Al Ain Hospital

STUDY QUESTION: What is the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature? SUMMARY ANSWER: The guideline development group formulated 77 recommendations answering 18 key questions on investigations and treatments for RPL, and on how care should be organized. WHAT IS KNOWN ALREADY: A previous guideline for the investigation and medical treatment of recurrent miscarriage was published in 2006 and is in need of an update. STUDY DESIGN SIZE DURATION: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 31 March 2017 and written in English were included. Cumulative live birth rate, live birth rate and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes. PARTICIPANTS/MATERIALS SETTING METHODS: Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 38 recommendations on risk factors, prevention and investigations in couples with RPL, and 39 recommendations on treatments. These include 60 evidence-based recommendations - of which 31 were formulated as strong recommendations and 29 as conditional - and 17 good practice points. The evidence supporting investigations and treatment of couples with RPL is limited and of moderate quality. Of the evidence-based recommendations, only 10 (16.3%) were supported by moderate quality evidence. The remaining recommendations were supported by low (35 recommendations: 57.4%), or very low quality evidence (16 recommendations: 26.2%). There were no recommendations based on high quality evidence. Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions investigations and treatments that should not be used for couples with RPL. LIMITATIONS REASONS FOR CAUTION: Several investigations and treatments are offered to couples with RPL, but most of them are not well studied. For most of these investigations and treatments, a recommendation against the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in RPL, based on the best evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. One of the most important consequences of the limited evidence is the absence of evidence for a definition of RPL. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. J.E. reports position funding from CARE Fertility. S.L. reports position funding from SpermComet Ltd. S.M. reports research grants, consulting and speaker's fees from GSK, BMS/Pfizer, Sanquin, Aspen, Bayer and Daiichi Sankyo. S.Q. reports speaker's fees from Ferring. The other authors report no conflicts of interest.ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.

Climate change will have far-reaching impacts on biodiversity, including increasing extinction rates. Current approaches to quantifying such impacts focus on measuring exposure to climatic change and largely ignore the biological differences between species that may significantly increase or reduce their vulnerability. To address this, we present a framework for assessing three dimensions of climate change vulnerability, namely sensitivity, exposure and adaptive capacity; this draws on species' biological traits and their modeled exposure to projected climatic changes. In the largest such assessment to date, we applied this approach to each of the world's birds, amphibians and corals (16,857 species). The resulting assessments identify the species with greatest relative vulnerability to climate change and the geographic areas in which they are concentrated, including the Amazon basin for amphibians and birds, and the central Indo-west Pacific (Coral Triangle) for corals. We found that high concentration areas for species with traits conferring highest sensitivity and lowest adaptive capacity differ from those of highly exposed species, and we identify areas where exposure-based assessments alone may over or under-estimate climate change impacts. We found that 608-851 bird (6-9%), 670-933 amphibian (11-15%), and 47-73 coral species (6-9%) are both highly climate change vulnerable and already threatened with extinction on the IUCN Red List. The remaining highly climate change vulnerable species represent new priorities for conservation. Fewer species are highly climate change vulnerable under lower IPCC SRES emissions scenarios, indicating that reducing greenhouse emissions will reduce climate change driven extinctions. Our study answers the growing call for a more biologically and ecologically inclusive approach to assessing climate change vulnerability. By facilitating independent assessment of the three dimensions of climate change vulnerability, our approach can be used to devise species and area-specific conservation interventions and indices. The priorities we identify will strengthen global strategies to mitigate climate change impacts.

Increasing the collective contribution of protected areas toward preventing species extinctions requires the strategic allocation of management efforts.

BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes. METHODS: The initial assay of mutant α-galactosidase forms that we used to categorize 67 patients with Fabry's disease for randomization to 6 months of double-blind migalastat or placebo (stage 1), followed by open-label migalastat from 6 to 12 months (stage 2) plus an additional year, had certain limitations. Before unblinding, a new, validated assay showed that 50 of the 67 participants had mutant α-galactosidase forms suitable for targeting by migalastat. The primary end point was the percentage of patients who had a response (≥50% reduction in the number of globotriaosylceramide inclusions per kidney interstitial capillary) at 6 months. We assessed safety along with disease substrates and renal, cardiovascular, and patient-reported outcomes. RESULTS: The primary end-point analysis, involving patients with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy, did not show a significant treatment effect: 13 of 32 patients (41%) who received migalastat and 9 of 32 patients (28%) who received placebo had a response at 6 months (P=0.30). Among patients with suitable mutant α-galactosidase who received migalastat for up to 24 months, the annualized changes from baseline in the estimated glomerular filtration rate (GFR) and measured GFR were -0.30±0.66 and -1.51±1.33 ml per minute per 1.73 m(2) of body-surface area, respectively. The left-ventricular-mass index decreased significantly from baseline (-7.7 g per square meter; 95% confidence interval [CI], -15.4 to -0.01), particularly when left ventricular hypertrophy was present (-18.6 g per square meter; 95% CI, -38.2 to 1.0). The severity of diarrhea, reflux, and indigestion decreased. CONCLUSIONS: Among all randomly assigned patients (with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy), the percentage of patients who had a response at 6 months did not differ significantly between the migalastat group and the placebo group. (Funded by Amicus Therapeutics; ClinicalTrials.gov numbers, NCT00925301 [study AT1001-011] and NCT01458119 [study AT1001-041].).

