Factors predicting the need for liver transplantation in biliary atresia patients after 18 years of age.

PURPOSE: We aimed to identify factors predicting the need for future liver transplantation (LT) at 18 years of age in patients with biliary atresia (BA). METHODS: BA patients with native liver survival at > 18 years of age were retrospectively reviewed. The clinical characteristics, outcomes, hepatobiliary function, and liver fibrosis markers of native liver survivors (NLS group) were compared with patients who subsequently underwent LT (LT group). RESULTS: The study population included 48 patients (NLS, n = 34; LT, n = 14). The male-to-female ratio, age at Kasai procedure, and type of BA in the two groups did not differ to a statistically significant extent. There was no significant difference in the MELD scores between the groups at 18 years of age. The aspartate aminotransferase-to-platelet ratio index (APRI), albumin-bilirubin (ALBI), and BA liver fibrosis (BALF) scores at 18 years of age were significantly higher in the LT group. The AUCs for APRI, ALBI, and BALF were 0.91, 0.79, and 0.85, respectively. CONCLUSION: Adult BA patients have limited options for LT owing to the lack of donor candidates and the low prevalence of deceased donors. The elucidation of prognostic factors for LT in adulthood is important. APRI was the most useful marker in this study.

Serum Lactate Clearance as a Predictive Biomarker for Optimal Graft Perfusion in Living Donor Liver Transplantation.

BACKGROUND: The optimal balance between the graft volume (GV) and portal venous flow (PVF) in living donor liver transplantation (LDLT) is unclear. As lactate is mainly metabolized in the liver, perioperative lactate levels are reportedly a useful biomarker for early graft dysfunction (EGD). The present study analyzed perioperative lactate levels according to the PVF. METHODS: The PVF/GV (mL/min per 100 g GV) of 97 recipients from 1996 to 2022 was retrospectively classified as low (LPVF; PVF/GV ≤ 100, N = 29), moderate (MPVF; PVF/GV 100-250, N = 40), or high (HPVF; PVF/GV > 250, N = 28). Lactate levels were obtained preoperatively (L0), immediately after graft reperfusion (L1), 4 h after reperfusion (L2), and on postoperative day 3 (L3). The lactate clearances were then calculated. RESULTS: The lower the PVF/GV ratio, the younger the age at LDLT and the higher the graft-to-recipient weight ratio. The median L2 and L3 in the HPVF group were significantly higher than those in the other groups (p = 0.019 and p = 0.003, respectively). The median ΔL1 in the HPVF group was lower than that in the LPVF and MPVF groups (0.23 vs. 0.50, p < 0.0001 and 0.23 vs. 0.41, p = 0.011, respectively). ΔL1 was negatively correlated with the PVF/GV. Although no patient had EGD, three patients with HPVF with low ΔL1 developed small-for-size syndrome. CONCLUSIONS: Graft hyperperfusion may delay the recovery of the graft function and result in poor lactate clearance. The combination of the PVF/GV and lactate clearance may be useful as a prognostic marker for optimal graft perfusion in LDLT. LEVEL OF EVIDENCE: IV.

Qualitative inductive analysis of the lives of women with persistent cloaca based on their narratives.

PURPOSE: The study aimed to explore and describe the lives of patients with persistent cloaca (PC) from childhood to adulthood. METHODS: Semistructured interviews were conducted with nine adult patients with PC. Their experiences and thoughts regarding this disease were analyzed qualitatively and inductively. RESULTS: After classifying the experiences and thoughts of patients with PC, 13 categories were extracted. The following five themes emerged from these categories. (1) Difficulties with excretion and vaginal management because of the disease. (2) The degree of understanding of those around them and society has a huge effect on their way of life. (3) The inferiority of a woman who is not a "normal woman." (4) A "never-ending disease" in which problems continue even after the transition period. (5) Differences in the central point of the narrative depending on the age group. CONCLUSIONS: In this study, qualitative and inductive analyses of data from semistructured interviews with patients with PC revealed their experiences and thoughts. The results will provide a guide for young patients and the medical professionals who treat them. Accordingly, monitoring their lives until adulthood is necessary.

A retrospective study investigating the risk of graft loss in living donor liver transplant cases where size mismatching is predicted from graft-to-recipient weight ratio.

