Rare recurrence pattern after complete response to chemotherapy in a patient with rectal cancer: a case report.

BACKGROUND: Colorectal cancer (CRC) often metastasizes to the liver, lungs, lymph nodes, and peritoneum but rarely to the bladder, small intestine, and skin. We here report the rare metastasis of anal cancer in the left bladder wall, followed by metastases to the small intestine and skin, after abdominoperineal resection and left lateral lymph node dissection with chemotherapy in a patient with clinician Stage IVa disease. CASE PRESENTATION: A 66-year-old man presented with 1-month history of bloody stool and anal pain and diagnosed with clinical Stage IVa anal cancer with lymph node and liver metastases (cT3, N3 [#263L], M1a [H1]). Systemic chemotherapy led to clinical complete response (CR) for the liver metastasis and clinical near-CR for the primary tumor. Robot-assisted laparoscopic perineal rectal resection and left-sided lymph node dissection were performed. Computed tomography during 18-month postoperative follow-up identified a mass in the left bladder wall, which was biopsied with transurethral resection, was confirmed as recurrent anal cancer by histopathologic evaluation. After two cycles of systemic chemotherapy, partial resection of the small intestine was performed due to bowel obstruction not responding to conservative therapy. The histopathologic evaluation revealed lymphogenous invasion of the muscularis mucosa and subserosa of all sections. Ten months after the first surgery for bowel obstruction and two months before another surgery for obstruction of the small intestine, skin nodules extending from the lower abdomen to the thighs were observed. The histopathologic evaluation of the skin biopsy specimen collected at the time of surgery for small bowel obstructions led to the diagnosis of skin metastasis of anal cancer. Although panitumumab was administered after surgery, the patient died seven months after the diagnosis of skin metastasis. CONCLUSIONS: This case illustrates the rare presentation of clinical Stage IVa anal cancer metastasizing to the bladder wall, small intestine, and skin several years after CR to chemotherapy.

[A Case of Conversion Surgery for Unresectable Advanced Gastric Cancer of Which Metastatic Site Was Disappear by Chemotherapy but the Primary Site Was Enlarged after Five Years].

A 77-year-old man presented to our hospital with a chief complaint of stomachache. He received a diagnosis of unresectable advanced gastric cancer classified as cT3, N+, M1(LYM, HEP, OSS), Stage ⅣB. He underwent first-line chemotherapy with SOX, second-line treatment with PTX plus Ram, and third-line treatment with nivolumab. The primary tumor showed a reduction in size, and liver and lymph node metastases were not detectable. However, after 5 years of chemotherapy, a re- enlargement was observed in the primary gastric lesion without progression of liver and lymph node metastases. Subsequently, conversion surgery was performed. Based on the pathological analysis, the diagnosis was ypT1b2(SM2), N0(0/17), M0, ypStage ⅠA, R0. After nivolumab administration postoperatively for 5 months, chemotherapy was discontinued as there was no recurrence.

Pronecroptotic Therapy Using Ceramide Nanoliposomes Is Effective for Triple-Negative Breast Cancer Cells.

Regulated necrosis, termed necroptosis, represents a potential therapeutic target for refractory cancer. Ceramide nanoliposomes (CNLs), considered potential chemotherapeutic agents, induce necroptosis by targeting the activating protein mixed lineage kinase domain-like protein (MLKL). In the present study, we examined the potential of pronecroptotic therapy using CNLs for refractory triple-negative breast cancer (TNBC), for which there is a lack of definite and effective therapeutic targets among the various immunohistological subtypes of breast cancer. MLKL mRNA expression in tumor tissues was significantly higher in TNBC patients than in those with non-TNBC subtypes. Similarly, among the 50 breast cancer cell lines examined, MLKL expression was higher in TNBC-classified cell lines. TNBC cell lines were more susceptible to the therapeutic effects of CNLs than the non-TNBC subtypes of breast cancer cell lines. In TNBC-classified MDA-MB-231 cells, the knockdown of MLKL suppressed cell death induced by CNLs or the active substance short-chain C6-ceramide. Accordingly, TNBC cells were prone to CNL-evoked necroptotic cell death. These results will contribute to the development of CNL-based pronecroptotic therapy for TNBC.

