Uveitis Patterns and Severity: An Epidemiologic Study from a Tertiary Care Private Referral Center in Buenos Aires, Argentina.

PURPOSE: To report uveitis' spectrum in a private practice cohort in the city of Buenos Aires, Argentina. METHODS: Retrospective review at Instituto de la Visión (November 2011-October 2015). Standard demographics, ethnicity and Native American aboriginal ancestry were recorded. RESULTS: Among 212 patients, median age 45 (6-97), 10% pediatric, 35% bilateral, 72% non-idiopathic, 36% infectious. Anterior uveitis presented in 50%, followed by posterior (32%), intermediate (9%) and panuveitis (8%). Frequent visits (≥ 6 per year) needed by 29%: posterior, non-idiopathic disease with 79% systemic immunosuppression requirement was their main presentation. Native American aboriginal ancestry was reported by 22.64% of the whole cohort and 37% of frequent visits' subgroup. CONCLUSIONS: Unilateral, non-idiopathic, non-infectious anterior uveitis was the most frequent presentation, in agreement with reports coming from western developed cities. The multi-racial Argentinian population with specific Native American aboriginal ancestry might contribute to certain forms of posterior uveitis and their response to treatment.

An unexpected cause of constipation and abdominal distension in COPD.

Question: A 62-year old man presented to our tertiary care hospital for a second opinion regarding end stage COPD GOLD 4D. He had a medical history of former alcohol use complicated by liver steatosis and former smoking. Upon admission the patient complained of constipation and abdominal distension. Physical examination showed diffuse hypertympanic percussion and diffuse abdominal pain upon palpation without signs of peritoneal irrita- tion. CRP, hemoglobin, lactate, liver enzymes, and serum creatinine were within limits of normal. Abdominal radiography showed dilatation of the colon transversum with intramural and intra-abdominal free air (Figure 1). Contrast-enhanced abdominal CT showed extensive intramural air in the right hemicolon (Figure 2). Answer: The findings are consistent with pneumatosis intestinalis (PI). Conservative management with oxygen, triple bronchodilator therapy, fasting, laxation and antibiotic therapy resulted in resolution of the clinical symptoms.

SARS-CoV-2-related Multisystem Inflammatory Syndrome in Adult complicated by myocarditis and cardiogenic shock.

Multisystem Inflammatory Syndrome in Adult (MIS-A) is a rare COVID-19 complication, presenting as fever with laboratory evidence of inflammation, severe illness requiring hospitalization and multisystem organ involvement. We report on a 25-year-old man presenting with fever, rash, abdominal pain, diarrhoea and vomiting following prior asymptomatic COVID-19 infection. He developed refractory shock and type 1 respiratory insufficiency requiring mechanical ventilation. Diagnostic testing revealed significant inflammation, anemia, thrombocytopenia, acute kidney injury, hepatosplenomegaly, colitis, lymphadenopathy and myocarditis necessitating inotropy. Ventilatory, vasopressor and inotropic support was weaned following pulse corticosteroids and intravenous immunoglobulins. Heart failure therapy was started. Short-term follow-up shows resolution of inflammation and cardiac dysfunction.

ESTRO-ACROP guideline on surface guided radiation therapy.

Surface guidance systems enable patient positioning and motion monitoring without using ionising radiation. Surface Guided Radiation Therapy (SGRT) has therefore been widely adopted in radiation therapy in recent years, but guidelines on workflows and specific quality assurance (QA) are lacking. This ESTRO-ACROP guideline aims to give recommendations concerning SGRT roles and responsibilities and highlights common challenges and potential errors. Comprehensive guidelines for procurement, acceptance, commissioning, and QA of SGRT systems installed on computed tomography (CT) simulators, C-arm linacs, closed-bore linacs, and particle therapy treatment systems are presented that will help move to a consensus among SGRT users and facilitate a safe and efficient implementation and clinical application of SGRT.

Are intravitreal injections essential during the COVID-19 pandemic? Global preferred practice patterns and practical recommendations.

