Increased risk of Parkinson's disease amongst patients with age-related macular degeneration and visual disability: A nationwide cohort study.

BACKGROUND AND PURPOSE: The association between Parkinson's disease (PD) and age-related macular degeneration (AMD) has been shown in previous reports. However, the association between the severity of AMD and PD development is unknown. The aim was to evaluate the association of AMD with/without visual disability (VD) with the risk of PD occurrence using the National Health Insurance data in South Korea. METHODS: A total of 4,205,520 individuals, 50 years or older and without a previous diagnosis of PD, participated in the Korean National Health Screening Program in 2009. AMD was verified using diagnostic codes, and participants with VD were defined as those with loss of vision or visual field defect as certified by the Korean Government. The participants were followed up until 31 December 2019, and incident cases of PD were identified using registered diagnostic codes. The hazard ratio was calculated for groups (control and AMD with/without VD) using multivariable adjusted Cox regression analysis. RESULTS: In total, 37,507 participants (0.89%) were diagnosed with PD. Amongst individuals with AMD, the risk of PD development was higher in individuals with VD (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.09-1.67) than in those without (aHR 1.22, 95% CI 1.15-1.30) compared with controls. Additionally, an increased risk of PD was observed in individuals with AMD compared with controls, regardless of the presence of VD (aHR 1.23, 95% CI 1.16-1.31). CONCLUSIONS: Visual disability in AMD was associated with the development of PD. This suggests that neurodegeneration in PD and AMD may have common pathways.

Enzymatic debridement for circumferential deep burns: the role of surgical escharotomy.

INTRODUCTION: Circumferential deep burns carry a high risk for a burn induced compartment syndrome. It was recently shown that an enzymatic bromelain-based debridement with Nexobrid® is a safe and efficient procedure to release pressure in deep circumferential extremity burns reducing the need for surgical escharotomy. We therefore herein aimed to analyze the conceptual relation between Nexobrid® and surgical escharotomy. PATIENTS AND METHODS: We conducted a retrospective study on all patients with circumferential deep partial-thickness or full-thickness burns requiring immediate escharotomy that was either performed by surgical incision or Nexobrid®. Medical records of 792 patients that were treated at the burn center of the University Hospital Zurich between 2016 and 2021 were analyzed. RESULTS: Overall, 62 patients with circumferential deep partial-thickness or full-thickness burns who received preventive decompression either by Nexobrid® (N = 29) or surgical escharotomy (N = 33), were included. Whilst distribution of age, sex, BMI and type of injury showed no difference between the groups, the ABSI score, TBSA, percentage of third degree burns and mortality were significantly higher in patients who received a surgical escharotomy. CONCLUSION: While the use of Nexobrid® to prevent burn induced compartment syndrome has steadily increased, surgical escharotomies were predominantly performed in severely burned patients with a high degree of full-thickness burns. Thus, higher mortality in this patient group needs to be considered with caution and is mainly attributed to the higher TBSA. Although evidence is lacking for the use of Nexobrid® for larger body areas exceeding 15%, escharotomy is also the more reliable and faster approach in such critically burned patients.

Coagulation side effects of enzymatic debridement in burned patients.

OBJECTIVES: Bromelain-based enzymatic debridement has emerged as a valuable option to the standard surgical intervention for debridement in burn injuries. Adverse effects on coagulation parameters after enzymatic debridement have been described. The purpose of this study was to compare the effect of enzymatic and surgical debridement on coagulation. METHODS: Between 03/2017 and 02/2021 patients with burn injuries with a total body surface area (TBSA) ≥ 1% were included in the study. Patients were categorized into two groups: the surgically debrided group and the enzymatically debrided group. Coagulation parameters were assessed daily for the first seven days of hospitalization. RESULTS: In total 132 patients with a mean TBSA of 17% were included in this study, of which 66 received enzymatic debridement and 66 received regular surgical-debridement. Patients receiving enzymatic debridement presented significantly higher factor-V concentration values over the first seven days after admission (p = <0.01). Regarding coagulation parameters, we found no difference in INR-, aPTT-, fibrinogen-, factor-XIII- and thrombocyte-concentrations over the first seven days (p = >0.05). CONCLUSION: Enzymatic debridement in burned patients does not appear to increase the risk of coagulation abnormalities compared with the regular surgical approach.

Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy.

BACKGROUND: Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs. METHODS: Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013-2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke. RESULTS: During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65-0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation. CONCLUSION: In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

Integrative Medicine and Plastic Surgery: A Synergy-Not an Antonym.

BACKGROUND: Integrative medicine focuses on the human being as a whole-on the body, mind, and spirit-to achieve optimal health and healing. As a synthesis of conventional and complementary treatment options, integrative medicine combines the pathological with the salutogenetic approach of therapy. The aim is to create a holistic system of medicine for the individual. So far, little is known about its role in plastic surgery. HYPOTHESIS: We hypothesize that integrative medicine based on a conventional therapy with additional anthroposophic therapies is very potent and beneficial for plastic surgery patients. Evaluation and consequence of the hypothesis: Additional anthroposophic pharmacological and non-pharmacological treatments are promising for all areas of plastic surgery. We are convinced that our specific approach will induce further clinical trials to underline its therapeutic potential.

The Effect of Hyperbaric Oxygen Therapy on Human Adipose-Derived Stem Cells.

BACKGROUND: Adipose-derived stem cells are considered as candidate cells for regenerative plastic surgery. Measures to influence cellular properties and thereby direct their regenerative potential remain elusive. Hyperbaric oxygen therapy-the exposure to 100% oxygen at an increased atmospheric pressure-has been propagated as a noninvasive treatment for a multitude of indications and presents a potential option to condition cells for tissue-engineering purposes. The present study evaluates the effect of hyperbaric oxygen therapy on human adipose-derived stem cells. METHODS: Human adipose-derived stem cells from healthy donors were treated with hyperbaric oxygen therapy at 2 and 3 atm. Viability before and after each hyperbaric oxygen therapy, proliferation, expression of surface markers and protein contents of transforming growth factor (TGF)-ß, tumor necrosis factor-α, hepatocyte growth factor, and epithelial growth factor in the supernatants of treated adipose-derived stem cells were measured. Lastly, adipogenic, osteogenic, and chondrogenic differentiation with and without use of differentiation-inducing media (i.e., autodifferentiation) was examined. RESULTS: Hyperbaric oxygen therapy with 3 atm increased viability, proliferation, and CD34 expression and reduced the CD31/CD34/CD45 adipose-derived stem cell subset and endothelial progenitor cell population. TGF-ß levels were significantly decreased after two hyperbaric oxygen therapy sessions in the 2-atm group and decreased after three hyperbaric oxygen therapy sessions in the 3-atm group. Hepatocyte growth factor secretion remained unaltered in all groups. Although the osteogenic and chondrogenic differentiation were not influenced, adipogenic differentiation and autodifferentiation were significantly enhanced, with osteogenic autodifferentiation significantly alleviated by hyperbaric oxygen therapy with 3 atm. CONCLUSION: Hyperbaric oxygen therapy with 3 atm increases viability and proliferation of adipose-derived stem cells, alters marker expression and subpopulations, decreases TGF-ß secretion, and skews adipose-derived stem cells toward adipogenic differentiation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Carbon monoxide intoxication: What we know.

Carbon monoxide (CO) is a toxic, color-, taste- and odorless gas with fatal consequences if undetected. Intoxication caused by CO is frequent possibly leading to a high morbidity and mortality. The disease involves multiple organ systems without a typical clinical presentation. The clinical picture is furthermore unrelated to levels of carboxyhemoglobin - the routine biomarker. Therefore the diagnosis and treatment can be very demanding. This article in detail reviews epidemiology, symptoms, diagnosis and the therapy of this multidisciplinary challenge.

YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity.

Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T(reg)-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T(reg) cells than T(conv) cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. YY1 is increased in T(reg) cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of T(reg) cells by blocking Foxp3.

Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis.

Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in Lsp1-deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T-cell-dependent chronic inflammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA.

Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA).

PURPOSE: Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort. METHODS: The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia. RESULTS: The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004). CONCLUSION: The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.