Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20-year systematic review and meta-analysis of randomized controlled trials.

Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ClinicalTrials.gov databases from inception to December 31, 2021. We included double-blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel-Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I-squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta-analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02-1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61-1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94-1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00-1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03-1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02-1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis.

Cigarette smoking and risk of herpes zoster: a population-based cohort study in Taiwan.

The effects of cigarette smoking on the risk of herpes zoster (HZ) infection remain unclear. This study aimed to examine the association between cigarette smoking and HZ. Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of HZ were identified from the Taiwanese National Health Insurance database. Of the 57 641 participants, 3346 developed HZ during the observation period. After controlling for confounders, current smokers had a lower risk of incident HZ than never-smokers (adjusted hazard ratio 0.69; 95% CI 0.62-0.77). There was a trend toward a decreased risk of HZ with increasing numbers of cigarettes per day, years of smoking and cumulative pack-years of smoking among current smokers (Ptrend < 0.001). Former smoking was not associated with risk of HZ. In conclusion, current smoking was significantly associated with a decreased risk of developing HZ.

Cigarette smoking and risk of rosacea: a nationwide population-based cohort study.

BACKGROUND: Most evidence regarding the relationship between cigarette smoking and risk of rosacea is obtained from cross-sectional or case-control studies. OBJECTIVE: To examine the association between smoking and risk of developing rosacea. METHODS: Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of rosacea were identified from the National Health Insurance database. Cox proportional hazard model was used for the analyses. RESULTS: Of the 59 973 participants, 379 developed rosacea during a mean follow-up of 10.8 years. After adjustment for potential confounders, current smokers had a lower risk of rosacea than never smokers [adjusted hazard ratio (aHR) 0.60; 95% confidence interval (CI) 0.39-0.92]. An increase in smoking intensity was associated with a decreased risk of rosacea among current smokers (Ptrend  = 0.0101). Compared with never smokers, current smokers of >15 cigarettes/day had an aHR of 0.51 (95% CI: 0.26-0.99) for rosacea. For incident rosacea, the aHRs (95% CIs) of current smokers of ≤10 years of smoking and ≤10 pack-years of smoking were 0.44 (0.22-0.88) and 0.51 (0.29-0.89), respectively. Former smoking was not associated with rosacea risk. CONCLUSION: Current smoking was significantly associated with a decreased risk of rosacea.

Cancer is not a risk factor for bullous pemphigoid: 10-year population-based cohort study.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune bullous disease. Whether there is an increased risk for subsequent BP among patients with cancer is still unclear. OBJECTIVES: To evaluate the risk for subsequent BP in patients with cancer. METHODS: This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database between 2000 and 2011. A total of 36 838 patients with cancer and 147 352 age-, sex- and index-date-matched controls were recruited. The hazard ratio (HR) of subsequent BP in the patients with cancer was analysed using a Fine-Gray competing risk regression model with mortality as the competing event. RESULTS: The incidence of BP per 100 000 person-years was 17·2 in the patients with cancer and 19·8 in the controls; therefore, the crude incidence rate ratio was 0·87 [95% confidence interval (CI) 0·53-1·36]. The HR of subsequent BP in the patients with cancer was 0·47 (95% CI 0·23-0·94) using the Fine-Gray competing risk regression model. Age (HR 1·05, 95% CI 1·03-1·07), diabetes mellitus (HR 1·69, 95% CI 1·10-2·59) and cerebrovascular disease (HR 2·14, 95% CI 1·36-3·34) were independent risk factors for BP. CONCLUSIONS: The incidence of BP in patients with cancer was not higher than in the control group. Cancer is not a risk factor for BP.

Measurement of the Dynamical Structure Factor of a 1D Interacting Fermi Gas.

