Incidence and Risk Factors of Mental Illnesses Among Patients with Systemic Autoimmune Rheumatic Diseases: An 18-year population-based study.

OBJECTIVE: This study aimed to assess the incidence and risk factors surrounding mental illnesses in patients diagnosed with systemic autoimmune rheumatic diseases (SARDs). METHODS: This retrospective cohort study used nationwide, population-based claim data taken from Taiwan's National Health Insurance Research Database (NHIRD) to identify patients certified as having a catastrophic illness for Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), Systemic sclerosis (SSc), Dermatomyositis (DM), Polymyositis (PM) or Sjogren's syndrome (SS) from the years 2002-2020. We furthermore calculated the incidence of mental illness in patients diagnosed with SARDs while exploring factors associated with the development of mental illness using multivariable Cox regression analysis shown as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among the 28 588 participants, the average age was 47.4 (SD 14.9) years, with most participants being female (76.4%). When compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.20, 95% CI: 1.10-1.32), SS (HR: 1.29, 95% CI: 1.19-1.39), and DM (HR: 1.28, 95% CI: 1.04-1.32) showed a significantly increased risk of developing mental illness. Additionally, when compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.32, 95% CI: 1.21-1.44), SSc (HR: 1.20, 95% CI: 1.02-1.41), SS (HR: 1.17, 95% CI: 1.08-1.26), DM (HR: 1.73, 95% CI: 1.44-2.07), and PM (HR: 1.64, 95% CI: 1.32-2.03) showed a significantly increased risk of antidepressant use. CONCLUSIONS: This population-based cohort study revealed that patients diagnosed with SLE, SS and DM had significantly higher risks of developing mental illness when compared with patients with RA.

Increased NAFLD risk in newly diagnosed patients with RA during the first 4 years of follow-up: a nationwide, population-based cohort study.

BACKGROUND: Although the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in patients with RA and identified the potential risk factors. DESIGN: Retrospective study. SETTING: Taiwan. PARTICIPANTS: 2281 newly diagnosed patients with RA and selected 91 240 individuals without RA to match with patients with RA (1:40) by age, gender, income status and urbanisation level of the residence. OUTCOMES: In this retrospective study using the 2000-2018 claim data from two-million representative Taiwanese population, we identified and compared the incidence rates (IRs) of NAFLD and alcoholic fatty liver disease (AFLD) between RA and non-RA groups. Using multivariable regression analyses, we estimated adjusted HR (aHR) of NAFLD development in patients with RA compared with individuals without RA, with 95% CIs. RESULTS: The incidences of NALFD and AFLD were not significantly different between individuals with RA and without RA during the 17-year follow-up period. However, patients with RA had significantly increased NAFLD risk during the first 4 years after RA diagnosis, with IR ratio of 1.66 fold (95% CI 1.18 to 2.33, p<0.005), but the risk was reduced after the first 4 years. Multivariable regression analyses revealed that aHR was 2.77-fold greater in patients not receiving disease-modifying anti-rheumatic drugs therapy than in non-RA subjects (p<0.05). Old age, women, low-income status and obesity could significantly predict NAFLD development. CONCLUSIONS: We demonstrated elevated risk of NAFLD in patients with RA during the first 4 years after RA diagnosis, and old age, women, low-income status and obesity were significant predictors of NAFLD.

Stratified analysis of the association between periodontitis and female breast cancer based on age, comorbidities and level of urbanization: A population-based nested case-control study.

