Clinical Insights: Antimicrobial Therapy for Infectious Uveitis.

Infectious uveitis is a major global cause of vision impairment. Despite the eye's immune privilege, afforded by the blood-ocular barrier that restricts microbial entry, several pathogens such as bacteria, viruses, fungi, and parasites can still infiltrate and cause ocular infections and complications. Clinicians often encounter significant challenges in treating infectious uveitis due to limited or ineffective treatment options. Modern molecular techniques and imaging can aid in diagnosing and assessing intraocular infections. Various antimicrobial therapies exist, spanning topical and systemic treatments, but these are constrained by issues like drug concentration, penetration, effective duration, toxicity, and side effects. Treatment approaches also differ based on the infection's etiology. This review provides recent updates on antimicrobial therapies from a clinical perspective, covering topical, systemic, and regional treatments for infectious uveitis.

Adalimumab Dose Reduction and Withdrawal in Stable Non-Infectious Pediatric Uveitis: An Open-Label, Prospective, Pilot Study.

PURPOSES: This study investigated the feasibility of adalimumab (ADA) dose reduction and withdrawal strategy in children with stable pediatric non-infectious uveitis (PNIU). METHODS: This open-label prospective pilot trial recruited 18 stable PNIU patients (33 eyes) between two and eighteen years old who were treated with standard doses of ADA (20/40 mg every 2 weeks) plus oral methotrexate. The interval of ADA injection was extended to 4 weeks and followed up for 24 weeks. If the uveitis remained stable, ADA was discontinued and followed up for another 24 weeks. ADA was considered successfully stopped if no relapse occurred during this period. The relapse-free survival rate, best corrected visual acuity (BVCA), anterior chamber cell (ACC), vitritis, macular thickness (MT), and serum ADA levels were evaluated. Approval Number: 2021KYPJ201. ClinicalTrials.gov identifier: NCT05155592. RESULTS: The relapse-free survival rate was 22.2% (4/18) at 48 weeks. 33.3% (6/18) of patients relapsed when ADA was given every 4 weeks, while 44.5% of patients (8/18) relapsed after ADA was stopped. The four patients successfully withdrawn from ADA were all diagnosed with BD. No statistically significant differences (p > 0.05) were observed in BCVA and MT between baseline and final follow-up. The proportion of ACC and vitritis exhibited an upward trend (p < 0.05) during follow-up. Serum ADA gradually decreased to zero during follow-up in both non-recurrence and recurrence groups. CONCLUSIONS: In PNIU children who reached remission for 6 months, ADA dose reduction and withdrawal were associated with a high risk of inflammation recurrence. Timely adjustment of ADA to the last effective dosage frequency can regain control of the inflammation. Detection of ADA serum levels in patients with recurrence may help find the appropriate interval of ADA use.

[Acute macular neuroretinopathy: a case report].

A 16-year-old female patient experienced a rapid decline in bilateral visual acuity accompanied by central scotomas for 5 days following coronavirus disease 2019 infection. Ocular examination revealed findings consistent with acute macular neuroretinopathy. Structural en face imaging using optical coherence tomography demonstrated a wedge-shaped lesion with low reflectivity directed towards the fovea in both eyes. B-scan images revealed localized hyperreflective bands involving the outer nuclear layer and photoreceptor layer, with discontinuity of the ellipsoid zone. Based on clinical presentation and examination findings, a diagnosis of bilateral acute macular neuroretinopathy was established.

[Effect of preoperative anterior bony impingement on lateral collateral ankle ligament reconstruction].

