Reporting standard for describing first responder systems, smartphone alerting systems, and AED networks.

Standardized reporting of data is crucial for out-of-hospital cardiac arrest (OHCA) research. While the implementation of first responder systems dispatching volunteers to OHCA is encouraged, there is currently no uniform reporting standard for describing these systems. A steering committee established a literature search to identify experts in smartphone alerting systems. These international experts were invited to a conference held in Hinterzarten, Germany, with 40 researchers from 13 countries in attendance. Prior to the conference, participants submitted proposals for parameters to be included in the reporting standard. The conference comprised five workshops covering different aspects of smartphone alerting systems. Proposed parameters were discussed, clarified, and consensus was achieved using the Nominal Group Technique. Participants voted in a modified Delphi approach on including each category as a core or supplementary element in the reporting standard. Results were presented, and a writing group developed definitions for all categories and items, which were sent to participants for revision and final voting using LimeSurvey web-based software. The resulting reporting standard consists of 68 core items and 21 supplementary items grouped into five topics (first responder system, first responder network, technology/algorithm/strategies, reporting data, and automated external defibrillators (AED)). This proposed reporting standard generated by an expert opinion group fills the gap in describing first responder systems. Its adoption in future research will facilitate comparison of systems and research outcomes, enhancing the transfer of scientific findings to clinical practice.

Andrological effects of SARS-Cov-2 infection: a systematic review and meta-analysis.

PURPOSE: The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated. METHODS: All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n = 19), as well as those reporting data on semen analysis (n = 5) and hormonal parameters (n = 11) in infected/recovered patients without any arbitrary restriction were included. RESULTS: Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality. CONCLUSIONS: The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.

Clinical outcomes from out-of-hospital cardiac arrest in low-resource settings - A scoping review.

AIM OF THE SCOPING REVIEW: Scientific recommendations on resuscitation are typically formulated from the perspective of an ideal resource environment, with little consideration of applicability in lower-income countries. We aimed to determine clinical outcomes from out-of-hospital cardiac arrest (OHCA) in low-resource countries, to identify shortcomings related to resuscitation in these areas and possible solutions, and to suggest future research priorities. DATA SOURCES: This scoping review was part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation (ILCOR), and was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. We identified low-resource countries as countries with a low- or middle gross national income per capita (World Bank data). We performed a literature search on outcomes after OHCA in these countries, and we extracted data on the outcome. We applied descriptive statistics and conducted a post-hoc correlation analysis of cohort size and ROSC rates. RESULTS: We defined 24 eligible studies originating from middle-income countries, but none from low-income regions, suggesting a reporting bias. The number of reported patients in these studies ranged from 54 to 3214. Utstein-style reporting was rarely used. Return of spontaneous circulation varied from 0% to 62%. Fifteen studies reported on survival to hospital discharge (between 1.0 and 16.7%) or favourable neurological outcome (between 1.0 and 9.3%). An inverse correlation was found for study cohort size and the rate of return of spontaneous circulation (ρ = -0.48, p = 0.034). CONCLUSION: Studies of OHCA outcomes in low-resource countries are heterogeneous and may be compromised by reporting bias. Minimum cardiopulmonary resuscitation standards for low-resource settings should be developed collaboratively involving local experts, respecting culture and context while balancing competing health priorities.

European Resuscitation Council COVID-19 guidelines executive summary.

Coronavirus disease 2019 (COVID-19) has had a substantial impact on the incidence of cardiac arrest and survival. The challenge is to find the correct balance between the risk to the rescuer when undertaking cardiopulmonary resuscitation (CPR) on a person with possible COVID-19 and the risk to that person if CPR is delayed. These guidelines focus specifically on patients with suspected or confirmed COVID-19. The guidelines include the delivery of basic and advanced life support in adults and children and recommendations for delivering training during the pandemic. Where uncertainty exists treatment should be informed by a dynamic risk assessment which may consider current COVID-19 prevalence, the person's presentation (e.g. history of COVID-19 contact, COVID-19 symptoms), likelihood that treatment will be effective, availability of personal protective equipment (PPE) and personal risks for those providing treatment. These guidelines will be subject to evolving knowledge and experience of COVID-19. As countries are at different stages of the pandemic, there may some international variation in practice.