PURPOSE: To conduct stratified analysis of the association between periodontitis exposure and the risk of female breast cancer based on age, comorbidities and level of urbanization. METHODS: Using claims data taken from the 1997-2013 Taiwanese National Health Insurance Research Database (NHIRD), we identified 60,756 newly-diagnosed female breast cancer patients during the period 2003-2013 from all beneficiaries. We then randomly selected 243,024 women without breast cancer matching (1:4) for age and the year of the index date during 1997-2013 from a one million representative population acting as the control group. A conditional logistic regression analysis was used to examine the association between periodontitis (ICD-9-CM codes 523.3-4) and the risk of breast cancer, shown as an odds ratio (OR) with a 95% confidence interval (CI) after adjustments for the Charlson Comorbidity Index (CCI) and level of urbanization. Subgroup analyses were conducted based on age, CCI and level of urbanization. RESULTS: The mean ± standard deviation age was 53 ± 14 years. After adjusting for potential confounders, the risk of female breast cancer was found to be associated with a history of periodontitis (OR, 1.12; 95% CI, 1.10-1.14). Such an association was significantly different between patients aged < 65 years (OR, 1.09; 95% CI, 1.06-1.11) and patients aged ≥ 65 years (OR, 1.23; 95% CI, 1.18-1.28; p for interaction <0.001), as well as between patients where the CCI = 0 (OR, 1.17; 95% CI, 1.15-1.20) and patients with CCI > 0 (OR, 0.99; 95% CI, 0.96-1.03; p for interaction <0.001). The highest level of urbanization was also associated with the risk of breast cancer. CONCLUSIONS: This population-based nested case-control study demonstrated that periodontitis was significantly associated with the risk of female breast cancer and such an association was modified by both age and comorbidities.

Factors Associated with the Risk of Major Adverse Cardiovascular Events in Patients with Ankylosing Spondylitis: A Nationwide, Population-Based Case-Control Study.

Background: Potential risk factors for major adverse cardiovascular events (MACE) in patients with ankylosing spondylitis (AS) requiring medical therapy should be investigated. Methods: We identified newly diagnosed AS patients without previous MACE from 2004 to 2012 using the National Health Insurance Research Database, matched MACE cases with non-MACE controls at a 1:4 ratio for age, gender, AS duration, and index date, and included 947 AS patients with MACE and 3896 matched controls for final analyses. By using conditional logistic regression analyses, we examined the associations of MACE with low income, urbanisation, comorbidities, common extra-articular manifestations (EAM), and medications, including nonsteroidal anti-inflammatory drugs (NSAID) of three categories (traditional NSAIDs, selective cyclooxygenase-2 inhibitors (COX-2i), and preferential COX-2is) with their annual cumulative defined daily dose (cDDD) within a year before MACE development. Results: MACE development was associated with the use of selective COX-2is (especially with annual cDDD > 132) and corticosteroids, residence in rural regions, and well-known associated comorbidities, but not with the use of traditional NSAIDs, preferential COX-2i, biologics, methotrexate, sulfasalazine, and common EAMs. Conclusions: The risk factors of MACE in newly diagnosed AS patients include residence in rural regions, well-known associated comorbidities, and the use of corticosteroids and selective COX-2is. A major limitation was the lack of information on individual lifestyle patterns and disease activity.

Prevalence of thyroid malignancy and hormonal dysfunction following radiation exposure in childhood.

INTRODUCTION: Childhood radiation exposure is a known risk factor for thyroid malignancy and dysfunction. However, local data are limited and there is no consensus on the modality and frequency of screening in this high-risk group. METHODS: Retrospective analysis study evaluating patients with childhood radiation exposure in 2006-2016 and minimum of 1-year follow-up. RESULTS: Of the 132 childhood cancer survivors in the study, thyroid malignancy was detected in 2 cases (1.5%) and thyroid nodules in 13 (9.8%). The earliest thyroid malignancy was detected 5 years post-radiotherapy via ultrasound. Of the 84 patients who had screening thyroid function test, 26 (31.0%) were detected with abnormal test results post-radiation, majority being subclinical hypothyroidism. CONCLUSION: Regular screening via clinical examination for thyroid nodules should be performed at least annually. Where feasible and if resources permit, consideration should be given to using ultrasound for thyroid nodule(s) and malignancy screening at 5 years post-radiation therapy. Screening for thyroid dysfunction can be considered from 6-12 months post-radiotherapy.

The association between infection incidence and autoimmune diseases in breast cancer patients after anti-cancer treatment.

