bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiological work‐up for proton beam therapy of uveal melanoma patients
Authors: Jaarsma‐Coes Myriam , Marinkovic Marina , Ferreira Teresa , Vu Khanh , van Vught Luc , van Haren Guido , Rodrigues Myra , Klaver Yvonne , Verbist Berit , Luyten Gregorius , Rasch Coen , Beenakker Jan‐Willem
Published: January 2022

Purpose

In ocular proton beam therapy (PBT), 2.5 mm tantalum clips are surgically sutured near the tumour border for clinical target volume marking. The clip‐tumour distances are assessed peroperative using transillumination, indentation and or fundoscopy. To support the clip localisation, target definition and 3D tumour modelling, a dedicated MRI‐protocol was developed and evaluated.

Methods

23 consecutive uveal melanoma (UM) patients, planned for PBT, were scanned on a 3T MRI. MRI based clip‐tumour distances were compared with the peroperative measurements. For clips with more than 1mm difference, the most likely origin of this discrepancy was discussed in a multidisciplinary setting.

Results

In 39/87 (45%) of the clips, both measurements differed more than 1 mm. For the majority of these clips, the MRI showed a larger clip‐tumour distance (n = 30). Largest differences were observed in flat UM (n = 13) where an average absolute difference of 3.9 mm was found. Here, MRI was generally considered less reliable as the extend of flat tumours is difficult to determine on MRI. In 15% of the clips, the discrepancy was attributed to a complex tumour geometry. Here an average absolute difference of 3.2 mm was observed. In these cases 3D imaging provided valuable additional information for the treatment planning. In 10% of the clips, the anterior localized tumour casted a shadow, resulting in an overestimation of the tumour dimensions during surgery, leading to an average absolute difference of 3.7 mm. For these patients, MR‐imaging was considered more reliable as obtaining correct peroperative measurements was difficult.

Conclusions

MRI and peroperative measurements were equal in 55% of the cases. For flat UM, MRI generally underestimates tumour dimensions. For complex and anterior UM, MRI‐based clip‐tumour measurements are more reliable, which could result in more accurate target definition, thereby possibly reducing toxicity and improving probability to retain vision.
Decreased docosahexaenoic acid and other specific fatty acids in a mouse model of retinal degeneration
Authors: José Ruiz Pastor María , Kutsyr Oksana , Albertos‐Arranz Henar , Sánchez‐Sáez Xavier , Sánchez‐Castillo Carla , Martínez‐Gil Natalia , Fernández‐Sánchez Laura , Noailles Agustina , Maneu Victoria , Lax Pedro , Cuenca Nicolas
Published: January 2022

Purpose

Retinal degeneration compromises retinal metabolism and signaling, including lipid pathways. Fatty acids are highly enriched in the retina and they impact photoreceptor survival. In this study, we aimed to identify fatty acids that could be relevant in retinal degeneration. For this purpose, we analyzed the fatty acid profile of the retina of rd10 mice, model of retinitis pigmentosa.

Methods

Fatty acids of the retina of C57BL/6J and rd10 mice were extracted by the Folch method and analyzed by GC/MS. Morphological changes were studied by immunohistochemistry.

Results

In the retina of rd10 mice, there was a drop of photoreceptor rows compared to healthy retinas. Rhodopsin, a protein expressed in outer segments, was delocalized into the cell bodies of photoreceptors in dystrophic retinas, and axons and outer segments of cones were shortened. In these animals, we found a decrease of specific saturated, monounsaturated and polyunsaturated fatty acids. Remarkably, docosahexaenoic acid (DHA) experienced a marked drop, leading to a heightening of the n‐3/n‐6 ratio, an indicator of inflammation. We found a positive correlation of cerotic acid, hypogeic acid, and DHA with photoreceptor rows.

Conclusions

Specific saturated and unsaturated fatty acids dropped in retinitis pigmentosa. Remarkably, diminished levels of the omega‐3 DHA could be contributing to the neurodegeneration process due to a shift to pro‐inflammatory pathways and a lack of neuroprotective signals, promoting photoreceptor death. Fatty acids could have decisive roles in the retinal degeneration outcome and should be considered to improve therapy.

MICINN‐FEDER PID2019‐106230RB‐I00; RETICS‐FEDER RD16/0008/0016; ACIF/2020/203; IDIFEDER/2017/064; FPU16/04114; FPU18/02964.
Biosimilars of anti‐vascular endothelial growth factors for ophthalmic disease – Clinical trial status 2021
Authors: McFadyen James , Votruba Marcela , Muenzberg Michael , Cornes Paul
Published: January 2022

Purpose

Global spending on retinal biologic medicines is expected to reach $28M USD by 2025. The first biosimilars (BioSim) of anti‐vascular endothelial growth factors (anti‐VEGF) are expected to launch in Europe in 2022; cutting costs and improving access to treatment. Physician surveys show concerns over Biosimilars – due to abbreviated regulatory pathways with confirmatory clinical trials directed to discover equivalence between drugs and rather than prove primary efficacy and safety. Pooling data from multiple trials permits greater clinical assessment.

Methods

BioSim of anti‐VEGF in development were identified searching Clinical Trials databases. Trials were compared for design, endpoints, size, power and equivalence margins.