Tertiary outpatient ophthalmology clinics are high-risk environments for COVID-19 transmission, especially retina clinics, where regular follow-up is needed for elderly patients with multiple comorbidities. Intravitreal injection therapy (IVT) for chronic macular diseases, is one of the most common procedures performed, associated with a significant burden of care because of the vigorous treatment regimen associated with multiple investigations. While minimizing the risk of COVID-19 infection transmission is a priority, this must be balanced against the continued provision of sight-saving ophthalmic care to patients at risk of permanent vision loss. This review aims to give evidence-based guidelines on managing IVT during the COVID-19 pandemic in common macular diseases such as age-related macular degeneration, diabetic macula edema and retinal vascular disease and to report on how the COVID-19 pandemic has affected IVT practices worldwide.To illustrate some real-world examples, 18 participants in the International Retina Collaborative, from 15 countries and across four continents, were surveyed regarding pre- and during- COVID-19 pandemic IVT practices in tertiary ophthalmic centers. The majority of centers reported a reduction in the number of appointments to reduce the risk of the spread of COVID-19 with varying changes to their IVT regimen to treat various macula diseases. Due to the constantly evolving nature of the COVID-19 pandemic, and the uncertainty about the normal resumption of health services, we suggest that new solutions for eye healthcare provision, like telemedicine, may be adopted in the future when we consider new long-term adaptations required to cope with the COVID-19 pandemic.

[What will cataract surgery look like in the future? Alternatives in the pipeline]. / Que sera la chirurgie de la cataracte du futur ? Alternatives et voies de développement.

Phacoemulsification is the most frequently performed surgery in the world. Over the past few years, this surgery seems to have reached a plateau with no further innovative breakthroughs. In this paper, we focus on alternatives techniques, the latest innovations, and the research and development pipeline in this field.

IL4-10 fusion protein: a novel immunoregulatory drug combining activities of interleukin 4 and interleukin 10.

The objective of this study was to test the capacity of a newly developed fusion protein of interleukin 4 (IL-4) and IL-10 [IL4-10 fusion protein (FP)] to shift multiple pro-inflammatory pathways towards immune regulation, and to inhibit pro-inflammatory activity in arthritis models. The effects of IL4-10 FP in comparison with IL-4, IL-10 and IL-4 plus IL-10 on pro- and anti-inflammatory mediators, T cells and immunoglobulin (Ig) receptors in favour of immunoregulatory activity were studied. In addition, the capacity of IL4-10 FP to inhibit pro-inflammatory activity in ex-vivo and in-vivo arthritis models was investigated. IL4-10 FP robustly inhibited pro-inflammatory cytokine [IL-1ß, tumour necrosis factor (TNF)-α, IL-6 and IL-8] production in whole blood cultures, mediated by both the IL-10 and the IL-4 moiety. IL4-10 fusion protein induced IL-1 receptor antagonist (IL-1RA) production and preserved soluble TNF receptor (sTNFR) levels, strongly increasing IL-1RA/IL-1ß and sTNFR/TNF-α ratios. In addition, IL4-10 FP strongly inhibited T helper (Th) type 1 and 17 cytokine secretion, while maintaining FoxP3 expression and up-regulating Th2 activity. In addition, while largely leaving expression of activating Fc gamma receptor (FcγR)I, III and Fc epsilon receptor (FcεR) unaffected, it significantly shifted the FcγRIIa/FcγRIIb ratio in favour of the inhibitory FcγRIIb. Moreover, IL4-10 FP robustly inhibited secretion of pro-inflammatory cytokines by rheumatoid arthritis synovial tissue and suppressed experimental arthritis in mice, without inducing B cell hyperactivity. IL4-10 fusion protein is a novel drug, signalling cells to induce immunoregulatory activity that overcomes limitations of IL-4 and IL-10 stand-alone therapy, and therefore has therapeutic potential for inflammatory diseases such as rheumatoid arthritis.

First-in-human study of the safety and viability of intraocular robotic surgery.

Microsurgery of the retina would be dramatically improved by instruments that offer supra-human precision. Here, we report the results of a first-in-human study of remotely controlled robot-assisted retinal surgery performed through a telemanipulation device. Specifically, 12 patients requiring dissection of the epiretinal or inner limiting membrane over the macula were randomly assigned to either undergo robot-assisted-surgery or manual surgery, under general anaesthesia. We evaluated surgical success, duration of surgery and amount of retinal microtrauma as a proxy for safety. Surgical outcomes were equally successful in the robotic-surgery and manual-surgery groups. Differences in the amount of retinal microtrauma between the two groups were statistically insignificant, yet dissection took longer with robotic surgery (median time, 4 min 5 s) than with manual surgery (1 min 20 s). We also show the feasibility of using the robot to inject recombinant tissue plasminogen activator under the retina to displace sight-threatening haemorrhage in three patients under local anaesthesia. A safe and viable robotic system for intraocular surgery would enable precise and minimally traumatic delivery of gene therapy or cell therapy to the retina.