Purpose: To evaluate the infection incidence in breast cancer patients whether they have a major autoimmune disease or not. Methods: This retrospective cohort study compared the infection incidence of 174 breast cancer patients with an autoimmune disease, including Sjogren's Syndrome (SS), Rheumatoid Arthritis (RA), and Systemic Lupus Erythematosus (SLE), along with 4429 patients without an autoimmune disease, for the period 2000 to 2016. Six-hundred and ninety six, age-, stage-, and diagnosis era-matched patients without any autoimmune disease were analyzed to eliminate the effects of these confounding factors may have on the results. Results: After adjusting for age, stage and diagnosis era, breast cancer patients with an autoimmune disease had a higher Infection Incidence Ratio (IRR: 2.62) than the patients without any autoimmune disease. In the univariate analysis, patients who had an autoimmune disease (p<0.001), underwent chemotherapy (p<0.001), radiotherapy (p=0.004), and monoclonal antibody therapy (p<0.001) had a higher infection rate. In the multivariate analysis, autoimmune disease was shown to be an independent factor for infection incidence. Conclusion: Autoimmune disease was a potential predictor of infection incidence in breast cancer patients post-treatment after adjusting for clinical confounding factors.

A short report on current fertility preservation strategies for boys.

BACKGROUND: Advances in cancer treatment have led to improved long-term survival after childhood cancer, but often at a price of impaired future fertility. Fertility preservation (FP) in male children and early adolescents poses unique challenges as efficacy is unproven. OBJECTIVES: To describe characteristics of testicular tissue cryopreservation (TTCP) specimens taken from paediatric and adolescent patients, stratified by age, and prior chemotherapy, if any, and to demonstrate evidence for germ cells. MATERIALS AND METHODS: Retrospective review of gonadal biopsies and clinical records of patients consented into the Royal Children's Hospital FP programme between 1987 and 2015. Tissue was sliced into blocks, with one section sent for histopathology prior to cryopreservation. In boys ≥12 years where spermatogenesis could be expected, a portion of tissue was disaggregated completely to look for mature sperm and if found, additional tissue was dissected and the resulting suspension frozen. RESULTS: Testicular tissue cryopreservation specimens in 44 males (0.3-16.8 years) provided an average of 7.8 slices per patient. All the specimens were taken at the same time as another necessary surgical procedure, under one general anaesthesic. There was only one complication of scrotal wound dehiscence. Seven of the forty-four (15.9%) patients had chemotherapy prior to testicular biopsy, while the rest were chemotherapy naïve. Five of these were prepubertal, and two were pubertal patients. Eleven subjects had tissue dissected with mature sperm found in eight. Of these eight patients where sperm were found, all were pubertal with testicular size of more than 10 mL and showing histological evidence of spermatogenesis. No histologic specimen demonstrated any malignant cells. CONCLUSIONS: Testicular tissue cryopreservation can be performed in young patients without delay, preferably prior to cancer treatment. As testicular tissue contains germ cells from which haploid spermatozoa are ultimately derived, future technologies may allow their utilization for fertility in humans. This may be the only hope for biological offspring in some patients undergoing fertility compromising treatment. Retrieval of mature sperm from some pubertal patients, however, offers realistic hope to these patients of future fertility.

Sirolimus therapy in a child with partially diazoxide-responsive hyperinsulinaemic hypoglycaemia.