Results

We identified 3307 patients with AMD in 7 parallel randomised trials of Ranibizumab BioSim vs Original Reference Product (RP) (range 25–705). Primary endpoints were Change in Best Corrected Visual Acuity (BCVA) using the ETDRS protocol. The timepoint varied between 2 and 12 months; but 5 of 6 trials (n = 2626) reported secondary endpoints at both 2 and 12 months.

There were 2326 patients in 6 parallel randomised trials of aflibercept BioSim vs RP (range 30–566); 5 studied AMD (n = 2002), 1 Diabetic Macular Oedema (n = 324); Primary endpoints were BCVA at 2 months in all.

To 31 May 31 2021 two trials report outcome and toxicity data on 905 patients. BCVA absolute difference is 0.59 letters at 8 weeks, with equivalence within prespecified limits in each trial.

Conclusions

5633 patients have been recruited into 13 randomised parallel ophthalmic trials of biosimilars of anti‐VEGF. All ranibizumab and aflibercept trials share identical primary or secondary end‐points, enabling direct rather than networked metanalysis to better assess the comparability, safety and efficacy of the regulatory process.
Ten differentially expressed proteins in the tear film of dogs with diabetic retinopathy
Authors: Winiarczyk Dagmara , Winiarczyk Mateusz , Michalak Katarzyna , Balicki Ireneusz , Szadkowski Mateusz , Winiarczyk Stanisław , Adaszek Łukasz , Winiarczyk Stanisław
Published: January 2022

Purpose

A common early lesion of diabetic retinopathy in human patients and a diverse range of animal models is retinal capillary basement membrane thickening occur within 6 months of induction of diabetes. This hallmark pathology of diabetic microvascular disease is used in the evaluation of drug‐mediated modulation of diabetic retinopathy in a range of animal models. Moreover results from published clinical practice have shown that more than 22% of dogs with naturally contracted diabetes mellitus develop ophtalmoscopic signs of retinal hemorrhages or microaneurysms in a relatively short time from onset of the disease. Therefore, we hypothesize that changes in the retina in such dogs results in changes in the protein profile of tear fluid, that can be of the diagnostic or therapeutic value and can contribute to the better understanding the pathophysiology mechanisms underlying that disease. The objective of this study was to identify the protein content of tear film in dogs with naturally contracted diabetes mellitus with and/ without retinopathy, and its comparison with the content of control group. That approach results with mapping out the comprehensive proteome of tear film in diabetic dog and the may contribute to development a noninvasive method to detect potential protein candidates for diabetic retinopathy biomarkers in tear film.

Methods

Tear film was collected with Schirmer strips from the canine diabetic patients with/ and without retinopathy and sex‐ and age‐matched control group.The study was conducted on 24 dogs (8 dogs in each group).Two‐dimensional electrophoresis was performed followed by MALDI‐TOF mass spectrometry identification of differential proteins. Quantitative analysis of the differentiating electrophoretic spots was done with 2Delta software. Metabolic pathways associated with those proteins were identified with Panther GO software.

Results

Altogether, 5 significantly differentially expressed proteins were identified. Of those, 4 were downregulated, and 1 was upregulated in the tear film of diabetic patients with retinopathy. Pathway analysis revealed that the proteins were associated with multiple pathways involved in biological regulation, cellular and metabolic process and cellular component organization.

Conclusions

Tear film protein analysis provides a novel way to screen diabetic retinopathy biomarkers in dogs.
Pigment epithelium detachment treated with sildenafil: a case report
Authors: Cellini Mauro , Tassi Filippo , Finzi Alessandro , Roda Matilde , Schiavi Costantino
Published: January 2022

Purpose

Central serous chorioretinopathy (CSCR) is a pathology of the retina that can be complicated by the appearance of a serous detachment of the pigment epithelium (PED). The exact molecular mechanisms of CSCR have remained uncertain as well as there is no effective medical therapy. We found it interesting to describe a case of CSCR with PED treated with Sildenafil.

Case Report

53‐year‐old male suffering from chronic CSCR with PED probably resulting from psychological stress and type A personality presented himself for an eye examination stating that he noticed an improvement in visual acuity and metamorphopsia after a daily intake of 15 mg of sildenafil tablets. The patient underwent fluorescein angiography (FA), indocyanine angiography (ICG), Optical coherence tomography angiography (OCTA) and Optical coherence tomography (OCT). The tests showed a resolution of the serous detachment of the neuroepithelium and pigment epithelium with residual dystrophy of the retinal pigment epithelium.

Conclusions

Several oral medications have been proposed for the treatment of CSCR based on the putative inhibition of different pathogenic pathways. Recently mineralocorticoid receptors antagonists were proposed as a treatment for CSCR patients with persistent subretinal fluid and the results seem encouraging. We believe that in our case the resolution of the clinical picture is due to the improvement of the choroidal vascular picture and in particular of the endothelial function of the choroidal vessels. Recent studies have shown that Phosphodiesterase type 5 (PDE‐5) inhibitors (i.e. sildenafil) have been implicated in improving endothelial function and that this would be at the basis of the vasodilation induced by these molecules.
ET‐1 plasma levels and scleral rigidity as risk factors in neovascular age‐related macular degeneration
Authors: Cellini Mauro , Finzi Alessandro , Corcioni Beniamino , Roda Matilde , Gaudiano Caterina , Golfieri Rita , Schiavi Costantino
Published: January 2022

Purpose

To study the ocular blood flow, the corneal biomechanics, the scleral rigidity and the endothelin‐1 (ET‐1) plasma levels in patients with neovascular age‐related macular degeneration (ARMD).

