMC, quality-adjusted life expectancy (QALE) and lifetime average cost per QALY/LY for catastrophic illnesses. By comparing with the age-, sex-, and calendar year-matched referents simulated from vital statistics, we obtained the loss-of-QALE and loss-of-life expectancy (LE). RESULTS: The lifetime cost-effectiveness ratios of ventilator-dependent comatose patients, dialysis, spinal cord injury, major trauma, and cancers were US$ 96,800, 16,200-20,000, 5500-5,900, 3400-3,600, and 2900-11,900 per QALY or LY, respectively. The successful prevention of lung, liver, oral, esophagus, stomach, nasopharynx, or ovary cancer would potentially save US$ 28,000-97,000 and > 10 QALYs; whereas those for end-stage kidney disease, stroke, spinal injury, or major trauma would be US$ 55,000-300,000 and 10-14 QALYs. Loss-of-QALE and loss-of-LE were less confounded indicators for comparing the lifetime health benefits of different technologies estimated from real-world data. CONCLUSIONS: Integration of prevention with treatment for resources allocation seems feasible and would improve equity and efficiency.

Developing a novel DNA methylation risk score for survival and identification of prognostic gene mutations in endometrial cancer: a study based on TCGA data.

BACKGROUND: Few studies have focused on DNA methylation in endometrial cancer. The aim of our study is identify its role in endometrial cancer prognosis. METHODS: A publicly available dataset was retrieved from The Cancer Genome Atlas. For validation of expression alteration due to methylation, RNA sequencing data were obtained from other independent cohorts. MethSurv was used to search for candidate CpG probes, which were then filtered by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression analyses to identify final set of CpG probes for overall survival. A methylation-based risk model was developed and receiver operating characteristic analysis with area under curve was used for evaluation. Patients were divided into high- and low-risk groups using an optimal cut-off point. Comprehensive bioinformatic analyses were conducted to identify hub genes, key transcription factors, and enriched cancer-related pathways. Kaplan-Meier curve was used for survival analysis. RESULTS: A 5-CpG signature score was established. Its predictive value for 5-year overall survival was high, with area under curve of 0.828, 0.835 and 0.816 for the training, testing and entire cohorts. cg27487839 and cg12885678 had strong correlation with their gene expression, XKR6 and PTPRN2, and lower PTPRN2 expression was associated with poorer survival in both The Cancer Genome Atlas and the validation datasets. Low-risk group was associated with significantly better survival. Low-risk group harboured more mutations in hub genes and key transcription factors, and mutations in SP1 and MECP2 represented favourable outcome. CONCLUSION: We developed a methylation-based prognostic stratification system for endometrial cancer. Low-risk group was associated with better survival and harboured more mutations in the key regulatory genes.

Depilatory laser miniaturizes hair by inducing bystander dermal papilla cell necrosis through thermal diffusion.

OBJECTIVES: Depilatory laser targeting melanin has been widely applied for the treatment of hypertrichosis. Both selective photothermolysis and thermal diffusion have been proposed for its effect, but the exact mechanism of permanent hair reduction remains unclear. In this study, we explore the role of thermal diffusion in depilatory laser-induced permanent hair loss and determine whether nonpigmented cells are injured by thermal diffusion. MATERIALS AND METHODS: C57BL/6 mice in anagen and telogen were treated with alexandrite laser (wavelength 755 nm, pulse duration 3 milliseconds, fluence 12 J/cm2 , spot size 12 mm), respectively. Histological analysis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and transmission electron microscopic imaging were employed to evaluate the injury to hair follicle (HF) cells. The proliferation status of HF cells was examined by 5-bromo-2'-deoxyuridine pulse labeling. The number of HF stem cells was quantified by fluorescence-activated cell sorting. The size of the regenerated hair was determined by measuring its length and width. RESULTS: We found that irradiating C57BL/6 mice in anagen with alexandrite laser led to hair miniaturization in the next anagen. In addition to thermal disruption of melanin-containing cells in the precortex region, we also detected necrosis of the adjacent nonpigmented dermal papilla cells due to thermal diffusion. Dermal papilla cells decreased by 24% after laser injury, while the number of bulge stem cells remained unchanged. When the laser was delivered to telogen HFs where no melanin was present adjacent to the dermal papilla, thermal necrosis and cell reduction were not detected in the dermal papilla and no hair miniaturization was observed. CONCLUSION: Our results suggest that depilatory laser miniaturizes hair by inducing thermal necrosis of dermal papilla cells due to secondary thermal diffusion from melanin-containing precortex cells in the anagen hair bulbs.

