Respiratory-syncytial virus immunoprophylaxis on asthma symptoms development in prematurity with bronchopulmonary dysplasia.

Background: Infants with respiratory-syncytial virus bronchiolitis hospitalization are more likely to develop wheezing and subsequent asthma. Reportedly, palivizumab prophylaxis effectively prevents respiratory-syncytial virus hospitalization in high-risk children-such as premature infants or infants with bronchopulmonary dysplasia (BPD). Objective: We sought to explore the effect of respiratory-syncytial virus immunoprophylaxis on the risk of asthma development in premature infants with BPD in subtropical areas. Methods: This case-control study included preterm children with BPD born at Mackay Memorial Hospital, Taipei, Taiwan, from 1999 to 2015. Overall, medical records of 616 eligible participants were retrospectively collected from their birth to the time they attained an age of 5 to 20 years. The primary outcome was onset of active asthma. Results: Overall, 576 consecutive cases met the inclusion criteria. Of these, 306 (53.2%) patients had palivizumab exposure and 191 (33.2%) were diagnosed with asthma. Patients with history of respiratory-syncytial virus bronchiolitis hospitalization had a higher risk of developing asthma in the future (adjusted odds ratio, 3.77; 95% CI, 2.30-6.20, P < .001; hazard ratio, 2.56; 95% CI, 1.81-3.62, P < .001). Palivizumab prophylaxis reduced future asthma development through the inhibition of respiratory-syncytial virus bronchiolitis hospitalization (coefficient, -0.021; 95% CI, -0.031 to -0.011, P = .027). Asthmatic children who received palivizumab immunoprophylaxis had a lesser active asthma duration than those who did not (P = .005). Conclusions: Children with BPD with hospitalization for respiratory-syncytial virus bronchiolitis had higher risk of developing asthma compared with those without respiratory-syncytial virus infection. Prophylactic palivizumab might reduce later asthma development through inhibition of respiratory-syncytial virus bronchiolitis hospitalization. For those already developing asthma, palivizumab could reduce active asthma duration.

Application of Cellular Resolution Full-Field Optical Coherence Tomography in vivo for the Diagnosis of Skin Tumours and Inflammatory Skin Diseases: A Pilot Study.

BACKGROUND: Optical coherence tomography (OCT) has been shown to provide non-invasive diagnosis of common skin neoplasms, especially basal cell carcinoma. OCT produces a cross-sectional view of the tissue, similar to a traditionally sectioned histopathological view, but the resolution of conventional OCT is low and thus limits clinical application. OBJECTIVES: This study aimed to investigate the application ability of a full-field (FF)OCT system which was newly developed to scan the skin at the cellular level. METHODS: Patients with skin tumours or inflammatory lesions warranting biopsy were consecutively enrolled. All lesions underwent clinical, dermoscopic, and OCT assessment, followed by routine biopsy. The adjacent normal skin was scanned for comparison. OCT images were interpreted (blinded to the biopsy results) and then compared with the histopathological diagnosis. RESULTS: A total of 111 patients with 115 lesions completed the protocol, including 80 skin tumours, 28 inflammatory diseases, and 7 other diseases. Of the OCT images, 43.5% were of good quality and show expected features. Identifiable features of actinic keratosis, Bowen's disease, basal cell carcinoma, extramammary Paget's disease, seborrheic keratosis, large cell acanthoma, bullous pemphigoid, interface dermatitis, lichenoid tissue reaction, and psoriasis were demonstrated. Lesions are located deeply, and so some features were out of the field of view, accounting for 40.0% (46/115). CONCLUSIONS: This study expanded the ability of FFOCT for the clinical diagnosis of various skin conditions. This new optical technique can clearly visualise skin lesions located in the epidermis and upper dermis. It provided an effective way to perform digital skin biopsy in superficial skin diseases.

Oncologic feasibility for negative pressure wound therapy application in surgical wounds: A meta-analysis.