Methods

We enrolled 20 patients with ARMD and 20 age‐matched control patients. Retrobulbar blood flow was examined by Colour Doppler Aplio 500 (Toshiba Medical System, Tokyo, Japan). Peak systolic velocity (PSV) and resistivity index (RI) was measured from ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary arteries (PCA’s). The corneal hysteresis CH and the corneal resistance force (CRF) values were achieved by Ocular Response Analyzer (ORA). Scleral rigidity (E) was determined by using Friedenwald nomograms. ET‐1 plasma levels were determined using a specific radioimmunoassay (Sigma‐Aldrich, Merck, Germany).

Results

We found a statistically significant difference in the CRF between patients with ARMD and control subjects (ARMD 11.23 ± 1.30 vs. Controls 9.82 ± 1.37; p<0.0025) was found. The CH index between patients with ARMD and control subjects was not statistically significant (ARMD 10.15 ± 1.25 vs. Controls 10.02 ± 1.70; p<0.617). With CDI in PCA’s we found PSV (ARMD 12.37 ± 2.80 cm/sec vs. Controls 15.44 ± 3.59 cm/sec; p<0.0063); RI (ARMD 0.80 ± 0.03 vs Controls 0.74 ± 0.02; p<0.0001). The E had a significant increase in ARMD group (ARMD 0.0358 ± 0.004 vs. Controls 0.0328 ± 0.004; p<0.008) as well as ET‐1 plasma levels (ARMD 2.060 ± 0.276 vs. Controls 1.492 ± 0.0.560; p<0.001). Finally, in ARMD we found that the decrease of PSV and the increase of RI in PCA’s was correlated with the ET‐1 plasma levels (PSV r‐0.615; p<0.0039 and r 0.764; p<0.0001) and not with the values of E, CH and CRF.

Conclusions

Our data indicate that patients with neovascular ARMD had a significant increase of RI in all vessels examined with increased corneal CRF index, scleral rigidity values and ET‐1 plasma levels. The decreased blood flow in APC’s was correlated to the increase of ET‐1 plasma levels. These data indicate that elevated plasma ET‐1 and not the scleral rigidity may be an important risk factor in the development of neovascular ARMD.
Multimodal imaging of a choroidal macrovessel
Authors: Hela Sassi , Meriem Ouederni , Nouri Slim , Fehmy Nafaa , Maamouri Rym , Monia Cheour
Published: January 2022

Purpose

To describe the features of a choroidal macrovessel (CM) in multimodal imaging and underline the importance of non‐invasive imaging techniques.

Methods

A 78‐year‐old man presented to our department for alteration of central vision of the right eye after uneventful cataract surgery. The patient had a complete ophthalmic examination with best corrected visual acuity (BCVA) measurement and slit lamp examination. Multimodal imaging was performed including fundus autofluorescence (FAF), Swept‐Source Optical Coherence Tomography (SS‐OCT), en‐face OCT, OCT‐angiography, Fluorescein Angiography (FA) and Indocyanine Angiography (ICG‐A).

Results

BCVA was 20/50 in the right eye and 20/80 in the left eye. Anterior segment examination was unremarkable except for a nuclear cataract in the left eye. Funduscopic examination showed a subretinal tortuous lesion starting in the fovea and extending toward the temporal periphery in the right eye and was normal in the left eye. FAF of the right eye showed increased autofluorescence of the lesion retracing its serpiginous shape. SS‐OCT revealed a choroidal hollowness. This lesion had a pattern corresponding to a choroidal macrovessel on en‐face OCT scans with a similar signal to the physiological choroidal vessels. OCT‐A showed a low signal within the choroidal vessel. FA of the right eye showed an early serpentine‐shaped hyperfluorescence and ICG‐A revealed early prominent filling with late hypofluorescence and persisting laminar flow. A choroidal macrovessel (CM) was diagnosed.

Conclusions

CM is a rare entity that is not always easy to recognize. ICGA is the most valuable tool for its diagnosis when the presentation is not typical. In cases of CM with a well delineated pattern, non‐invasive imaging modalities and particularly SS‐OCT and en‐face OCT can be very helpful for the diagnosis while avoiding dye injection.
Microglia activation and cone disruption are the main alterations in the retina of human donors with COVID‐19
Authors: Albertos‐Arranz Henar , Sánchez‐Sáez Xavier , Martínez‐Gil Natalia , Noailles Gil Agustina , Calvo Andrés Ramón , Monferrer Adsuara Clara , Remoli Sargues Lidia , Montero Hernández Javier , Cuenca Nicolás
Published: January 2022

Purpose

The presence of SARS‐CoV‐2 in the eye and different alterations in the ocular tissues have been described. However, the health state of the retinal cells in these patients is unknown. The aim was to analyze the morphology of the retinal cells and glial activation in human donor deceased by COVID‐19.

Methods

Retinas from human donors with COVID‐19 (n = 9) and from a group control (n = 5) were analyzed. Samples were obtained from the General University Hospital Consortium of Valencia. Photoreceptors, Müller cells, astrocytes, microglia and retinal blood vessels and the location of ACE2 protein were studied through immunohistochemistry staining in cross‐sections and wholemount retinas (using calbindin, recoverin, GFAP, CRALBP and Collagen Type IV, Iba‐1 and ACE2). Confocal microscopy and a quantitative analysis of Iba‐1 positive cells were performed.