Objective: To explore whether the combination of anterior bony impingement before surgery will affect the efficacy of the lateral collateral ankle ligament reconstruction surgery in patients with chronic ankle instability (CAI). Methods: A prospective cohort study. Patients with CAI who underwent lateral collateral ankle ligament reconstruction from January 2014 to October 2017 in the Department of Sports Medicine, Huashan Hospital, Fudan University were enrolled in this study. The patients were divided into no bony impingement group (NI group) and bony impingement group (BI group) according to the presence of bone impingement in front of the ankle during the operation. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson ankle functional socre (KAFS), Tegner score, visual analogue scale (VAS) of pain were extracted and were reevaluated at least 2 years after surgery as well as imaging evaluation of ankle. Results: A total of 59 patients were enrolled in this study. There were 29 patients in the NI group, 23 males and 6 females with a mean age of (28.4±7.1) years. And there were 30 cases in the BI group, 28 males and 2 females with a mean age of (31.9±8.6) years. The AOFAS, KAFS and Tegner scores in NI group increased from 65.8±10.6, 65.9±10.1 and 3.0 (3.0, 4.0) before the operation to 97.5±4.3, 97.8±4.7 and 6.0(5.0,6.0) after the operation, respectively; and the VAS decreased from 3.0(3.0, 4.0) to 0(0, 0); there were significant differences in those indexes before and after the operation (all P<0.05). The scores of AOFAS, KAFS and Tegner in BI group increased from 65.2±11.0, 64.2±10.0 and 3.0(3.0, 4.0) before the operation to 97.1±4.3, 97.3±4.3 and 5.0(4.0, 6.0) post the operation, respectively; and the VAS scores decreased from 3.0(3.0, 5.0) to 0(0, 1.0); there were significant differences in up-mentioned indexes before and after the surgery (all P<0.05). There was no significant differences in baseline and preoperative clinical function scores between the two groups (all P>0.05). No significant difference was found in postoperative AOFAS, KAFS and VAS scores between the two groups (all P>0.05), while postoperative Tegner score in the NI group was significantly higher than that in the BI group [6.0(5.0, 6.0) vs 5.0(4.0, 6.0), P=0.026]. Imaging evaluation of all patients showed that the reconstructed ligament was clearly visible, and the intraarticular injuries existing before surgery showed obvious signs of healing. Conclusion: Ankle lateral collateral ligament reconstruction for CAI with or without anterior bony impingement results in similar outcomes in ankle function, stability and pain levels.

[Clinical features and treatment outcome of patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis].

Objective: To investigate the clinical features and effect of prognostic factors in patients with different pathological types of non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis. Methods: We collected and analyzed the clinical data of 89 patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis who were treated at Huadong Hospital from March 2013 to May 2020. The data were analyzed via log-rank and Cox multivariate analyses. Results: The median overall survival time of the 89 cases was 10.2 months. Patients with B-cell lymphoma-associated hemophagocytic lymphohistiocytosis did not reach the median overall survival time. The median overall survival times of T-cell lymphoma-associated hemophagocytic lymphohistiocytosis and NK-cell lymphoma-associated hemophagocytic lymphohistiocytosis were 10.2 and 3.0 months, respectively. The pathological type of non-Hodgkin lymphoma (OS: P=0041, PFS: P=0.015) , ECOG score ≥ 3 (OS: P=0.031, PFS: P=0.030) , hematopoietic stem cell transplantation (OS: P=0.005, PFS: P=0.040) , lymphadenopathy (OS: P=0.007, PFS: P=0.012) , and splenomegaly (OS: P=0.276, PFS: P=0.324) were related to the overall survival and progression-free survival of patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis. Splenectomy could improve the prognosis of patients with lymphoma-associated hemophagocytic lymphohistiocytosis, especially T-cell lymphoma-associated hemophagocytic lymphohistiocytosis. Conclusion: The clinical characteristics of patients with different pathological types of non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis were similar but were different in the overall survival rate and the effect of prognostic factors. We suggested that patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis should receive more than combined chemotherapy. To improve the prognosis and survival rate of patients, those with B-cell lymphoma-associated hemophagocytic lymphohistiocytosis and NK-cell lymphoma-associated hemophagocytic lymphohistiocytosis promptly require hematopoietic stem cell transplantation. Moreover, patients with T-cell lymphoma-associated hemophagocytic lymphohistiocytosis should consider splenectomy.

Transcriptome analysis reveals TOR signalling-mediated plant flush shoots governing Diaphorina citri Kuwayama oviposition.

