The International Working Group on the Diabetic Foot (IWGDF) has published evidence‐based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the ...diagnosis and treatment of foot infection in persons with diabetes and updates the 2015 IWGDF infection guideline. On the basis of patient, intervention, comparison, outcomes (PICOs) developed by the infection committee, in conjunction with internal and external reviewers and consultants, and on systematic reviews the committee conducted on the diagnosis of infection (new) and treatment of infection (updated from 2015), we offer 27 recommendations. These cover various aspects of diagnosing soft tissue and bone infection, including the classification scheme for diagnosing infection and its severity. Of note, we have updated this scheme for the first time since we developed it 15 years ago. We also review the microbiology of diabetic foot infections, including how to collect samples and to process them to identify causative pathogens. Finally, we discuss the approach to treating diabetic foot infections, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and for bone infections, when and how to approach surgical treatment, and which adjunctive treatments we think are or are not useful for the infectious aspects of diabetic foot problems. For this version of the guideline, we also updated four tables and one figure from the 2016 guideline. We think that following the principles of diagnosing and treating diabetic foot infections outlined in this guideline can help clinicians to provide better care for these patients.
Background
Avoidant/restrictive food intake disorder (ARFID) was a new diagnosis in DSM‐5. This systematic review explores what is known to date about the epidemiology of ARFID in children and ...adolescents.
Method
Embase, Medline and PsycInfo were used to identify studies meeting inclusion criteria. PRISMA guidelines were followed.
Results
Thirty studies met inclusion criteria, with most coming from specialised eating disorder services where prevalence rates were 5%–22.5%. Three studies from specialist feeding clinics showed the highest prevalence rates, ranging from 32% to 64%. Studies from non‐clinical samples reported ARFID prevalence estimates ranging from 0.3% to 15.5%. One study, using national surveillance methodology, reported the incidence of ARFID in children and adolescents reaching clinical care to be 2.02 per 100,000 patients. Psychiatric comorbidity was common, especially anxiety disorders (9.1%–72%) and autism spectrum disorder (8.2%–54.75%).
Conclusion
The current literature on the epidemiology of ARFID in children and adolescents is limited. Studies are heterogeneous with regard to setting and sample characteristics, with a wide range of prevalence estimates. Further studies, especially using surveillance methodology, will help to better understand the nature of this disorder and estimate clinical service needs.
Highlights
ARFID prevalence estimates vary widely across studies and are highest in specialist feeding clinics. The one incidence study to date suggests that new presentations to clinical care are relatively rare.
ARFID has a high rate of psychiatric comorbidity especially with anxiety disorders.
Further epidemiological studies, especially using national surveillance methodology, will help planning and resource allocation for this patient group.
Recommendations
Classification/diagnosis
Diabetic foot infection must be diagnosed clinically, based on the presence of local or systemic signs or symptoms of inflammation (strong; low).
Assess the ...severity of any diabetic foot infection using the Infectious Diseases Society of America/International Working Group on the Diabetic Foot classification scheme (strong; moderate).
Osteomyelitis
For an infected open wound, perform a probe‐to‐bone test; in a patient at low risk for osteomyelitis, a negative test largely rules out the diagnosis, while in a high‐risk patient, a positive test is largely diagnostic (strong; high).
Markedly elevated serum inflammatory markers, especially erythrocyte sedimentation rate, are suggestive of osteomyelitis in suspected cases (weak; moderate).
A definite diagnosis of bone infection usually requires positive results on microbiological (and, optimally, histological) examinations of an aseptically obtained bone sample, but this is usually required only when the diagnosis is in doubt or determining the causative pathogen's antibiotic susceptibility is crucial (strong; moderate).
A probable diagnosis of bone infection is reasonable if there are positive results on a combination of diagnostic tests, such as probe‐to‐bone, serum inflammatory markers, plain X‐ray, magnetic resonance imaging (MRI) or radionuclide scanning (strong; weak).
Avoid using results of soft tissue or sinus tract specimens for selecting antibiotic therapy for osteomyelitis as they do not accurately reflect bone culture results (strong; moderate).
Obtain plain X‐rays of the foot in all cases of non‐superficial diabetic foot infection (strong; low).
Use MRI when an advanced imaging test is needed for diagnosing diabetic foot osteomyelitis (strong; moderate).
When MRI is not available or contraindicated, consider a white blood cell‐labelled radionuclide scan, or possibly single‐photon emission computed tomography (CT) and CT (SPECT/CT) or fluorine‐18‐fluorodeoxyglucose positron emission tomography/CT scans (weak; moderate).
Assessing severity
At initial evaluation of any infected foot, obtain vital signs and appropriate blood tests, debride the wound and probe and assess the depth and extent of the infection to establish its severity (strong; moderate).
At initial evaluation, assess arterial perfusion and decide whether and when further vascular assessment or revascularization is needed (strong; low).