Hyperinsulinaemic hypoglycaemia (HH), which causes persistent neonatal hypoglycaemia, can result in neurological damage and it's management is challenging. Diazoxide is the first-line treatment, albeit not all patients will fully respond to it, as episodes of hypoglycaemia may persist and it entails unpleasant adverse effects. Sirolimus, an mTOR inhibitor, has reportedly been successful in treating children with severe diffuse HH, thus obviating the need for pancreatectomy. We report a girl with HH, with a novel heterozygous ABCC8 gene missense mutation (c.4154A>T/ p.Lys1385Thr), who was initially responsive to diazoxide therapy. After 11 months of diazoxide treatment, she developed intermittent, unpredictable breakthrough episodes of hypoglycaemia, in addition to generalized hypertrichosis and weight gain from enforced feeding to avoid hypoglycaemia. Sirolimus, which was commenced at 15 months of age, gradually replaced diazoxide, with significant reduction and abolition of hypoglycaemia. The hypertrichosis resolved and there was less weight gain given the reduced need for enforced feeding. Sirolimus, which was administered over the next 15 months, was well tolerated with no significant side effects and was gradually weaned off. After stopping sirolimus, apart from hypoglycaemia developing during an episode of severe viral gastroenteritis, the capillary glucose concentrations were maintained >3.5 mmol/L, even after a 10 h fast. Sirolimus may have a role in the treatment of partially diazoxide-responsive forms of HH who experience breakthrough hypoglycaemia, but the long-term safety and efficacy of sirolimus are not established. LEARNING POINTS: Conventional treatment of diffuse HH with diazoxide is not always effective in controlling hypoglycaemia and can be associated with unpleasant side effects.Sirolimus was successfully used to abolish recurrent hypoglycaemia in partially diazoxide-responsive HH, with resolution of unacceptable diazoxide-associated side effects.Sirolimus was well tolerated with no clinically significant side effects.Shortly after stopping sirolimus, the capillary glucose levels remained normoglycemic.

Thyroid carcinoma in children, adolescents and adults, both spontaneous and after childhood radiation exposure.

UNLABELLED: Thyroid carcinoma is the most common second malignancy for childhood cancer survivors. Radiation exposure is linked to risk. Thyroid nodules in children have a high risk for malignancy, whether spontaneous or after radiation. Due to the extremely limited available paediatric data, we sought to review a series of patients with thyroid carcinoma, seen over 25 years. Forty-six patients were identified. Thirty-nine (84.8 %) had papillary thyroid carcinoma, five (10.9 %) follicular carcinoma and 2 (4.3 %) medullary thyroid carcinoma (MEN2B). Thirty-three (71.7 %) had childhood radiation exposure (17 females) with thyroid malignancy occurring 6-37 years later. The smallest nodule size found on surveillance to have thyroid malignancy was 4 mm. Thyroid cancer in patients 16 years and under was seen in 22 patients (47.8 %). All had total thyroidectomy, with initial central node clearance from 2005. Diagnostic rTSH stimulated I(123) scan was followed by ablative I(131) if any uptake was seen. Sixteen (32.6 %) had metastases. Twenty-four (52.2 %) had I(131), four requiring multiple courses. Forty-two remain alive and well. CONCLUSION: Ultrasound screening is required for early diagnosis as small nodule size is not predictive of benign histology or absence of metastases. Central node clearance provides better outcome. Despite metastatic disease at presentation for some, prognosis is favourable. WHAT IS KNOWN: • Incidence of thyroid cancer has been increasing and radiation exposure in childhood cancer survivors is clearly linked to risk. • Published guidelines in many places can only provide very low level evidence due to extremely limited available paediatric data. What is New: • Paper provides good evidence to confirm existing views with the largest cohort of thyroid cancer reported to date in the paediatric age group in Australia, and the largest cohort in Australia where there have been specific high risks of radiation exposure. The only other reported larger studies have come from the Children's Oncology Group and Childhood Cancer Survivor Study [24]. • Using diagnostic rTSH stimulated I(123) scan 6 weeks after surgery helps to determine if radioactive iodine ablation is necessary and limits unnecessary bone marrow exposure for young patients in whom future leukaemia is of greater concern.

Sub-lethal heat treatment affects the tolerance of Cronobacter sakazakii BCRC 13988 to various organic acids, simulated gastric juice and bile solution.