Abstract Governments have committed to conserving ≥17% of terrestrial and ≥10% of marine environments globally, especially “areas of particular importance for biodiversity” through “ecologically representative” Protected Area (PA) systems or other “area‐based conservation measures”, while individual countries have committed to conserve 3–50% of their land area. We estimate that PAs currently cover 14.6% of terrestrial and 2.8% of marine extent, but 59–68% of ecoregions, 77–78% of important sites for biodiversity, and 57% of 25,380 species have inadequate coverage. The existing 19.7 million km 2 terrestrial PA network needs only 3.3 million km 2 to be added to achieve 17% terrestrial coverage. However, it would require nearly doubling to achieve, cost‐efficiently, coverage targets for all countries, ecoregions, important sites, and species. Poorer countries have the largest relative shortfalls. Such extensive and rapid expansion of formal PAs is unlikely to be achievable. Greater focus is therefore needed on alternative approaches, including community‐ and privately managed sites and other effective area‐based conservation measures.

Abstract Background Anxiety disorders comprise some of the most common mental health conditions. This study examined the global and regional burden of anxiety disorders over the last three decades. The study was designed to help accurately target preventative and management efforts by highlighting trends and high-risk groups. Epidemiological data relating to anxiety disorders from the latest Global Burden of Disease dataset were analyzed to determine the prevalence, incidence, and disability adjusted life years (DALYs) rates from 1990 to 2019 for 204 countries and regions. Results An estimated 4.05% of the global population has an anxiety disorder, translating to 301 million people. The number of persons affected has increased by more than 55% from 1990 to 2019. Anxiety disorder metrics show a continuous increase in prevalence, incidence, and DALY rates. Portugal has the highest prevalence (8,671 cases per 100,000), followed by Brazil, Iran, and New Zealand. The prevalence is higher in high-income regions. Women are 1.66 times more likely to be affected by anxiety disorders than men. Age-standardized rates have remained stable, indicating the possible stability of risk factors. Conclusions The prevalence of anxiety disorders has been rising over the last three decades. The prevalence of anxiety appears to increase with socioeconomic development, a higher dependent older population, and urbanization. Future research on this topic could include the development of more accurate cross-cultural metrics to assess anxiety and its correlates, as well as population-based studies to assess trends in anxiety over time.

STUDY QUESTION: What are the updates for the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature from 2017 to 2022? SUMMARY ANSWER: The guideline development group (GDG) updated 11 existing recommendations on investigations and treatments for RPL, and how care should be organized, and added one new recommendation on adenomyosis investigation in women with RPL. WHAT IS KNOWN ALREADY: A previous ESHRE guideline on RPL was published in 2017 and needs to be updated. STUDY DESIGN SIZE DURATION: The guideline was developed and updated according to the structured methodology for development and update of ESHRE guidelines. The literature searches were updated, and assessments of relevant new evidence were performed. Relevant papers published between 31 March 2017 and 28 February 2022 and written in English were included. Cumulative live birth rate, live birth rate, and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes. PARTICIPANTS/MATERIALS SETTING METHODS: Based on the collected evidence, recommendations were updated and discussed until consensus was reached within the GDG. A stakeholder review was organized after the updated draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The new version of the guideline provides 39 recommendations on risk factors, prevention, and investigation in couples with RPL, and 38 recommendations on treatments. These includes 62 evidence-based recommendations-of which 33 were formulated as strong recommendations and 29 as conditional-and 15 good practice points. Of the evidence-based recommendations, 12 (19.4%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (34 recommendations; 54.8%), or very low-quality evidence (16 recommendations; 25.8%). Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions those investigations and treatments that should not be used for couples with RPL. LIMITATIONS REASONS FOR CAUTION: The guidelines have been updated; however, several investigations and treatments currently offered to couples with RPL have not been well studied; for most of these investigations and treatments, a recommendation against using the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in RPL, based on the best and most recent evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. Still, the absence of a unified definition of RPL is one of the most critical consequences of the limited scientific evidence in the field. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment.O.B.C. reports being a member of the executive board of the European Society for Reproductive Immunology and has received payment for honoraria for giving lectures about RPL in Australia in 2020. M.G. reports unconditional research and educational grant received by the Centre for Reproductive Medicine, Amsterdam UMC from Guerbet, Merck and Ferring, not related to the presented work. S.L. reports position funding from EXAMENLAB Ltd. and ownership interest by stock or partnership of EXAMENLAB Ltd (CEO). S.Q. reports being a deputy director of Tommy's National centre for miscarriage research, with payment received by the institution for research, staff time, and consumables for research. H.S.N. reports grants with payment to institution from Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, the Danish ministry of Education, Novo Nordic Foundation, Augustinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, Ole Kirks Fond, and Independent Research Fund Denmark and speakers' fees for lectures from Ferring Pharmaceuticals, Merck A/S, Astra Zeneca, IBSA Nordic and Cook Medical. She also reports to be an unpaid founder and chairman of a maternity foundation. M.-L.v.d.H. received small honoraria for lectures on RPL care. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained.Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type.ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.).