Diabetic retinopathy, a vascular and inflammatory disease: Therapeutic implications.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in the working-age population in the Western world. Diabetic macular oedema (DME) is one of the major complications of DR. Therapy with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs has become the gold standard treatment for DR and its complications. However, these drugs have no effect on the pathogenesis of DR and must be administered frequently via invasive intravitreal injections over many years. Thus, there is a pressing need to develop new therapeutic strategies to improve the treatment of this devastating disease. Indeed, an increasing volume of data supports the role of the inflammatory process in the pathogenesis of DR itself and its complications, including both increased retinal vascular permeability and neovascularization. Inflammation may also contribute to retinal neurodegeneration. Evidence that low-grade inflammation plays a critical role in the pathogenesis of DME has opened up new pathways and targets for the development of improved treatments. Anti-inflammatory compounds such as intravitreal glucocorticoids, topical non-steroidal anti-inflammatory drugs (NSAIDs), antioxidants, inflammatory molecule inhibitors, renin-angiotensin system (RAS) blockers and natural anti-inflammatory therapies may all be considered to reduce the rate of administration of antineovascularization agents in the treatment of DR. This report describes the current state of knowledge of the potential role of anti-inflammatory drugs in controlling the onset and evolution of DR and DME.

ILM peeling in nontractional diabetic macular edema: review and metanalysis.

PURPOSE: To evaluate the effect of internal limiting membrane (ILM) peeling during vitrectomy for nontractional diabetic macular edema. METHODS: PUBMED, MEDLINE and CENTRAL were reviewed using the following terms (or combination of terms): diabetic macular edema, nontractional diabetic macular edema, internal limiting membrane peeling, vitrectomy, Müller cells. Randomized and nonrandomized studies were included. The eligible studies compared anatomical and functional outcomes of vitrectomy with or without ILM peeling for tractional and nontractional diabetic macular edema. Postoperative best-corrected visual acuity and central macular thickness were considered, respectively, the primary and secondary outcomes. Meta-analysis on mean differences between vitrectomy with and without ILM peeling was performed using inverse variance method in random effects. RESULTS: Four studies with 672 patients were eligible for analysis. No significant difference was found between postoperative best-corrected visual acuity or best-corrected visual acuity change of ILM peeling group compared with nonpeeling group. There was no significant difference in postoperative central macular thickness and central macular thickness reduction between the two groups. CONCLUSIONS: The visual acuity outcomes in patients affected by nontractional diabetic macular edema using pars plana vitrectomy with ILM peeling versus no ILM peeling were not significantly different. A larger prospective and randomized study would be necessary.

["Kids Save Lives"-resuscitation training for schoolchildren : Systematic review]. / "Kids Save Lives" ­ Wiederbelebungstrainings für Schulkinder : Systematische Übersichtsarbeit.

BACKGROUND: Even in western developed countries, the probability of survival after out-of-hospital cardiac arrest (OHCA) is only 6-10%. In order to improve survival after OHCA, early initiation of cardiopulmonary resuscitation (CPR) by laypersons is essential. Introduction of CPR training in schoolchildren seems to be effective to increase lay-CPR rates. OBJECTIVE: The objective of the present investigation was to elucidate educational aspects of teaching schoolchildren in CPR and to summarize campaigns related to a comprehensive establishment of lay-CPR worldwide. MATERIALS AND METHODS: A literature research in PubMed was performed, the cutoff date was 27 February 2017. Overall, 192 abstracts were analyzed; 51 articles were considered relevant and included in the manuscript. An additional keyword research in Google revealed >230,000 entries, and 20 of those were included in the present manuscript. RESULTS: A minimum age of 12-13 years is required to achieve a comparable quality of CPR to adult basic life support (BLS). Key issues are (i) the correct detection of a cardiac arrest, (ii) a correctly performed call for help, (iii) thoracic compressions and (iv) if applicable, the initiation of adequate mouth-to-mouth ventilation. Practical training showed a significantly higher CPR quality compared to theoretical training only or to the use of instruction or online videos only. Worldwide implementation of a 2-h BLS training per year in children from the age of 12 or younger is recommended by the "Kids Save Lives"- statement since 2015. In Germany, implementation at the level of the federal states has progressed to different degrees.

