Seven-year outcome after 1-year fixed regimen of intravitreal aflibercept injections followed by pro re nata treatment for neovascular age-related macular degeneration.

PURPOSE: The study aims to investigate the 7-year best-corrected visual acuity (BCVA) course after 1-year fixed regimen of intravitreal aflibercept injection (IVA) for neovascular age-related macular degeneration (nAMD) and to identify factors affecting this BCVA. METHODS: This longitudinal, observational study included 63 treatment-naïve eyes (61 patients) with nAMD, treated with 1-year fixed regimen of IVA-3 monthly injections and 4 subsequent bimonthly injections-essentially followed by PRN regimen of IVA but sometimes followed by agent switching, photodynamic therapy (PDT), or vitrectomy, as needed. We assessed BCVA changes over a 7-year period. Morphologically, we assessed central retinal thickness (CRT), central choroidal thickness (CCT), subfoveal pigment epithelial detachment (PED) height, vitreomacular traction/adhesion (VMT/VMA), epiretinal membrane (ERM), and macular atrophy involving the fovea. RESULTS: Logarithm of the minimum angle of resolution (logMAR) BCVA changed from 0.20 ± 0.24 to 0.29 ± 0.45 over 7 years. BCVA improved significantly after years 1 and 2 (P = 0.002 and 0.001, respectively) and then slowly decreased. BCVA after years 3-7 did not significantly differ from baseline. CRT and CCT decreased significantly during follow-up, while PED height did not. VMT/VMA decreased significantly, whereas ERM and macular atrophy increased significantly. Seven-year and baseline BCVA positively correlated (P = 0.007, ß = 0.35). CONCLUSIONS: BCVA was maintained for 7 years in nAMD eyes after 1-year fixed regimen of IVA, essentially followed by PRN regimen, but sometimes followed by agent switching, PDT, or vitrectomy, without severe drug-induced complications. Thus, early diagnosis and treatment of nAMD are essential for maintaining good long-term BCVA, even in eyes with relatively poor baseline vision.

A small proportion of litter-derived nitrogen is assimilated by plant biomass or immobilized in sediments regardless of harvest management as detected by 15N-labeled Phragmites litter in a constructed wetland.

Emergent aquatic macrophytes play an important role in the removal of nutrients in constructed wetlands (CWs). However, plant biomass supplies litter after the onset of senescence. Although litter-derived nitrogen (N) has been considered a nutrient source for the internal loading that may reduce CW performance, little is known about the quantitative N dynamics associated with litter decomposition. Thus, a controversial question remains about whether plant harvest is needed to manage CWs. In this study, we evaluated the decomposition and the fate of N derived from 15N-labeled Phragmites litter in a CW for 1 year. To simulate respective natural conditions, two treatments, including (1) a single winter harvest and (2) no harvest where the latter supplies a greater stem litterfall, were compared. Although the dry weight of the added stem litter was approximately 4.7 times larger in the no harvest plot than in the harvest plot, the total N content of the initial 15N-labeled litter was only 1.2 times higher in the no harvest plot than in the harvest plots because of the low N concentration in the stem litter. The litter functioned as a minor N sink within the first 6 months of decomposition, and it then shifted to functioning as a minor N source after 1 year of decomposition. The recovery of litter-derived N in the sediment and plant biomass was low (less than 10% of the initial litter N), and much of the remaining N might have been released into ambient water or lost through denitrification. Furthermore, our results suggested a potentially low contribution of litter-derived N to internal N loading for at least 1 year regardless of the harvest management treatment.

Recording the direct surgeon's view with an operating microscopic view improves microscopic ophthalmic surgery training.