This study examines the frequency of consanguineous marriage and the coefficient of inbreeding in the United Arab Emirates (UAE). The study was conducted in Al Ain and Dubai cities between October 1994 and March 1995. A sample of 2033 married UAE females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and the degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (50.5%) with a coefficient of inbreeding of 0.0222. The commonest type of consanguineous marriage was between first cousins (26.2%). Double first cousin marriages were common (3.5%) compared to other populations. The consanguinity rate in the UAE has increased from 39% to 50.5% in one generation. The level of consanguinity was higher in Al Ain (54.2%) than in Dubai (40%).

OBJECTIVES: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies. METHODS: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review. The evidence derived was discussed and overarching principles, recommendations and future research agenda were iteratively developed with voting rounds. RESULTS: The task force agreed on 22 recommendations covering 8 clinical/organ domains including Raynaud's phenomenon, digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis, skin fibrosis, interstitial lung disease (ILD), gastrointestinal manifestations and arthritis. Most new recommendations are related to skin fibrosis and ILD. These included novel recommendations for the use of mycophenolate mofetil, nintedanib, rituximab and tocilizumab for the treatment of these crucial disease manifestations. The recommendations also included first-line and second-line interventions, providing increased utility for rheumatology practitioners. Important additions to the future research agenda included consideration of novel interventions for the management of vascular, musculoskeletal and gastrointestinal manifestations and calcinosis, as well as for the local management of digital ulcers. CONCLUSION: These updated recommendations include the first set of synthetic and biological targeted therapies recommended for key fibrotic manifestations of SSc as well as first-line combination treatment for newly diagnosed pulmonary artery hypertension and prioritise a new research agenda for the coming years.

BACKGROUND: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. METHODS: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. RESULTS: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. CONCLUSIONS: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.

Previous studies show that conservation actions have prevented extinctions, recovered populations, and reduced declining trends in global biodiversity. However, all studies to date have substantially underestimated the difference conservation action makes because they failed to account fully for what would have happened in the absence thereof. We undertook a scenario-based thought experiment to better quantify the effect conservation actions have had on the extinction risk of the world's 235 recognized ungulate species. We did so by comparing species' observed conservation status in 2008 with their estimated status under counterfactual scenarios in which conservation efforts ceased in 1996. We estimated that without conservation at least 148 species would have deteriorated by one International Union for Conservation of Nature (IUCN) Red List category, including 6 species that now would be listed as extinct or extinct in the wild. The overall decline in the conservation status of ungulates would have been nearly 8 times worse than observed. This trend would have been greater still if not for conservation on private lands. While some species have benefited from highly targeted interventions, such as reintroduction, most benefited collaterally from conservation such as habitat protection. We found that the difference conservation action makes to the conservation status of the world's ungulate species is likely to be higher than previously estimated. Increased, and sustained, investment could help achieve further improvements.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

[No abstract available]

Peste des petits ruminants virus was suspected to be the cause of a disease outbreak in a zoological collection at Al Ain in the Arabian Gulf. Clinically the outbreak affected gazelles (Gazellinae), ibex and sheep (Caprinae) and gemsbok (Hippotraginae); subclinical involvement of Nilgai (Tragelaphinae) was suspected. A morbillivirus was isolated and using monoclonal antibodies and biological tests in cattle, sheep and goats the virus of peste des petits ruminants was identified.