Microbiological considerations
Obtain cultures, preferably of a tissue specimen rather than a swab, of infected wounds to determine the causative microorganisms and their antibiotic sensitivity (strong; high).
Do not obtain repeat cultures unless the patient is not clinically responding to treatment, or occasionally for infection control surveillance of resistant pathogens (strong; low).
Send collected specimens to the microbiology laboratory promptly, in sterile transport containers, accompanied by clinical information on the type of specimen and location of the wound (strong; low).
Surgical treatment
Consult a surgical specialist in selected cases of moderate, and all cases of severe, diabetic foot infection (weak; low).
Perform urgent surgical interventions in cases of deep abscesses, compartment syndrome and virtually all necrotizing soft tissue infections (strong; low).
Consider surgical intervention in cases of osteomyelitis accompanied by spreading soft tissue infection, destroyed soft tissue envelope, progressive bone destruction on X‐ray or bone protruding through the ulcer (strong; low).
Antimicrobial therapy
While virtually all clinically infected diabetic foot wounds require antimicrobial therapy, do not treat clinically uninfected wounds with antimicrobial therapy (Strong; Low)
Select specific antibiotic agents for treatment based on the likely or proven causative pathogens, their antibiotic susceptibilities, the clinical severity of the infection, evidence of efficacy of the agent for diabetic foot infection and costs (strong; moderate).
A course of antibiotic therapy of 1–2 weeks is usually adequate for most mild and moderate infections (strong; high).
Administer parenteral therapy initially for most severe infections and some moderate infections, with a switch to oral therapy when the infection is responding (strong; low).
Do not select a specific type of dressing for a diabetic foot infection with the aim of preventing an infection or improving its outcome (strong; high).
For diabetic foot osteomyelitis, we recommend 6 weeks of antibiotic therapy for patients who do not undergo resection of infected bone and no more than a week of antibiotic treatment if all infected bone is resected (strong; moderate).
We suggest not using any adjunctive treatments for diabetic foot infection (weak; low).
When treating a diabetic foot infection, assess for use of traditional remedies and previous antibiotic use and consider local bacterial pathogens and their susceptibility profile (strong; low).
Gentrification demands updated frameworks to assess the impact of some major global trends on the local populations’ access to housing. Short-term accommodation using digital platforms in previously ...gentrified central urban areas is playing a significant role in outlining a new wave of ‘transnational gentrification’ in a number of global cities. Having undergone classical patterns of gentrification over the last two decades, the central district of Madrid and its surroundings are showing patterns of a new wave of gentrification in a context of economic crisis, planetary rent gaps, increasing global tourism and an increase in rental prices in central areas that may be related to the emergence of short-term rentals – making Madrid a relevant case for depicting transnational gentrification in the Southern European capitals. Based on empirical data, this work explores the holiday rental supply in Madrid over three years (2015–2018), verifying a strong association between the growth in tourist arrivals, the settlement of new residents from wealthy economic backgrounds and increasing rental prices. Since this process is accompanied by deregulation of local rental contracts and the growth of transnational Real Estate Investment Trusts (REITs), even in some of the most vulnerable areas located beyond the M-30 ring road, this wave of gentrification has the potential to produce displacement and substitution of residents.
绅士化要求更新框架，以评估一些重要的全球趋势对当地居民获得住房的影响。在此前已完成绅士化的中心城市地区，使用数字平台出租的短租房在描绘一些全球城市的新一波“跨国绅士化”方面发挥着重要作用。在过去20年里经历了传统的绅士化模式后，马德里市中心及其周边地区正呈现出新一轮绅士化的模式，其背景是经济危机、全球租金差距、全球旅游业增长以及中心地区租金价格上涨（这些都可能与短租房的出现有关），这使得马德里成为了描绘南欧国家首都跨国绅士化的一个相关案例。基于实证数据，本研究探讨了马德里在三年内（2015-2018年）的假日租赁供应，验证了游客数量的增长、来自富裕经济背景的新居民的定居和租金价格的上涨之间的高相关性。由于这一过程伴随着对当地租赁合同的放松管制和跨国房地产投资信托 (REIT) 的发展，即使在位于M-30环路以外的一些最脆弱的地区，这一绅士化浪潮也有可能造成居民被排挤和取代。
Summary Background Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ...(NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. Methods We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m2 on day 1 plus docetaxel (75 mg/m2 on day 1) or gemcitabine (1250 mg/m2 on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m2 or AUC 5 with gemcitabine 1000 mg/m2 ) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥1 dose). This study is registered with ClinicalTrials.gov , number NCT00446225. Findings Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p<0·0001). Main grade 3 or 4 toxicities were rash (11 13% of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 22%), anaemia (one 1% vs three 4%), and increased amino-transferase concentrations (two 2% vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Interpretation Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer.
It is well known that graphene deposited on hexagonal boron nitride produces moiré patterns in scanning tunnelling microscopy images. The interaction that produces this pattern also produces a ...commensurate periodic potential that generates a set of Dirac points that are different from those of the graphene lattice itself.
Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell ...lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment.
