Comparison of Surgical Times Between Manual and Robot-Assisted Epiretinal Membrane Peeling.

Purpose: Epiretinal membranes (ERM) pose a common challenge in vitreoretinal pathology, often causing vision impairment in older adults. The Preceyes Surgical System (PSS) supports the surgical removal of ERM through robot-assisted membrane peeling (RA-MP). This study compares surgical times and iatrogenic hemorrhages between manual membrane peeling (MMP) and RA-MP using PSS. Methods: Nine patients underwent RA-MP with PSS, whereas 16 patients (18 eyes) underwent MMP for comparative analysis. Surgical durations were categorized into RA-MP, manual forceps utilization in PSS surgeries (mRA-MP), and traditional MMP. Cumulative manual manipulation duration (cMMP), instrument grasps, and intraoperative hemorrhages were statistically analyzed using the Mann-Whitney U test. Results: RA-MP showed significantly longer peeling times compared to MMP (P < 0.001). Flap initiation grasps were similar between methods (P = 0.86), RA-MP demonstrated a significant reduction in peeling grasps (P = 0.01) and mean grasps per minute (P < 0.001). Although RA-MP resulted in fewer hemorrhages, the difference did not reach statistical significance relative to MMP (P = 0.08). Discussion: Although RA-MP tended to extend surgical time, it offered advantages in reducing tissue trauma and intraoperative hemorrhages. Further research is needed to explore the learning curve for novice surgeons and evaluate the safety profile of RA-MP. Translational Relevance: RA-MP may offer potential advantages over manual surgery, particularly in terms of reduced tissue trauma and intraoperative hemorrhages. Despite its longer duration compared with manual techniques, RA-MP may lead to fewer grasping maneuvers and lower rates of hemorrhages, thereby enhancing the safety and precision of vitreoretinal surgeries.

m6A Methylation of Transcription Leader Sequence of SARS-CoV-2 Impacts Discontinuous Transcription of Subgenomic mRNAs.

The SARS-CoV-2 genome has been shown to be m6A methylated at several positions in vivo. Strikingly, a DRACH motif, the recognition motif for adenosine methylation, resides in the core of the transcriptional regulatory leader sequence (TRS-L) at position A74, which is highly conserved and essential for viral discontinuous transcription. Methylation at position A74 correlates with viral pathogenicity. Discontinuous transcription produces a set of subgenomic mRNAs that function as templates for translation of all structural and accessory proteins. A74 is base-paired in the short stem-loop structure 5'SL3 that opens during discontinuous transcription to form long-range RNA-RNA interactions with nascent (-)-strand transcripts at complementary TRS-body sequences. A74 can be methylated by the human METTL3/METTL14 complex in vitro. Here, we investigate its impact on the structural stability of 5'SL3 and the long-range TRS-leader:TRS-body duplex formation necessary for synthesis of subgenomic mRNAs of all four viral structural proteins. Methylation uniformly destabilizes 5'SL3 and long-range duplexes and alters their relative equilibrium populations, suggesting that the m6A74 modification acts as a regulator for the abundance of viral structural proteins due to this destabilization.

The Use of the RETeval Portable Electroretinography Device for Low-Cost Screening: A Mini-Review.

Electroretinography (ERG) provides crucial insights into retinal function and the integrity of the visual pathways. However, ERG assessments classically require a complicated technical background with costly equipment. In addition, the placement of corneal or conjunctival electrodes is not always tolerated by the patients, which restricts the measurement for pediatric evaluations. In this short review, we give an overview of the use of the RETeval portable ERG device (LKC Technologies, Inc., Gaithersburg, MD, USA), a modern portable ERG device that can facilitate screening for diseases involving the retina and the optic nerve. We also review its potential to provide ocular biomarkers in systemic pathologies, such as Alzheimer's disease and central nervous system alterations, within the framework of oculomics.

TGF-ß specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf.

T follicular helper (TFH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse TFH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-ß (TGF-ß) induces robust expression of TFH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4+ T cells in vitro. TGF-ß-induced mouse CXCR5+ TFH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated TFH cells and provide critical help to B cells. The study further reveals that TGF-ß-induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-ß-containing T helper 17 (TH17)-inducing conditions also yield separate CXCR5+ and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of TFH and TH17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-ß-induced TFH cell program, that TFH and TH17 cells share a common developmental stage, and that c-Maf acts as a switch factor for TFH versus TH17 cell fates in TGF-ß-rich environments in vitro and in vivo.

Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease.

Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.

Indications, Complications, and Early Postoperative Course of Recovery of Intraocular Lens Exchange Surgery: a Single-Center Retrospective Study.

PURPOSE: To analyze the indications, complications, and early course of recovery of intraocular lens (IOL) exchange surgery. MATERIAL AND METHODS: Records of patients who underwent IOL exchange during a 6-year period at a tertiary referral center were reviewed and the indications and complications after surgical intervention were analyzed. Their effects on postoperative corrected distance visual acuity (CDVA), intraocular pressure (IOP), use of IOP-lowering medications, and refractive cylindrical power were assessed. RESULTS: One hundred and seventy-one eyes (165 patients) were investigated. The most frequent indication for IOL exchange was lens dislocation in 163 eyes (95.32%). The main causes of IOL dislocation were pseudoexfoliation syndrome (PEX) in 98 eyes (57.31%) and complications during cataract surgery in 40 eyes (23.39%). During IOL exchange, an anterior iris-claw fixation was performed in 159 eyes (92.98%). After significant initial deterioration to 1.59 ± 1.08 logMAR on postoperative day 1 (p ≤ 0.001), the CDVA recovered to preoperative levels within 28 days. A significant decrease in IOP was observed on postoperative day 1 (p = 0.04). The most common postoperative complications were corneal edema in 114 eyes (66.67%) and vitreous hemorrhage in 67 eyes (39.18%). CONCLUSION: The high early postoperative prevalence of corneal edema and intraocular hemorrhage was found to affect visual recovery after IOL exchange, causing a significant initial deterioration of CDVA and a delay of full visual recovery. These findings suggest that surgical approaches minimizing the risk of this type of complications should be favored.

Robot-Assisted Epiretinal Membrane Peeling: A Prospective Assessment of Pre- and Intra-Operative Times and of Surgeons' Subjective Perceptions.

PURPOSE: The Preceyes Surgical System (PSS) is a robotic assistive device that may enhance surgical precision. This study assessed pre- and intra-operative times and surgeons' perceptions of robot-assisted epiretinal membrane peeling (RA-MP). METHODS: We analyzed the time requirement of three main tasks: the preparation of the PSS (I), patient preparation (II), and surgery (III). Following surgery, the surgeons were asked questions about their experience. RESULTS: RA-MP was performed in nine eyes of nine patients. Task I required an average time of 12.3 min, initially taking 15 min but decreasing to 6 min in the last surgery. Task II showed a mean time of 47.2 (range of 36-65) min. Task III had a mean time of 72.4 (range of 57-100) min. A mean time of 27.9 (range of 9-46) min was necessary for RA-MP. The responses to the questionnaire revealed a trend towards increasing ease and reduced stress as familiarity with the PSS increased. CONCLUSIONS: A substantial reduction in pre- and intra-operative times, decreasing to a total of 115 min, was demonstrated. RA-MP was positively anticipated by the surgeons and led to no hand or arm strain while being more complex than manual MP.

[Diagnostic and Therapeutic Management of Episcleritis and Scleritis]. / Diagnostisches und therapeutisches Management der Episkleritis und Skleritis.

While episcleritis is a benign disease only affecting the episclera, scleritis is an ocular inflammation with typically severe pain and not rarely affecting adjacent tissue.Scleritis is classified into anterior and posterior forms. Anterior scleritis is further subdivided into diffuse, nodular, necrotizing with inflammation, and necrotizing scleritis without inflammation (scleromalacia perforans). A systemic disease such as rheumatoid arthritis or granulomatosis with polyangiitis is associated with up to 50% of all patients with scleritis or episcleritis, consequently a systemic work-up with blood sampling and imaging as well as collaboration with internists are necessary.Differentiating these two entities is of high importance for planning the treatment: episcleritis has a self-limited course, whereas treatment of scleritis is obligatory to protect patients from irreversible visual loss, organ damage, and furthermore reduce the risk of mortality.Treatment depending of subtype and associated systemic disease may involve non-steroidal anti-inflammatory drugs, corticosteroids, and disease-modifying anti-rheumatic drugs.

