Modular, Vascularized Hypertrophic Cartilage Constructs for Bone Tissue Engineering Applications.

Insufficient vascularization is a main barrier to creating engineered bone grafts for treating large and ischemic defects. Modular tissue engineering approaches have promise in this application because of the ability to combine tissue types and to localize microenvironmental cues to drive desired cell function. In direct bone formation approaches, it is challenging to maintain sustained osteogenic activity, since vasculogenic cues can inhibit tissue mineralization. This study harnessed the physiological process of endochondral ossification to create multiphase tissues that allowed concomitant mineralization and vessel formation. Mesenchymal stromal cells in pellet culture were differentiated toward a cartilage phenotype, followed by induction to chondrocyte hypertrophy. Hypertrophic pellets exhibited increased alkaline phosphatase activity, calcium deposition, and osteogenic gene expression relative to chondrogenic pellets. In addition, hypertrophic pellets secreted and sequestered angiogenic factors, and supported new blood vessel formation by co-cultured endothelial cells and undifferentiated stromal cells. Multiphase constructs created by combining hypertrophic pellets and vascularizing microtissues and maintained in unsupplemented basal culture medium were shown to support robust vascularization and sustained tissue mineralization. These results demonstrate a new in vitro strategy to produce multiphase engineered constructs that concomitantly support the generation of mineralize and vascularized tissue in the absence of exogenous osteogenic or vasculogenic medium supplements.

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023.

On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.

In stage IV pulmonary adenocarcinoma patients, treatment with Traditional Chinese Medicine alone gives prognostically superior results to treatment with Platinum-Based Chemotherapy alone.

BACKGROUND: About 30% of pulmonary stage IV adenocarcinomas die within 3 months of diagnosis. Western medical treatments with Platinum-Based Chemotherapy=PBC and tyrosine-kinase inhibitors Targeted Therapy=TT can improve prognosis. In China, Traditional Chinese Medicine herbal treatments (TCM) are often used in addition to PBC and TT. A considerable number of patients refuse Western medical treatments and use TCM alone. However, the survival impact of the latter is unknown. HYPOTHESES TESTED: Treatment with TCM alone is prognostically superior to PBC alone. Addition of PBC or TT or both TT to TCM improves survival. METHODS: In this prospective observational, non-interventional study of 1017 consecutive first-onset stage IV NSCLC patients with up to 10 years follow-up, 261 who Died of Disease (DOD) within 3 months were omitted, as they never got the optimal Western medical therapies. All 218 non-adenocarcinomas were also omitted, leaving 538 stage IV adenocarcinomas treated by TCM alone (n = 29), PBC alone (N = 19) and TCM and other Western medical combinations (299 TCM and PBC, 50 TCM and TT, 141 TCM and PBC and TT) with 3 - 120 months follow-up. Survivals were compared using Alive with Disease (AWD) and DOD as endpoints. RESULTS: The patients treated only with TCM had 7 months better median survival than those that received PBC alone (17 and 10 months). The patients that received TCM and PBC had a better median survival (24 months) than TCM alone and much better than PBC alone. None of the patients that received TCM alone survived > 54 months, whereas 18% of TCM and PBC patients survived much longer. Over the observation period of 3 - 120 months, survivals of TCM and TT, TCM and PBC and TT, and TCM and PBC were not different and therefore grouped as TCM and Western medicines. Median survival times of PBC alone and TCM alone were lower than that of TCM and Western medical treatments (p < 0.0001, 10, 17 and 27 months). CONCLUSIONS: Pulmonary stage IV adenocarcinoma patients with at least 3 months survival, treated with TCM alone have a significantly better survival than those treated with PBC alone. Adding Western PBC, TT or both to TCM further improves prognosis.

The Effects of Honeysuckle (Lonicera caerulea L.) Berry Iridoid-Anthocyanin Extract on the Intestinal and Muscle Histopathology in Mice during Experimental Trichinellosis.

