Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BACKGROUND: Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. DISCUSSION: We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of ‘translational research’. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. SUMMARY: As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from ‘bench to bedside and back again’) with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease

Respiratory quotient estimations as additional prognostic tools in early septic shock

Central venous-to-arterial carbon dioxide difference (PcvaCO2), and its correction by the arterial-to-venous oxygen content difference (PcvaCO2/CavO2) have been proposed as additional tools to evaluate tissue hypoxia. Since the relationship between pressure and content of CO2 (CCO2) might be affected by several factors, some authors advocate for the use of CcvaCO2/CavO2. The aim of the present study was to explore the factors that might intervene in the difference between PcvaCO2/CavO2 and CcvaCO2/CavO2, and to analyze their association with mortality. Observational study in a 30-bed mixed ICU. Fifty-two septic shock patients within the first 24 h of ICU admission were studied. After restoration of mean arterial pressure, hemodynamic and metabolic parameters were evaluated. A total of 110 sets of measurements were performed. Simultaneous PcvaCO2/CavO2 and CcvaCO2/CavO2 values were correlated, but agreement analysis showed a significant proportional bias. The difference between PcvaCO2/CavO2 and CcvaCO2/CavO2 was independently associated with pH, ScvO2, baseline CcvaCO2/CavO2 and hemoglobin. A stepwise regression analysis showed that pH was the single best predictor for the magnitude of such difference, with very limited effect of other variables. At inclusion, variables associated with ICU-mortality were lactate, pH, PcvaCO2/CavO2, and the difference between PcvaCO2/CavO2 and CcvaCO2/CavO2. Initial ScvO2, PcvaCO2, CcvaCO2/CavO2, and cardiac index were not different in survivors and non-survivors. In a population of early septic shock patients, simultaneous values of PcvaCO2/CavO2 and CcvaCO2/CavO2 were not equivalent, and the main determinant of the magnitude of the difference between these two parameters was pH. The PcvaCO2/CavO2 ratio was associated with ICU mortality, whereas CcvaCO2/CavO2 was not.info:eu-repo/semantics/publishedVersio

Pars Plana Vitrectomy for the Treatment of Uveitis

To review and summarize evidence in the medical literature regarding the use of pars plana vitrectomy in the management of uveitis. Systematic literature review. A systematic literature search was conducted for relevant articles on pars plana vitrectomy for the management of uveitis. Results from the studies were compiled and analyzed. Thirty-four articles, published from 2005 through 2014, were included in the final data analysis. Thirty-two manuscripts were from retrospective case series and 2 manuscripts were from randomized pilot studies. The median Scottish Intercollegiate Guidelines Network level of evidence grade was 3 and the median Oxford Center for Evidence-based Medicine level of evidence grade was 4. Fewer than 50% of the articles in the current study applied Standardization of Uveitis Nomenclature (SUN) criteria in regard to reporting the anatomic location of uveitis, fewer than 25% of studies applied SUN criteria in regard to the reporting of anterior chamber cells before and after PPV, fewer than 10% of studies applied SUN criteria to the grading of anterior chamber flare before and after PPV, and fewer than 10% of studies applied standardized criteria to the grading of vitreous haze after PPV. Overall, 627 patients and 708 total eyes undergoing PPV for uveitis were included. The average reported age of all patients was 43.4 years. The median duration of uveitis prior to PPV reported in the studies was 36.1 months (range 4-198 months). The median follow-up after PPV reported in the studies was 18.9 months (range 2-114 months). Vision was reported for 519 eyes and was improved in 356 eyes (69%), unchanged in 95 eyes (18%), and worse in 68 eyes (13%) following PPV. Preoperatively, 157 of 300 (52%) eyes in these studies had documented cystoid macular edema compared to 112 of 300 (37%) postoperatively. Median use of oral corticosteroids improved from 48% preoperatively to 12% postoperatively among the reporting studies. Median use of other immunosuppressive medications decreased from 56% preoperatively to 36% postoperatively among the reporting studies. Although nearly all studies continue to report favorable outcomes of PPV in the management of uveitis, the quality of data remains limited by a lack of application of standardized reporting outcomes, limitations in study design, and a paucity of prospective data

Update on Imaging in Posterior Segment Uveitis

Multimodal imaging is required to comprehensively evaluate and follow posterior uveitides. Specific applications of the most commonly used modes of imaging in posterior segment uveitis are described.Ultra-wide field imaging, fundus autofluorescence, spectral domain optical coherence tomography, and optical coherence tomography angiography are increasingly used to diagnose and follow patients with uveitis. Pertinent findings in the literature are reviewed.The evaluation of patients with uveitis has been greatly enhanced with the use of different imaging modalities. Both invasive and non-invasive tests provide invaluable information on diagnosis, classification, and disease monitoring leading to better understanding and treatment decisions