OBJECTIVES: To analyze the concept of "case series" in the medical literature compared with case reports. METHODS: A PubMed search for articles published during 2009 which had "case series" in their title was performed. A total number of 621 articles were retrieved. 586 papers were included in the analysis and 35 were excluded (18 were commentary letters, 5 were not in English, and twelve could not be retrieved by our Library). The number of patients and category of these articles were analyzed. RESULTS: The median (range) of the number of cases of articles having "case series" in their title was 7 (1-6432) cases. 186/ 586 articles had less than 5 cases (31.7%, 95% CI (28.3-35.1%)). The median (range) of the number of cases of articles having "case report" as their publication type was 4 (1-178) cases. Out of the 219 articles categorized as case reports 114 (52.1%, 95% CI (45.6-58.6%)) had less than five cases. CONCLUSIONS: The concept of "case series" is not well defined in the literature and does not reflect a specific research design. We suggest that a case series should have more than four patients while four paitents or less should be reported individually as case reports.

The performance of the Fungitell assay was investigated in 100 patients with haematological malignancy undergoing chemotherapy who developed antibiotic-unresponsive neutropenic fever (AUNF). Serum beta-D-glucan (BG) concentrations were significantly elevated on the first day of AUNF and all subsequent alternate days to day 10 in 38 patients who developed an invasive fungal infection (IFI) compared to 42 patients remaining free of such infections. The mean and median values of BG were 171.9+/-29.6 and 95.8 pg ml(-1), respectively, for patients with IFI and 64.4+/-17.1 and 32.9 pg ml(-1) for patients with only AUNF (P<0.0001). The differences remained significant over the 10 days despite antifungal therapy. The occurrence of > or =2 sequential concentrations of > or =80 pg ml(-1) ('positive' test) was found to give the best overall option for diagnosis, with an accuracy of 81.3%, sensitivity of 86.8%, positive predictive value of 76.7% and negative predictive value of 86.5%. Of the patients with an IFI, 78% developed a positive test at or before the clinical diagnosis was made -- this occurred at a mean (range) of 1.25 (-14 to +14) days prior to the IFI diagnosis. By starting sampling of blood from the first day of neutropenia rather than from the first day of AUNF, 50% of the patients with subsequent IFI would have been identified 5 days earlier. Increasing sampling to daily from alternate-day frequency did not further improve this earlier timing of an IFI diagnosis. A greater proportion of patients with persistent high levels of BG without overt IFI had severe enterocyte damage or mucositis than those with lower levels of BG without IFI (P=0.002). If the results of the initial BG test had been acted on to change antifungal therapy, discontinuation would have been inappropriate in 30% of patients and would have delayed definitive antifungal therapy. Although the findings for the cohort of patients studied are very useful, there is inter-patient variability in the test's performance. An holistic diagnostic approach is therefore necessary to interpret the test results optimally. Future studies should address this in further detail as well as the impact of empirical antifungal drug use and patient outcome.

This study examined a possible aetiological agent, namely, Helicobacter pylori, in perforated peptic ulcer disease and its relationship to persisting ulcer. Twenty-nine patients with perforated peptic ulcer underwent simple closure of the perforation at laparotomy. A 13C urea breath test carried out on the eighth day after operation was positive in 24 patients. Fourteen of 17 patients who underwent upper gastrointestinal endoscopy 6 weeks after discharge from hospital had a positive 13C urea breath test. The biopsy urease test performed on mucosal samples taken at endoscopy was positive in 12 of these 14 patients, indicating continuing active infection with H. pylori. Seven patients with positive 13C urea breath and biopsy urease tests had persisting duodenal ulceration. None of the three patients with a negative 13C urea breath test had evidence of duodenal ulceration at endoscopy. The association between a high rate of duodenal ulcer persistence and a high incidence of H. pylori infection suggests that antibiotic therapy to eradicate this microorganism should be given to all patients with perforated peptic ulcer disease.