The aim of the study was to determine the effect of iridoid-anthocyanin extract from honeysuckle (Lonicera caerulea L.) (LC) berries on histopathological changes in the intestines and muscles during experimental trichinellosis in mice. The LC extract was administered to uninfected mice (LC group) and Trichinella-spiralis-infected mice (T+LC) orally at a dose of 2 g/kg bw, six times at 24 h intervals, from day 3 prior to infection to day 3 post-infection (dpi). Jejunum samples were collected on 5, 7, 14, and 21 dpi, and their histological assessment involved the villus height to crypt depth ratio (VH/CD), goblet cell (GC) number, and morphological changes. In the T. spiralis-infected muscles, the extent of inflammatory infiltration on the 14th and 21st dpi was assessed. LC in the infected mice restored the VH/CD ratio to control values on 14 dpi. A beneficial effect of the LC extract on the villus height was also observed 14 dpi in the LC and T+LC groups. No differences in the extent of inflammatory infiltration in the muscles between the T+LC and T groups were observed. In conclusion, the iridoid-anthocyanin extract from honeysuckle berry contributed to alleviating the symptoms of the intestinal phase of T. spiralis infection.

Molecular consequences of peripheral Influenza A infection on cell populations in the murine hypothalamus.

Infection with Influenza A virus (IAV) causes the well-known symptoms of the flu, including fever, loss of appetite, and excessive sleepiness. These responses, mediated by the brain, will normally disappear once the virus is cleared from the system, but a severe respiratory virus infection may cause long-lasting neurological disturbances. These include encephalitis lethargica and narcolepsy. The mechanisms behind such long lasting changes are unknown. The hypothalamus is a central regulator of the homeostatic response during a viral challenge. To gain insight into the neuronal and non-neuronal molecular changes during an IAV infection, we intranasally infected mice with an H1N1 virus and extracted the brain at different time points. Using single-nucleus RNA sequencing (snRNA-seq) of the hypothalamus, we identify transcriptional effects in all identified cell populations. The snRNA-seq data showed the most pronounced transcriptional response at 3 days past infection, with a strong downregulation of genes across all cell types. General immune processes were mainly impacted in microglia, the brain resident immune cells, where we found increased numbers of cells expressing pro-inflammatory gene networks. In addition, we found that most neuronal cell populations downregulated genes contributing to the energy homeostasis in mitochondria and protein translation in the cytosol, indicating potential reduced cellular and neuronal activity. This might be a preventive mechanism in neuronal cells to avoid intracellular viral replication and attack by phagocytosing cells. The change of microglia gene activity suggest that this is complemented by a shift in microglia activity to provide increased surveillance of their surroundings.

When you are ill, your behaviour changes. You sleep more, eat less and are less likely to go out and be active. This behavioural change is called the 'sickness response' and is believed to help the immune system fight infection. An area of the brain called the hypothalamus helps to regulate sleep and appetite. Previous research has shown that when humans are ill, the immune system sends signals to the hypothalamus, likely initiating the sickness response. However, it was not clear which brain cells in the hypothalamus are involved in the response and how long after infection the brain returns to its normal state. To better understand the sickness response, Lemcke et al. infected mice with influenza then extracted and analysed brain tissue at different timepoints. The experiments showed that the major changes to gene expression in the hypothalamus early during an influenza infection are not happening in neurons ­ the cells in the brain that transmit electrical signals and usually control behaviour. Instead, it is cells called glia ­ which provide support and immune protection to the neurons ­ that change during infection. The findings suggest that these cells prepare to protect the neurons from influenza should the virus enter the brain. Lemcke et al. also found that the brain takes a long time to go back to normal after an influenza infection. In infected mice, molecular changes in brain cells could be detected even after the influenza infection had been cleared from the respiratory system. In the future, these findings may help to explain why some people take longer than others to fully recover from viral infections such as influenza and aid development of medications that speed up recovery.

Network module analysis and molecular docking-based study on the mechanism of astragali radix against non-small cell lung cancer.