Asian Citrus Psyllid (ACP), Diaphorina citri, is a key vector transmitting the causative agent of Huanglongbing (HLB) disease. Population growth of ACP is evident after feeding on plant flush shoots, as they only oviposit here. However, the underlying mechanism as to why flush shoots govern oviposition is unclear. This study compares the fecundity and ovarian morphology of ACP between young flush and mature leaves. Furthermore, the transcriptome of mated females infesting Murraya paniculata was analysed. Finally, the gene of the key Target of Rapamycin (TOR) signalling pathway was silenced by RNAi. Results indicated that flush shoot feeding activated the development of the psyllids ovary and therefore induced oviposition. A total of 126 and 2794 differentially expressed genes were detected at 1 and 5 days, respectively, after pest infestation of flush shoots compared to mature leaves. Many genes are involved in protein metabolism, Mitogen-Activated Protein Kinase (MAPK) signalling pathway, hormone synthesis, and TOR signalling pathway: all thought to activate reproduction. Silencing of the positive regulator gene DcRheb in the TOR pathway resulted in lower levels of ecdysone and juvenile hormone and decreased vitellogenin synthesis, further disrupting reproductive ability. This study enhances understanding of the molecular mechanism underlying ACP's reproductive strategy.

[Chronic multifocal osteomyelitis: A case report and literature review].

A case of chronic multifocal osteomyelitis was described in terms of its clinical manifestations, serological and imaging examinations, diagnostic criteria, treatment options, and follow-up evaluation after discharge. The pathogenesis, diagnosis, differential diagnosis and treatment of chronic multifocal osteomyelitis were reviewed, and the characteristics of autoinflammatory osteopathy were reviewed. The patient with onset from youth had developed severe skin lesions, progressive arthralgia and rachialgia. The clinical manifestation and the auxiliary examination of the patient accorded with the diagnosis of chronic multifocal osteomyelitis. After poor anti-inflammatory and analgesic effects, the switch to tumor necrosis factor alpha (TNF-α) inhibitor resulted in pain relief, normalization of inflammation indexes, and significant improvement in rash and imaging examination. Chronic recurrent multifocal osteomyelitis was a kind of autoinflammatory bone disease of multiple genes in disease with low incidence, unknown mechanism and unified diagnostic criteria. It was also known as chronic nonbacterial osteomyelitis, which was a rare, noninfectious inflammatory disorder that caused multifocallytic bone lesions characterized by periodic exacerbations and remissions. The exact pathophysiology or mechanism of the sterile bone inflammation was poorly understood, although chronic nonbacterial osteomyelitis was probably an osteoclast-mediated disease. In addition, an imbalance between pro- and anti-inflammatory cytokines was suspected to play a role. The available data so far pointed to the interplay among genetics, environmental, and immunologic factors as the causes of chronic nonbacterial osteomyelitis. Infectious etiology did not seem to play a crucial role in the pathogenesis of chronic nonbacterial osteomyelitis. It was often confused with metabolic bone disease, infection, tumor and other diseases. Its clinical manifestations were bone pain, fever, rash, fracture and so on. Laboratory examination showed significant increase in inflammatory markers. Radiographic examination revealed osteolytic or sclerosing changes. Magnetic resonance imaging was very useful for identifying bone lesions and tissue edema and was more accurate than bone emission computed tomography (ECT). Most of the patients begin to use non-steroidal anti-inflammatory drugs (NSAIDs) for treatment, but they are prone to relapse and new lesions appear. Other treatment options can be selected, including glucocorticoids, TNF-α inhibitors, bisphosphonates, methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs). Early diagnosis and treatment can prevent and reduce complications and improve prognosis.

[Ergonomic risk factors of carpal tunnel syndrome in workers of an automobile factory].

Objective: To investigate the occurrence of pain symptoms and risk factors of carpal tunnel syndrome (CTS) in automobile manufacturing workers and provide theoretical basis for the prevention of CTS. Methods: From Nov.5th to Nov.19th, 2017, 446 workers in an automobile factory whose work age was above one year participate in questionnaires by cluster sampling. Chi square test and multifactor logistics regression analysis were used to analyze the factors related to the occurrence of CTS pain symptoms in workers. Results: The incidence of CTS pain among workers in this automobile factory was 20.8%. Working in the same position for a long time (OR=2.137, 95% CI:1.183-3.862) and unable to work reasonably because of uncomfortable posture (OR =2.067, 95% CI: 1.075-3.974) were identified as the risk factors of CTS pain symptoms by multifactor logistics regression analysis. Working age (OR=0.537, 95%CI:0.311-0.926) and work break (OR= 0.489, 95% CI: 0.282-0.849) were identified as the benefit factors of CTS pain symptoms. Conclusion: The incidence of CTS pain in automobile manufacturing workers is related to the posture in the process of labor . Effective ergonomic interventions should be carried out to prevent the occurrence of CTS pain in automobile manufacturing workers.