Effects of continuity of care on hospitalizations and healthcare costs in older adults with dementia.

INTRODUCTION: People with dementia have high rates of hospitalization, and a share of these hospitalizations might be avoidable with appropriate ambulatory care, also known as potentially preventable hospitalization (PAH). This study investigates the associations between continuity of care and healthcare outcomes in the following year, including all-cause hospitalization, PAHs, and healthcare costs in patients with dementia. METHODS: This is a longitudinal retrospective cohort study of 69,658 patients with dementia obtained from the Taiwan National Health Insurance Research Database. The Continuity of Care Index (COCI) was calculated to measure the continuity of dementia-related visits across physicians. The PAHs were classified into five types as defined by the Medicare Ambulatory Care Indicators for the Elderly (MACIEs). Logistic regression models were used to examine the effect of COCI on all-cause hospitalizations and PAHs, while generalized linear models were used to analyze the effect of COCI on outpatient, hospitalization, and total healthcare costs. RESULTS: The high COCI group was significantly associated with a lower likelihood of all-cause hospitalization than the low COCI group (OR = 0.848, 95%CI: 0.821-0.875). The COCI had no significant effect on PAHs but was associated with lower outpatient costs (exp(ß) = 0.960, 95%CI: 0.941 ~ 0.979), hospitalization costs (exp(ß) = 0.663, 95%CI: 0.614 ~ 0.717), total healthcare costs (exp(ß) = 0.962, 95%CI: 0.945-0.980). CONCLUSION: Improving continuity of care for dementia-related outpatient visits is recommended to reduce hospitalization and healthcare costs, although there was no statistically significant effect of continuity of care found on PAHs.

Lower proximal cup and outer root sheath cells regenerate hair bulbs during anagen hair follicle repair after chemotherapeutic injury.

The cell dynamics and cell origin for anagen hair follicle (HF) repair following chemotherapeutic injury are unclear. We first mapped the HF response to cyclophosphamide (CYP) at natural anagen VI in mice. We found that 30-60 mg/kg of CYP leads to dose-dependent HF dystrophy that was spontaneously repaired with anagen resumption, while 120 mg/kg of CYP prematurely induced catagen/telogen entry. To explore how anagen HF repair is achieved in the dystrophic anagen pathway, we analysed the cell dynamics at 30 mg/kg of CYP. Hair bulbs first shrunk due to matrix cell apoptosis associated with DNA double-strand breaks. DNA damage was repaired, and ordered hair bulb structures were restored within 96 hours. Bulge stem cells did not undergo apoptosis nor proliferation. K5+ basal lower proximal cup cells and outer root sheath cells quickly replenished the cells in the germinative zone and regenerated the concentric layered structures of the lower HF segment. Therefore, anagen HFs are able to summon extra-bulge progenitor cells in close proximity to the damaged matrix for quick repair after CYP injury.

Gene-associated methylation status of ST14 as a predictor of survival and hormone receptor positivity in breast Cancer.

BACKGROUND: Genomic profiles of specific gene sets have been established to guide personalized treatment and prognosis for patients with breast cancer (BC). However, epigenomic information has not yet been applied in a clinical setting. ST14 encodes matriptase, a proteinase that is widely expressed in BC with reported prognostic value. METHODS: In this present study, we evaluated the effect of ST14 DNA methylation (DNAm) on overall survival (OS) of patients with BC as a representative example to promote the use of the epigenome in clinical decisions. We analyzed publicly available genomic and epigenomic data from 1361 BC patients. Methylation was characterized by the ß-value from CpG probes based on sequencing with the Illumina Human 450 K platform. RESULTS: A high mean DNAm (ß > 0.6779) across 34 CpG probes for ST14, as the gene-associated methylation (GAM) pattern, was associated with a longer OS after adjusting age, stage, histology and molecular features in Cox model (p value < 0.001). A high GAM status was also associated with a higher XBP1 expression level and higher proportion of hormone-positive BC (p value < 0.001). Pathway analysis revealed that altered GAM was related to matrisome-associated pathway. CONCLUSIONS: Here we show the potential role of ST14 DNAm in BC prognosis and warrant further study.