A Case of Closure of Recurrent Full-Thickness Macular Hole by Spontaneous Retinal Detachment around the Macular Hole and Gas Tamponade.

Introduction: Here, we present a case of full-thickness macular hole (FTMH) recurrence following two vitrectomies, accompanied by additional internal limiting membrane (ILM) peeling and gas tamponade. Ultimately, FTMH closure was accomplished by spontaneous retinal detachment around the macular hole and gas tamponade alone. Case Presentation: The patient, a 54-year-old woman with a lamellar macular hole, had a visual acuity of 20/100 in her left eye. The treatment regimen included cataract surgery, a 25-gauge pars plana vitrectomy involving ILM peeling, application of the lamellar hole epiretinal proliferation embedding technique, and subsequent gas tamponade. Closure of the lamellar macular hole was observed a month post-surgery, improving visual acuity to 20/40. However, FTMH developed 3 months after the initial surgery, resulting in visual acuity decline to 20/100. A 25-gauge pars plana vitrectomy was performed with extensive ILM peeling and 20% sulfur hexafluoride gas tamponade. FTMH closure was noted within 19 days after reoperation, enhancing visual acuity to 20/66. Approximately 1.5 months after reoperation, a pinhole-shaped macular hole was identified, and the patient opted for follow-up observation due to her refusal to undergo additional surgery. As the macular hole gradually enlarged resembling retinal detachment, outpatient fluid-gas exchange with 14% perfluoropropane was performed 3.5 months after reoperation. The FTMH closed within a week post-gas injection and remained closed for more than 1 year. Consequently, visual acuity in the left eye was sustained at 20/50. Conclusion: We encountered a case that might highlight the significance of releasing subretinal adhesions surrounding a FTMH for successful closure.

Comparison of Loading Dose between Aflibercept and Faricimab for Neovascular Age-Related Macular Degeneration.

BACKGROUND: Recently, faricimab was approved as the new drug for neovascular age-related macular degeneration (nAMD). We lack the knowledge to choose between the existing drug and this new drug to use for treatment-naïve nAMD cases. In this study, we compared the functional and morphologic effects in loading dose between patients with treatment-naïve nAMD treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in a clinical setting. METHOD: This retrospective study included 30 eyes of 28 patients who started treatment with IVA between June and September 2022 and 30 eyes of 29 patients who were administered IVF between October 2022 and March 2023. All patients received three monthly IVA or IVF. The best corrected visual acuity (BCVA), central retinal thickness (CRT), and the proportion of eyes with residual exudative change at baseline and 1,2, and 3 months after initial treatment were compared between the groups. RESULTS: The mean BCVA significantly improved from pre-treatment after the loading dose in the IVA group (0.46 ± 0.46-0.36 ± 0.37, p = 0.0047) but not in the IVF group (0.46 ± 0.41-0.44 ± 0.45, p = 0.60). The mean CRT significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group 2 months after the first treatment (p = 0.026). The analysis of cases that achieved complete resolution of exudative changes after the loading dose showed that the IVA group had a significant improvement in the BCVA, whereas the IVF group did not (p = 0.0047 and 0.20, respectively). CONCLUSIONS: Although both IVA and IVF significantly improved CRT, the BCVA improved significantly in the IVA group but not in the IVF group.

Optical Bistability in Nanosilicon with Record Low Q-Factor.

We demonstrated optical bistability in an amorphous silicon Mie resonator with a size of ∼100 nm and Q-factor as low as ∼4 by utilizing photothermal and thermo-optical effects. We not only experimentally confirmed the steep intensity transition and the hysteresis in the scattering response from silicon nanocuboids but also established a physical model to numerically explain the underlying mechanism based on temperature-dependent competition between photothermal heating and heat dissipation. The transition between the bistable states offered particularly steep superlinearity of scattering intensity, reaching an effective nonlinearity order of ∼100th power over excitation intensity, leading to the potential of advanced optical switching devices and super-resolution microscopy.