BACKGROUND: Most lung cancer patients worldwide (stage IV non-small cell lung cancer, NSCLC) have a poor survival: 25%-30% patients die < 3 months. Yet, of those surviving > 3 months, 10%-15% patients survive (very) long. Astragali radix (AR) is an effective traditional Chinese medicine widely used for non-small cell lung cancer (NSCLC). However, the pharmacological mechanisms of AR on NSCLC remain to be elucidated. METHODS: Ultra Performance Liquid Chromatography system coupled with Q-Orbitrap HRMS (UPLC-Q-Orbitrap HRMS) was performed for the qualitative analysis of AR components. Then, network module analysis and molecular docking-based approach was conducted to explore underlying mechanisms of AR on NSCLC. The target genes of AR were obtained from four databases including TCMSP (Traditional Chinese Medicine Systems Pharmacology) database, ETCM (The Encyclopedia of TCM) database, HERB (A high-throughput experiment- and reference-guided database of TCM) database and BATMAN-TCM (a Bioinformatics Analysis Tool for Molecular mechanism of TCM) database. NSCLC related genes were screened by GEO (Gene Expression Omnibus) database. The STRING database was used for protein interaction network construction (PIN) of AR-NSCLC shared target genes. The critical PIN were further constructed based on the topological properties of network nodes. Afterwards the hub genes and network modules were analyzed, and enrichment analysis were employed by the R package clusterProfiler. The Autodock Vina was utilized for molecular docking, and the Gromacs was utilized for molecular dynamics simulations Furthermore, the survival analysis was performed based on TCGA (The Cancer Genome Atlas) database. RESULTS: Seventy-seven AR components absorbed in blood were obtained. The critical network was constructed with 1447 nodes and 28,890 edges. Based on topological analysis, 6 hub target genes and 7 functional modules were gained. were obtained including TP53, SRC, UBC, CTNNB1, EP300, and RELA. After module analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that AR may exert therapeutic effects on NSCLC by regulating JAK-STAT signaling pathway, PI3K-AKT signaling pathway, ErbB signaling pathway, as well as NFkB signaling pathway. After the intersection calculation of the hub targets and the proteins participated in the above pathways, TP53, SRC, EP300, and RELA were obtained. These proteins had good docking affinity with astragaloside IV. Furthermore, RELA was associated with poor prognosis of NSCLC patients. CONCLUSIONS: This study could provide chemical component information references for further researches. The potential pharmacological mechanisms of AR on NSCLC were elucidated, promoting the clinical application of AR in treating NSCLC. RELA was selected as a promising candidate biomarker affecting the prognosis of NSCLC patients.

Implementing Four Transitional Care Interventions for Older Adults: A Retrospective Collective Case Study.

BACKGROUND AND OBJECTIVES: Four interventions to improve care transitions between hospital and home or community settings for older adults were implemented in Leuven, Belgium over the past 4 years. These complex interventions consist of multiple components that challenge their implementation in practice. This study examines the influencing factors, strategies used to address challenges in implementing these interventions, and implementation outcomes from the perspectives of health care professionals involved. RESEARCH DESIGN AND METHODS: This was a qualitative, collective case study that was part of the TRANS-SENIOR research network. Authors conducted semistructured interviews with health care professionals about their perceptions regarding the implementation. Thematic analysis was used, and the Consolidated Framework for Implementation Research guided the final data interpretation. RESULTS: Thirteen participants were interviewed. Participants reported major implementation bottlenecks at the organizational level (resources, structure, and information continuity), while facilitators were at the individual level (personal attributes and champions). They identified engagement as the primary strategy used, and suggested other important strategies for the future sustainability of the interventions (building strategic partnerships and lobbying for policies to support transitional care). They perceived the overall implementation favorably, with high uptake as a key outcome. DISCUSSION AND IMPLICATIONS: This study highlights the strong role of health care providers, being motivated and self-driven, to foster the implementation of interventions in transitional care in a bottom-up way. It is important to use implementation strategies targeting both the individual-level factors as well as the organizational barriers for transitional care interventions in the future.

Effects of multivitamin, mineral and n-3 polyunsaturated fatty acid supplementation on aggression among long-stay psychiatric in-patients: randomised clinical trial.