A Modification of the Inverted Internal Limiting Membrane Flap Technique without Heavy Liquids and Prone Posturing. / Eine Modifikation der inversen Membrana-limitans-interna-Lappentechnik ohne Einsatz schwerer Flüssigkeiten und Bauchlagerung.

Primary closure of large macular holes remains challenging, and variations of inverted inner limiting membrane (ILM) flap surgery have been described. In the present retrospective, interventional, single-centre case series, we propose a superior flap design with minimal posturing. Eight eyes of eight patients (four women and four men) in the period between July 2020 and March 2022 underwent 23 G three-port vitrectomy with a superior inverted ILM flap and 20% SF6 endotamponade for a full thickness macular hole (MH) by the same experienced surgeon (F. M. H.). Seven MHs were classified as large (> 400 µm) and one as medium (250 - 400 µm). The mean MLD was 638.0 ± 166.4 µm (range: 353 - 851 µm). MH closure was achieved in all (8/8, 100%) patients with a single surgery. The median best-corrected visual acuity (BCVA) improved from 6/120 (Snellen) (range: finger counting [FC] to 6/19) preoperatively to 6/19 (range: FC to 6/9.5) after surgery, without any intra- or postoperative complications. The superior inverted ILM flap technique seems to be a safe and successful approach for the primary closure of large MHs. Further studies should investigate our proposed surgical technique on a larger population, potentially without air or gas endotamponade.

Incidence of severe rise in intraocular pressure after intravitreous injection of aflibercept with prefilled syringes.

Our aim was to analyze the intraocular pressure (IOP) changes following different intravitreous injection (IVI) procedures with or without prefilled syringes (PFS) and to elaborate their possible causes. Clinical study and laboratory assessment. 173 eyes of 141 patients. The IOP was prospectively measured pre- and postoperatively in three groups of patients receiving IVI either with ranibizumab (RP), aflibercept PFS (AP) or aflibercept vials (AV). The AP emptying volume (EV) was assessed using 40 aflibercept PFS vials: the plunger was aligned precisely (normal volume, NV) or right below the indication line (high volume, HV) and the drug was ejected with (wP) or without forced pressure (nP). Primary outcome was post-treatment IOP with type of IVI and pre-treatment IOP as fixed factors. Secondary outcome was identification of possibly confounding factors (age, sex, pathology, presence of pseudophakia, spherical error, and number of injections) and IOP > 30 mmHg post-treatment. An IOP rise above 30 mmHg was observed in 8/38 (22%), 16/51 (31%) and 35/86 (41%) cases in the RP, AV and AP groups, respectively (p = 0.129). Pre-treatment IOP was the only predictive variable for IOP rise (p < 0.001). The EV values in the NVnP, NVwP, HVnP and HVwP groups were 56.06 ± 10.32, 70.69 ± 4.56, 74.22 ± 7.41 and 81.63 ± 3.67 µl, respectively (p < 0.001). We observed a marked, although not significantly higher incidence of IOP elevations with the aflibercept PFS. One possible reason may be the error-proneness of administering the correct volume with the AP. Caution should be taken when using the aflibercept PFS in order to prevent potential optic nerve damage in cases with marked elevation in IOP.

Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation.

Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-ß1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.

Multimodal Imaging in a Case of Presumed Solitary Circumscribed Retinal Astrocytic Proliferation.

Provisionally referred to as presumed solitary circumscribed retinal astrocytic proliferation (PSCRAP), the lesion is a rare, benign retinal tumour that typically presents as white-yellow, opaque, and well circumscribed. Typically, the lesion is stable or may regress spontaneously. In light of the adjacent pigmentation of the tumour and from our retinal imaging, we suggest that the lesion originates from the deep neurosensory retina or the retinal pigment epithelium. Herein, we present a case of this entity in a 36-year-old man with a roundish, parapapillary tumour in his right eye and share its characteristics in the different diagnostic imaging modalities.

Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus.

Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF shunting as the leading reason for brain surgery in children despite considerable disease heterogeneity. In this study, by integrating human brain transcriptomics with whole-exome sequencing of 483 patients with congenital hydrocephalus (CH), we found convergence of CH risk genes in embryonic neuroepithelial stem cells. Of all CH risk genes, TRIM71/lin-41 harbors the most de novo mutations and is most specifically expressed in neuroepithelial cells. Mice harboring neuroepithelial cell-specific Trim71 deletion or CH-specific Trim71 mutation exhibit prenatal hydrocephalus. CH mutations disrupt TRIM71 binding to its RNA targets, causing premature neuroepithelial cell differentiation and reduced neurogenesis. Cortical hypoplasia leads to a hypercompliant cortex and secondary ventricular enlargement without primary defects in CSF circulation. These data highlight the importance of precisely regulated neuroepithelial cell fate for normal brain-CSF biomechanics and support a clinically relevant neuroprogenitor-based paradigm of CH.

Biologics in the Treatment of Uveitis. / Therapie der Uveitis mit Biologika.

GOAL: To provide an overview of biologics that are used to treat noninfectious uveitis, including their different targets, modes of actions, and indications. MATERIAL AND METHODS: A review of recent and well-established literature was used to present the biochemical and pathophysiological background of biologics and to provide an account of evidence-based decision making for their use, not only in noninfectious uveitis in general, but with special regard to indications for their use in particular types of uveitis. RESULTS: Extensive clinical data for adalimumab shows that it is currently the only approved biologic for the treatment of uveitis. However, there is sufficient evidence to argue that many other biologics, notably TNF-α inhibitors, certain Interleukin inhibitors, Interferons, and B cell and T cell inhibitors, are also suitable for use in uveitis. CONCLUSIONS: Biologics have revolutionized the treatment of noninfectious uveitis and are now considered indispensable. They are used in cases of insufficient response to or intolerance of conventional immunosuppressive agents. However, they can also be indicated as a first-line therapy for certain types of uveitis (e.g., Behçet's disease). TNF-α inhibitors are the most commonly used biologics in the treatment of uveitis.

Tare Soil Disinfestation from Cyst Nematodes Using Inundation.

The dissemination of soil tares in the potato and sugar beet processing industry is one of the main paths for the spread of potato cyst nematodes (PCN), a severe quarantine pest. Efficient measures for the disinfestation of tare soil from PCN, but also from beet cyst nematodes (BCN), are needed. In our study, Globodera pallida (a PCN) and Heterodera schachtii (a BCN) cysts were sealed in gauze bags and imbedded in sedimentation basins. The cysts were either placed (a) in a presedimentation basin (Brukner basin) for three days, (b) in the presedimentation basin for three days and subsequently in sedimentation basins for nine weeks or (c) in sedimentation basins for nine weeks (without presedimentation). We tested the viability of the eggs and juveniles by hatching assays and using the reproduction rates in bioassays. We demonstrated that PCN and BCN imbedded in a sedimentation basin were only still showing some hatching activity after 2.5 weeks, while no hatching was observed when an additional Brukner basin treatment was conducted before sedimentation.

SEVTAR-A multicenter randomized controlled trial to investigate the impact of prophylactic endoluminal placed vacuum sponge for prevention of anastomotic leakage after low rectal resections.

Background: Low anterior resection for rectal cancer is commonly associated with a diverting stoma. In general, the stoma is closed 3 months after the initial operation. The diverting stoma reduces the rate of anastomotic leakage as well as the severeness of a potential leakage itself. Nevertheless, anastomotic leakage is still a life-threatening complication and might reduce the quality of life in the short and long term. In case of leakage, the construction can be converted into a Hartmann situation or it could be treated by endoscopic vacuum therapy or by leaving the drains. In recent years, endoscopic vacuum therapy has become the treatment of choice in many institutions. In this study, the hypothesis is to be evaluated, if a prophylactic endoscopic vacuum therapy reduces the rate of anastomotic leakage after rectal resections. Methods: A multicenter parallel group randomized controlled trial is planned in as many as possible centers in Europe. The study aims to recruit 362 analyzable patients with a resection of the rectum combined with a diverting ileostoma. The anastomosis has to be between 2 and 8 cm off the anal verge. Half of these patients receive a sponge for 5 days, and the control group is treated as usual in the participating hospitals. There will be a check for anastomotic leakage after 30 days. Primary end point is the rate of anastomotic leakages. The study will have 60% power to detect a difference of 10%, at a one-sided alpha significance level of 5%, assuming an anastomosis leakage rate of 10%-15%. Discussion: If the hypothesis proves to be true, anastomosis leakage could be reduced significantly by placing a vacuum sponge over the anastomosis for 5 days. Trial registration: The trial is registered at DRKS: DRKS00023436. It has been accredited by Onkocert of the German Society of Cancer: ST-D483. The leading Ethics Committee is the Ethics Committee of Rostock University with the registration ID A 2019-0203.