Multipole engineering by displacement resonance: a new degree of freedom of Mie resonance.

The canonical studies on Mie scattering unravel strong electric/magnetic optical responses in nanostructures, laying foundation for emerging meta-photonic applications. Conventionally, the morphology-sensitive resonances hinge on the normalized frequency, i.e. particle size over wavelength, but non-paraxial incidence symmetry is overlooked. Here, through confocal reflection microscopy with a tight focus scanning over silicon nanostructures, the scattering point spread functions unveil distinctive spatial patterns featuring that linear scattering efficiency is maximal when the focus is misaligned. The underlying physical mechanism is the excitation of higher-order multipolar modes, not accessible by plane wave irradiation, via displacement resonance, which showcases a significant reduction of nonlinear response threshold, sign flip in all-optical switching, and spatial resolution enhancement. Our result fundamentally extends the century-old light scattering theory, and suggests new dimensions to tailor Mie resonances.

Clinical Impact of Transanal Drainage Tube on Anastomosis Leakage Following Minimally Invasive Resection Without Diverting Stoma in Patients With Rectal Cancer: A Propensity Score-matched Analysis.

OBJECTIVES: As one of the most serious complications of rectal cancer (RC) surgery, preventing anastomotic leakage (AL) is crucial. Several studies have suggested a positive role of the transanal drainage tube (TaDT) in AL prevention. However, whether TaDT is beneficial for AL in patients with RC remains controversial. The present study aimed to evaluate the clinical impact of TaDT on AL following minimally invasive resection without diverting stoma (DS) in patients with RC. MATERIALS AND METHODS: We retrospectively analyzed 392 consecutive patients with RC who had undergone minimally invasive resection without DS between 2010 and 2021. Propensity score matching (PSM) was performed to reduce selection bias. AL was classified as grade A, B, or C. RESULTS: A TaDT was used in 214 patients overall. After PSM, we enrolled 316 patients (n=158 in each group). Before PSM, significant group-dependent differences were observed in terms of age, American Society of Anesthesiologists physical status, and the use of antiplatelet/anticoagulant agents. The frequency of AL was 7.3% in the overall cohort and was significantly lower in the TaDT group (3.7%) than in the non-TaDT group (11.8%). The rate of grade B AL was significantly lower in the TaDT group than in the non-TaDT group (before PSM, P <0.01; after PSM, P =0.02). However, no significant differences between groups were found for grade C AL. Moreover, multivariate analysis identified the lack of a TaDT as an independent risk factor for AL in the overall and matched cohorts [before PSM, odds ratio, 3.64, P <0.01; after PSM, odds ratio, 2.91, P =0.02]. CONCLUSION: These results indicated that TaDT may play a beneficial role in preventing AL, particularly of grade B, for patients with RC undergoing minimally invasive resection without DS. However, further randomized controlled trials, including patient-reported outcomes, are still needed to understand better the role of TaDT in preventing ALs in patients with RC undergoing minimally invasive resection without DS.

Aggressive surgical intervention may improve prognosis in patients with ovarian metastasis from colorectal cancer.

PURPOSE: The current study aimed to investigate the prognostic clinicopathological factors of synchronous and metachronous ovarian metastasis (OM) from colorectal cancer (CRC) in patients with and without oophorectomy. METHODS: Female patients with OM from CRC who underwent primary tumor resection at our institution from January 2013 to December 2020 were evaluated. RESULTS: Of 661 female patients, 22 (3.3%) were diagnosed with OM. Among 22 patients with OM, 12 underwent OM resection. Twenty (91%) patients had extra OM upon diagnosis. Thirteen (59%) patients in the non-surgery group had peritoneal dissemination at surgery or on computed tomography scan or positron emission tomography-computed tomography. Two patients in the OM surgery group had emergency surgery because of abdominal pain. Four patients had postoperative complications, and the median duration of hospital admission was 16.5 days. The median survival time from OM diagnosis to mortality was 20.9 months. Then, the association between the clinicopathological factors and overall survival (OS) was investigated. Tumor location and surgery were found to be related to OS (p = 0.03, 0.006, respectively) in the univariate analysis. However, only surgery was associated with OS (p = 0.02) in the multivariate analysis. CONCLUSION: Surgery is an important prognostic clinicopathological factor of OM from CRC. OM tumors should be resected because OM surgery is less likely to cause complications and symptoms.