From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment.
EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progression-free survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P=0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P=0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%).
Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.
Aims
In addition to systemic inflammatory response syndrome (SIRS), various clinical signs, microbiological findings and inflammatory markers could be associated with severe diabetic foot infections ...(DFI).
Methods
This study included a retrospective cohort of 245 patients with DFI treated at San Juan de Dios Hospital in San José de Costa Rica. Erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), CRP/albumin ratio, peripheral blood leucocyte ratios and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) scoring system were evaluated. Univariate analysis was carried out between moderate and severe infections. ROC curves were plotted. Cut‐off value of inflammatory markers for diagnosing severe infections was established and then dichotomized to be included in a logistic regression model. A score was designed based on its results.
Results
Skin necrosis (p < 0.01, OR = 8.5, 95% CI = 3.5–20.9), ESR > 94 mm/h (p < 0.01, OR = 2.5, 95% CI = 1.2–5.1), albumin < 2.8 g/dl (p = 0.04, OR = 2.0, 95% CI = 1.0–4.1) and neutrophil‐to‐lymphocyte ratio (NLR) > 4.52 (p < 0.01, OR = 3.3, 95% CI = 1.6–6.5) were found to be predictive of severe infections. Score >5 had a good diagnosis performance for classifying severe infections. Moderate infections with a score >5 had a worse prognosis than moderate ones.
Conclusions
We found an association of necrosis, serum albumin, ESR and NLR values with severe DFI. The presence of these predictive factors of severity in cases of moderate infections was significantly associated with a higher rate of amputations and recurrences, longer duration of antibiotic treatment and longer hospital stays. DFI could be classified as mild, moderate, severe without SIRS and severe.
The Andean Schkuhria pinnata species commonly known as ‘Canchalagua’ is used as an infusion in Andean countries to treat various anti-inflammatory and skin-related pathologies.
This study determined ...the anti-inflammatory activity of the aqueous extract from Schkuhria pinnata, identified compounds with high biological activity and performed a structure-activity relationship analysis to determine their binding mechanism.
A bio-guided isolation of the active compounds of Schkuhria pinnata was carried out by selecting the most active sub-extracts and fractions to test their anti-inflammatory activity against the ASK1 and TNF-α cytokines.
Three compounds were obtained, and their structures were elucidated by nuclear magnetic resonance. The compounds were (3R,4R)-4-(3,4-dimethoxybenzyl)-3-(4-hydroxy-3-methoxybenzyl) dihydrofuran-2(3H)-one (1), N-2,3-dihydro-1,3-dimethyl-6-(2R)-2-methyl-1-piperazinyl-2-oxo-1H-benzimidazol-5-yl-2-methoxybenzamide (2), and N-hydroxy-1-cyclopentene-1-carboxamide (3). Regarding their anti-inflammatory activity, the three compounds inhibited the TNF-α and ASK1 cytokines, however, compound 2 was the most active, with an IC50 of 19.08 and 8.94 nM, respectively.
The anti-inflammatory activity of the aqueous extract of Schkuhria pinnata was evaluated, followed by the isolation of three compounds and the study of their pharmacological activity. The three compounds have been shown as promising treatment against dermatitis, confirming at the same time their traditional use.
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•An aqueous extract was used to study the anti-inflammatory topical activity of the Schkuhria pinnata species.•Three lactones and nitrogenous type compounds were isolated.•All compounds had anti-TNF-α and anti-ASK1 activities in the HEK001, WS1, and THP-1 cell lines.
Abstract
In acute heart failure (AHF) syndromes significant respiratory failure (RF) is essentially seen in patients with acute cardiogenic pulmonary oedema (ACPE) or cardiogenic shock (CS). ...Non-invasive ventilation (NIV), the application of positive intrathoracic pressure through an interface, has shown to be useful in the treatment of moderate to severe RF in several scenarios. There are two main modalities of NIV: continuous positive airway pressure (CPAP) and pressure support ventilation (NIPSV) with positive end expiratory pressure. Appropriate equipment and experience is needed for NIPSV, whereas CPAP may be administered without a ventilator, not requiring special training. Both modalities have shown to be effective in ACPE, by a reduction of respiratory distress and the endotracheal intubation rate compared to conventional oxygen therapy, but the impact on mortality is less conclusive. Non-invasive ventilation is also indicated in patients with AHF associated to pulmonary disease and may be considered, after haemodynamic stabilization, in some patients with CS. There are no differences in the outcomes in the studies comparing both techniques, but CPAP is a simpler technique that may be preferred in low-equipped areas like the pre-hospital setting, while NIPSV may be preferable in patients with significant hypercapnia. The new modality ‘high-flow nasal cannula’ seems promising in cases of AHF with less severe RF. The correct selection of patients and interfaces, early application of the technique, the achievement of a good synchrony between patients and the ventilator avoiding excessive leakage, close monitoring, proactive management, and in some cases mild sedation, may warrant the success of the technique.
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