Does the total dysphagia risk score correlate with swallowing function examined by videofluoroscopy?

OBJECTIVE: The purpose of this study was to correlate the total dysphagia risk score (TDRS) with swallowing function as measured by videofluoroscopy of swallowing using the swallowing performance scale (SPS) and the penetration aspiration scale (PAS). METHODS: 63 patients from two different centres treated with radiotherapy for head and neck cancer were evaluated in the current study. Swallowing videofluoroscopies at baseline, 6 and 12 months following radiotherapy were evaluated by two observers. The TDRS of all patients was calculated and correlated with the consensus PAS and SPS scores of the two observers. RESULTS: Regarding the PAS scale, we did not observe a significant correlation with the TDRS. Regarding SPS, we found a significant correlation at 6 months (p = 0.01) and a borderline significant correlation at 12 months (p = 0.05). We observed statistically lower SPS scores for patients in the intermediate-risk category when compared to the high-risk category. When we compared low vs high TDRS risk patients, we did not observe a significant difference regarding SPS scores. When comparing low- vs intermediate-risk patients, we observed higher SPS scores in the low-risk group (p = 0.01). When the low- and intermediate-risk patients were grouped together, we observed less swallowing problems as measured by SPS in the low and intermediate group when compared to the high-risk group (p = 0.05) at 6 months. CONCLUSION: Patients with high-risk TDRS scores have higher SPS scores when compared to the intermediate group and the intermediate- and low-risk group together. However, low-risk patients in our patient cohort could not be distinguished from high or intermediate-risk patients. Advances in knowledge: TDRS was never correlated with videofluoroscopies in past studies. The hypothesis of this paper was to see if the TDRS could guide us to see which patients are at risk for high scores on SPS and PAS and might need a videofluoroscopic examination in the follow up. Given the poor correlations in our study, however, we cannot recommend the use of the TDRS to select patients who might benefit from the additional information provided by videofluoroscopies.

Sex steroids in relation to cardiac structure and function in men.

The prevalence of testosterone substitution as well as of androgen deprivation therapy in men is increasing. This review aims to summarise available knowledge of the effects of sex steroids on cardiac structure and function in men. MEDLINE was searched through PubMed. Original studies, systematic reviews and meta-analyses, and relevant citations were screened. A short-term hormonal intervention study in healthy young men with respect to echocardiographic parameters of structure and function was performed. Preclinical research provides sufficient evidence for the heart as a substrate for sex hormones. In animals, administration of oestradiol appears to have beneficial effects on cardiac structure and function, whereas administration of testosterone to noncastrated animals adversely affects cardiac function. However, the effects of sex steroids on cardiac function and structure appear more heterogeneous in human observational studies while comparative, prospective studies in humans are lacking. It is concluded that although effects of testosterone substitution as well as of androgen deprivation on cardiac structure and function can be expected based on pre-clinical research, there exists an important knowledge gap of the effects of hormonal intervention in men. As such, there is a need to address this question in future prospective intervention trials.

Focused ultrasound mediated drug delivery from temperature-sensitive liposomes: in-vitro characterization and validation.