Results

The mean age of COVID‐19 and control group was 77 ± 11 and 68 ± 7 years, respectively. Müller cells, retinal pigment epithelium and outer segment of photoreceptors showed ACE2 immunostaining. The staining of ACE2 protein in the outer segment of photoreceptors was weaker in some COVID‐19 patients. Several patients presented a swelling of the axon terminal of cone photoreceptors and disruptions in the structure of Müller cells. The ramified resident microglial cells changed to an ameboid shape and most of these cells migrated to the retinal vessels. Moreover, the microglia activation in the retina of COVID‐19 patients was confirmed by a reduction of the total area occupied by these cells.

Conclusions

Morphological alterations in the cone photoreceptors and Müller cells, variations in the staining of ACE2 protein and microglia activation was found in human donor retinas with COVID‐19. Support: FEDER‐PID2019‐106230RB‐I00. FPU16/04114, FPU18/02964. RETICS‐FEDER RD16/0008/0016. Retina Asturias/Cantabria. FARPE‐FUNDALUCE. IDIFEDER/2017/064.
Different patterns of autofluorescence within the same family in carriers of a novel choroideremia mutation
Authors: Dolores Díaz‐Barreda Mª , Boned‐Murillo Ana , Bakkali El Bakkali Ismael , Pérez Rivasés Guillermo , Orejudo deRivas Marta , Josefina Núñez Moscarda Eva , Cisneros Pablo , Ascaso Francisco , Bartolome Isabel , Pinilla Isabel
Published: January 2022

Purpose

Choroideremia (CHM) is a rare retinal dystrophy. It affects both the retina (retinal pigment epithelium (RPE) and outer retina) and the choroidal layers. It is inherited X‐linked and therefore affects all males with a theoretical penetrance of 100%. Female carriers, due to the phenomenon of lionisation may be asymptomatic or suffer from the disease in a similar way to males. On examination, they may have changes in pigment distribution and autofluorescence (AF) changes. They may also have some degree of retinal dysfunction.

Methods

We report a family with two cousins affected by CHM and their carrier mothers. After the diagnosis of an 11‐year‐old male, a complete ophthalmological examination including optical coherence tomography (OCT), microperimetry (MAIA) and AF was performed on all family members. A genetic study was conducted on those cases suggestive of CHM. One other case (a 10‐year‐old cousin) and two carriers, the mothers of the two confirmed cases, were identified. The sisters were not affected.

Results

All four showed an undescribed mutation in the CHM gene c.1083_1084dupT (p.L362Sfs*56) at location Xp21.2. AF findings were different in both carriers, with a fine speckle pattern on the periphery in one of them and a course and geographic pattern shown low‐density peripapillary pattern and coarse mottled on periphery in the other one. Both affected males showed a clear decrease in the AF pattern with a geographic central persistence (male pattern). During the evolution, one of the patients showed a more aggressive form than the other, which could be justified by the concomitant high myopia in this case. The AF of the carriers remained similar.

Conclusions

Considering that AF is a non‐invasive, fast and accessible test, could serve to diagnose both patients and carriers of CHM. In addition, the pattern of AF in carriers may be different in members of the same family despite having the same mutation.
Comparison of diabetic retinopathy lesions identified using ultrawide field color photography, ultrawide field fluorescein angiography and optical coherence tomography angiography
Authors: Salongcay Recivall , Anne Aquino Lizzie , Michael Salva Claude , Peto Tunde , Silva Paolo S.
Published: January 2022

Purpose

To determine the correlation of diabetic retinopathy (DR) findings identified on ultrawide field (UWF) color photos, ultrawide field fluorescein angiograms (UWF‐FA) and optical coherence tomography (OCT) angiograms (OCTA).

Methods

This was a cross‐sectional study. Images taken on the same visit were prospectively collected from adult patients with diabetes at a tertiary center in the Philippines. Patients underwent imaging with UWF and UWF‐FA (Optos plc, Dunfermline, Scotland, UK), and OCT with OCTA (Carl Zeiss Meditec Inc, Dublin, CA, USA). Images were evaluated for the presence of DR lesions and center‐involving diabetic macular edema (ciDME). Ischemia was identified on UWF‐FA using Image J Fiji software (National Institutes of Health, Bethesda, MD, USA) and nonperfusion index (NPI) was determined using previously validated protocols. Automated measurements of the macular vessel density (VD), vessel perfusion (VP) and foveal avascular zone (FAZ) metrics were obtained on OCTA.

Results

Images from 69 eyes were included in the analysis. Increasing DR severity was associated with higher NPI (r = 0.55944, p < 0.001) and remained significant after distinguishing between cones (Cone Nonperfusion Index [CPI]: r = 0.55617, p < 0.0001) and rods (Rod Nonperfusion Index [RPI]: r = 0.55285, p < 0.0001). In eyes with NPDR, higher NPI is correlated with the presence of ciDME (r = 0.51156, p 0.0017). Furthermore, macular nonperfusion on UWF‐FA was correlated with higher NPI (r = 0.42899, p 0.0101), CPI (r = 0.50028, p 0.0022) and RPI (r = 0.49027, p 0.0028). Central VD and VP were correlated with the presence of ciDME (r = 0.52456, p < 0.0001; r = 0.51952, p < 0.0001) on OCT. A larger FAZ area was correlated with decreased central VD (r = −0.60089, p 0.0001) and decreased central VP (r = −0.59224, p 0.0001).