Negative pressure wound therapy (NPWT) decreases postoperative complications of various surgeries. However, the use of NPWT for oncological surgical wounds remains controversial. To evaluate the association of NPWT with oncologic recurrence in surgical wounds without residual malignancy, we analysed studies that compared NPWT with conventional non-pressure dressings for cancer surgical wounds without residual tumour by August 12, 2020. We compared tumour recurrence rates and postoperative complications between the two procedures. The six studies included 118 patients who received NPWT, and 149 patients who received conventional non-pressure wound care. The overall quality of the included studies was high based on the Newcastle-Ottawa scale score of 7.5. Tumour recurrence after NPWT was not significantly different compared with conventional non-negative pressure wound care (9.3% versus 11.4%, P = 0.40). There was no significant heterogeneity between the studies (I2  = 3%). Although NTWT was associated with a lower complication rate compared with the control group, the result was non-significant (P = 0.15). Application of NPWT in oncologic resection wounds without residual malignancy revealed no difference in local recurrence and may reduce the risk of postoperative complications compared with conventional non-negative pressure dressings. NPWT can be considered an alternative method for reconstruction in challenging cases.

Galectin-3 regulates UVB-induced inflammation in skin.

BACKGROUND: Galectin-3 is widely expressed in many immunocytes and epithelial cells including skin keratinocytes. Galectin-3 can regulate immunological or inflammatory processes and plays a proinflammatory role in some disease models. Galectin-3 has a role in disorders related to ultraviolet (UV) photodamage such as apoptosis, skin squamous cell carcinoma and basal cell carcinoma. However, the evidence of galectin-3 in UVB-induced skin inflammation is still limited and the underlying molecular mechanism remains elusive. OBJECTIVE: We aimed to investigate the effects of galectin-3 in human epidermal keratinocytes and in mice after UVB irradiation. METHODS: Primary human epidermal keratinocytes with galectin-3 knockdown were used as the in vitro model. ELISA, QPCR, and western blotting were applied to evaluate the released cytokine, mRNA and protein expression. Histologic analysis, measurement of erythema and transepidermal water loss (TEWL) were applied to evaluate UVB-induced skin damage in galectin-3 knockout mice. RESULTS: In UVB-irradiated human keratinocytes, galectin-3 knockdown downregulated the UVB-induced ASC crosslinking, cleavage of caspase-1, and formation of active IL-1ß. Galectin-3 knockdown also decreased UVB-induced production of reactive oxygen species, p38 phosphorylation, and COX2 expression in human keratinocytes. After four days of UVB irradiation, galectin-3 knockout mice showed reduced gross erythema, histologic features of tissue inflammation, quantified levels of erythema and TEWL compared to wild type mice. The skin tissue lysate also showed less expression of active IL-1ß and COX2 in galectin-3 knockout mice. CONCLUSION: Galectin-3 may play a positive regulatory role in UVB-induced skin inflammation.

Ex vivo full-field cellular-resolution optical coherence tomography of basal cell carcinomas: A pilot study of quality and feasibility of images and diagnostic accuracy in subtypes.

BACKGROUND: Studies have reported the application of conventional optical coherence tomography (OCT) in the diagnosis of basal cell carcinoma (BCC). The new OCT provides cellular details similar to those in pathology slides and may reduce user learning time. This study aimed to demonstrate the quality of ex vivo full-field cellular-resolution OCT images and compare the diagnostic accuracy between physicians with varying pathology experience. MATERIALS AND METHODS: Sixty histologically confirmed BCCs were selected. Tissue samples were sectioned and scanned using OCT, and their features were compared with those of hematoxylin and eosin (H&E)-stained sections. Thirty images were selected for the test administered to dermatology residents, dermatopathology fellows, and board-certified general pathologists without any OCT experience. The pretest learning included a 3-min instruction and 10-min self-study of four BCC variants. RESULTS: Histopathological BCC and normal histological features were clearly recognizable on the OCT images. The pathological BCC features observed in the OCT images correlated with those found in the H&E-stained sections. Seven participants completed the test. The correct answer rates of the residents, fellows, and pathologists were 71%, 68%, and 83% for BCC and 44%, 57%, and 57% for the BCC subtypes, respectively. CONCLUSION: All the participants identified BCC in >70% cases with a learning time of only 13 minutes. The results indicated that cellular-resolution OCT provided high-quality images similar to the conventional pathology slides. Pathology experience did reflect the diagnostic accuracy. However, a longer training time is still needed at all levels to recognize the BCC subtypes correctly.