External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.

Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.

Oral tegafur-uracil as a metronomic therapy in stage IVa and IVb cancer of the oral cavity.

PURPOSE: This study aimed to evaluate the impact of accumulated oral tegafur-uracil (UFUR) as maintenance chemotherapy on overall survival (OS) and disease-free survival (DFS) rates after definitive treatment for non-distant metastatic stage IV cancer of the oral cavity. MATERIALS AND METHODS: This retrospective, hospital center-based study analyzed data of patients diagnosed with stage IVa and IVb cancer of the oral cavity who underwent surgical resection and concurrent chemoradiotherapy (CCRT) obtained from a database between October 2008 and December 2014. RESULTS: Forty-two patients were treated with CCRT (non-UFUR group); the remaining 51 patients received the same regimen, followed by additional oral UFUR (UFUR group). For all study patients, the 3-year DFS rates were 53.05% and 35.41% in the UFUR and non-UFUR groups, respectively (p = 0.011), while the 3-year OS rates were 74.96% and 48.47%, respectively (p = 0.001). CONCLUSIONS: Adding UFUR to CCRT significantly improved the DFS and OS rates in patients with non-distant metastatic stage IV cancer of the oral cavity.

Stereotactic body radiation therapy vs. radiofrequency ablation in Asian patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Few studies have been conducted to compare the efficacies of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Thus, in this multinational study, we compared the effectiveness of SBRT and RFA in patients with unresectable HCC. METHODS: The retrospective study cohort included 2,064 patients treated in 7 hospitals: 1,568 and 496 in the RFA and SBRT groups, respectively. More than half of the patients (56.5%) developed recurrent tumors, mainly after transarterial chemoembolization (44.8%). Propensity score matching was performed to adjust for clinical factors (n = 313 in each group). RESULTS: At baseline, the SBRT group had unfavorable clinical features compared to the RFA group, including BCLC stage (B-C 65% vs. 16%), tumor size (median 3.0 cm vs. 1.9 cm), and frequent history of liver-directed treatment (81% vs. 49%, all p <0.001). With a median follow-up of 27.7 months, the 3-year cumulative local recurrence rates in the SBRT and RFA groups were 21.2% and 27.9%, respectively (p <0.001). After adjusting for clinical factors, SBRT was related to a significantly lower risk of local recurrence than RFA in both the entire (hazard ratio [HR] 0.45, p <0.001) and matched (HR 0.36, p <0.001) cohorts. In subgroup analysis, SBRT was associated with superior local control in small tumors (≤3 cm) irrespective of location, large tumors located in the subphrenic region, and those that progressed after transarterial chemoembolization. Acute grade ≥3 toxicities occurred in 1.6% and 2.6% of the SBRT and RFA patients, respectively (p = 0.268). CONCLUSIONS: SBRT could be an effective alternative to RFA for unresectable HCC, particularly for larger tumors (>3 cm) in a subphrenic location and tumors that have progressed after transarterial chemoembolization. LAY SUMMARY: It is currently not known what the best treatment option is for patients with unresectable hepatocellular carcinoma. Here, we show that stereotactic body radiation therapy provides better local control than radiofrequency ablation, with comparable toxicities. Stereotactic body radiation therapy appears to be an effective alternative to radiofrequency ablation that should be considered when there is a higher risk of local recurrence or toxicity after radiofrequency ablation.

Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration.

Stem cell activity is subject to non-cell-autonomous regulation from the local microenvironment, or niche. In adaption to varying physiological conditions and the ever-changing external environment, the stem cell niche has evolved with multifunctionality that enables stem cells to detect these changes and to communicate with remote cells/tissues to tailor their activity for organismal needs. The cyclic growth of hair follicles is powered by hair follicle stem cells (HFSCs). Using HFSCs as a model, we categorize niche cells into 3 functional modules, including signaling, sensing and message-relaying. Signaling modules, such as dermal papilla cells, immune cells and adipocytes, regulate HFSC activity through short-range cell-cell contact or paracrine effects. Macrophages capacitate the HFSC niche to sense tissue injury and mechanical cues and adipocytes seem to modulate HFSC activity in response to systemic nutritional states. Sympathetic nerves implement the message-relaying function by transmitting external light signals through an ipRGC-SCN-sympathetic circuit to facilitate hair regeneration. Hair growth can be disrupted by niche pathology, e.g. dysfunction of dermal papilla cells in androgenetic alopecia and influx of auto-reacting T cells in alopecia areata and lichen planopilaris. Understanding the functions and pathological changes of the HFSC niche can provide new insight for the treatment of hair loss.