Conclusions

The collective findings of UWF, UWF‐FA and OCTA provide complementary information on diabetic eyes, and may offer insights on the pathogenesis and progression of DR.
The degradation of mutant RhodopsinIle256del follows the VCP‐dependent endoplasmic‐reticulum‐associated protein degradation pathway
Authors: Cao Bowen , Sen Merve , Beyer Tina , Leonhard Tobias , Williamson Sally , Cristina Almansa Garcia Ana , Bolz Sylvia , Arango Gonzalez Blanca , Ueffing Marius
Published: January 2022

Purpose

In Europe, the Rholle256del mutation (deletion of isoleucine at position 255 or 256 in Rho gene) accounts for over 17% of familial ADRP cases (C. F. Inglehearn, 1991). From a clinical perspective, the severity of this mutation can be compared to RhoP23H. In previous studies, we found that the degeneration of misfolded RHOP23H follows the ERAD pathway and the clearance of RHOP23H requires the ERAD effector valosin‐containing protein (VCP). This study aims to characterize the subcellular structural and functional changes in Rholle256del transfected mammalian cells, evaluate VCP inhibition's effects, and understand the pathological similarity between Rholle256del and RhoP23H transfected cells.

Methods

HEK293 and COS‐7 cells were transfected with plasmids encoding RhoWT, Rholle256del, or RhoP23H, tagged with GFP. Immunostaining was performed to reveal the localization of transfected RHO‐GFP and the co‐localization between RHO‐GFP with ER, endogenous VCP, ubiquitin, and proteasome subunit (PSMB5). Formation and degree of Rho protein aggregates were analyzed in transfected cells before and after proteasome‐ and VCP‐inhibition.

Results

We found that RHOWT mainly localizes at the plasma membrane, while mutant RHOlle256del and RHOP23H accumulates in the cytosol forming cytoplasmic aggregates. Co‐staining results suggest that both RHOlle256del and RHOP23H aggregates are retained within the ER, partially co‐localizing with VCP. RHOlle256del and RHOP23H aggregates were ubiquitinated and partially transported to the proteasome system for degradation. VCP inhibition led to enhanced accumulation of high molecular weight (HMW) RHO‐containing oligomers and aggregates.

Conclusions

Our results indicate similar clearance characteristics between Rholle256del and RhoP23H in transfected cells, including the excessive formation of misfolded RHO aggregates, retention in the ER, and, at least partially, interaction with VCP. Moreover, VCP inhibition affects the abundance of RHO aggregates. This suggests that the clearance of RHOlle256del also follows the VCP/ERAD/proteasome axis, raising a possibility that modulation of VCP could be considered as a potential therapy for Rholle256del‐related RP as well.
Comparison of systemic and topical isotretinoin in the treatment of facial lichen planopilaris: A randomized controlled trial
Authors: Saber Mina , Bahraminejad Mahsa , Fatemi Naeini Farahnaz , Mohaghegh Fatemeh , Faghihi Gita , Hosseini Sayed Mohsen
Published: January 2022

Background

Facial papules reflecting the lichenoid inflammation of facial vellus hair follicles can occur in the backgrounds of frontal fibrosing alopecia, lichen planopilaris (LPP), or even alone. In the present study, we aimed to compare systemic and topical isotretinoin in the treatment of facial LPP.

Method

In a prospective randomized trial, 26 patients with facial LPP were randomly allocated to receive either 20 mg/day oral isotretinoin or isotretinoin 0.05% gel every night for 6 months. Global Aesthetic Improvement Scale (GAIS) and patient's satisfaction questionnaire were used at 1, 3, and 6 months after treatment to evaluate the outcomes.

Results

In both oral and topical isotretinoin groups, facial papules were significantly improved at all follow‐up visits, resulting in statistically significant improvements (p = 0.005 and p = 0.007, respectively, for oral and topical groups) in GAIS score mean difference from month 1 to month 6. Overall levels of patient satisfaction were high in both groups, and no significant difference was observed between two groups (p = 0.107). However, the mean GAIS score at 3 and 6 months after treatment showed significantly greater improvements in oral isotretinoin group compared to topical group (1.85 ± 0.62 vs. 1.03 ± 0.49 at month 3, p = 0.004; 2.45 ± 54 vs. 1.59 ± 0.62 at month 6, p = 0.008). Overall, patients could well tolerate the treatments; however, topical therapy was associated with fewer side effects.