We present measurements of the dynamical structure factor S(q,ω) of an interacting one-dimensional Fermi gas for small excitation energies. We use the two lowest hyperfine levels of the ^{6}Li atom to form a pseudospin-1/2 system whose s-wave interactions are tunable via a Feshbach resonance. The atoms are confined to one dimension by a two-dimensional optical lattice. Bragg spectroscopy is used to measure a response of the gas to density ("charge") mode excitations at a momentum q and frequency ω, as a function of the interaction strength. The spectrum is obtained by varying ω, while the angle between two laser beams determines q, which is fixed to be less than the Fermi momentum k_{F}. The measurements agree well with Tomonaga-Luttinger theory.

The symptom burden of autonomic dysfunction is positively associated with chronic rhinosinusitis status.

BACKGROUND: Dysregulation of the autonomic system can affect sinonasal physiological function and may exacerbate the symptom burden associated with rhinosinusitis. However, the association between autonomic dysfunction and chronic rhinosinusitis (CRS) has seldom been studied. Here, we investigated the relationship between autonomic dysfunction and CRS. METHODS: Patients with CRS who failed medical treatment were prospectively enrolled. All patients underwent pre-operative examinations and completed questionnaires, including the reflux symptom index (RSI) and the Sino-nasal Outcome Test-22 (SNOT-22). Autonomic dysfunction was scored using the 31-item Composite Autonomic Symptom Score (COMPASS 31), a validated simple instrument used to evaluate dysautonomia. RESULTS: We prospectively enrolled a total of 89 CRS patients, including 37 with polyps (CRSwNP) and 52 without polyps (CRSsNP). The most common dysautonomic symptoms were dry eye, dry mouth, postural dizziness, and a sensation of excessive fullness after meals. Significant positive correlations were evident between COMPASS 31 and SNOT-22 scores in CRSwNP patients. CRS-associated symptoms, including cough, post-nasal drip, sleep, and psychological dysfunction, were correlated with the level of autonomic dysfunction. CONCLUSIONS: We found a positive correlation between the symptom burdens of autonomic dysfunction and CRSwNP. The relationship between autonomic dysfunction and CRS is highly complex; further work is needed.

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development.

BACKGROUND & OBJECTIVES: Chromatin structure is the single most important feature that distinguishes a cancer cell from a normal cell histologically. Chromatin remodeling proteins regulate chromatin structure and high mobility group A (HMGA1) proteins are among the most abundant, nonhistone chromatin remodeling proteins found in cancer cells. These proteins include HMGA1a/HMGA1b isoforms, which result from alternatively spliced mRNA. The HMGA1 gene is overexpressed in cancer and high levels portend a poor prognosis in diverse tumors. HMGA1 is also highly expressed during embryogenesis and postnatally in adult stem cells. Overexpression of HMGA1 drives neoplastic transformation in cultured cells, while inhibiting HMGA1 blocks oncogenic and cancer stem cell properties. Hmga1 transgenic mice succumb to aggressive tumors, demonstrating that dysregulated expression of HMGA1 causes cancer in vivo. HMGA1 is also required for reprogramming somatic cells into induced pluripotent stem cells. HMGA1 proteins function as ancillary transcription factors that bend chromatin and recruit other transcription factors to DNA. They induce oncogenic transformation by activating or repressing specific genes involved in this process and an HMGA1 "transcriptome" is emerging. Although prior studies reveal potent oncogenic properties of HMGA1, we are only beginning to understand the molecular mechanisms through which HMGA1 functions. In this review, we summarize the list of putative downstream transcriptional targets regulated by HMGA1. We also briefly discuss studies linking HMGA1 to Alzheimer's disease and type-2 diabetes. CONCLUSION: Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and possibly for other diseases associated with aberrant HMGA1 expression.

Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway.

The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.

Protective effects of morphine preconditioning in delayed phase on myocardial ischemia-reperfusion injury in rabbits.