Targeting ROS and cPLA2/COX2 Expressions Ameliorated Renal Damage in Obese Mice with Endotoxemia.

Obesity is associated with metabolic endotoxemia, reactive oxygen species (ROS), chronic inflammation, and obese kidney fibrosis. Although the fat-intestine-kidney axis has been documented, the pathomechanism and therapeutic targets of obese kidney fibrosis remain unelucidated. To mimic obese humans with metabolic endotoxemia, high-fat-diet-fed mice (HF group) were injected with lipopolysaccharide (LPS) to yield the obese kidney fibrosis-metabolic endotoxemia mouse model (HL group). Therapeutic effects of ROS, cytosolic phospholipases A2 (cPLA2) and cyclooxygenase-2 (COX-2) inhibitors were analyzed with a quantitative comparison of immunohistochemistry stains and morphometric approach in the tubulointerstitium of different groups. Compared with basal and HF groups, the HL group exhibited the most prominent obese kidney fibrosis, tubular epithelial lipid vacuoles, and lymphocyte infiltration in the tubulointerstitium. Furthermore, inhibitors of nonspecific ROS, cPLA2 and COX-2 ameliorated the above renal damages. Notably, the ROS-inhibitor-treated group ameliorated not only oxidative injury but also the expression of cPLA2 and COX-2, indicating that ROS functions as the upstream signaling molecule in the inflammatory cascade of obese kidney fibrosis. ROS acts as a key messenger in the signaling transduction of obese kidney fibrosis, activating downstream cPLA2 and COX-2. The given antioxidant treatment ameliorates obese kidney fibrosis resulting from a combined high-fat diet and LPS-ROS could serve as a potential therapeutic target of obese kidney fibrosis with metabolic endotoxemia.

Genital basal cell carcinoma, a different pathogenesis from sun-exposed basal cell carcinoma? A case-control study of 30 cases.

BACKGROUND: Genital basal cell carcinoma (BCC) accounts for <1% of all BCCs. We aimed to elucidate the pathogenesis of genital BCC. METHODS: We retrospectively evaluated cases of pathologically diagnosed genital BCC between 1990 and 2016 in an Asian tertiary referral center. The control group was composed of consecutive cases, from 2016, of BCCs occurring in sun-exposed areas. Presence of human papillomavirus (HPV) was evaluated by polymerase chain reaction (PCR). Immunohistochemical p16 and p53 staining was performed and analyzed. RESULTS: We found 33 genital BCCs (33/1837, 1.8%) over 26 years. The mean follow-up duration was 30.0 ± 33.2 months. Genital BCCs had a larger size (14.05 vs 8.92 mm, P = 0.014), more common presence of ulcers (61.3% vs 32.0%, P = 0.035), shorter epidermal p53 clone (0.33 vs 1.20 mm, P = 0.007), and high p53 expression levels. Most cases (29/30, 96.7%) showed negative or faint spotty p16 staining. Patient age, tumor depth, presence of pigment, or histology subtype did not differ significantly. Thirty genital BCCs were negative for HPV. CONCLUSIONS: HPV infection is mostly likely not involved in genital BCC pathogenesis. A greater level of p53 expression in genital BCCs implicates pathways other than ultraviolet (UV)-specific p53 mutations in their pathogenesis.

Risk factors for infective endocarditis in children with congenital heart diseases - A nationwide population-based case control study.

