Purpose
The International Neonatal Consortium recently published a proposed retinopathy of prematurity (ROP) activity scale intended for use in clinical trials after validation. The aim of this study ...was to validate the ROP activity scale (ROP‐ActS) in a ROP screened cohort with protocol based collected data by evaluating the ability of the ROP‐Act scores to predict ROP treatment. In addition, we aimed to evaluate the scale’s sensitivity characteristic of disease severity by studying association with gestational age (GA) in comparison with conventionally used ROP stage and zone.
Methods
A cohort of 535 preterm infants with 3324 ROP examinations with an end‐point of ROP treatment or end of screening in Gothenburg, Sweden, was included. Median GA was 28.1 weeks, 47.5% were girls, and 74 (13.8%) infants were treated for ROP. The validation was performed by estimating probabilities for ROP treatment, and by applying logistic and linear regression.
Results
The original ROP‐ActS was overall well‐ordered with respect to ability to predict ROP treatment but could be improved by re‐ordering score 3 (zone II stage 1) and 5 (zone III stage 3) based on our clinical cohort data. The modified ROP‐ActS was superior to ROP stage and zone in the prediction analysis of ROP treatment. Modified ROP‐ActS was more strongly related to GA than currently used ROP stage, but not zone.
Conclusion
In the studied cohort, the modified ROP‐ActS could better predict ROP treatment compared to ROP stage and zone. Retinopathy of Prematurity Activity Scale (ROP‐ActS) had a superior sensitivity characteristic studied through association to GA than conventionally used ROP stage.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
This study advances research in offensive technology by proposing return oriented programming (ROP) as a means to achieve code obfuscation. The key inspiration is that ROP's unique structure poses ...various challenges to malware analysis compared to traditional shellcode inspection and detection. The proposed ROP-based attack vector provides two unique features: (i) the ability to automatically analyse and generate equivalent ROP chains for a given code, and (ii) the ability to reuse legitimate code found in an executable in the form of ROP gadgets. To this end, a software tool named ROPInjector was developed which, given any piece of shellcode and any legitimate executable file, it transforms the shellcode to its ROP equivalent re-using the available code in the executable and finally patches the ROP chain infecting the executable. After trying various combinations of evasion techniques, the results show that ROPInjector can evade nearly and completely all antivirus software employed in the online VirusTotal service, making ROP an effective ingredient for code obfuscation. This attack vector poses a serious threat which malicious actors can take advantage to perform cyber-attack campaigns.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To report reactivation rate after bevacizumab treatment for retinopathy of prematurity (ROP) in eyes with classic ROP (CROP) versus aggressive posterior ROP (APROP) and to report peripheral ...fluorescein angiography findings in these eyes.
Retrospective chart review was conducted on consecutive infants treated with bevacizumab for ROP, followed by fluorescein angiography and prophylactic laser to persistent avascular retina.
Sixty-four eyes of 33 patients were included. Mean gestational age was 25 weeks with mean birth weight of 674 g. Mean follow-up was 125 weeks post-menstrual age (PMA). Reactivation requiring treatment after initial bevacizumab was more common in eyes with APROP (8/16) than with CROP (2/48; P < 0.0001). At mean 73 weeks PMA, eyes with APROP had more avascular retina (mean 4.4 disk diameters vs. 2.6 disk diameters; P = 0.0004) and higher percentage of leakage (11/11 eyes vs. 22/38 eyes; P = 0.01) on fluorescein angiography than in eyes with CROP. Unfavorable outcome occurred in 1 of 16 eyes with APROP and in no eyes with CROP. No eye that underwent prophylactic laser after bevacizumab had a poor structural outcome.
In our study, bevacizumab-treated eyes with APROP have a higher likelihood of recurrence and larger area of persistent nonperfusion than in eyes with CROP. Treatment of ROP with bevacizumab followed by prophylactic laser has a low rate of unfavorable structural outcome.
To determine trends in retinopathy of prematurity (ROP) in a Colorado cohort between 2006 and 2017 and compare trends in risk factors between our cohort and statewide data.
A retrospective cohort ...study was conducted by the use of records from two registry databases: 1) an academic center's ROP registry, and 2) vital statistics birth data from the Colorado Department of Public Health and Environment (CDPHE). ROP was categorized as severe (type 1 or type 2), low grade (not type 1 or type 2), or no ROP. Other variables included in the analyses were gestational age and birth weight at delivery, and infant mortality. Trends over time were evaluated for both registry databases using generalized linear models.
In our ROP registry cohort of 1,267 eligible infants, 134 (10.6%) developed severe ROP and 279 (22%) developed low-grade ROP. We found no overall trend in severe ROP rates (p = .23), and a decreasing trend in rates of low-grade ROP (p < .01) over the study period. Trends in gestational age, birth weight, and mortality rates remained stable during the study period in both the ROP registry and the CDPHE cohorts.