Facilitating ventilator weaning through rib fixation combined with video-assisted thoracoscopic surgery in severe blunt chest injury with acute respiratory failure.

BACKGROUND: Severe blunt chest injury sometimes induces acute respiratory failure (ARF), requiring ventilator use. We aimed to evaluate the effect of performing rib fixation with the addition of video-assisted thoracoscopic surgery (VATS) on patients with ARF caused by blunt thoracic injury with ventilator dependence. METHODS: This observational study prospectively enrolled patients with multiple bicortical rib fractures with hemothorax caused by severe blunt chest trauma. All patients received positive pressure mechanical ventilation within 24 h after trauma because of ARF. Some patients who received rib fixation with VATS were enrolled as group 1, and the others who received only VATS were designated as group 2. The length of ventilator use was the primary clinical outcome. Rates of pneumonia and length of hospital stay constituted secondary outcomes. RESULTS: A total of 61 patients were included in this study. The basic demographic characteristics between the two groups exhibited no statistical differences. All patients received operations within 6 days after trauma. The length of ventilator use was shorter in group 1 (3.19 ± 3.37 days vs. 8.05 ± 8.23, P = 0.002). The rate of pneumonia was higher in group 2 (38.1% vs. 75.0%, P = 0.005). The length of hospital stay was much shorter in group 1 (17.76 ± 8.38 days vs. 24.13 ± 9.80, P = 0.011). CONCLUSION: Rib fixation combined with VATS could shorten the length of ventilator use and reduce the pneumonia rate in patients with severe chest blunt injury with ARF. Therefore, this operation could shorten the overall length of hospital stay.

Anagen hair follicle repair: Timely regenerative attempts from plastic extra-bulge epithelial cells.

Anagen hair follicle repair (AHFR) is the regenerative scheme activated to restore the structure and hair growth following injuries to anagen hair follicles. Compared with telogen-to-anagen regeneration and hair follicle neogenesis, AHFR is a clinically important, yet relatively unexplored regenerative feature of hair follicles. Due to their highly proliferative character, germinative cells and matrix cells within hair bulbs are highly susceptible to injuries, such as chemotherapy and radiotherapy. Clinical and experimental observations suggest that damaged anagen hair follicles are able to repair themselves to resume anagen growth, bypassing premature catagen/telogen entry. Mechanistically, extra-bulge epithelial cells in the outer root sheath and the lower proximal cup are quickly mobilized for regeneration. These cells acquire stem cell-like properties, exhibiting high plasticity by breaking lineage restriction to regenerate all cell types in the lower segment of anagen hair follicles. Facilitating extra-bulge epithelial cells' mobilization ameliorates hair loss from chemo- and radiotherapy. On the other hand, quiescent bulge stem cells can also be activated, but only after more severe injuries and with slower activation dynamics. They show limited plasticity and regenerate part of the outer root sheath only. The dysrhythmic activation might render bulge stem cells susceptible to concomitant injuries due to their exit from quiescence.

An automatic integrated microfluidic system for allergy microarray chips.

Billions of people suffer from allergies, though in many cases, the source allergen is unknown. If one knows which allergens to avoid, this would result in an improved quality of life. Since a rapid, high-throughput, automatic allergen detection method is of great need, an integrated system combining microfluidic techniques and microarray chips has been developed herein to automate the allergen detection process. The developed microfluidic system could automatically carry out the entire procedure such as reagent incubation, hybridization, transport, and washing without any intermediate step. The microarray chip could be easily detached from the microfluidic chip afterwards, enabling it to be read under a fluorescence scanner. The experimental results indicated that the developed microfluidic system can automatically perform all the incubation processes, including hybridization, reagent transportation, and washing. It is worth noting that active mixing has been applied in the present study which is different from our previous study using micro-channels for passive incubation. Comparable results to a conventional benchtop approach were obtained in ∼30% less time with ∼25% less samples/reagents. Similar results were also demonstrated while detecting immunoglobulin E samples. The developed system could therefore provide a rapid, reliable, and automated approach for detecting allergen-specific antibodies in human serum.