BACKGROUND: Aggression and violent incidents are a major concern in psychiatric in-patient care. Nutritional supplementation has been found to reduce aggressive incidents and rule violations in forensic populations and children with behavioural problems. AIMS: To assess whether multivitamin, mineral and n-3 polyunsaturated fatty acid supplementation would reduce the number of aggressive incidents among long-stay psychiatric in-patients. METHOD: The trial was a pragmatic, multicentre, randomised, double-blind placebo-controlled study. Data were collected from 25 July 2016 to 29 October 2019, at eight local sites for mental healthcare in The Netherlands and Belgium. Participants were randomised (1:1) to receive 6-month treatment with either three supplements containing multivitamins, minerals and n-3 polyunsaturated fatty acid, or placebo. The primary outcome was the number of aggressive incidents, determined by the Staff Observation Aggression Scale - Revised (SOAS-R). Secondary outcomes were patient quality of life, affective symptoms and adverse events. RESULTS: In total, 176 participants were randomised (supplements, n = 87; placebo, n = 89). Participants were on average 49.3 years old (s.d. 14.5) and 64.2% were male. Most patients had a psychotic disorder (60.8%). The primary outcome of SOAS-R incidents was similar in supplement (1.03 incidents per month, 95% CI 0.74-1.37) and placebo groups (0.90 incidents per month, 95% CI 0.65-1.19), with a rate ratio of 1.08 (95% CI 0.67-1.74, P = 0.75). Differential effects were not found in sensitivity analyses on the SOAS-R or on secondary outcomes. CONCLUSIONS: Six months of nutritional supplementation did not reduce aggressive incidents among long-stay psychiatric in-patients.

Traditional Chinese Medicine Aconiti Radix Cocta Improves Rheumatoid Arthritis via Suppressing COX-1 and COX-2.

According to Traditional Chinese Medicine (TCM), Aconiti Radix Cocta (AC) is clinically employed to expel wind, remove dampness, and relieve pain. We evaluated the antirheumatoid arthritis (RA) activities and underlying mechanisms of AC. The chemical constituents of AC were analyzed by high-performance liquid chromatography (HPLC) using three reference compounds (benzoylaconitine, benzoylmesaconine, and benzoylhypacoitine). The anti-RA effects of AC were evaluated in adjuvant-induced arthritis (AIA) rats by hind paw volume and histopathological analysis. The effects of AC on inflammatory cytokines (IL-1ß and IL-17A) were determined by enzyme-linked immunosorbent assay. The regulation of cyclooxygenases (COX-1 and/or COX-2) was determined by Western blot and real-time quantitative reverse transcription polymerase chain reaction analyses. AC significantly reduced paw swelling, attenuated the inflammation and bone destruction in joint tissues, and reduced IL-1ß and IL-17A in the serum. Moreover, AC downregulated the expression of COX-1 and COX-2 in the synovial tissues. We also identified that AC possesses significant anti-RA activities on AIA, which may be ascribed to the regulation of inflammatory cytokines IL-1ß and IL-17, as well as to the inhibition of arachidonic acid signaling pathways. Our findings provide theoretical support for AC as an effective nature-derived therapeutic agent for RA treatment.

Major bioactive chemical compounds in Astragali Radix samples from different vendors vary greatly.

The worldwide traditional Chinese medicine (TCM) herbs sales figures have increased considerably to 50 billion US$ (2018). Astragali Radix (AR) is amongst the most often sold TCM herbs; sales in the European Union (EU) need European Medicines Agency (EMA) approval. However, comparisons of characteristic bioactive molecules concentrations in AR from different EU vendors are lacking. This study uses liquid chromatography-tandem mass spectrometry (LC-MS/MS) with standard addition to evaluate the influence of different sample and preparation types and ammonia treatment on bioactive molecules concentrations in AR. We also compare AR samples from different EU-vendors. Astragaloside IV (AG-IV), ononin and calycosin 7-O-ß-D-glucoside concentrations were higher in root powder samples when extracted with boiled water than with ultrasonication using 70% methanol. AG-IV content was by far the highest in granulates from vendor 1 (202 ± 35 µg/g) but very low in hydrophilic concentrates from vendor 1 (32 ± 7 µg/g) and granulates from vendor 4 (36 ± 3 µg/g). Ammonia-treatment significantly increased AG-IV concentrations in all samples (e.g., to 536 ± 178 µg/g in vendor 1 granulates). Comparable effects were found for most other bioactive molecules. AG-IV and other bioactive molecules concentrations differed strongly depending on sample types, extraction processes, ammonia treatment-or-not and especially between different vendors samples. Ammonia-treatment is debatable, as it is supposed to convert other astragalosides, to AG-IV. The results indicate that routine quantitative analysis of major bioactive compounds present in AR, helps in quality control of AR and to guarantee the quality of commercial products.