[Investigation of drug resistance and multilocus sequence typing for differentiation of strains of Candida tropicalis of Shanghai].

Objective: To analyze the drug resistance of clinical isolates of Candida tropicalis in patients with infectious diseases, and preliminarily study their molecular characteristics. Methods: 95 strains of Candida tropicalis were isolated from the fungal culture specimens of 87 patients with infectious diseases in Shanghai Public Health Clinical Center from 2012 to 2015. Meanwhile, basic clinical data of patients were collected. The drug resistance of the strains to fungal drugs was analyzed by ATB FUNGUS 3 drug sensitivity test strips. All strains were classified by Multilocus sequence typing(MLST). Then, homology analysis was conducted by MEGA 5.2 software, and the evolutionary tree was mapped by using UPGMA method. Results: Patients distribution of strains was rendered as following: 31 strains from TB patients, 21 strains from HIV/AIDS patients, 19 strains from patients with liver disease, and 24 strains from rare cause infection or fever patients. The drug resistance rate to five antifungal drugs commonly used in clinical (amphotericin B, 5-fluorine cytosine, fluconazole, itraconazole, voriconazole) were 2.11% (2 strains), 0, 26.32% (25 strains), 26.32% (25 strains), and 26.32% (25 strains) respectively. Among the 25 azole-resistant strains: 14 strains were from rare cause infection or fever patients, 8 strains were from HIV/AIDS patients, and 3 strains were from tuberculosis patients. In MLST, 72 sequence types (ST types) were produced, 70 of which were new types. Evolutionary tree analysis showed that 95 strains of clinical strains distribute as three large clusters. 24 azole resistant strains (96.0%) were located in CLUSER Ⅰ. Conclusion: The isolated Candida tropicalis were mainly resistant to azole drugs. MLST typing indicates that they was closely related to their genetic background.

[Molecular epidemiological study of human coronavirus OC43 in Shanghai from 2009-2016].

Objective: To understand the epidemiological characteristics of Human coronavirus (HCoV), the patterns of emergence and circulation, and the genotype distribution of human coronavirus OC43 (HCoV-OC43) from November, 2009 to April, 2016 in Shanghai. Methods: A total of 6 059 respiratory specimens, including pharyngeal swab, sputum, nasopharyngeal aspirates and alveolar lavage fluid, as well as relative clinical data were collected from patients with acute respiratory infections from seven sentinel hospitals during November, 2009 to April, 2016 in Shanghai. Respiratory specimens were tested by RT-PCR with HCoV-conserved primers and subsequently genotyped by DNA sequencing. Using specific primers to amplify and sequence full-length Spike (S), RNA-dependent RNA polymerase (RDRP) and nucleocapsid (N) gene from HCoV-OC43 positive samples. Further genotype and phylogenetic analysis of HCoV-OC43 were performed by conducting phylogenetic trees. Results: Among 6 059 patients, the total frequency of HCoV was 63 (1.04%), in which HCoV-OC43 was the most frequently detected species with 34 positive samples, followed by human coronavirus 229E (HCoV-229E) and human coronavirus HKU1 (HCoV-HKU1) with 18 and 10 positive sample respectively. However, other HCoV like human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle-East Respiratory Syndrome Coronavirus (MERS-CoV), were not been detected, which illustrated that HCoV-OC43 was the dominant subtype. The full-length of S, RDRP and N gene were obtained from 29 HCoV-OC43 positive samples. According to the sequence-analysis, 27 of which was genotype D, 2 of which was genotype B and others genotype, including genotype E, F and G, were not detected. The result indicated that the genotype D may be the dominant genotype. Further analysis of S protein that help HCoV-OC43 to entry host cell and stimulate the host immune system to produce neutralizing antibody found that two important functional domains in S protein, N-terminal domain (NTD) and receptor-binding domain (RBD) contained more amino acid substitution and positive selection sites, accompanied with amino acid insertion/deletion. 13 positive selection sites were all located in the NTD or RBD, 10 of which were located in the NTD and 3 in the RBD. Conclusion: Human coronavirus OC43 was the major circulation human coronaviurs in Shanghai from 2009 to 2016, in which genotype D was the dominant genotype. NTD and RBD regions of the S protein were hypervariable region during HCoV-OC43 evolution, and had amino acid substitutions as well as amino acid insertion/deletion.