Discussion

Both oral and topical isotretinoin were found to be effective in improving facial papules; however, oral isotretinoin was significantly more efficacious. Considering safety profile of topical isotretinoin, it can be administrated as maintenance therapy for patients with facial LPP.
Gender‐affirming hormone therapy: An updated literature review with an eye on the future
Authors: D'hoore Laurens , T'Sjoen Guy
Published: January 2022

In line with increasing numbers of transgender (trans) and gender nonbinary people requesting hormone treatment, the body of available research is expanding. More clinical research groups are presenting data, and the numbers of participants in these studies are rising. Many previous review papers have focused on all available data, as these were scarce, but a more recent literature review is timely. Hormonal regimens have changed over time, and older data may be less relevant for today's practice. In recent literature, we have found that even though mental health problems are more prevalent in trans people compared to cisgender people, less psychological difficulties occur, and life satisfaction increases with gender‐affirming hormone treatment (GAHT) for those who feel this is a necessity. With GAHT, body composition and contours change towards the affirmed sex. Studies in bone health are reassuring, but special attention is needed for adolescent and adult trans women, aiming at adequate dosage of hormonal supplementation and stimulating therapy compliance. Existing epidemiological data suggest that the use of (certain) estrogens in trans women induces an increased risk of myocardial infarction and stroke, the reason that lifestyle management can be an integral part of trans health care. The observed cancer risk in trans people does not exceed the known cancer‐risk differences between men and women. Now it is time to integrate the mostly reassuring data, to leave the overly cautious approach behind, to not copy the same research questions repeatedly, and to focus on longer follow‐up data with larger cohorts.
Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial
Authors: Myhre Peder L. , Kalstad Are A. , Tveit Sjur H. , Laake Kristian , Schmidt Erik B. , Smith Pal , Nilsen Dennis W.T. , Tveit Arnljot , Solheim Svein , Arnesen Harald , Seljeflot Ingebjørg
Published: January 2022

Background

The cardiovascular benefit from n‐3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear.

Objectives

To assess changes in EPA and DHA serum concentrations during n‐3 PUFA supplementation and their association with incident cardiovascular events.

Methods

In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all‐cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new‐onset atrial fibrillation (AF).

Results

EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on‐treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high‐density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on‐treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75–0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07–1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant (HR 0.84 [0.66–1.06] for MACE and 1.39 [0.90–2.13] for AF).

Conclusion

Greater on‐treatment increases in EPA were associated with lower risk of MACE and higher risk of new‐onset AF. These data suggest that the cardiovascular effects of increasing n‐3 PUFA levels through supplements are complex, involving both potential benefits and harm.
Trauma Made in America: The Consequences of Violent Victimization for Immigrant Youth in Early Adulthood
Authors: Kuper Julie L. , Turanovic Jillian J.
Published: January 2022

Research finds that adolescent violent victimization results in numerous lasting negative life consequences. However, the long‐term impacts of victimization are understudied among immigrant youth. Using a subsample of 952 immigrants from Waves I–III of the National Longitudinal Study of Adolescent to Adult Health, regression models are specified to determine whether violent victimization in adolescence is related to negative outcomes in early adulthood (poor health, depressive symptoms, low self‐esteem, suicidality, alcohol problems, drug use, property offending, and violent offending). Results indicate that victimization has no robust associations with any long‐term adverse outcomes among immigrants. The findings are discussed using perspectives on immigrant resilience and highlight the need for research to further explore how immigrant youth overcome their experiences with violence.
Patient involvement in assessment of postgraduate medical learners: A scoping review
Authors: Khalife Roy , Gupta Manika , Gonsalves Carol , Park Yoon Soo , Riddle Janet , Tekian Ara , Horsley Tanya
Published: January 2022

Context

Competency‐based assessment of learners may benefit from a more holistic, inclusive, approach for determining readiness for unsupervised practice. However, despite movements towards greater patient partnership in health care generally, inclusion of patients in postgraduate medical learners' assessment is largely absent.

Methods

We conducted a scoping review to map the nature, extent and range of literature examining the inclusion (or exclusion) of patients within the assessment of postgraduate medical learners. Guided by Arskey and O'Malley's framework and informed by Levac et al. and Thomas et al., we searched two databases (MEDLINE® and Embase®) from inception until February 2021 using subheadings related to assessment, patients and postgraduate learners. Data analysis examined characteristics regarding the nature and factor influencing patient involvement in assessment.

Results

We identified 41 papers spanning four decades. Some literature suggests patients are willing to be engaged in assessment, however choose not to engage when, for example, language barriers may exist. When stratified by specialty or clinical setting, the influence of factors such as gender, race, ethnicity or medical condition seems to remain consistent. Patients may participate in assessment as a stand‐alone group or part of a multi‐source feedback process. Patients generally provided high ratings but commented on the observed professional behaviours and communication skills in comparison with physicians who focused on medical expertise.

Conclusion

Factors that influence patient involvement in assessment are multifactorial including patients' willingness themselves, language and reading‐comprehension challenges and available resources for training programmes to facilitate the integration of patient assessments. These barriers however are not insurmountable. While understudied, research examining patient involvement in assessment is increasing; however, our review suggests that the extent which the unique insights will be taken up in postgraduate medical education may be dependent on assessment systems readiness and, in particular, physician readiness to partner with patients in this way.
Negotiating national identity in postcolonial Zimbabwe through a national dress
Authors: Chitima Simbarashe Shadreck
Published: January 2022