Cronobacter spp., formerly Enterobacter sakazakii, are considered emerging opportunistic pathogens and the etiological agent of life-threatening bacterial infections in infants. In the present study, C. sakazakii BCRC 13988 was first subjected to sub-lethal heat treatment at 47°C for 15min. Survival rates of the heat-shocked and non-shocked C. sakazakii cells in phosphate buffer solution (PBS, pH 4.0) containing organic acids (e.g. acetic, propionic, citric, lactic or tartaric acid), simulated gastric juice (pH 2.0-4.0), and bile solution (0.5 and 2.0%) were examined. Results revealed that sub-lethal heat treatment enhanced the test organism's tolerance to organic acids, although the extent of increased acid tolerance varied with the organic acid examined. Compared with the control cells, heat-shocked C. sakazakii cells after 120-min of exposure, exhibited the largest increase in tolerance in the lactic acid-containing PBS. Furthermore, although heat shock did not affect the behavior of C. sakazakii in bile solution, it increased the test organism's survival when exposed to simulated gastric juice with a pH of 3.0-4.0.

Combining capillary electrophoresis with laser-induced fluorescence detection for the analysis of Escherichia coli lysates.

With the goal of improving water quality control, in this study we combined CE-LIF for the analysis of Escherichia coli lysates under discontinuous conditions. Prior to injecting a large-volume protein sample, a plug of 0.2% w/v SDS was injected into the capillary filled with 2.0 M Tris-borate (TB) solution (pH 10.3). During the courses of the process stacking, proteins migrated against the electroosmotic flow (EOF) and entered a 1.7% w/v poly(ethylene oxide) solution that has been prepared in 200 mM TB (pH 9.0). The stacked proteins were then separated through sieving and then detected at the cathodic end. The use of TB solutions containing 0.01% w/v poly(ethylene oxide) was essential for the preparation of the protein samples and E. coli lysates to minimize the extent of protein adsorption on the capillary wall. Under the optimized CE-LIF conditions, we detected beta-Galactosidase with and without concentration at levels as low as 0.23 and 7.52 nM, respectively. Our approach allowed the detection of 3 x 10(2) E. coli cells based on the characteristic peaks of its lysates; in addition, we could detect the presence of 20 E. coli cells in a 50 mL sample of pond water within 24 h. In terms of the analyte migration time, the relative standard deviation of this CE-LIF method was less than 1.3%. We also extended the practicality of this technique by applying it to the separation of mixtures of E. coli, Enterobacter aerogenes, and Salmonella enterica.

Protein expression in Vibrio parahaemolyticus 690 subjected to sublethal heat and ethanol shock treatments.

Cells of Vibrio parahaemolyticus 690 were subjected either to heat shock at 42 degrees C for 45 min or to ethanol shock in the presence of 5% ethanol for 60 min. The protein profiles of the unstressed and stressed V. parahaemolyticus cells were compared. Additionally, the induction of DnaK- and GroEL-like proteins in the unstressed and stressed cells of V. parahaemolyticus was also examined. Analysis with one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that three proteins with molecular masses of 93, 77, and 58 kDa were induced by both heat shock and ethanol shock. The protein patterns revealed by two-dimensional electrophoresis were more detailed than those revealed by one-dimensional SDS-PAGE. It was found that heat shock and ethanol shock affected the expression of a total of 28 proteins. Among them, four proteins with molecular masses of 94, 32.1, 26.7, and 25.7 kDa were enhanced by both heat shock and ethanol shock. Furthermore, immunoblot analysis showed the presence of a GroEL-like protein with a molecular mass of 61 kDa in the test organism, with the heat-shocked and ethanol-shocked cells producing a GroEL-like protein in a larger quantity than the unstressed cells. However, DnaK-like protein was not detectable in either the unstressed or the stressed cells.

Ethanol shock changes the fatty acid profile and survival behavior of Vibrio parahaemolyticus in various stress conditions.