Relationship between Full-Thickness Macular Hole Onset and Posterior Vitreous Detachment: A Temporal Onset Theory.

Purpose: To evaluate the relationship between full-thickness macular hole (FTMH) onset and perifoveal posterior vitreous detachment using OCT data. Design: Retrospective study. Participants: A total of 742 patients with FTMH or impending macular hole (MH) in ≥ 1 eye, as determined by ophthalmoscopy and OCT. Methods: Macular holes were staged using OCT results. Patients with the posterior vitreous membrane clearly detected in the OCT images and vitreoretinal adhesion size ≤ 1500 µm-eyes with MH stages 1-3-were included in the study. The contralateral eyes were also included in the analyses if they showed the focal type of vitreomacular adhesion (VMA) (i.e., vitreoretinal adhesion ≤ 1500 µm). The distance between the posterior vitreous membrane and the surface of the retina was defined as the posterior vitreous separation height (PVSH). Using the OCT images, PVSHs of each eye in 4 directions (nasal, temporal, superior, and inferior) at 1 mm from the center of the MH or fovea were calculated. Main Outcome Measures: The main outcome measures were PVSHs according to the MH stage and VMA, the relationship of the foveal inner tear with PVSH, and the likelihood of a foveal inner tear based on the direction. Results: The PVSH trends in each of the 4 directions were as follows: VMA < MH stage 1 = MH stage 2 < MH stage 3. Initial MH stage 2 (onset of FTMH) was defined as the presence of a gap in only 1 of the 4 directions from the center of the MH. With increased PVSH, the likelihood of a gap increased (P = 0.002), and a temporal gap was more likely to occur than a nasal gap (P = 0.002). Conclusions: At FTMH onset, a foveal inner tear likely appears on the temporal side or the side showing a high PVSH value. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Single-incision laparoscopic surgery for intestinal intussusception due to neuroendocrine tumor.

BACKGROUND: Small intestinal neuroendocrine tumor (NET) is uncommon, but intestinal intussusception caused by NET is even rare. We report a rare case of single-incision laparoscopic surgery (SILS) for intestinal intussusception due to NET G1. CASE PRESENTATION: A 72-year-old woman presented with vomiting, diarrhea, and abdominal pain. Contrast-enhanced computed tomography (CT) revealed the target sign in the ascending colon. An enhanced nodule was detected at the lead point, leading us to suspect a tumor. Colonoscopy showed a tumor at the lead point of the intestinal intussusception. Histological findings led to a diagnosis of NET G1. Single-incision laparoscopic ileocecal resection with regional lymphadenectomy was then performed. The patient was discharged 10 days postoperatively with no complications. CONCLUSION: We achieved SILS with regional lymphadenectomy for preoperatively diagnosed intestinal intussusception due to NET G1. Although this condition is rare, surgeons should take this possibility into consideration in cases showing similar findings.

The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy.