[Protective effect and mechanism of tHBQ on acute silica dust exposure in rats].

Objective: To study the protective effects and possible mechanisms of tBHQ in rats exposed to acute silicadust. Methods: Male Wistar rats without specific pathogen SPF were randomly divided into control group、model group and intervention group, 32 rats for each group. Rats in the model group and the intervention group were treated with a single non exposed tracheal dust method to establish the rats exposed to silica model. The intervention group was intervened with 1% tBHQ solution, once a day. Each group 8 rats were sacrificed at 3,14,28,60d, respectively.The contents of IL-1,TNF-α, HYP,TGF-ß in the lung tissue of rats were determined by enzyme linked immunosorbent assay(ELISA), the contents of MDA and the GSH-PX activity in lung tissue and serum of rats were determined by colorimetry. Results: Compared with the control group, the contents of IL-1 in the lung tissue of the model group and the intervention group at each time point increased with time, the contents of IL-1 of model group reached the maximum at 60d, the contents of IL-1 in intervention group reached the maximum at 28d(P<0.05), except 3 d. Compared with the control group, the contents of TGF-ß and HYP in the lung tissue of the model group and the intervention group at 28 and 60 d increased with time and reached the maximum at 60d(P<0.05). Compared with the model group at each time point, the contents of IL-1, TGF-ß, HYP in the intervention group were lower than those in the model group(P<0.05). Compared with the control group, the contents of MDA in lung tissue and serum of rats in model group and intervention group at different time points increased with time(P<0.05). Compared with the control group,the activity of GSH-PX in serum and lung tissue of rats in model group and intervention group decreased with time,there was no significant difference in 3d(P<0.05), compared with the control group, the activity of GSH-PX in the lung and serum tissue of in-tervenetion group was higher than model group except the 3d(P<0.05). Conclusion: The intervention of tBHQ can alleviate oxidative stress in rats exposed to silica dust to some extent, improve the antioxidant capacity of the body, and reduce the contents of IL-1, TNF-α, TGF-ß,HYP in lung tissue,it has acertain impediment and inhibition effect on the inflammation and fibrosis caused by acute silica dust exposure.

Incorporating TiO2 nanotubes with a peptide of D-amino K122-4 (D) for enhanced mechanical and photocatalytic properties.

Titanium dioxide (TiO2) nanotubes are promising for a wide variety of potential applications in energy, biomedical and environmental sectors. However, their low mechanical strength and wide band gap limit their widespread technological use. This article reports our recent efforts to increase the mechanical strength of TiO2 nanotubes with lowered band gap by immobilizing a peptide of D-amino K122-4 (D) onto the nanotubes. Topographies and chemical compositions of the peptide-coated and uncoated TiO2 nanotubular arrays were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy (XPS). Properties of the peptide-coated and uncoated TiO2 nanotubular arrays, including hardness, elastic modulus, electron work function and photocurrent, were evaluated using micromechanical probe, Kelvin Probe and electrochemical system. Effect of the peptide on surface conductivity was also investigated through current mapping and I-V curve analysis with conductive atomic force microscopy. It is demonstrated that the peptide coating simultaneously enhances the mechanical strength, photocatalytic and electrical properties of TiO2 nanotubes.

Increased risk of pulmonary tuberculosis in patients with gastroesophageal reflux disease.

BACKGROUND: Previous studies have suggested a close correlation between gastroesophageal reflux disease (GERD) and various respiratory disorders. However, the association between GERD and tuberculosis (TB) remains unexplored. METHODS: Using data retrieved from Taiwan's National Health Insurance Research Database from 2000 to 2009, this longitudinal nationwide cohort study included a total of 63,930 patients with GERD and controls matched by age, sex and comorbidities. Risk factors associated with the development of pulmonary TB (PTB) were investigated. RESULTS: Active PTB was documented in 65 (0.20%) patients with GERD and 41 (0.13%) matched cohorts within 1 year of GERD diagnosis. The incidence rate of PTB in the GERD group and the matched cohort was respectively 24.1 and 15.2 cases per 10,000 person-years. In multivariate analysis, GERD was an independent risk factor for PTB (adjusted HR 1.63, 95%CI 1.10-2.40, P = 0.015). Among patients with GERD, independent predictors for PTB included older age, male sex, chronic obstructive pulmonary disease, asthma and exposure to proton pump inhibitors (PPIs). CONCLUSION: Patients with GERD have a significantly increased risk of PTB within 1 year of GERD diagnosis. Exposure to PPIs is an independent predictor for PTB among patients with GERD.

MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3ß expression.

MicroRNAs are emerging to be important epigenetic factors that control axon regeneration. Here, we report that microRNA-26a (miR-26a) is a physiological regulator of mammalian axon regeneration in vivo. We demonstrated that endogenous miR-26a acted to target specifically glycogen synthase kinase 3ß (GSK3ß) in adult mouse sensory neurons in vitro and in vivo. Inhibition of endogenous miR-26a in sensory neurons impaired axon regeneration in vitro and in vivo. Moreover, the regulatory effect of miR-26a was mediated by increased expression of GSK3ß because downregulation or pharmacological inhibition of GSK3ß fully rescued axon regeneration. Our results also suggested that the miR-26a-GSK3ß pathway regulated axon regeneration at the neuronal soma by controlling gene expression. We provided biochemical and functional evidences that the regeneration-associated transcription factor Smad1 acted downstream of miR-26a and GSK3ß to control sensory axon regeneration. Our study reveals a novel miR-26a-GSK3ß-Smad1 signaling pathway in the regulation of mammalian axon regeneration. Moreover, we provide the first evidence that, in addition to inhibition of GSK3ß kinase activity, maintaining a lower protein level of GSK3ß in neurons by the microRNA is necessary for efficient axon regeneration.

IL-37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2-like Phenotype.

Interleukin-37 (IL-37), a member of the IL-1 family, primarily functions as an anti-inflammatory cytokine, reducing inflammation and suppressing the immune response. However, the expression and role of IL-37 in tuberculosis (TB) remains unknown. We aimed to measure serum levels of IL-37 and several important cytokines in 25 patients with active TB and to analyse their association with disease activity. We found that IL-37 levels decreased in patients with TB and recovered after treatment. IL-37 levels negatively correlated with the serum concentration of IFN-γ and IL-12 but positively correlated with IL-10 and TGF-ß levels. After IL-37, secretion was blocked in peripheral blood mononuclear cells from active patients with TB, IFN-γ and IL-10 production was significantly upregulated; this was not observed in healthy donors or patients after treatment. IL-37 knockdown significantly enhanced the phagocytic activity of THP1-derived macrophages towards Mycobacterium tuberculosis (M. tb). M1/M2 polarization-associated markers were detected simultaneously, and IL-37 induced a phenotypic shift in THP1-derived macrophages towards a high CD206(+) and low CD86(+) macrophage subtype. Furthermore, this phenotypic shift was accompanied by upregulated mRNA levels of arginase 1, TGF-ß and IL-10, which are characteristic hallmarks of M2 macrophages. In conclusion, our results suggest that increased levels of IL-37 in patients with TB are associated with IFN-γ, IL-12, IL-10 and TGF-ß levels and that IL-37 plays a pathological role in TB infection by inhibiting the production of pro-inflammatory cytokines and inducing macrophages towards an M2-like phenotype. Thus, IL-37 may be a novel research target to understand the pathogenesis of TB infection.

Incidence and Risk Factors for Tuberculosis After Liver Transplantation in an Endemic Area: A Nationwide Population-Based Matched Cohort Study.

Morbidity and mortality from tuberculosis (TB) are high in Taiwan. We conducted a nationwide population-based matched cohort study using data retrieved from the Taiwan's National Health Insurance Research Database to determine the impact of TB after liver transplantation (LT). During 2000-2011, we identified 3202 liver transplant recipients and selected subjects from the general population matched for age, sex, and comorbidities on the same index date of recognition of LT with a 1:10 ratio. The data were analyzed using Cox proportional hazards models. Compared to the matched cohort, liver transplant patients had a higher risk for TB (adjusted HR 2.25, 95% CI 1.65-3.05, p < 0.001), and those with TB showed higher mortality (HR 2.27, 95% CI 1.30-3.97, p = 0.004). Old age (HR 2.64, 95% CI 1.25-5.54, p = 0.011) and mammalian target of rapamycin inhibitors (mTORis) (HR 3.09, 95% CI 1.68-5.69, p < 0.001) were significant risk factors for TB in LT; mTORis were also associated with mortality after adjusting for confounders (HR 2.13, 95% CI 1.73-2.62, p < 0.001). Therefore, regular surveillance of TB and treatment of latent TB infection in high-risk patients after LT are important, especially in TB-endemic areas.