Network pharmacology analysis of the therapeutic mechanisms of the traditional Chinese herbal formula Lian Hua Qing Wen in Corona virus disease 2019 (COVID-19), gives fundamental support to the clinical use of LHQW.

BACKGROUND: The traditional Chinese Medicine (TCM) herbal formula Lian Hua Qing Wen (LHQW) improves the results of COVID-19 treatment. Three very recent studies analyzed with network pharmacology some working mechanisms of LHQW. However, we used more techniques and also included Angiotensin converting enzyme 2 (ACE2) (a SARS-CoV receptor, possibly the viral entry point in alveolar lung cells) and the immune system, as cytokine storm is essential in the late phase. PURPOSE: Extensive detailed Network Pharmacology analysis of the LHQW- treatment mechanism in COVID-19. METHODS: TCM-herb-meridian and protein interaction network (PIN) of LHQW, based on LHQW herbs meridian information and the protein-protein interaction (PPI) information of the LHQW-component targets. Hub and topological property analyses to obtain crucial targets and construct the crucial LHQW-PIN. Functional modules determination using MCODE, GO and KEGG pathway analysis of biological processes and pathway enrichment. Intersection calculations between the LHQW-proteins and ACE2 co-expression-proteins. RESULTS: LHQW herbs have relationships to Stomach-, Heart-, Liver- and Spleen-systems, but most (10 of the 13 herbs) to the Lung system, indicating specific effects in lung diseases. The crucial LHQW PIN has the scale-free property, contains 2,480 targets, 160,266 PPIs and thirty functional modules. Six modules are enriched in leukocyte-mediated immunity, the interferon-gamma-mediated signaling pathway, immune response regulating signaling pathway, interleukin 23 mediated signaling pathway and Fc gamma receptor-mediated phagocytosis (GO analysis). These 6 are also enriched in cancer, immune system-, and viral infection diseases (KEGG). LHQW shared 189 proteins with ACE2 co-expression proteins. CONCLUSIONS: Detailed network analysis shows, that LHQW herbal TCM treatment modulates the inflammatory process, exerts antiviral effects and repairs lung injury. Moreover, it also relieves the "cytokine storm" and improves ACE2-expression-disorder-caused symptoms. These innovative findings give a rational pharmacological basis and support for treating COVID-19 and possibly other diseases with LHQW.

Attract and kill: spinosad containing spheres to control onion maggot (Delia antiqua).

BACKGROUND: Onion maggot (Delia antiqua) is a pest of onions worldwide. Current means of managing this pest rely heavily on prophylatic insecticide treatments at planting. These options may not be viable in organic production systems or situations where insecticide-resistant populations occur. Here we explore the efficacy of an attract and kill strategy for control of D. antiqua evaluating the ability of attractive, spinosad containing spheres to kill adult D. antiqua and reduce crop losses. RESULTS: Spinosad containing spheres were able to consistently kill D. antiqua adults over the course of the field season (mortality range: between 49% and 59% on average). Pairing spinosad spheres with Delia Lure increased efficacy by 72% compared with the spheres alone. Performance of this attract and kill strategy also can reduce damage by D. antiqua larvae in the field, but it did not achieve a level of control comparable to the level provided by a conventional insecticide treatment. CONCLUSION: Implementation of this attract and kill strategy could be a valuable tool in situations where conventional pesticides are either not available or desired, where additional control techniques are needed, or to provide a season-long option for control of D. antiqua populations. © 2020 Society of Chemical Industry.

Digital Competencies and Attitudes Toward Digital Adherence Solutions Among Elderly Patients Treated With Novel Anticoagulants: Qualitative Study.