A national dress is a reflection of national consciousness towards the nation and its cultural heritage. Instead of simply being functional, a national dress is also a script that exhibits people's identities. This study examines how Zimbabweans identify with the national dress as a facet of achieving national identity. Qualitative research methods and Gramscianism were employed in the study. It is revealed that the majority of Zimbabweans fail to identify with the national dress due to political, cultural and economic reasons. The national dress is perceived as a campaign strategy being used by the state to achieve political expediency and to be seen as champion of moral as well as cultural regeneration. Some participants associate the dress with cultural imperialism and waste of resources. Very few participants take the dress as a positive step towards the decolonisation of cultural spaces and identities. Conclusively, the majority of Zimbabweans find the dress insignificant in their lives and in national identity construction.
Leadless pacemaker implantation sites confirmed by computed tomography and their parameters and complication rates
Authors: Arai Hirofumi , Mizukami Akira , Hanyu Yoshihiro , Kawakami Takuya , Shimizu Yuki , Hiroki Jiro , Yoshioka Kenji , Ohtani Hirofumi , Ono Maki , Yamashita Shu , Iwatsuka Ryota , Ueshima Daisuke , Matsumura Akihiko , Goya Masahiko , Sasano Tetsuo
Published: January 2022

Background

Implantations of leadless pacemakers in the septum lower the risk of cardiac perforation. However, the relationship between the implantation site and the success rate, complication rate, and pacemaker parameters are not well‐investigated.

Methods

Patients who underwent leadless pacemaker implantation with postprocedural computed tomography (CT) between September 2017 and November 2020 were analyzed. Septum was targeted with fluoroscopic guidance with contrast injection. We divided patients into two groups based on the implantation site confirmed by CT: septal and non‐septal, which included the anterior/posterior edge of the septum and free wall. We compared the complication rates and pacemaker parameters between the two groups.

Results

A total of 67 patients underwent CT after the procedure; among them, 28 were included in the septal group and 39 were included in the non‐septal group. The non‐septal group had significantly higher R wave amplitudes (6.5 ± 3.3 vs. 9.7 ± 3.9 mV, p = .001), lower pacing threshold (1.0 ± 0.94 vs. 0.63 ± 0.45 V/0.24 ms, p = .02), and higher pacing impedance (615 ± 114.1 vs. 712.8 ± 181.3 ohms, p = .014) after the procedure compared to the septal group. Cardiac injuries were observed in four patients (one cardiac tamponade, one possible apical hematoma, two asymptomatic pericardial effusion), which were only observed in the non‐septal group.

Conclusions

Leadless pacemaker implantation may be technically challenging with substantial number of patients with non‐septal implantation when assessed by CT. Septal implantation may have a lower risk of cardiac injury but may lead to inferior pacemaker parameters than non‐septal implantation.
The Black Box in Stoic Axiology
Authors: Vazquez Michael
Published: January 2022

The ‘black box’ in Stoic axiology refers to the mysterious connection between the input of Stoic deliberation (reasons generated by the value of indifferents) and the output (appropriate actions). In this paper, I peer into the black box by drawing an analogy between Stoic and Kantian axiology. The value and disvalue of indifferents is intrinsic, butconditional. An extrinsic condition on the value of a token indifferent is that one's selection of that indifferent is sanctioned by context‐relative ethical principles. The value of an indifferent that does not meet this condition is normatively silenced, such that it fails to constitute a reason for action.
The First Emperor: Solipsism, Power and the State☆
Authors: Lynch Tony
Published: January 2022

It is not usually thought that Wittgenstein has much to show us about political power and the state. This essay disputes this claim by showing how the Mausoleum and career of the First Emperor can be understood in terms of political solipsism, so illuminating the nature and logic of centralized state building.
Saving migrants’ lives at sea: Improving search and rescue operations
Authors: Kosmas Vasileios , Acciaro Michele , Besiou Maria
Published: January 2022

The present study focuses on the Mediterranean Sea migration crisis and investigates the effectiveness of search and rescue (SAR) operations alongside measures to reduce the number of deaths of migrants at sea. It also describes the stakeholders involved in SAR activities. The paper first analyzes secondary data and the results of 24 in‐depth interviews in order to develop an analytical framework, which is then complemented by a system dynamics model to explore the complexity and interactions among stakeholders in SAR operations. The study shows that the death toll at sea can be reduced by enhancing cooperation among stakeholders by providing legal migration pathways under certain conditions and by engaging in more effective migrant detection and interception at sea. Lastly, raising potential migrants’ awareness about the risk of death during the sea crossing should be seen as an additional measure, while SAR activities should be maintained to prevent loss of life at sea.
Effects of public health measures during the SARS‐CoV‐2 pandemic on the winter respiratory syncytial virus epidemic: An interrupted time series analysis
Authors: Reyes Domínguez Ana Isabel , Pavlovic Nesic Svetlana , Urquía Martí Lourdes , Pérez González María del Carmen , Reyes Suárez Desiderio , García‐Muñoz Rodrigo Fermín
Published: January 2022

Background

Public health measures (PHM) designed to contain the spread of COVID‐19 pandemic have influenced the epidemiological characteristics of other viral infections. Its impact on acute RSV bronchiolitis in infants of ≤24 months old has not been systematically studied in our setting.

Objectives

To describe the monthly pattern of visits to the Paediatric Emergency Department (PED) of patients 0 to 14 years of age, the rate of patients diagnosed with RSV acute bronchiolitis per thousand inhabitants of 0 to 24 months, and the rate of them requiring hospital admission during the winter 2020–2021, in the context of local and national COVID‐19 restrictions and compare them to the four previous seasons.