Use of azathioprine for graft-vs-host disease is the major risk for development of secondary malignancies after haematopoietic stem cell transplantation: a nationwide population-based study.

BACKGROUND: As more patients are treated by haematopoietic stem cell transplantation (HSCT), development of secondary malignancy (SM) becomes an increasingly common issue in long-term survivors. METHODS: We conducted a nationwide population-based study of the Taiwanese population to analyse patients who received HSCT between January 1997 and December 2010. Standardised incidence ratios (SIRs) were used to compare the risk of SM in HSCT patients and the general population. Multivariate analysis was performed to identify independent predictors of SM. RESULTS: Patients receiving HSCT had a significantly greater risk of developing SM (SIR 2.00; 95% confidence interval (CI) 1.45-2.69; P<0.001). Specifically, the incidence increased for cancers of the oral cavity (SIR 14.18) and oesophagus (SIR 14.75) after allogeneic HSCT. Multivariate analysis revealed an increased SIR for cancer in patients who received the immunosuppressant azathioprine. The risk of SM also increased with greater cumulative doses of azathioprine. CONCLUSIONS: This study demonstrates an increased incidence of SM in Taiwanese patients who received allogeneic HSCT, especially for cancers of the oral cavity and oesophagus. This finding is different from results in populations of Western countries. Physicians should be cautious about azathioprine use for graft-vs-host disease after HSCT.

Clinical epidemiology and molecular profiling of human bocavirus in faecal samples from children with diarrhoea in Guangzhou, China.

To understand the clinical epidemiology and molecular characteristics of human bocavirus (HBoV) infection in children with diarrhoea in Guangzhou, South China, we collected 1128 faecal specimens from children with diarrhoea from July 2010 to December 2012. HBoV and five other major enteric viruses were examined using real-time polymerase chain reaction. Human rotavirus (HRV) was the most prevalent pathogen, detected in 250 (22·2%) cases, followed by enteric adenovirus (EADV) in 76 (6·7%) cases, human astrovirus (HAstV) in 38 (3·4%) cases, HBoV in 17 (1·5%) cases, sapovirus (SaV) in 14 (1·2%) cases, and norovirus (NoV) in 9 (0·8%) cases. Co-infections were identified in 3·7% of the study population and 23·5% of HBoV-positive specimens. Phylogenetic analysis revealed 14 HBoV strains to be clustered into species HBoV1 with only minor variations among them. Overall, the detection of HBoV appears to partially contribute to the overall detection gap for enteric infections, single HBoV infection rarely results in severe clinical outcomes, and HBoV sequencing data appears to support conserved genomes across strains identified in this study.

Increased cancer risk in patients with haemophilia A: a nationwide population-based 14-year study in Taiwan.

Haemostasis is associated with the development and dissemination of cancer. Whether cancer incidence is increased in haemophiliacs remains uncertain; thus, we aimed to further examine this issue. By using data from the National Health Insurance Research Database in Taiwan, we obtained a cohort of 683 patients with haemophilia A, and compared the incidence rate ratio (IRR) of cancer in this cohort with an age- and sex-matched control of 6830 patients. The log-rank test was used to compare Kaplan-Meier curve of the cumulative cancer incidence between two cohorts. Cox regressions were used to identify independent risk factors of cancer in the study patients. The cancer incidence of patients with haemophilia A was significantly higher compared to the control group (IRR 1.95, 95% CI 1.18-3.09, P = 0.008) during the 14-year follow-up period. The non-lymphoma and non-liver cancer incidence in the haemophilia A cohort remained higher than that of the matched control (P = 0.050 by the log-rank test). The multivariate Cox proportional hazards analysis indicated that age (per year, HR 1.09, 95% CI 1.06-1.12, P < 0.001) was the only significant risk factor for cancer development in haemophilia patients. Patients with haemophilia A had higher cancer incidence than the age- and sex-matched patients, especially for the elderly. With increasing life expectancy for haemophiliacs, physicians should be aware of their cancer development.