To assess the potential clinical utility of cell-free DNA (cfDNA)-based biomarkers for identifying gastric cancer (GC) patients who benefit from nivolumab. From 31 GC patients treated with nivolumab monotherapy (240 mg/body, Bi-weekly) in 3rd or later line setting, we prospectively collected blood samples at baseline and before the 3rd dose. We compared cfDNA-based molecular findings, including microsatellite instability (MSI) status, to tissue-based biomarkers. We assessed the clinical value of blood tumor mutation burden (bTMB) and copy number alterations (CNA) as well as the cfDNA dynamics. The concordance between deficient-MMR and cfDNA-based MSI-high was 100% (3/3). Patients with bTMB ≥ 6 mut/Mb had significantly better progression-free survival (PFS) and overall survival (OS); however, such significance disappeared when excluding MSI-High cases. The combination of bTMB and CNA positivity identified patients with survival benefit regardless of MSI status (both PFS and OS, P < 0.001), with the best survival in those with bTMB≥6mut/Mb and CNAnegative. Moreover, patients with decreased bTMB during treatment had a better disease control rate (P = 0.04) and longer PFS (P = 0.04). Our results suggest that a combination of bTMB and CNA may predict nivolumab efficacy for GC patients regardless of MSI status. bTMB dynamics have a potential utility as an on-treatment biomarker.

[A Case of Advanced Gastric Cancer in Which Tumor Relapse Was Observed after Discontinuation of Nivolumab Due to Complete Response, and for Which Re-Administration Was Initiated].

A 61-year-old male was diagnosed with unresectable advanced gastric cancer(cT4b[SI; panc], N+, M0, cStage ⅣA). However he was administered S-1 plus oxaliplatin as a primary treatment and ramucirumab plus paclitaxel as a secondary treatment, the primary tumor and lymph nodes were enlarged. We judged PD and switched to the third-line treatment with nivolumab. After starting nivolumab, both the primary tumor and the lymph nodes shrank, and the PET-CT scan after 24 courses showed no FDG accumulation in the primary tumor or lymph nodes, so we judged the response as CR. The patient requested discontinuation of nivolumab, and nivolumab administration was stopped. Twenty months later after nivolumab administration was discontinued, CT scan showed re-growth of the primary tumor, and nivolumab administration was resumed. After resumption, he received 22 courses of nivolumab for 10 months with maintenance of SD.

The influence of stimulating electrode conditions on electrically evoked potentials and resistance in suprachoroidal transretinal stimulation.

PURPOSE: To determine the influence of stimulating electrode conditions on the amplitudes and latencies of electrically evoked potentials (EEPs) and the resistance at the electrode-tissue interface in the suprachoroidal transretinal stimulation (STS) system. STUDY DESIGN: Experimental study. METHODS: A scleral pocket (3 × 5 mm) was created just over the visual streak in anesthetized pigmented rabbits (weight, 1.9-2.7 kg), and STS stimulating electrodes were implanted into the pocket. Measurements were obtained with stimulating electrodes of different lengths (0.3 or 0.5 mm) and different surface characteristics (smooth or porous). EEPs elicited with a fixed current under each set of electrode conditions were recorded; three measurement sessions were performed for each rabbit. The resistance at each electrode-tissue interface was measured. RESULTS: The latencies and amplitudes of the EEPs did not differ significantly with changes in the height and surface characteristics of the stimulating electrodes, but the resistances at the electrode-tissue interface differed significantly (P = 0.001; the resistance values for the 0.3-mm-long electrode with a porous surface was 5.24 ± 0.67 kΩ and with the 0.3- and 0.5-mm-long electrodes with smooth surfaces were 7.63 ± 0.12 kΩ and 6.77 ± 0.20 kΩ). CONCLUSION: Being shorter did not affect the EEPs of the stimulating electrodes with a porous surface while decreasing the resistance at the electrode-tissue interface.

Embedding Technique versus Conventional Internal Limiting Membrane Peeling for Lamellar Macular Holes with Epiretinal Proliferation.