BACKGROUND: Nonadherence to medication is a driver of morbidity and mortality, and complex medication regimens in patients with chronic diseases foster the problem. Digital technology might help, but despite numerous solutions being developed, none are currently widely used, and acceptance rates remain low, especially among the elderly. OBJECTIVE: This study aimed to better understand and operationalize how new digital solutions can be evaluated. Particularly, the goal was to identify factors that help digital approaches targeting adherence to become more widely accepted. METHODS: A qualitative study using a conceptual grounded theory approach was conducted. We included patients aged 65 years and older who routinely took new oral anticoagulants. To generate theses about the digital competencies of the target group with daily medication intake, face-to-face interviews were conducted, recorded, and anonymized. After coding the interviews, categories were generated, discussed, and combined with several theses until saturation of the statements was reached. RESULTS: The methodological approach led to the finding that after interviews in 20 of 77 potentially available patients, a saturation of statements was reached. The average patient's age was 75 years, and 50% (10/20) of the subjects were female. The data identified five main coding categories-Diseases and medicine, Technology, Autonomy, Patient narrative, and Attitude toward technologies-each including positive and negative subcategories. Main categories and subcategories were summarized as Adherence Radar, which can be considered as a framework to assess the potential of adherence solutions in the process of prototyping and can be applied to all adherence tools in a holistic manner. CONCLUSIONS: The Adherence Radar can be used to increase the acceptance rate of digital solutions targeting adherence. For a patient-centric design, an app should be adapted to the individual patient's needs. According to our results, this application should be based on gender and educational background as well as the individual physician-patient relationship. If used in a proper, individualized manner, digital adherence solutions could become a new cornerstone for the treatment of chronically ill individuals.

Auditory Agnosia for Environmental Sounds in Alzheimer's Disease: Not Hearing and Not Listening?

Auditory agnosia for environmental sounds (AES) is an example of central auditory dysfunction. It is presumed to be independent of language deficits and in presence of normal hearing. We undertook a detailed neuropsychological assessment including environmental sound naming and recognition in 34 clinically mild Alzheimer's disease (AD) patients and 29 age-matched healthy control subjects. In patients with AD, audiometry was performed to assess the impact on test performance, and in normal controls the Hearing Handicap Inventory for the Elderly - Screening Version to exclude more than mild hearing loss. We adapted a validated environmental sound battery and found near perfect scores in controls. We found that environmental sound agnosia is common in mild AD. We found a statistically significant difference in mean pure tone audiometry in the best ear between patients with and those patients without naming deficits of 11.3 dB (p = 0.010) and of 14.7 dB (p = 0.000) between those with and without recognition deficits. Statistical significance remained after correcting for age, aphasia, Mini-Mental State Examination score, and working memory. Slight and moderate peripheral hearing loss increases the odds ratio of recognition deficits by 13.75 (confidence interval 2.3-81.5) compared to normal hearing patients. We did not find evidence for different forms of AES. This work suggests that an interaction between peripheral hearing loss and AD pathology produces problems with environmental sound recognition. It confirms that the relationship between hearing and dementia is complex but also suggests that interventions to prevent and treat hearing loss could have an effect on AD in its clinical expression.

Skin Exposure to Narrow Band Ultraviolet (UVB) Light Modulates the Human Intestinal Microbiome.

The recent worldwide rise in idiopathic immune and inflammatory diseases such as multiple sclerosis (MS) and inflammatory bowel diseases (IBD) has been linked to Western society-based changes in lifestyle and environment. These include decreased exposure to sunlight/UVB light and subsequent impairment in the production of vitamin D, as well as dysbiotic changes in the makeup of the gut microbiome. Despite their association, it is unclear if there are any direct links between UVB light and the gut microbiome. In this study we investigated whether exposing the skin to Narrow Band Ultraviolet B (NB-UVB) light to increase serum vitamin D levels would also modulate the makeup of the human intestinal microbiota. The effects of NB-UVB light were studied in a clinical pilot study using a healthy human female cohort (n = 21). Participants were divided into those that took vitamin D supplements throughout the winter prior to the start of the study (VDS+) and those who did not (VDS-). After three NB-UVB light exposures within the same week, the serum 25(OH)D levels of participants increased on average 7.3 nmol/L. The serum response was negatively correlated to the starting 25-hydroxy vitamin D [25(OH)D] serum concentration. Fecal microbiota composition analysis using 16S rRNA sequencing showed that exposure to NB-UVB significantly increased alpha and beta diversity in the VDS- group whereas there were no changes in the VDS+ group. Bacteria from several families were enriched in the VDS- group after the UVB exposures according to a Linear Discriminant Analysis (LDA) prediction, including Lachnospiracheae, Rikenellaceae, Desulfobacteraceae, Clostridiales vadinBB60 group, Clostridia Family XIII, Coriobacteriaceae, Marinifilaceae, and Ruminococcus. The serum 25(OH)D concentrations showed a correlation with the relative abundance of the Lachnospiraceae, specifically members of the Lachnopsira and Fusicatenibacter genera. This is the first study to show that humans with low 25(OH)D serum levels display overt changes in their intestinal microbiome in response to NB-UVB skin exposure and increases in 25(OH)D levels, suggesting the existence of a novel skin-gut axis that could be used to promote intestinal homeostasis and health. Clinical Trial Registration: clinicaltrials.gov, NCT03962673. Registered 23 May 2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03962673?term=NCT03962673&rank=1.