Methods

Interrupted time series analysis of patients assisted in the PED and diagnosed with or admitted for RSV acute bronchiolitis in a tertiary University Hospital from January 2016 to February 2020 (pre‐intervention period) and from March 2020 to June 2021 (post‐intervention period). Intervention: Preventive PHM implemented by the Spanish government weighted by the Containment and Health Index of the Oxford COVID‐19 Government Response Tracker.

Results

The intervention was followed by an immediate reduction of the rate of visits to the PED of –19.5 (95% confidence interval [CI] –24.0, –14.9) per thousand, and the rate of diagnoses and admissions for RSV acute bronchiolitis of –44.3 (95% CI –73.8, –14.8) and –1.4 (95% CI –2.7, –0.1) per thousand, respectively, with a delayed rebound.

Conclusions

After the implementation of PHM to prevent the spread of SARS‐CoV‐2 infection, an immediate and important decline in the visits to the PED was observed, with an upward change thereafter. There was also an initial reduction in the diagnoses of and admissions by RSV acute bronchiolitis. An upward trend was observed six to nine months after the usual time of the winter RSV epidemic, coinciding with the relaxation of the preventive PHM.
Judicial Self‐Governance Index: Towards better understanding of the role of judges in governing the judiciary
Authors: Šipulová Katarína , Spáč Samuel , Kosař David , Papoušková Tereza , Derka Viktor
Published: January 2022

The aim of this article is to introduce a novel view on how to evaluate the share of power held by judges in judicial governance. Its contribution to court administration and the regulation of judges is three‐fold. First, it provides a novel empirically tested conceptualization of judicial governance that includes 60 competences grouped into eight dimensions (ranging from selection and education of judges to case allocation and publication of judicial decisions). Second, it proposes a new Judicial Self‐Governance (JSG) Index that measures how much power domestic judges hold in these eight dimensions of judicial governance. Third, by applying the JSG Index to the longitudinal data for Germany, Italy, Czechia, and Slovakia this article demonstrates that the Judicial Council model is not the only institutional model of judicial governance leading to the empowerment of judges. This means that judges can hold many powers without the existence of judicial councils and even in the Ministry of Justice model.
COVID-19 challenges and changes for home care agencies and providers: a scoping review protocol
Authors: Barr Laura Lyn Barnes , Christian Robin , Palokas Michelle , Hinton Elizabeth
Published: January 2022

Objective:

This scoping review will explore the challenges experienced by home care agencies and home care providers during the COVID-19 pandemic and the changes made to overcome these challenges.

Introduction:

The COVID-19 pandemic has presented many challenges to home care agencies and providers worldwide. In response, home care agencies and providers were forced to make changes to the way they operate in order to continue providing quality care to homebound patients.

Inclusion criteria:

This scoping review will consider studies that explore the challenges experienced by home care agencies and providers during the COVID-19 pandemic and the changes implemented, or strategies, used to overcome the identified challenges. All geographic locations will be considered for inclusion.

Methods:

This review will be conducted in accordance with the JBI methodology for scoping reviews. Key information sources will include MEDLINE, CINAHL, Embase, Scopus, and Web of Science. Sources of unpublished studies and gray literature will include ProQuest Dissertations and Theses, OpenGrey, medRxiv, and bioRxiv. The review will be limited to articles published in English, from 2020 until present day. Two independent reviewers will use a data extraction tool to collect data. Along with a narrative summary, the results will be presented in diagrammatic or tabular format in a manner that aligns with the review objective and questions.
The Relationship Between Cardiorespiratory and Accelerometer-Derived Measures in Trail Running and the Influence of Sensor Location
Authors: Staunton Craig A. , Swarén Mikael , Stöggl Thomas , Born Dennis-Peter , Björklund Glenn
Published: January 2022

Purpose: To examine the relationship between cardiorespiratory and accelerometer-derived measures of exercise during trail running and determine the influence of accelerometer location. Methods: Eight trail runners (7 males and 1 female; age 26 [5] y; maximal oxygen consumption [] 70 [6] mL·kg−1·min−1) completed a 7-km trail run (elevation gain: 486 m), with concurrent measurements of , heart rate, and accelerations recorded from 3 triaxial accelerometers attached at the upper spine, lower spine, and pelvis. External exercise intensity was quantified from the accelerometers using PlayerLoad™ per minute and accelerometry-derived average net force. External exercise volume was calculated using accumulated PlayerLoad and the product of average net force and duration (impulse). Internal intensity was calculated using heart rate and -metrics; internal volume was calculated from total energy expenditure (work). All metrics were analyzed during both uphill (UH) and downhill (DH) sections of the trail run. Results: PlayerLoad and average net force were greater during DH compared with UH for all sensor locations (P ≤ .004). For all accelerometer metrics, there was a sensor position × gradient interaction (F2,1429.003; P <.001). The upper spine was lower compared with both pelvis (P ≤ .003) and lower spine (P ≤ .002) for all accelerometer metrics during both UH and DH running. Relationships between accelerometer and cardiorespiratory measures during UH running ranged from moderate negative to moderate positive (r = −.31 to .41). Relationships were stronger during DH running where there was a nearly perfect correlation between work and impulse (r = .91; P < .001). Conclusions: Simultaneous monitoring of cardiorespiratory and accelerometer-derived measures during trail running is suggested because of the disparity between internal and external intensities during changes in gradient. Sensor positioning close to the center of mass is recommended.