The aim of this study was to investigate the protective mechanisms of delayed-phase morphine preconditioning on myocardial ischemia-reperfusion injury. Thirty healthy male New Zealand white rabbits were randomly divided into three groups: a sham operation group (C), ischemia-reperfusion group (I/R), and delayed-phase morphine preconditioning group (M) (N = 10/group). Rabbits in the C group received thoracotomy for 160 min. Rabbits in the I/R group received left artery blockage for 40 min and reperfusion for 120 min. Rabbits in the M group received 1.0 mg/kg intravenous morphine 24 h prior to the identical treatment as the rabbits in the I/R group. In each group, the interleukin (IL)-10 and tumor necrosis factor (TNF)-α levels were detected at five time points: 20 min before the left coronary artery blockage (T1), 20 and 40 min after the left coronary artery blockage (T2 and T3, respectively), and 1 and 2 h after the myocardial reperfusion (T4 and T5, respectively). After reperfusion, the infarction size was measured with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Compared with the C group, serum IL-10 and TNF-α concentrations increased in the I/R and M groups; the difference was significant (P < 0.05). When compared with the I/R group, the IL-10 concentrations in the M group were significantly increased (P < 0.05), but the infarction size and TNF-α concentrations were significantly decreased (P < 0.05). These results suggested that delayed-phase morphine preconditioning might achieve myocardial protection through the regulation and balance of inflammatory cytokines.

Effect of morphine preconditioning in the delayed phase on the expression of p38 mitogen-activated protein kinase in a rabbit model of myocardial ischemia-reperfusion injury.

This study aimed to investigate the protective effects of delayed morphine preconditioning on myocardial ischemia-reperfusion injury. We randomly divided 30 rabbits into three groups with 10 rab-bits in each group as follows: sham operation group (C group), isch-emia-reperfusion group (I/R group), and morphine pretreatment group (M group). Rabbits in C Group received left coronary without blocking for 160 min. The left descending artery of rabbits in the I/R group was blocked for 40 min and reperfused for 120 min. Rabbits in the M group received intravenous administration of 1.0 mg/kg morphine; after 24 h, rabbits in this group received the same treatment as that administered to the I/R group. We determined tumor necrosis factor alpha (TNF-α) levels in blood samples from the internal carotid artery of rabbits in each group 20 min before occlusion of the left descending coronary artery, 20 and 40 min after occlusion of the left descending coronary artery, and 1 and 2 h after myocardial reperfusion. After 120 min of reperfusion, immunoblotting was used to measure the activity levels of myocardial p38 mitogen-activated protein kinase (MAPK); in addition, the infarct size was measured. Compared to the I/R group, the M group showed a significant decrease in TNF-α levels, p38 MAPK activity, and the myocardial infarct size (I/R group 37.8% ± 1.7% vs 21.5% ± 2.4%; P < 0.05). Thus, morphine preconditioning in the delayed phase may exert protective effects on myocardial I/R injury by inhibiting myocar-dial p38 MAPK activity and decreasing TNF-α production.

Effects of isoflurane preconditioning in the delayed phase on myocardial tumor necrosis factor alpha levels and caspase-3 protein expression in a rabbit model of ischemia-reperfusion injury.

This study aimed to investigate the protective effects and the mechanisms underlying these effects of isoflurane preconditioning in the delayed phase of myocardial ischemia-reperfusion injury. We randomly divided 30 healthy male New Zealand white rabbits into three groups with 10 rabbits in each group as follows: sham operation group (C group), ischemia-reperfusion group (I/R group), and 2.0% isoflurane preconditioning group (S group). Rabbits in the C group received thoracotomy for 160 min. Rabbits in the I/R group underwent left coronary artery occlusion for 40 min and reperfusion for 120 min. Rabbits in the S group received inhalation of 2.0% isoflurane and 100% oxygen for 2 h; after 24 h, rabbits in this group received the same treatment as that administered to rabbits in the I/R group. We examined the tumor necrosis factor alpha (TNF-α) levels in each group 20 min before occlusion of the left coronary, 20 and 40 min after occlusion of the left coronary artery, and 1 and 2 h after myocardial reperfusion. After reperfusion, immunoblotting was used to measure the myocardial caspase-3 expression levels, and the infarct size was measured using Evans blue and tetrazolium chloride staining. The levels of TNF-α and caspase-3 were lower in the S group than in the I/R group, and the myocardial infarct size decreased in the S group. Thus, isoflurane preconditioning in the delayed phase exerted protective effects by decreasing the myocardial caspase-3 expression and TNF-α production in a rabbit model of ischemia-reperfusion injury.