The effect of a multidisciplinary outpatient team approach on outcomes in diabetic foot care: a single center study.

BACKGROUND: Recent studies showed no reduction in major amputation rates after introduction of a multidisciplinary team (MDT) approach for the treatment of diabetic foot ulcer. The efficacy of MDTs in the current standard of care is being questioned. This retrospective single-center study evaluated the efficacy of an outpatient MDT approach on limb salvage and ulcer healing in treating diabetic foot ulcers. METHODS: Patients with a diabetic foot ulcer treated before (2015) and after (2017) implementation of an MDT in a single center were compared. The MDT met weekly and consisted of a vascular surgeon, physiatrist, internist, shoe technician, wound care nurse, nurse practitioner, cast technician, and podiatrist. The primary outcome was limb salvage at 1 year. Secondary outcomes were ulcer healing, amputation-free survival, freedom from any amputation, and overall survival. Multivariable Cox regression models were used to assess predictors for major amputation. RESULTS: A vascular surgeon treated 104 patients with 148 ulcers in 2015, and the multidisciplinary team treated 133 patients with 188 ulcers in 2017. Limb salvage (90.9% vs. 95.5%, P=0.050), freedom from any amputation (56.5% vs. 78.0%, P<0.001), and ulcer healing (48.3% vs. 69.2%, P<0.001) were significantly lower in the non-MDT group than in the MDT group. Amputation-free survival and overall survival did not differ significantly between the groups. Predictors for major amputation were University of Texas Wound Classification 3D (hazard ratio, 2.8; 95% confidence interval, 1.17-6.45) and being treated in the non-MDT group (hazard ratio, 3.7; 95% confidence interval, 1.25-11.08). CONCLUSIONS: This retrospective study found an MDT dedicated to diabetic foot care was highly effective in increasing limb salvage and ulcer healing. We advise that such an MDT is an integrated part of the patient's chain-based care.

Is opioid-free general anesthesia for breast and gynecological surgery a viable option?

PURPOSE OF REVIEW: Opioid-free anesthesia (OFA) was introduced to avoid tolerance and hyperalgesia, allowing reduction in postoperative opioids. OFA focused initially on postoperative respiratory safety for patients undergoing ambulatory surgery and for obstructive sleep apnea syndrome patients otherwise requiring intensive care admission. What about using OFA in plastic and oncological breast surgery, in deep inferior epigastric perforators flap surgery, and in gynecological laparoscopy? RECENT FINDINGS: OFA requires the use of other drugs to block the unwanted reactions from surgical injury. This can be achieved with a single drug at a high dose or with a combination of different drugs at a lower dose, such as with alpha-2-agonists, ketamine, lidocaine, and magnesium, each working on a different target and therefore described as multitarget anesthesia. Three factors can explain OFA success: improved analgesia with less postoperative opioids, the near absence of postoperative nausea and vomiting if no opioid is needed postoperatively, and reduced inflammation enhancing the recovery after surgery. SUMMARY: Opioid-free general anesthesia is a viable option for breast and gynecological surgery and its use will only increase when anesthesiologists listen to their patients' experiences after undergoing surgery under general anesthesia.

Prognostic Understanding and Quality of Life in Patients With Advanced Lung Cancer: A Multicenter Study.