AIMS AND OBJECTIVES: The aim of the review was to identify intimate partner violence screening interventions used in emergency departments and to explore factors affecting intimate partner violence screening in emergency departments. BACKGROUND: Intimate partner violence against women is now clearly recognised as a global health and societal issue. Nurses working in emergency and urgent care settings can play a crucial role in identification, prevention and management of intimate partner violence. Research exploring optimal methods of intimate partner violence screening and factors affecting intimate partner violence screening in emergency departments are relatively limited. DESIGN: Literature review: Rapid Evidence Synthesis. METHODS: Literature published between 2000-2015 was reviewed using the principles of rapid evidence assessment. Six electronic databases: CINAHL, MEDLINE, EMBASE, Psych Info, the Cochrane Library and Joanna Briggs Library. RESULTS: Twenty-nine empirical studies meeting the eligibility criteria were independently assessed by two authors using appropriate Critical Appraisal Skills Programme Checklists. Intimate partner violence screening in emergency departments is usually performed using electronic, face to face or pen- and paper-based instruments. Routine or universal screening results in higher identification rates of intimate partner violence. Women who screen positive for intimate partner violence in emergency departments are more likely to experience abuse in subsequent months. Factors that facilitate partner violence screening can be classified as healthcare professionals related factors, organisational factors and patient-related factors. CONCLUSIONS: Emergency departments provide a unique opportunity for healthcare professionals to screen patients for intimate partner violence. Competence in assessing the needs of the patients appears to be a very significant factor that may affect rates of intimate partner violence disclosure. RELEVANCE TO CLINICAL PRACTICE: Knowledge of appropriate domestic violence screening methods and factors affecting intimate partner violence screening in emergency can help nurses, and other healthcare professionals provide patient-centred and effective care to victims of abuse attending emergency department.

BACKGROUND: To date, few studies have been published reporting the 5-year follow-up of clinical and radiological outcomes for chondral defects treated with matrix-induced autologous chondrocyte implantation (MACI). HYPOTHESIS: A significant improvement in clinical and radiological outcomes after treatment of symptomatic, traumatic chondral defects of the knee with the MACI implant will be maintained up to 5 years after surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A prospective evaluation of the MACI procedure was performed in 21 patients with chondral defects of the knee. After the MACI procedure, patients were clinically assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner-Lysholm score, the International Knee Documentation Committee (IKDC) Subjective Knee Form, and the modified Cincinnati score at years 1, 2, and 5. The quality of repair tissue was assessed by magnetic resonance imaging using the magnetic resonance observation of cartilage repair tissue (MOCART) score at months 3 and 6 and years 1, 2, and 5. RESULTS: Significant improvements (P < .05) were observed for all 5 KOOS subcategories at year 1 and were maintained through year 5 in 90.5% of patients (19/21). Treatment failure occurred in only 9.5% of patients (2/21). Significant improvements (P < .05) from baseline to year 5 were also observed for the IKDC score (30.1 to 74.3), the modified Cincinnati score (38.1 to 79.6), and the Tegner-Lysholm activity score (1.8 to 4.3). Similarly, the MOCART score significantly improved (P < .001) from baseline to year 5 (52.9 to 75.8). After 5 years, complete filling (83%) and integration (82%) of the graft were seen in the majority of patients. Signs of subchondral bone edema were still present in 47% of patients at 5 years. No product-specific adverse events were reported over the 5-year follow-up period. CONCLUSION: Patients treated with a MACI implant demonstrated significant clinical improvement and good quality repair tissue 5 years after surgery. The MACI procedure was shown to be a safe and effective treatment for symptomatic, traumatic chondral knee defects in this study.

The world's governments have committed to preventing the extinction of threatened species and improving their conservation status by 2020. However, biodiversity is not evenly distributed across space, and neither are the drivers of its decline, and so different regions face very different challenges. Here, we quantify the contribution of regions and countries towards recent global trends in vertebrate conservation status (as measured by the Red List Index), to guide action towards the 2020 target. We found that>50% of the global deterioration in the conservation status of birds, mammals and amphibians is concentrated in <1% of the surface area, 39/1098 ecoregions (4%) and eight/195 countries (4%) - Australia, China, Colombia, Ecuador, Indonesia, Malaysia, Mexico, and the United States. These countries hold a third of global diversity in these vertebrate groups, partially explaining why they concentrate most of the losses. Yet, other megadiverse countries - most notably Brazil (responsible for 10% of species but just 1% of deterioration), plus India and Madagascar - performed better in conserving their share of global vertebrate diversity. Very few countries, mostly island nations (e.g. Cook Islands, Fiji, Mauritius, Seychelles, and Tonga), have achieved net improvements. Per capita wealth does not explain these patterns, with two of the richest countries - United States and Australia - fairing conspicuously poorly. Different countries were affected by different combinations of threats. Reducing global rates of biodiversity loss will require investment in the regions and countries with the highest responsibility for the world's biodiversity, focusing on conserving those species and areas most in peril and on reducing the drivers with the highest impacts.