Trace elements and diabetes: Assessment of levels in tears and serum.

Tear film is critical for the well-being and homeostasis of the ocular surface. Although the composition of the tear film is well known, the composition of metallic elements have yet to be analysed. Despite trace elements metabolism has been reported to play a role in the pathogenesis of diabetes mellitus, a metabolic disease that affects several aspects of homeostasis, little is known in the literature regarding concentration and possible variation of metallic elements in tear film. We studied the concentrations of several essential and non-essential metallic elements in the tear fluid and serum of patients with type II diabetes mellitus and a group of non-diabetic controls. Serum and tear fluid were collected from 97 patients: 47 type II diabetic patients and 50 non-diabetic controls. Regarding tear film, there were statistically significant differences in Zinc, Chrome, Cobalt, Manganese, Barium, and Lead between groups; the values of all metallic elements were found to be statistically significant higher in patients with mellitus type II diabetes. Regarding serum values there was a statistically significant difference in Chrome, Cobalt, and Selenium values; the concentrations of Chrome and Cobalt were higher in the control group, while Selenium concentration was higher in diabetic patients. In patients with type II diabetes, metal elements with higher concentrations in tears compared to serum were: Lead, Barium, Manganese, Cobalt, and Chrome. In the control group, the metal elements with the highest concentration in tear film compared to serum were Chrome, Manganese, Barium, and Lead. In this study, we attempted to evaluate the possible effect of a disease, such as diabetes, on the metabolism of metallic elements. Although our evidence was very interesting, it is probably limited in its accuracy due to the fact that individuals in the control group harboured ocular pathologies. This work lays the foundation for future studies.

Is aceruloplasminemia treatable? Combining iron chelation and fresh-frozen plasma treatment.

We report the case of a patient with hereditary ceruloplasmin deficiency due to a novel gene mutation in ceruloplasmin gene (CP), treated with fresh frozen plasma (FFP) and iron chelation therapy. A 59-year-old man with a past history of diabetes was admitted to our department due to progressive gait difficulties and cognitive impairment. Neurological examination revealed a moderate cognitive decline, with mild extrapyramidal symptoms, ataxia, and myoclonus. Brain T2-weighted MR imaging showed bilateral basal ganglia hypointensity with diffuse iron deposition. Increased serum ferritin, low serum copper concentration, undetectable ceruloplasmin, and normal urinary copper excretion were found. The genetic analysis of the CP (OMIM #604290) reported compound heterozygosity for two mutations, namely c.848G > A and c.2689_2690delCT. Treatment with FFP (500 mL i.v./once a week) and administration of iron chelator (Deferoxamine 1000 mg i.v/die for 5 days, followed by Deferiprone 500 mg/die per os) were undertaken. At the 6-month follow-up, clinical improvement of gait instability, trunk ataxia, and myoclonus was observed; brain MRI scan showed no further progression of basal ganglia T2 hypointensity. This case report suggests that the early initiation of combined treatment with FFP and iron chelation may be useful to reduce the accumulation of iron in the central nervous system and to improve the neurological symptoms.

Reduced-fluence verteporfin photodynamic therapy plus ranibizumab for choroidal neovascularization in pathologic myopia.