Nanomedicine-based delivery with non-invasive techniques is a promising approach to increase local drug concentration and to reduce systemic side effects. Focused ultrasound (FUS) has become a promising strategy for non-invasive local drug delivery by mild hyperthermia. In this study, traditional temperature-sensitive liposomes (TTSLs) encapsulating doxorubicin (DOX) were evaluated for FUS-mediated drug delivery with an in-vitro FUS setup. In-vitro studies showed quantitative release of the DOX from the lumen of the temperature-sensitive liposomes when heated to 42 °C with FUS using 1 MHz sinusoidal waves at 1.75 MPa for 10 min. No release was observed when heated at 37 °C. Moreover, we showed that DOX released from TTSLs by FUS is as efficiently internalized by glioblastoma cells as free DOX at 37 °C. In-vitro therapeutic evaluation showed that exposure of a cell monolayer to FUS-activated TTSLs induced a 60% and a 50% decrease in cell viability compared to cell medium and to TTSLs preheated at 37 °C, respectively. Using an in-vitro 3D cell culture model, the results showed that after FUS-mediated hyperthermia, preheated liposomes induced a 1.7-fold decrease in U-87 MG spheroid growth in comparison to the preheated liposomes at 37 °C. In conclusion, our results show that in-vitro FUS allows the evaluation of TTSLs and does not modify the cellular uptake of the released DOX nor its cytotoxic activity.

Simultaneous T1 measurements and proton resonance frequency shift based thermometry using variable flip angles.

A method is presented which allows precise temperature and longitudinal (T(1)) relaxation time measurements with high spatial and temporal resolution. This is achieved by combining dynamic variable flip angle based T(1) relaxation mapping with proton resonance frequency shift based thermometry. Herein, dynamic T(1) mapping is either used as a complementary measure of temperature or for the detection of T(1) contrast agent release. For the first application, the temperature evolution during a high-intensity focused ultrasound tissue ablation experiment was measured in both, porcine fat and muscle, simultaneously. In this application, temperature accuracies of 2.5 K for T(1)-based thermometry in fat and 1.2 K for proton resonance frequency shift-based thermometry in muscle were observed. The second application relates to MR-guidance of high-intensity focused ultrasound-induced local drug delivery by means of thermo-sensitive liposomes labeled with a T(1) contrast agent (Gd-HPDO3A). When the measured temperature exceeded the phase transition temperature of the liposomes, T(1) was observed to decrease with a good temporal and spatial correlation due to the release of Gd-HPDO3A. The presented results demonstrate the feasibility of the proposed method for two important applications in MR-guided noninvasive therapy. It offers a high temporal resolution when compared with interleaved Look-Locker based T(1) mapping techniques and thus represents an interesting candidate for simultaneous real-time monitoring of T(1) and temperature changes.

The effects of TPA023, a GABAAα2,3 subtype-selective partial agonist, on essential tremor in comparison to alcohol.

Essential tremor (ET) is a relatively frequent neurological disorder that responds in some patients to gamma-aminobutyric acid A (GABA(A)) agonists such as the benzodiazepines. Partial subtype-selective GABA(A) agonists may have an improved side effect profile compared to non-selective GABA(A) agonists. However, it is unknown which GABA(A) subtypes are involved in the therapeutic effects of benzodiazepines in ET. The effects of 2 mg TPA023, a GABA(A) α2,3 subtype-selective partial agonist, on ET were compared to the effects of a stable alcohol level (0.6 g/L) and placebo in nine patients with ET. Tremor evaluation included laboratory accelerometry and a performance-based scale. Additional measurements were performed to evaluate other effects on the central nervous system (CNS). Alcohol significantly diminished tremor symptoms in the postural and kinetic condition, as assessed by laboratory accelerometry, but the performance-based rating scale was unaffected. Tremor was also reduced after TPA023 treatment in the kinetic condition, albeit not significantly. Additionally, TPA023 decreased saccadic peak velocity, while alcohol decreased subjective feelings of alertness. This study showed that alcohol reduced maximum tremor power, as assessed by laboratory accelerometry, unlike TPA023, which decreased tremor symptoms to some extent but not significantly. This study showed that treatment with an α2,3 subunit-selective GABA(A) partial agonist was less effective than a stable level of alcohol in reducing ET symptoms. These results provide no support for a therapeutic role of TPA023 in the suppression of ET symptoms.

The additional value of blood culture bottles in the diagnosis of endophthalmitis.