Retinal Manifestation of an Epstein-Barr Virus-Associated Plasma Cell Neoplasm.

We report a case of an uncommon presentation of Epstein-Barr virus (EBV)-associated plasma cell neoplasm in a patient with a history of prostate cancer and hairy cell leukemia (HCL) in remission after chemotherapy. The diagnosis of an EBV-associated plasma cell neoplasm was challenging as initially the findings were also compatible with a recurrence of HCL. We highlight the value of diagnostic vitrectomy to achieve the diagnosis. Our particular case demonstrates the importance of diagnostic pars plana vitrectomy and aqueous analyses in patients with uveitis of an unknown cause to confirm the diagnosis.

Cellular response of blood-borne immune cells to PEEU fiber meshes.

BACKGROUND: Polymeric materials have been widely used as artificial grafts in cardiovascular applications. These polymeric implants can elicit a detrimental innate and adaptive immune response after interacting with peripheral blood. A surface modification with components from extracellular matrices (ECM) may minimize the activation of immune cells from peripheral blood. The aim of this study is to compare the cellular response of blood-born immune cells to the fiber meshes from polyesteretherurethane (PEEUm) and PEEUm with ECM coating (PEEUm + E). MATERIALS AND METHODS: Electrospun PEEUm were used as-is or coated with human cardiac ECM. Different immune cells were isolated form human peripheral blood. Cytokine release profile from naïve and activated monocytes was assessed. Macrophage polarization and T cell proliferation, as indication of immune response were evaluated. RESULTS: There was no increase in cytokine release (IL-6, TNF-α, and IL-10) from activated monocytes, macrophages and mononuclear cells on PEEUm; neither upon culturing on PEEUm + E. Naïve monocytes showed increased levels of IL-6 and TNF-α, which were not present on PEEUm + E. There was no difference on monocyte derived macrophage polarization towards pro-inflammatory M1 or anti-inflammatory M2 on PEEUm and PEEUm + E. Moreover, T cell proliferation was not increased upon interacting with PEEUm directly. CONCLUSION: As PEEUm only elicits a minimal response from naïve monocytes but not from monocytes, peripheral blood mononuclear cells (PBMCs) or T cells, the slight improvement in response to PEEUm + E might not justify the additional effort of coating with a human ECM.

KDM6A, a histone demethylase, regulates stress hematopoiesis and early B-cell differentiation.

Histone methylases and demethylases regulate gene expression programs in hematopoiesis. The molecular function of the demethylase KDM6A in normal hematopoiesis and, in particular, for the hematopoietic stem and progenitor cell (HSPC) compartment remains only partially understood. Female but not male Kdm6a-/- HSPCs were functionally impaired in adoptive transfer experiments as well as upon proliferative stress induced by 5-fluorouracil. Loss of Kdm6a affected primarily early B cells and erythroid and myeloid progenitor cells with respect to both number and function. Global gene expression analyses revealed a shared altered gene signature in Kdm6a-/- pro-B and pre-B cells that is also present in HSPCs, supporting that altered B-cell differentiation in Kdm6a-/- animals is already initiated in HSPCs. Interestingly, loss of KDM6A did not affect the global level of methylation of H3K27, its presumed target, in hematopoietic cells. Our data indicate a critical role for KDM6A in the regulation of hematopoietic differentiation and differentiation-specific gene expression programs, with a prominent role in early B-cell differentiation that is likely independent of H3K27 methylation status.