From Bola-Surfactant Templated Bimetal Phosphites to the Design of Crystalline Inorganic Mesoporous Frameworks.

Reproducing inorganic modules in situ for pore augmentation of pure inorganic frameworks is challenging but can be a key to rational synthesis. After the first success of using monoamines of varied lengths as a template in producing a set of building blocks that led to a series of growing channels up to a 72-membered ring (72R), research continued into those building blocks to seek any new topologies from them. In this study, another type of template is reported that can control the same building blocks to repeatedly form in situ. By using long linear-chain bola-type surfactants, two new bimetal phosphites, a monoclinic phase exhibiting remarkable quasi-channels of 1.15 nm and an orthorhombic phase with 28R channels of 1.06 nm have been created. By taking them as the first members, two series of novel topologies can be devised, each having a general formula to predict the size and channel wall compositions.

ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.

The ATP-binding cassette transporter ABCG2 is expressed in the interfollicular epidermis and mediates the side-population phenotype in skin cells. However, the role of ABCG2 in skin is unclear. Increased expression levels of ABCG2 were found at the basal layer of transitional epidermis adjacent to cutaneous wounds in human patients, indicating that ABCG2 may be involved in regulating the wound healing process. To investigate the role of ABCG2 in cutaneous wound healing, full-thickness skin wounds were created in ABCG2 knockout (ABCG2-KO) and wild-type mice. The healing process was analysed and revealed that ABCG2 deficiency in skin results in delays in wound closure and impairments in re-epithelialization, as evidenced by reductions in both suprabasal differentiation and in p63-expressing keratinocytes migrating from transitional epidermis to epithelial tongues. The reduction in p63-expressing cells may be due to elevated levels of reactive oxygen species in ABCG2-KO epidermis, which can cause DNA damage and lead to proliferation arrest. To determine whether ABCG2 deficiency affects the potency of epidermal stem/progenitor cells (EPCs), transplantation studies were carried out, which demonstrated that ABCG2-KO EPCs display higher levels of γH2AX and lose the capacity to differentiate into suprabasal keratinocytes. A competitive repopulation assay confirmed that ABCG2 expression is critical for the proper expansion and differentiation of EPCs in cutaneous wounds. As EPCs are known to contribute to the healing of larger wounds, the current findings imply a functional role for ABCG2 in the expansion and differentiation of p63-expressing EPCs. Thus, ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.

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.

Association between colonic diverticular disease and colorectal cancer: a nationwide population-based study.

BACKGROUND & AIMS: We investigated whether a diagnosis of colonic diverticular disease is associated with an increased risk for subsequent development of colorectal cancer (CRC) in a nationwide population-based retrospective study. METHODS: We identified 41,359 individuals diagnosed with colonic diverticular disease as inpatients from 2000 through 2009 from the Taiwan National Health Insurance Research Database (study cohort) and collected data for 165,436 randomly selected additional subjects, matched by sex, age, and baseline year (comparison cohort). Data were collected until individuals developed CRC or withdrew from the National Health Insurance system, or until December 31, 2010. Cumulative incidences and hazard ratios (HRs) of CRC development were determined. To assess for ascertainment bias, we conducted an analysis excluding the first 12 months of follow-up evaluation. RESULTS: The risk of CRC was significantly higher in the study cohort than in the comparison cohort (HR adjusted for age, sex, and comorbidities, 4.54; 95% confidence interval, 4.19-4.91; P < .0001). In a sensitivity analysis, we excluded the first 12 months of follow-up evaluation after a diagnosis of colonic diverticular disease; subsequent incidence rates for CRC in the study and comparison cohorts were 15.13 and 15.74 per 10,000 person-years, respectively (adjusted HR, 0.96; 95% confidence interval, 0.83-1.11). CONCLUSIONS: Colonic diverticular disease is not associated with an increased risk of subsequent CRC after the first year of diagnosis of colonic diverticular disease. An increased risk was observed in the first year, possibly owing to misclassification and screening effects.