PURPOSE: To assess the additional value of blood culture bottles (BCBs) in the diagnosis of endophthalmitis by comparing its culture yield with that of conventional media (CM). DESIGN: Retrospective consecutive case series. METHODS: We included patients who were treated between January 2001 and January 2010 for clinically suspected endophthalmitis of any etiology, and had vitreous specimens cultivated in both BCB and CM. RESULTS: Specimens from 85 eyes from 85 patients were included. The culture yield of BCB was 69%, and that of CM was 72% (difference not significant). Adding the results of BCB improved the yield of CM significantly by 13%, resulting in a combined yield of 81%. The sensitivity of detection of Haemophilus influenzae in BCB seemed lower compared with CM, possibly due to the lack of growth factors in the BCB. There was no difference in yield between specimens obtained by tap or by vitrectomy. CONCLUSION: In contrast with earlier reports, we did not find BCB superior to CM. The combined use of BCB and CM increased the pathogen detection rate significantly and should therefore be considered as the microbiological method of choice in the work-up of endophthalmitis.

Ultrasound-mediated intracellular drug delivery using microbubbles and temperature-sensitive liposomes.

A novel two-step protocol for intracellular drug delivery has been evaluated in vitro. As a first step TO-PRO-3 (a cell-impermeable dye that displays a strong fluorescence enhancement upon binding to nucleic acids) encapsulated in thermosensitive liposomes was released after heating to 42°C. A second step consisted of ultrasound-mediated local permeabilization of cell membrane allowing TO-PRO-3 internalization observable as nuclear staining. Only the combination of two consecutive steps - heating and sonication in the presence of SonoVue microbubbles led to the model drug TO-PRO-3 release from the thermosensitive liposomes and its intracellular uptake. This protocol is potentially beneficial for the intracellular delivery of cell impermeable drugs that suffer from rapid clearance and/or degradation in blood and are not intrinsically taken up by cells.

Intestinal barrier function in patients undergoing colectomy.

AIM: The aim of this pilot study was to determine whether the type of approach (open or laparoscopic) and the order of devascularization during laparoscopic colectomy affect intestinal barrier function, local inflammatory response and clinical outcome. METHOD: Twenty-two patients undergoing elective colectomy from April 2006 to July 2008 were randomized to two sequences of vascular ligation, starting with either the inferior mesenteric artery or the ileocolic artery. Eighteen patients scheduled for open surgery served as a prospective control group. To assess the intestinal barrier function, release of intestinal fatty-acid binding protein (I-FABP; a marker of mucosal injury and ischaemia) was measured pre- and postoperatively. Mesenteric lymph nodes were harvested to assess the expression of inflammatory mediator-related genes using multiplex ligation probe amplification. The study was registered under NTR1025. RESULTS: Laparoscopic devascularization starting at the ileocolic artery resulted in a significantly increased excretion of I-FABP over time (P = 0.002). In this group, the I-FABP levels were significantly increased on postoperative days 1 and 3 compared with preoperative values (P = 0.011 and P = 0.001, respectively). There were no differences in expression of inflammatory mediator-related genes or postoperative morbidity among the groups. CONCLUSIONS: In this pilot study, devascularization commencing at the ileocolic artery during laparoscopic colectomy was associated with prolonged intestinal mucosal ischaemia.

Use of heavy Trypan blue in macular hole surgery.

PURPOSE: Intraocular dyes facilitate the identification of the inner limiting membrane (ILM) during surgery. Appropriate dyes should be safe, provide adequate staining, and be easy to use. Heavy Trypan blue eliminates the need for an air-fluid exchange (AFX) and appears to have little retinal toxicity. This study refers to a prospective, consecutive trial with heavy Trypan blue in macular hole surgery. PATIENTS AND METHODS: A consecutive group of 20 patients with full thickness macular holes was recruited in a single institution study. Patients were operated using conventional methods. Heavy Trypan blue was prepared by mixing isovolumetrically glucose 10% with MembraneBlue (DORC, Zuidland, The Netherlands). Patients were assessed for ease of surgery and post-operatively at 3 and 6 months (vision and ocular coherence tomography) for hole closure and vision. RESULTS: Twenty eyes were included in the study. Reapplication of dye was used in 75% of the cases, leading to improved contrast further facilitating the ILM peel. In no case was an AFX necessary to obtain sufficient staining. Macular hole closure was achieved in 19 of 20 patients with one surgery. No retinal detachment or other complication was observed in the follow-up period. CONCLUSION: Heavy Trypan blue can be delivered efficiently to the retinal surface without the need for an AFX. Staining was sufficient to help visualise and peel the ILM. Repeat applications were easily performed. The macular hole closure rate was similar to that of other series with a comparable visual improvement.