BACKGROUND: Infective endocarditis (IE) is uncommon in childhood. Its associated epidemiological characteristics in patients with congenital heart disease (CHD) remain unclear. METHODS: The study population included children born in Taiwan during the years 1997 to 2005 who were diagnosed as having CHD before 3years of age. All children were followed up until the end year of 2010, the diagnosis of infective endocarditis, or death. The demographic characteristics of patients with and without IE, the invasive procedures performed during 6months before the index date, the prophylactic antibiotics related to dental procedures, and in-hospital mortality were collected. RESULTS: Information of 24,729 children with CHD were retrieved for our analysis and 237 patients with newly diagnosed IE were identified. The incidence rate of IE in all CHD lesions was 11.13 per 10,000person-years. Taking ASD for reference, the following CHD lesions were at risk for IE: cyanotic CHD (adjusted OR, 9.58; 95% confidence interval, 5.38-17.05), endocardial cushion defect (ECD) (8.01; 2.73-23.50), Left-sided lesions (4.36; 1.90-10.01) and VSD (2.93; 1.64-5.23). Patients who underwent procedures have a higher risk of acquiring IE which include central venous catheter (CVC) insertion (3.17; 2.36-4.27), cardiac catheterization (3.74; 2.67-5.22), open-heart surgery (2.47; 1.61-3.77), valve surgery (3.20; 1.70-6.02), and shunt surgery (7.43; 2.36-23.41). However, dental procedures did not increase the risk of IE, irrespective of antibiotic usage. CONCLUSIONS: The risk of IE varies markedly among CHD lesions in our study. Invasive heart procedures but not dental procedures, are more significantly associated with IE among children with CHD.

Combined effect of individual and neighbourhood socioeconomic status on mortality of rheumatoid arthritis patients under universal health care coverage system.

BACKGROUND: The National Health Insurance program in Taiwan is a public insurance system for the entire population of Taiwan initiated since March 1995. However, the association of socioeconomic status (SES) and prognosis of rheumatoid arthritis (RA) patients under this program has not been identified. OBJECTIVES: Using the National Health Insurance Research Database in Taiwan, we aimed to examine the combined effect of individual and neighbourhood SES on the mortality rates of RA patients under a universal health care coverage system. MEASURES: A study population included patients with RA from 2004 to 2008. The primary end point was the 5-year overall mortality rate. Individual SES was categorized into low, moderate and high levels based on the income-related insurance payment amount. Neighbourhood SES was defined by household income and neighbourhoods were grouped as an 'advantaged' area or a 'disadvantaged' area. The Cox proportional hazards regression model was used to compare outcomes between different SES categories. A two-sided P value < 0.05 was considered statistically significant. RESULTS: Medical data of 23900 RA patients from 2004 to 2008 were reviewed. Analysis of the combined effect of individual SES and neighbourhood SES revealed that 5-year mortality rates were worse among RA patients with a low individual SES compared to those with a high SES (P < 0.001). In the Cox proportional hazards regression model, RA patients with low individual SES in disadvantaged neighbourhoods incurred the highest risk of mortality (Hazard ratio = 1.64; 95% confidence interval, 1.26-2.13, P < 0.001). CONCLUSIONS: RA patients with a low SES have a higher overall mortality rate than those with a higher SES, even with a universal health care system. It is crucial that more public policy and health care efforts be put into alleviating the health disadvantages, besides providing treatment payment coverage.

Low socioeconomic status increases short-term mortality of acute myocardial infarction despite universal health coverage.

BACKGROUND: This nationwide population-based study investigated the relationship between individual and neighborhood socioeconomic status (SES) and mortality rates for acute myocardial infarction (AMI) in Taiwan. METHODS: A population-based follow-up study included 23,568 patients diagnosed with AMI from 2004 to 2008. Each patient was monitored for 2 years, or until their death, whichever came first. The individual income-related insurance payment amount was used as a proxy measure of patient's individual SES. Neighborhood SES was defined by household income, and neighborhoods were grouped as advantaged or disadvantaged. The Cox proportional hazards model was used to compare the mortality rates between the different SES groups after adjusting for possible confounding risk factors. RESULTS: After adjusting for potential confounding factors, AMI patients with low individual SES had an increased risk of death than those with high individual SES who resided in advantaged neighborhoods. In contrast, the cumulative readmission rate from major adverse cardiovascular events did not differ significantly between the different individual and neighborhood SES groups. AMI patients with low individual SES had a lower rate of diagnostic angiography and subsequent percutaneous coronary intervention (P<0.001). The presence of congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease, pneumonia, septicemia, and shock revealed an incremental increase with worse SES (P<0.001). CONCLUSIONS: The findings indicate that AMI patients with low individual SES have the greatest risk of short-term mortality despite being under a universal health-care system. Public health strategies and welfare policies must continue to focus on this vulnerable group.