AIM: To establish a recording system with a direct view of the surgeon to supplement video recording under an operating microscope, which lacks information on the movement and position of the surgeon's hands, and to facilitate the reproduction of a skilled surgeon's technique by a surgeon in training. METHODS: A small camera was attached to the operating microscope with a custom adapter. Microscopic surgeon's view and direct surgeon's view through this new camera were recorded in the surgical recording system. Both movies were synchronized and analyzed how do surgeons handle the instruments. RESULTS: A small camera attached to the operating microscope allowed the surgeon's hands motion to be recorded without interfering with the surgeon's movements. Different surgeons used different methods to manipulate the ultrasound handpiece and the irrigation/aspiration device. Even in the simple paracentesis procedure, different surgeons used different methods. Surgeons-in-training were able to identify and improve their weaknesses by watching synchronized movies of their hand motions and microscopic view. CONCLUSION: Simultaneous recording the surgical field out of the operating microscopic view by a small camera set on the microscope is comprehensive and improves surgeons-in-training understanding and learning surgeries.

Rapid Screening Using Pathomorphologic Interpretation to Detect BRAFV600E Mutation and Microsatellite Instability in Colorectal Cancer.

PURPOSE: Rapid decision-making is essential in precision medicine for initiating molecular targeted therapy for patients with cancer. This study aimed to extract pathomorphologic features that enable the accurate prediction of genetic abnormalities in cancer from hematoxylin and eosin images using deep learning (DL). EXPERIMENTAL DESIGN: A total of 1,657 images (one representative image per patient) of thin formalin-fixed, paraffin-embedded tissue sections from either primary or metastatic tumors with next-generation sequencing-confirmed genetic abnormalities-including BRAFV600E and KRAS mutations, and microsatellite instability high (MSI-H)-that are directly relevant to therapeutic strategies for advanced colorectal cancer were obtained from the nationwide SCRUM-Japan GI-SCREEN project. The images were divided into three groups of 986, 248, and 423 images to create one training and two validation cohorts, respectively. Pathomorphologic feature-prediction DL models were first developed on the basis of pathomorphologic features. Subsequently, gene-prediction DL models were constructed for all possible combinations of pathomorphologic features that enabled the prediction of gene abnormalities based on images filtered by the combination of pathomorphologic feature-prediction models. RESULTS: High accuracies were achieved, with AUCs > 0.90 and 0.80 for 12 and 27, respectively, of 33 analyzed pathomorphologic features, with high AUCs being yielded for both BRAFV600E (0.851 and 0.859) and MSI-H (0.923 and 0.862). CONCLUSIONS: These findings show that novel next-generation pathology methods can predict genetic abnormalities without the need for standard-of-care gene tests, and this novel next-generation pathology method can be applied for colorectal cancer treatment planning in the near future.

Effects of Parenteral Amino Acid Administration on the Postoperative Nutritional Status and Wound Healing of Protein-Malnourished Rats.

In Japan, parenteral nutrition (PN) solutions are frequently administered to patients in the postoperative short-term period. In these cases, amino acid-containing peripheral parenteral nutrition (PPN) solutions, amino acid-free maintenance solutions or combinations of the two are used. However, consensus regarding the most beneficial solution for these patients is lacking. Here, we examined the nutritional status and wound healing outcomes in protein-malnourished rats receiving postoperative administrations of PPN solution, maintenance solution or combinations of the two solutions. Protein malnutrition was induced in Sprague-Dawley rats by feeding an AIN-93G-based low-protein diet (5% casein) for 2 wk. After laparotomy, dorsal skin incision, and placement of a jugular vein catheter, the rats were divided into 3 groups. Each group was administered 113 kcal/kg/d, with group A receiving maintenance solutions without amino acid, group B receiving PPN with 1.5% amino acid, and group C receiving PPN with 3% amino acid. After 5 d post-operative administration, we measured the tensile strength of the wound area, skeletal muscle weights, and nutritional parameters. Significantly higher plasma nutritional parameters and gastrocnemius and extensor digitorum longus (EDL) muscle weights were observed in groups B and C than in group A. Group C exhibited significantly elevated tensile strength of the wound area along with up-regulation of type I collagen mRNA expression compared to group A. These findings demonstrate the nutritional status and wound healing benefits of short-term postoperative administration of PPN solutions containing amino acids in protein-malnourished rats.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.