Vibrio parahaemolyticus 690, a clinical strain, was subjected to ethanol shock in the presence of 5% ethanol for a period of 30 and 60 min. Survival behaviors of the ethanol shocked and control cells of V. parahaemolyticus in the presence of H(2)O(2) (20 ppm), crystal violet (3 ppm), NaCl (20%), and low pH solution (pH 4.4) containing various organic acids including lactic acid, acetic acid, citric acid and tartaric acid (25 mM) were compared. In addition, the effects of ethanol shock on the fatty acid profile and recovery of V. parahaemolyticus on tryptic soy agar (TSA) plus various amounts of NaCl were also investigated. After ethanol shock, it was found that the proportion of vaccenic acid (18:1) increased, while the proportion of palmitic acid (16:0) and ratio of saturated fatty acid to unsaturated fatty acid decreased in cells of V. parahaemolyticus. The recovery of the ethanol-shocked cells on TSA plus 6.0% or 7.5% NaCl was significantly less than the control cells. Furthermore, ethanol shock increased the survival of V. parahaemolyticus in the presence of H(2)O(2), while made the test organism less resistant to crystal violet, high NaCl and organic acids. The degree of decreased acid tolerance observed on the ethanol-shocked cells of test organism varied with the organic acid examined. Finally, ethanol shock for 60 min exhibited either a higher or similar degree of effect on the test organism (depending on the type of stress encountered) than did ethanol shock for 30 min. Data obtained from the present study does provide useful information that is indispensable when control measure of V. parahaemolyticus is to be performed efficiently and adequately.

Response of Vibrio parahaemolyticus to ethanol shock.

In this study, the growth and survival of Vibrio parahaemolyticus in the presence of 0.0-8.0% ethanol was first examined. V. parahaemolyticus was then exposed to a sub-lethal dose of 5.0% ethanol for 30 and 60 min (ethanol shock). Morphological changes and alterations in cell leakage, thermal tolerance at 47 degrees C, and susceptibility to 8% ethanol and low temperature (4 and -18 degrees C) of V. parahaemolyticus caused by ethanol shock were investigated. In addition, recoveries of the ethanol-shocked cells of V. parahaemolyticus on thiosulfate-citrate-bile salts-sucrose agar (TCBS) and TSA-3.0% NaCl were also compared. The findings revealed that the presence of ethanol in TSB-3.0% NaCl at 6.0-8.0% and 5.0% or less, exerted bactericidal and partial growth inhibition effect, respectively, on V. parahaemolyticus. Recovery of ethanol-shocked cells of V. parahaemolyticus was significantly (P<0.05) less on TCBS than on TSA-3.0% NaCl. A significantly (P<0.05) marked increase of protein and nucleic acid material in the supernatant of cell suspension was found after cells of V. parahaemolyticus were exposed to ethanol shock. Extensive cell disruption, wrinkling and cell-wall pitting, indicative of cell-surface damage were also noted on the ethanol-shocked cells. Ethanol-shocked cells of V. parahaemolyticus exhibited a similar yet higher susceptibility at 4 and -18 degrees C compared with the control cells. Moreover, there was a marked increase in the thermal tolerance and resistance to 8.0% ethanol with cells of V. parahaemolyticus after ethanol shock. Finally, the duration of ethanol shock testing did not affect the extent of increased thermal tolerance. While cells of V. parahaemolyticus subjected to ethanol shock for 60 min showed an increase in their resistance to 8.0% ethanol, they also showed an increase in susceptibility at -18 degrees C, than those ethanol shocked for 30 min.

Effect of iron limitation on the growth and cytotoxin production of Salmonella choleraesuis SC-5.

This study investigated the effect of iron limitation on the growth and cytotoxin production of Salmonella choleraesuis and examined the iron-accruing capability of various Salmonella strains. It was found that the growth of S. choleraesuis SC-5 was retarded by the presence of iron-chelating agents, 2,2'-dipyridyl or ethylenediamine di-o-hydroxyphenylactic acid (EDDA). Addition of 2,2'-dipyridyl to Trypticase soy broth (TSB) resulted in a smaller maximum population of S. choleraesuis noted at the stationary phase, while addition of EDDA in TSB only caused an extended period of lag phase. A significant increase in cytotoxin production was found when S. choleraesuis SC-5 was cultured in iron-limited TSB containing 2,2'-dipyridyl. On the other hand, pre-culture in an iron-limited medium increased the growth of S. choleraesuis SC-5 in mouse serum with or without complement inactivated. Testing with a plate assay method revealed that the ability and efficiency of Salmonella to acquire iron under iron-limited condition varied with strains, and the kinds and dosages of iron-containing compounds present.