Helical irradiation of the total skin with dose painting to replace total skin electron beam therapy for therapy-refractory cutaneous CD4+ T-cell lymphoma.

A 36-year-old woman was diagnosed with a therapy-refractory cutaneous CD4+ T-cell lymphoma, T3N0M0B0, and stage IIB. Helical irradiation of the total skin (HITS) and dose painting techniques, with 30 Gy in 40 fractions interrupted at 20 fractions with one week resting, 4 times per week were prescribed. The diving suit was dressed whole body to increase the superficial dose and using central core complete block (CCCB) technique for reducing the internal organ dose. The mean doses of critical organs of head, chest, and abdomen were 2.1 to 29.9 Gy, 2.9 to 8.1 Gy, and 3.6 to 15.7 Gy, respectively. The mean dose of lesions was 84.0 cGy. The dosage of left side pretreated area was decreased 57%. The tumor regressed progressively without further noduloplaques. During the HITS procedure, most toxicity was grade I except leukocytopenia with grade 3. No epitheliolysis, phlyctenules, tumor lysis syndrome, fever, vomiting, dyspnea, edema of the extremities, or diarrhea occurred during the treatment. HITS with dose painting techniques provides precise dosage delivery with impressive results, sparing critical organs, and offering limited transient and chronic sequelae for previously locally irradiated, therapy-refractory cutaneous T-cell lymphoma.

Risk of colorectal cancer in type 2 diabetic patients: a population-based cohort study.

OBJECTIVE: Most of the existing findings on the association between diabetes mellitus and colorectal cancer were generated from studies in Western societies. However, significant differences in cancer incidence and cancer-prone lifestyles are apparent between Asian and Western countries. This study aims to estimate the risks of colorectal cancer in the diabetic population in Taiwan by conducting a large-scale, controlled cohort study. METHODS: From Taiwan's Longitudinal Health Insurance Database 2005 (LHID2005), a total of 37 001 diabetic patients were identified. We also obtained data for four controls per patient, matched for sex, age and year of first entry into the LHID2005. All patients were followed up from the date of entry into the LHID2005 until they developed colorectal cancer or to the end of 2006, whichever was earlier. We used Cox's regression models to assess the risk of developing colorectal cancer, with adjustment for sex, age, comorbid disorders, and socioeconomic characteristics. RESULTS: We identified 37 001 diabetic patients and 148 004 controls. The adjusted hazard ratio for colorectal cancer in diabetes mellitus patients was 2.1 (95% confidence interval, 1.82-2.42) compared with controls. The risk was significant to both men and women. The adjusted hazard ratios for colorectal cancer were 2.03 (95% confidence interval, 1.68-2.47) in male diabetes mellitus patients and 2.17 (95% confidence interval, 1.77-2.67) in female diabetes mellitus patients. CONCLUSIONS: Our findings based on a large population-based cohort study provide evidence that diabetes mellitus may increase the risk of colorectal cancer in Asians.

Idiopathic pulmonary fibrosis in Taiwan - a population-based study.