Ginkgo biloba extract postconditioning reduces myocardial ischemia reperfusion injury.

We examined the protective effects of Ginkgo biloba extract (EGb761) postconditioning on myocardial ischemia reperfusion injury in rabbits. Four groups of 8 white rabbits were allocated to: pseudo surgery group: the left coronary was lined without blocking for 160 min after thoracotomy; ischemia and reperfusion group (IR): the left anterior descending coronary artery was blocked for 40 min and reperfused for 120 min; ischemic postconditioning group: the left anterior descending artery was ligated for 40 min, reopened for 30 s and ligated for 30 s, repeated three times, and then reperfused for 120 min; EGb761 postconditioning group (E): 100 mg/kg EGb761 was injected into a vein while the left coronary artery was opened for 1 min. The reperfusion took 120 min. Internal carotid arterial blood in each group was collected for cTnI measurement at five times: 20 min before occlusion of the left coronary artery, 20 min after left coronary artery occlusion, 40 min after left coronary artery occlusion, 1 h after myocardial reperfusion, and 2 h after myocardial reperfusion. Superoxide dismutase (SOD), malondialdehyde (MDA) in the centrifuged blood and myocardial infarction area were measured at the end of reperfusion. We found that the serum cTnI concentrations in the E group during reperfusion decreased significantly compared with those in the IR group. The infarction area was significantly lower in the E group than that in the IR group. The SOD activity in the E group was increased compared with that in the IR group; the MDA content decreased significantly in the E group compared with that in the IR group. We conclude that G. biloba extract postconditioning had myocardial protection effects by reducing the generation of oxygen-free radicals and increasing the antioxidant capacity of the myocardial cells.

Intraoperative anastomotic dye test significantly decreases incidence of anastomotic leaks in patients undergoing resection for rectal cancer.

BACKGROUND: Anastomotic leakage is still a major complication in colorectal surgery. Prompt recognition and immediate treatment of anastomotic leak during surgery may reduce postoperative morbidity and mortality. Various types of intraoperative anastomotic test have been proposed to reduce the incidence of this complication. The aim of this study was to assess our experience with intraoperative dye test in rectal cancer surgery. METHODS: Between 2006 and 2009, a retrospective review of a single general surgeon's practice identified 76 patients who underwent the intraoperative dye test in rectal cancer surgery. Seventy-three of these 76 patients underwent elective surgery without creation of a diverting stoma. Diluted dye was routinely introduced into the rectal lumen to test anastomotic integrity. Intraoperative leak was repaired prior to the completion of the procedure. No routine radiological survey assessed anastomotic integrity postoperatively. RESULTS: In 11 (14.5 %) out of 76 patients, anastomotic leaks were found and treated intraoperatively. None of the 65 patients without intraoperative leaks developed clinical leaks during the follow-up period. Postoperative leakage only occurred in one patient (1.3 %). He developed pelvic abscess evidenced by abdominal computed tomography scan and was treated non-operatively. CONCLUSIONS: The favorable results allow the authors to recommend the routine use of the intraoperative dye test for colorectal anastomoses.

Cancer risk in patients with pyogenic liver abscess: a nationwide cohort study.