PURPOSE: To examine the outcomes of pars plana vitrectomy (PPV) with lamellar hole-associated epiretinal proliferation (LHEP) embedding and conventional internal limiting membrane (ILM) peeling for lamellar macular holes (LMHs) with LHEP. DESIGN: Retrospective observational study. SUBJECTS: Forty eyes of 39 consecutive patients with LMHs and LHEP who underwent 3-port PPV with a minimum follow-up of 3 months. METHODS: We compared the results of eyes that underwent PPV with LHEP embedding and ILM peeling (group E) with those of eyes that underwent PPV with ILM peeling only (group I) from September 2010 to September 2021. We confirmed whether the LHEP was embedded using postoperative OCT in all the cases. MAIN OUTCOME MEASURES: Postoperative best-corrected visual acuity (BCVA) and the development of macular holes (MHs) were assessed. RESULTS: The mean patient age was 73.3 years. The mean follow-up duration was 23.1 months. There were 23 and 17 eyes in groups E and I, respectively. Preoperative BCVA (P = 0.774) and central retinal thickness (CRT) (P = 0.800) did not differ significantly between the 2 groups. The final BCVA in group E was better than that in group I (P = 0.059). The final CRT in group E was thicker than that in group I (P < 0.001). Postoperatively, a significant improvement in BCVA was observed in group E at 3 months (P = 0.001) and at the final visit (P < 0.001). None of the eyes in group E developed postoperative MHs, whereas 5 eyes in group I developed postoperative MHs. CONCLUSIONS: Pars plana vitrectomy using the LHEP embedding technique improved visual acuity significantly and yielded better anatomic outcomes than those with PPV using conventional ILM peeling; MH formation did not occur. Embedding LHEP is more effective than conventional surgical procedures for LMHs.

Expression profile of the zinc transporter ZnT3 in taste cells of rat circumvallate papillae and its role in zinc release, a potential mechanism for taste stimulation.

Zinc is an essential trace element, and its deficiency causes taste dysfunction. Zinc accumulates in zinc transporter (ZnT)3-expressing presynaptic vesicles in hippocampal neurons and acts as a neurotransmitter in the central nervous system. However, the distribution of zinc and its role as a signal transmitter in taste buds remain unknown. Therefore, we examined the distribution of zinc and expression profiles of ZnT3 in taste cells and evaluated zinc release from isolated taste cells upon taste stimuli. Taste cells with a spindle or pyriform morphology were revealed by staining with the fluorescent zinc dye ZnAF-2DA and autometallography in the taste buds of rat circumvallate papillae. Znt3 mRNA levels were detected in isolated taste buds. ZnT3-immunoreactivity was found in phospholipase-ß2-immunopositive type II taste cells and aromatic amino acid decarboxylase-immunopositive type III cells but not in nucleoside triphosphate diphosphohydrolase 2-immunopositive type I cells. Moreover, we examined zinc release from taste cells using human transient receptor potential A1-overexpressing HEK293 as zinc-sensor cells. These cells exhibited a clear response to isolated taste cells exposed to taste stimuli. However, pretreatment with magnesium-ethylenediaminetetraacetic acid, an extracellular zinc chelator - but not with zinc-ethylenediaminetetraacetic acid, used as a negative control - significantly decreased the response ratio of zinc-sensor cells. These findings suggest that taste cells release zinc to the intercellular area in response to taste stimuli and that zinc may affect signaling within taste buds.

The Caliber of Optociliary Shunt Vessels Is Associated with Macular Blood Flow and Visual Acuity in Central Retinal Vein Occlusion.