BACKGROUND: This study took advantage of a large population-based database of the Taiwan National Health Insurance (NHI) to investigate the epidemiology of idiopathic pulmonary fibrosis (IPF) in Taiwan. METHODS: This is a retrospective cohort study based on secondary analysis of prospectively collected data in the NHI system and governmental data on death registry in Taiwan during 1997-2007. By using the broad and narrow definitions for IPF, we estimated incidence and prevalence rates of IPF, and its associated clinical outcomes. RESULTS: The estimates of annual IPF incidence rates became more stable after 2000, ranging between 0.9 and 1.6 cases per 100,000 persons. The prevalence rates became more than twofold from 2000 to 2007 (from 2.8 to 6.4 cases per 100,000 persons for the broad definition, and from 2.0 to 4.9 cases per 100,000 persons for the narrow definition). Men of age older than 75 years had markedly higher incidence and prevalence rates than other groups. Around 40% of all incidences and about 30% of prevalent cases occurred in this population group. The median survival time after IPF diagnosis was 0.9 year (interquartile range (IQR), 0.2-2.5 years) and 0.7 year (IQR, 0.1-2.3 years) for the broad and narrow definitions, respectively. Progression of IPF was the leading cause of death, followed by cancer. CONCLUSIONS: In Taiwan, elderly men were the major group suffering from IPF. Survival time was short after IPF diagnosis, and the poor survival was largely attributable to quick IPF progression after diagnosis.

Diagnostic usefulness of enzyme-linked immunospot assay for interferon-gamma for tuberculosis in cancer patients.

The interferon-γ enzyme-linked immunospot assay (ELISPOT) has been demonstrated to be useful in the diagnosis of active tuberculosis (TB). In this study we aimed to evaluate the diagnostic performance of the ELISPOT assay in cancer patients with suspected pulmonary TB. Eighty-one cancer patients with suspected pulmonary TB were prospectively enrolled from April 2007 to December 2008, to investigate the diagnostic sensitivity and specificity of the ELISPOT assay. Of the 38 patients with TB, 33 (86.8%) had positive ELISPOT results. Of the 43 patients without TB, the results of the ELISPOT assay were negative in 35 (81.3%) patients. The overall sensitivity was 86.8%, specificity 81.3%, positive predictive value 80.5% and negative predictive value 87.5%. No significant difference was noted for the diagnostic performance of the ELISPOT assay for diagnosing TB between solid cancer and haematological cancer patients. In addition, a quantitative study did not show that TB patients with solid cancers have a better response than haematological cancer patients as measured by spot-forming cells per 10(6) peripheral blood mononuclear cells after exposure to early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10). In conclusion, the ELISPOT assay could be a useful supplementary tool for the diagnosis of pulmonary TB among cancer patients, irrespective of cancer type.

Invasive infections of Aggregatibacter (Actinobacillus) actinomycetemcomitans.

BACKGROUND/PURPOSE: Aggregatibacter (Actinobacillus) actinomycetemcomitans, part of the normal flora of the mouth, is frequently found in human periodontal cultures and is an important pathogen causing various invasive infections, particularly infective endocarditis. In this study, we describe the clinical course and outcome of patients with A. actinomycetemcomitans infection. METHODS: All patients suffering invasive A. actinomycetemcomitans infections at the National Taiwan University Hospital from January 1985 to December 2004 were included in this study. Relevant data regarding clinical presentation, antimicrobial treatment and outcome of these patients were analyzed. RESULTS: During the study period, there were 11 patients with invasive A. actinomycetemcomitans infections, including eight patients with infective endocarditis, one with osteonecrosis and two with pneumonia and chest wall lesions. Among the patients with infective endocarditis, four had prosthetic valve replacement, four suffered from rheumatic heart disease and one had undergone surgical repair of ventricular septal defect. Lesions in the oral cavity were the probable portals of entry of the microorganism, and included carious teeth, periodontitis or radiotherapy of the ear-nose-throat field, and were noted in nine patients. Transthoracic echocardiography and/or transesophageal echocardiography were performed on the patients with probable infective endocarditis but growth was demonstrated in only four of these patients. Blood culture yielded A. actinomycetemcomitans after prolonged incubation. Three isolates were resistant to penicillin and two of these were also resistant to ampicillin. CONCLUSION: The diagnosis of invasive A. actinomycetemcomitans infection was delayed due to the indolent clinical course, non-specific presentation and slow growth of the organism. Antibiotic therapy using amoxicillin/clavulanic acid, ampicillin, ampicillin/sulbactam, ceftriaxone, clindamycin, cefotaxime, or levofloxacin was successful in all patients. None of the patients demonstrated recurrence of infection 2-36 months following treatment.