BACKGROUND: There has been no large-scale population-based study on the relationship between pyogenic liver abscesses (PLA) and subsequent cancer risk. AIM: To estimate all cancer risk following a diagnosis of PLA. METHODS: Based on Taiwan's National Health Insurance Research Database, 1257 patients with PLA without prior cancers in the period 1996-2008 were identified and followed-up. The standard incidence ratio (SIR) of each cancer was calculated as the number of observed cancer cases arising among the PLA patients divided by the expected case number of cancer cases according to the national cancer rates. RESULTS: Of the 1257 PLA patients identified, 598 (47.6%) had diabetes mellitus. After a median (±s.d.) follow-up of 3.33 ± 3.45 years, 186 were diagnosed with cancers, including 56 liver cancer, 22 biliary tract cancer and 40 colorectal cancer patients. Patients with PLA had a higher risk of all cancers (SIR, 3.83; 95% CI, 3.30-4.42), liver cancer (SIR, 7.87; 95% CI, 5.94-10.21), biliary tract cancer (SIR, 34.58; 95% CI, 21.67-52.36) and colorectal cancer (SIR, 5.27; 95% CI, 3.76-7.18). The highest SIRs of all cancers, liver cancer, biliary tract cancer and colorectal cancer occurred within 90 days of follow-up (360.82; 95% CI, 278.46-459.91, 257.28; 95% CI, 186.17-346.56, 1153.38; 95% CI 694.08-1801.24, and 52.63; 95% CI 25.2-96.8 respectively). CONCLUSIONS: Pyogenic liver abscesses may herald the onset of cancer, especially hepato-biliary and colon cancer. Further surveys should be conducted for the detection of occult cancers in such patients.

Characteristic dermoscopic features of primary cutaneous amyloidosis: a study of 35 cases.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder among Asians and South Americans. It is usually diagnosed clinically. However, for cases with atypical presentations, the diagnosis can be a challenge and skin biopsy may be necessary. Dermoscopy has been proved to be a valuable, noninvasive tool in the diagnosis of cutaneous pigmented diseases. Most lesions of PCA show hyperpigmentation and the major histopathological abnormalities of PCA occur in the epidermis and dermal papillae. Dermoscopy might be a powerful tool to provide valuable information for the diagnosis of PCA. OBJECTIVES: We aimed to find characteristic dermoscopic features of PCA. MATERIALS AND METHODS: Cases with typical clinical presentations of PCA, either macular or lichen subtypes, were included in this study. All were evaluated using a hand-held, polarized and nonpolarized dermoscope. RESULTS: A total of 35 patients with clinically diagnosed PCA were enrolled. Eighteen patients had lesions consistent with macular amyloidosis and 17 with lichen amyloidosus. We found two major dermoscopic patterns characteristic of PCA. The most common dermoscopic finding of PCA was a central hub, which could be either white or brown, surrounded by various configurations of pigmentation. For cases of lichen amyloidosus with prominent hyperkeratosis, the central hub was replaced by a scar-like morphology. CONCLUSIONS: This is the first study to report the characteristic dermoscopic features of PCA. We demonstrate that the use of a dermoscope may assist in achieving an accurate diagnosis of PCA.

Association of primary cutaneous amyloidosis with atopic dermatitis: a nationwide population-based study in Taiwan.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a pruritic skin disorder most commonly seen in Southeast Asia and South America. Association of PCA with atopic dermatitis (AD) has been reported in the literature. However, no large-scale epidemiological study of PCA and its associations with other diseases has been conducted so far. OBJECTIVES: We aimed to provide overall demographic data and comorbidities of patients with PCA based on a nationwide database in Taiwan. METHODS: Cases of PCA were collected from records of National Health Insurance claims from 2000 to 2007. We analysed patients' gender, age when the diagnosis was first made, and the overall 8-year prevalence. We also investigated comorbidities. RESULTS: The overall 8-year prevalence of PCA was 7·87 per 10,000 persons. Although there was no significant gender difference in the prevalence of PCA, men and women showed a different peak age (men, 71-80 years; women, 41-50 years) and a different age distribution at diagnosis. The mean age at diagnosis of PCA was significantly younger for women than for men. Men sought medical assistance for PCA more frequently than women. There was a higher disease activity from May to September than during other months. PCA was strongly associated with AD (odds ratio 7·18). Patients with PCA had a higher comorbidity of hyperlipidaemia and diabetes mellitus. CONCLUSIONS: This is the first nationwide population-based epidemiological study of PCA. We demonstrate that PCA can be associated with other disorders, especially AD.