Purpose: To define the role of optociliary shunt vessels (OSVs) in eyes with central retinal vein occlusion (CRVO) using OCT angiography (OCTA) with macular parameters. Design: Retrospective, observational, consecutive case series. Participants: Forty-one eyes in 38 consecutive patients with CRVO were analyzed in this study. Methods: Optic disc and macula were imaged by swept-source OCTA (3 × 3 mm) as well as by high-quality fundus photography. Main Outcome Measures: We compared macular vessel density (VD) and visual acuity between eyes in which OSVs developed and those in which they did not. Furthermore, we measured the diameter of the OSVs and analyzed the correlation with macular VD and visual acuity. Results: Optociliary shunt vessels were found in 25 eyes (61%). Central retinal vein occlusion with OSVs did not show any statistical difference compared with CRVO without OSVs in either macular VD of the total retina (0.31 ± 0.07 and 0.26 ± 0.09, respectively; P = 0.0937) or final best-corrected visual acuity (BCVA) (0.30 ± 0.43 logarithm of the minimum angle of resolution [logMAR] and 0.59 ± 0.54 logMAR, respectively; P = 0.0705). The mean OSV diameter was 71 ± 30 µm in CRVO with OSV. The diameter of the OSVs was correlated positively with superficial VD (r = 0.443; P = 0.027), deep VD (r = 0.494; P = 0.012), and total VD (r = 0.491; P = 0.013). Furthermore, the OSV diameter was also negatively correlated with BCVA (logMAR) at the final visit (r = -0.531; P = 0.006). Conclusions: The results demonstrated that the diameter of the OSVs was associated with macular VD and visual acuity in patients with CRVO. The development of large OSVs on the optic disc may be a good indicator of the maintenance of blood flow in the macula.

Spontaneous Resolution of Macular Edema with Abnormal Vessel Crossing near the Central Macula by Congenital Retinal Macrovessel.

We present a case of a congenital retinal macrovessel (CRM) with spontaneous resolution of cystoid macular edema. A 39-year-old woman with sudden decreased vision in her right eye was referred to our clinic and found to have a CRM with macular edema. Her visual acuity was 20/25. A week later, the macular edema disappeared without any treatment, and her visual acuity was 20/15. We performed optical coherence tomography angiography and fluorescein angiography (FA), which revealed no obstruction of retinal flow but a slight disturbance of retinal flow near the central fovea on FA. We encountered a case of spontaneous resolution of macular edema with abnormal vessel crossing near the central macula by a CRM, and multimodal imaging was useful for investigating the pathology of the disease.

The conserved C-terminal residues of FAM83H are required for the recruitment of casein kinase 1 to the keratin cytoskeleton.

The casein kinase 1 (CK1) family of serine/threonine protein kinases is involved in diverse cellular events at discrete subcellular compartments. FAM83H acts as a scaffold protein that recruits CK1 to the keratin cytoskeleton or to the nuclear speckles, which are storage sites for splicing factors. We determined the amino acid region of FAM83H required for recruiting CK1 to the keratin cytoskeleton. The subcellular localization of mutant FAM83H proteins with deletions of amino acid residues at different positions was evaluated via immunofluorescence. FAM83H mutants with deleted C-terminal residues 1134-1139, which are conserved among vertebrates, lost the ability to localize and recruit CK1 to the keratin cytoskeleton, suggesting that these residues are required for recruiting CK1 to the keratin cytoskeleton. The deletion of these residues (1134-1139) translocated FAM83H and CK1 to the nuclear speckles. Amino acid residues 1 to 603 of FAM83H were determined to contain the region responsible for the recruitment of CK1 to the nuclear speckles. Our results indicated that FAM83H recruits CK1 preferentially to the keratin cytoskeleton and alternatively to the nuclear speckles.

Analysis of optic disc tilt angle in intrapapillary hemorrhage adjacent to peripapillary subretinal hemorrhage using swept-source optical coherence tomography.

Purpose: To report findings on the tilt angle of optic nerve heads (ONHs) that developed intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage (IHAPSH) using swept-source optical coherence tomography (SS-OCT). Observations: Five consecutive patients who presented with IHAPSH were reviewed retrospectively. We reviewed five consecutive eyes from the five patients, analyzed the optic tilt angle obtained from SS-OCT B-scans, and compared the results and other clinical characteristics. All patients had larger optic disc tilt angles in the eyes with IHAPSH than in the contralateral, unaffected eye. The mean ratio of the tilt angle in the eyes with IHAPSH to that in the contralateral eye was 1.37 (95% confidence interval 1.15-1.58). Conclusions and Importance: The ONH of IHAPSH was evaluated quantitatively with SS-OCT for the first time in this study. Larger angle tilted discs in IHAPSH-affected eyes are anatomically and histologically more vulnerable and may explain why IHAPSH develops monocularly.