INTRODUCTION: Communication about the palliative setting remains a barrier for many physicians because they are afraid to harm the patient by giving bad news. We sought to determine whether this a valid concern; the influence of prognostic understanding on patients' quality of life (QoL); and which factors influence this relationship. METHODS: The present multicenter, cross-sectional study used a questionnaire to measure patients' prognostic understanding, QoL, mood, and coping strategy. RESULTS: We surveyed 125 patients with advanced lung cancer. Prognostic understanding correlated significantly with emotional well-being (r = -0.20; P = .01) and pain (r = 0.43; P = .00) but not with anxiety (r = 0.12, P = .12) or depression (r = 0.05; P = .29). Patients with anxiety (r = -0.23; P = .01) and patients with depressive feelings (r = -0.63; P = .00) experienced poorer QoL. Four in 10 patients reported feelings of anxiety and/or depression. Positive reframing as a coping strategy was associated with a better QoL (r = 0.25; P = .00). CONCLUSION: Prognostic understanding was related to poorer emotional well-being and more pain but does not affect mood. Four in 10 patients reported feelings of anxiety and/or depression, which were associated with a poorer QoL. A holistic approach seems necessary when physicians communicate about the palliative setting.

Variation in Integrated Head and Neck Cancer Care: Impact of Patient and Hospital Characteristics.

Background: Monitoring and effectively improving oncologic integrated care requires dashboard information based on quality registrations. The dashboard includes evidence-based quality indicators (QIs) that measure quality of care. This study aimed to assess the quality of current integrated head and neck cancer care with QIs, the variation between Dutch hospitals, and the influence of patient and hospital characteristics. Methods: Previously, 39 QIs were developed with input from medical specialists, allied health professionals, and patients' perspectives. QI scores were calculated with data from 1,667 curatively treated patients in 8 hospitals. QIs with a sample size of >400 patients were included to calculate reliable QI scores. We used multilevel analysis to explain the variation. Results: Current care varied from 29% for the QI about a case manager being present to discuss the treatment plan to 100% for the QI about the availability of a treatment plan. Variation between hospitals was small for the QI about patients discussed in multidisciplinary team meetings (adherence: 95%, range 88%-98%), but large for the QI about malnutrition screening (adherence: 50%, range 2%-100%). Higher QI scores were associated with lower performance status, advanced tumor stage, and tumor in the oral cavity or oropharynx at the patient level, and with more curatively treated patients (volume) at hospital level. Conclusions: Although the quality registration was only recently launched, it already visualizes hospital variation in current care. Four determinants were found to be influential: tumor stage, performance status, tumor site, and volume. More data are needed to assure stable results for use in quality improvement.

Reduction of bacteria and somatic coliphages in constructed wetlands for the treatment of combined sewer overflow (retention soil filters).

Combined sewer overflows (CSOs) introduce numerous pathogens from fecal contamination, such as bacteria and viruses, into surface waters, thus endangering human health. In Germany, retention soil filters (RSFs) treat CSOs at sensitive discharge points and can contribute to reducing these hygienically relevant microorganisms. In this study, we evaluated the extent of how dry period, series connection and filter layer thickness influence the reduction efficiency of RSFs for Escherichia coli (E. coli), intestinal enterococci (I. E.) and somatic coliphages. To accomplish this, we had four pilot scale RSFs built on a test field at the wastewater treatment plant Aachen-Soers. While two filters were replicates, the other two filters were installed in a series connection. Moreover, one filter had a thinner filtration layer than the other three. Between April 2015 and December 2016, the RSFs were loaded in 37 trials with pre-conditioned CSO after dry periods ranging from 4 to 40 days. During 17 trials, samples for microbial analysis were taken and analyzed. The series connection of two filters showed that the removal increases when two systems with a filter layer of the same height are operated in series. Since the microorganisms are exposed twice to the environmental conditions on the filter surface and in the upper filter layers, there is a greater chance for abiotic adsorption increase. The same effect could be shown when filters with different depths were compared: the removal efficiency increases as filter thickness increases. This study provides new evidence that regardless of seasonal effects and dry period, RSFs can improve hygienic situation significantly.