The rate of severe ROP in our ROP registry cohort did not change over time. There was evidence of a decreasing trend in low grade ROP during the 12-year study period that was not explained by a change in the primary ROP risk factors in either the ROP registry cohort or the Colorado statewide data.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aggressive retinopathy of prematurity (AROP) is a severe and progressive variant of retinopathy of prematurity (ROP) rapidly forming fibrous tissue extending from the disc toward the posterior lens ...surface progressing to Stage 5 disease without traversing the classical course that includes Stages 1 to 3. Since AROP behaves differently from type 1 ROP, this study was undertaken to evaluate the surgical outcome of AROP-related detachments.
Retrospective analysis of data from electronic medical records of babies diagnosed with AROP-related detachments who underwent micro-incision vitrectomy surgery (MIVS) was included. The demographic data, details of primary intervention (laser and/or intravitreal bevacizumab), and surgery were noted. In a subset of patients, surgical intervention was planned early at the onset of fibrovascular tissue.
43 eyes of 26 babies with median birth weight 1175 g and median gestational age of 29 weeks were analyzed. 42/43 eyes underwent primary intervention in form of laser and/or anti-VEGF injection before surgery. 41.8%, 25.5%, and 32.5% eyes progressed to stages 4A, 4B, and 5, respectively, requiring surgical intervention. 66% eyes underwent lensectomy and vitrectomy (LV), and 44% eyes underwent lens sparring vitrectomy (LSV). 58% eyes had attached macula. 44% eyes that had a relatively less vascular diseases had better anatomical outcome (P = 0.019). At final follow-up, 53.4% eyes followed or at least had light fixation, and 77.7% eyes undergoing LSV fixated and/or followed light compared to 33% for LV (P = 0.04).
Challenges in AROP include rapid progression to advanced stages of ROP requiring close monitoring and multiple interventions. Surgeries for AROP have a favorable anatomical and functional outcome in 58% and 53%, respectively. Eyes undergoing lens sparing vitrectomy had better visual outcomes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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Miktoarm star polymers display asymmetric architectures with combinations of multiple polymeric arms of different chemical nature emanating from a shared core. Their unique ...structure–property relationships in comparison to linear counterparts (with same molecular weight) make these architectures interesting for the design of novel polymeric species and the development of nanosized delivery systems. However, the synthesis of such structures is often demanding. Based on polypept(o)ides, we herein report on the synthesis of AA'B- and ABC-type miktoarm star polymers by introducing a multifunctional lysine end group to a polysarcosine (pSar) chain end, comprising orthogonal amine-protective groups. Therefore, each polymeric arm could be synthesized separately by living ring-opening polymerization (ROP) of respective N-carboxyanhydrides (NCAs), offering high reaction control and a resulting structure completely based on amino acids. We demonstrate the utility and versatility of this approach by designing a small, asymmetric and big AA'B miktoarm star polymer comprising two pSar arms with chain lengths of ∼50 or ∼150 in different combinations and a poly(Nε-trifluoroacetate-lysine) (pLys(TFA)) arm, as well as an ABC architecture by introducing a poly(γ-benzyl-glutamate) (pGlu(OBn)). 1H NMR, including 1H DOSY experiments, as well as size-exclusion chromatography (SEC) proof the successful and controlled synthesis of asymmetric miktoarm star polymers with precise control over degree of polymerization of the individual arms with narrow molecular weight distributions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To evaluate the feasibility and outcome of a real-time retinopathy of prematurity (ROP) telescreening strategy using videoconferencing in a community setting in India.
In a prospective study, trained ...allied ophthalmic personnel obtained the fundus images in the presence of the parents and local childcare providers. Analysis of images and parental counseling were done in real time by an ROP specialist located at a tertiary center using videoconferencing software. A subset of babies was also examined using bedside indirect ophthalmoscopy by an ROP care-trained ophthalmologist. The data were analyzed using descriptive statistics, sensitivity, specificity, positive and negative predictive values, and correlation coefficient.
Over 9 months, we examined 576 babies (1152 eyes) in six rural districts of India. The parents accepted the model as they recognized that a remotely located specialist was evaluating all images in real time. The strategy saved the travel time for ROP specialists by 477 h (47.7 working days) and for parents (47,406 h or 1975.25 days), along with the associated travel cost. In a subgroup analysis (100 babies, 200 eyes), the technology had a high sensitivity (97.2%) and negative predictivity value (92.7%). It showed substantial agreement (k = 0.708) with the bedside indirect ophthalmoscopy by ROP specialists with respect to the detection of treatment warranting ROP. Also, the strategy helped train the participants.