BACKGROUND: To demonstrate the efficacy of intravitreal ranibizumab (IVR) in combination with reduced-fluence photodynamic therapy (RF-PDT) in patients with choroidal neovascularization (CNV) secondary to pathologic myopia. METHODS: Sixty patients affected by myopic CNV (mCNV) were randomized to receive either ranibizumab 0.5 mg monotherapy (RM; n = 20), standard fluence PDT (SF-PDT, n = 20) or RF-PDT combination therapy (n = 20). Subsequently, IVR was injected as needed. All patients were evaluated for 48 weeks. RESULTS: Mean BCVA change at 48 weeks was + 0.2 and +15 letters with SF or RFPDT plus ranibizumab, respectively, compared with +16.8 letters with RM. At 48 weeks, mean central foveal thickness (CFT) decrease from baseline was 58 ± 15 µm, 91.4 ± 43.8 µm, and 85 ± 41.5 µm for the verteporfin SF, RF and RM groups, respectively. Macular sensitivity improvement was + 0.4 db, + 1.9 dB and + 2.7 dB for the verteporfin SF, RF and RM groups, respectively. CONCLUSIONS: Ranibizumab monotherapy or combined with RF-PDT improved BCVA and macular sensitivity in patients affected by mCNV, whereas CFT results were reduced. SF-PDT combination regimen mostly stabilized vision at 48 weeks. Among all groups, the RF-PDT seemed to reduce the number of ranibizumab retreatments.

Diabetic Retinopathy: Vascular and Inflammatory Disease.

Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted.

Effect of intravitreal bevacizumab on serum, aqueous, and vitreous humor levels of erythropoietin in patients with proliferative diabetic retinopathy.

AIM: The aim of this study was to evaluate concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in serum, aqueous and vitreous humour of diabetic patients with proliferative retinopathy (PDR) and to verify their possible modifications induced by intravitreal injection of bevacizumab (IVB). METHODS: This prospective observational study was performed on patients who underwent vitrectomy for proliferative diabetic retinopathy and macular hole or pucker. The study sample consisted of 33 patients with proliferative diabetic retinopathy and 20 non-diabetic patients with macular hole or pucker. EPO and VEGF levels in serum, aqueous and vitreous humour were measured in both groups. In diabetic patients measures were performed before and after IVB. RESULTS: EPO and VEGF levels in aqueous and vitreous humour were markedly increased in diabetic patients with PDR as compared with those recorded in the control group (P<0.001); contrarily, EPO serum levels were similar in both groups (p=not significant). IVB did not affect EPO levels (aqueous 39.1 ± 29.2 vs. 38.6 ± 26.1; vitreous 179.3 ± 88.3 vs. 131.6 ± 67.8; serum 9.2 ± 5.8 vs. 6.9 ± 3.7 mUI/mL); conversely, VEGF concentration significantly decreased 15 days after IVB in serum and ocular fluids (aqueous 141.6 ± 12.3 vs. 81.4 ± 5.4; vitreous 180.4 ± 45.8 vs. 95.8 ± 23.6; serum 113.9 ± 52.8 vs. 73.2 ± 65.6 mUI/mL). CONCLUSION: These findings demonstrate that the production of VEGF and EPO is regulated by different mechanisms. Intraocular levels of EPO in diabetic patients were significantly higher than those recorded in serum, suggesting a local production. In addition, bevacizumab does not influence intraocular levels of EPO.

Histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells.

BACKGROUND: Extracellular histones exert part of their prothrombotic activity through the stimulation of blood cells. Besides platelets, histones can bind to red blood cells (RBCs), which are important contributors to thrombogenesis, but little is known about the functional consequences of this interaction. OBJECTIVES: To evaluate the effect of histones on the procoagulant potential of human RBCs with particular regard to the expression of surface phosphatidylserine (PS). METHODS: PS exposure on human RBCs treated with a natural mixture of histones or recombinant individual histones was evaluated with fluorescein isothiocyanate-annexin-V binding and measured with flow cytometry. Calcium influx in RBCs loaded with the calcium-sensitive fluorophore Fluo-4 AM was assessed with flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated with a purified prothrombinase assay and a one-stage plasma recalcification clotting test. RESULTS: Natural histones induced PS exposure on RBCs in a dose-dependent manner, and neutralization or cleavage of histones by heparin or activated protein C, respectively, abolished PS externalization. H4 was mainly responsible for the stimulating activity of histones, whereas the other subtypes were almost ineffective. Similarly, natural histones and H4 induced influx of calcium into RBCs, whereas the other individual histones did not. Histone-induced exposure of PS on RBCs translated into increased prothrombinase complex-mediated prothrombin activation and accelerated fibrin formation in plasma. CONCLUSIONS: Histones induce RBCs to express a procoagulant phenotype through the externalization of PS. This finding provides new insights into the prothrombotic activity of extracellular histones.