Real-time ROP telescreening using videoconferencing is sensitive enough to detect treatment warranting ROPs and saves skilled workforce and time. The real-time audiovisual connection allows optimal supervision of imaging, provides excellent training opportunities, and connects ophthalmologists directly with the parents.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
2‐methyltetrahydrofuran (2‐MeTHF) is a readily available, inexpensive, neoteric, bio‐based solvent. It has been adopted across a wide range of chemical processes including the batch manufacture of ...fine chemicals, enzymatic polycondensations and ring opening polymerizations. To reduce the environmental burden related to the synthesis of pharmaceutical‐grade polymers based on lactide and caprolactone, we envisaged the use of 2‐MeTHF. For the first time, we combined a series of metal‐free and enzymatic ROPs with free radical and controlled RAFT polymerizations (carried out separately and in tandem) in 2‐MeTHF, in order to easily tune the chemistry and the architecture of the final polymers. After a simple purification, the amphiphilic polymers were formulated into nanoparticles and tested for their cytocompatibility in three model cell lines, to assess their application as potential polymeric excipients for nanomedicines.
In this article, the suitability of 2‐MeTHF was tested as a green solvent for organo‐and enzymatically catalyzed ROP of simple diblocks and in the production of more interesting A–B–C block copolymers using a single or double catalyst system. Labileester ROP initiators HEMA and PEGMA were also used to initiate LA macromonomers. To further demonstrate the versatility of 2‐MeTHF as “multipolymerization” green solvent, the produced macromonomers were tested in FRP and RAFT tandem polymerization.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Artificial Intelligence (AI) is a revolutionary technology that has the potential to develop into a widely implemented system that could reduce the dependence on qualified professionals/experts for ...screening the large at-risk population, especially in the Indian scenario. Deep learning involves learning without being explicitly told what to focus on and utilizes several layers of artificial neural networks (ANNs) to create a robust algorithm that is capable of high-complexity tasks. Convolutional neural networks (CNNs) are a subset of ANNs that are particularly useful for image processing as well as cognitive tasks. Training of these algorithms involves inputting raw human-labeled data, which are then processed through the algorithm's multiple layers and allow CNN to develop their own learning of image features. AI systems must be validated using different population datasets since the performance of the AI system would vary according to the population. Indian datasets have been used in AI-based risk model that could predict whether an infant would develop treatment-requiring retinopathy of prematurity (ROP). AI also served as an epidemiological tool by objectively showing that a higher ROP severity was in Neonatal intensive care units (NICUs) that did not have the resources to monitor and titrate oxygen. There are rising concerns about the medicolegal aspect of AI implementation as well as discussion on the possibilities of catastrophic life-threatening diseases like retinoblastoma and lipemia retinalis being missed by AI. Computer-based systems have the advantage over humans in not being susceptible to biases or fatigue. This is especially relevant in a country like India with an increased rate of ROP and a preexisting strained doctor-to-preterm child ratio. Many AI algorithms can perform in a way comparable to or exceeding human experts, and this opens possibilities for future large-scale prospective studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The incidence of retinopathy of prematurity (ROP) continues to rise due to the improved survival of very low birth weight infants in developed countries. This epidemic is also fueled by increased ...survival of preterm babies with variable use of oxygen and a lack of ROP awareness and screening services in resource-limited regions. Improvements in technology and a basic understanding of the disease pathophysiology have changed the way we screen and manage ROP, educate providers and patients, and improve ROP awareness. Advancements in imaging techniques, expansion of telemedicine services, and the potential for artificial intelligence-assisted ROP screening programs have created opportunities to improve ROP care in areas with a shortage of ophthalmologists trained in ROP. To address the gap in provider knowledge regarding ROP, the Global Education Network for Retinopathy of Prematurity (GEN-ROP) created a web-based tele-education training module that can be used to educate all providers involved in ROP, including non-physician ROP screeners. Over the past 50 years, the treatment of severe ROP has evolved from limited treatment modalities to cryotherapy and laser photocoagulation. More recently, there has been growing evidence to support the use of anti-vascular endothelial growth factor (VEGF) agents for the treatment of severe ROP. However, VEGF is known to be important in organogenesis and microvascular maintenance, and given that intravitreal anti-VEGF treatment can result in systemic VEGF suppression over a period of at least 1–12 weeks, there are concerns regarding adverse effects and long-term ocular and systemic developmental consequences of anti-VEGF therapy.
Future research in ophthalmology to address the growing burden of ROP should focus on cost-effective fundus imaging devices, implementation of artificial intelligence platforms, updated treatment algorithms with optimal use of anti-VEGF and careful investigation of its long-term effects, and surgical options in advanced ROP. Addressing these unmet needs will aid the global effort against the ROP epidemic and optimize our understanding and treatment of this blinding disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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