Serum and intraocular concentrations of erythropoietin and vascular endothelial growth factor in patients with type 2 diabetes and proliferative retinopathy.

AIM: This study compared systemic and intraocular concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in patients with type 2 diabetes (T2D) and proliferative diabetic retinopathy (PDR) with levels in patients without diabetes, and looked for possible correlations between the concentrations found and other variables analyzed. METHODS: Concentrations of EPO and VEGF were measured in the aqueous and vitreous humours and serum of patients undergoing vitrectomy for PDR (33 patients) or for macular holes or puckers (20 control patients). EPO was assayed by radioimmunoassay, with a lower limit of detection (LOD) of 1.0 mIU/mL. VEGF was assayed using enzyme-linked immunosorbent assay (ELISA), with a lower LOD of 10.0 pg/mL. RESULTS: EPO concentrations in serum did not differ significantly between the two groups, whereas EPO in vitreous and aqueous were higher in diabetic than in non-diabetic patients. VEGF in serum was lower in diabetic patients than in non-diabetics; conversely, VEGF concentrations in vitreous were significantly higher in diabetic patients. A direct correlation was found between vitreous and aqueous EPO concentrations, and between vitreous EPO and blood glucose concentrations. A significant, negative correlation between vitreous EPO concentration and age was also recorded. CONCLUSION: High EPO concentrations in the vitreous of patients with PDR and its correlation with blood glucose suggest that EPO could play a role in the pathogenesis of PDR. All possible factors affecting serum and ocular concentrations of EPO and VEGF should be determined to identify compounds able to prevent and control this serious microvascular complication of diabetes.

Results from a pilot study on amiodarone administration in monogenic frontotemporal dementia with granulin mutation.

Frontotemporal dementia (FTD) is one of the most important neurodegenerative conditions and Granulin (GRN) is one of the major genes associated to the disease. FTD-GRN patients are still orphan for any evidence-based target-therapy approach. Interestingly, it has been recently found that alkalizing agents rescued haploinsufficiency in cellular models expressing FTD-GRN mutations. We set up a pilot phase II clinical trial in five FTD patients with GRN Thr272s(g.1977_1980delCACT) mutation, to determine if amiodarone (200 mg/day) may (1) reverse progranulin deficiency and (2) delay disease progression. Each patient was scheduled for 7 study visits over 12 months period. We assessed GRN levels at baseline and after amiodarone administration during the treatment course. Somatic and neurologic examinations, along with cognitive and behavioral assessment were recorded as well. No significant effect on peripheral GRN levels was observed. In treated FTD, disease course did not differ when compared with a group of untreated FTD-GRN patients. This is the first trial targeting progranulin rescue in FTD-GRN patients using amiodarone. Despite the negative findings, it may be interesting to extend this attempt to a larger sample of subjects and to other alkalizing agents to restore granulin haploinsufficiency.

Neurotrophic keratitis.

Neurotrophic keratitis (NK) is a rare degenerative corneal disease that occurs as a result of partial or total impairment of trigeminal innervations, leading to a reduction (hypoesthesia) in or loss (anaesthesia) of corneal sensitivity. The impairment of sensory innervation causes a reduction in the lacrimation reflex and the vitality, metabolism and mitosis of epithelial cells, with subsequent deficiency in epithelial repair, stromal and intracellular oedema, loss of microvilli, and abnormal development of the basal lamina. Several recent studies have proposed different therapies based on different aetiopathogenetic theories. The aim of the therapy is to treat aetiopathogenesis and, at the same time, promote corneal healing. In this paper, we report the aetiology, diagnosis, management, and medical and surgical treatment of NK, also indicating future treatments based on the most recent studies.