BACKGROUND/PURPOSE: Living donor liver transplantation (LDLT) is vital for pediatric end-stage liver disease due to organ shortages. The graft-to-recipient weight ratio (GRWR) preoperatively measured predicts the outcomes of LDLT. We typically target between 0.8 and 3.0-4.0%, but the ideal GRWR remains controversial. We compared the outcomes of LDLT according to the GRWR to examine whether the criteria could be expanded while ensuring safety. METHODS: We retrospectively reviewed 99 patients who underwent LDLT in our department by dividing them into three groups according to their GRWR: Group S, with GRWR values lower than the normal range (GRWR < 0.8%); Group M, with GRWR values in the normal range (GRWR ≥ 0.8 to < 3.5%); and Group L, with GRWR values above the normal range (GRWR ≥ 3.5%). RESULTS: In Groups S and L, 46.2 and 44.4% of patients underwent splenectomy and delayed abdominal wall closure, respectively. After these intraoperative adjustments, there were no significant differences between the groups in 5-year patient survival, 5-year graft survival, or the occurrence of post-transplantation thrombosis. CONCLUSION: When the GRWR is beyond the normal threshold, the risk of complications associated with graft size might be reduced by adjustments to provide appropriate portal blood flow and by delayed abdominal wall closure.

Reproducibility of Portable OCT and Comparison with Conventional OCT.

Optical coherence tomography (OCT) is an indispensable instrument in ophthalmology; however, some facilities lack permanent OCT devices. ACT100, a portable SD-OCT system, allows for medical examinations at hospitals that do not have OCT and house calls. We investigated the usefulness of ACT100 by examining the reproducibility of retinal thickness measurements in 35 healthy participants with normal eyes using ACT100 and Cirrus. Using two OCTs, the OCT imaging of both eyes of each subject was performed. Macular retinal thickness was evaluated using the average value in nine lesions of the Early Treatment Diabetic Retinopathy Study (ETDRS) circle. Both models captured images in all cases. In the right eye, mean retinal thickness was significantly lower than in the ACT100 group in all regions; however, the measured values correlated well. The intraclass correlation coefficients showed the same high reliability as the Cirrus. The coefficients of variation (CVs) of both models showed little variation and high stability; however, the CV of ACT100 was significantly higher. The left eye was almost identical. Macular retinal thickness measured using ACT100 showed slightly greater variability than that by Cirrus; the reproducibility was good and correlated well with that of Cirrus. This technique is a suitable alternative to conventional OCT.

Early and late outcomes of congenital biliary dilatation in pediatric patients.

BACKGROUND: This study aimed to reveal the early and late postoperative complications and outcomes after surgery for congenital biliary dilatation (CBD) by reviewing cases over the past 40 years. METHODS: We retrospectively evaluated 59 patients with CBD who underwent radical surgery for complications and outcomes, based on medical records. Early complications were defined as those requiring treatment within 5 years of the initial operation. Late complications were defined as those treated more than 5 years later. RESULTS: The median age at the first surgery was 37 months. Regarding biliary reconstruction, 54 of the 59 patients (91.5%) underwent hepaticojejunostomy. Although three patients underwent cholecystoduodenostomy and one patient underwent hepaticoduodenostomy, all were converted to hepaticojejunostomy after a median of 12.5 years. One patient developed synchronous biliary carcinoma and underwent pancreaticoduodenectomy. Early complications occurred in seven patients with 10 events (surgical site infection, n = 3 bile leakage, n = 3; ileus, n = 3; bile duct obstruction, n = 1 and intussusception, n = 1). Late complications occurred in nine patients with 12 events (ileus, n = 3; anastomotic stricture, n = 3; hepatolithiasis, n = 3; asynchronous biliary carcinoma, n = 2; pancreatolithiasis, n = 1). Two of the three patients with hepatolithiasis underwent hepatectomy refractory to the endoscopic approach. Two patients developed asynchronous biliary carcinoma at 34 and 13 years after last operation; both ultimately died of the carcinoma. Only 35 patients (61.4%) underwent a follow-up examination. A total of 11 female patients (45.8%) eventually married, and all successfully gave birth. CONCLUSION: Although the long-term prognosis is excellent with complete cyst excision and hepaticojejunostomy, we emphasize the importance of long-term follow-up.

Malignancy After Living Donor Liver Transplantation.

OBJECTIVES: De novo malignancy (DNM) is a major cause of death in long-term recipients of liver transplantation (LT). We herein report our experience with DNM after living-donor LT (LDLT). PATIENTS AND METHODS: A total of 111 LDLT procedures were performed in our institute from 1999 to 2022. Among them, 70 adult (>13 years old) LDLT recipients who survived for more than 1 year were included in this study. RESULTS: During a median follow-up of 146 (range, 12-285) months, 7 out of 70 recipients developed 8 DNMs, including lung cancer in 4, post-transplant lymphoproliferative disease in 3, and skin cancer in 1. One patient developed metachronal skin cancer and post-transplant lymphoproliferative disease. The pre-LT smoking history rate in patients with DNM was higher than in patients without DNM (P = .004). The survival time after DNM was 6 (1-166) months. Only 2 patients underwent R0 resection. DNM did not recur during follow-up. Other patients who underwent R1 resection and/or chemotherapy and/or radiotherapy all died due to DNMs during the follow-up. The cumulative DNM incidence was 3.5% at 10 years and 18.4% at 20 years after LDLT. The cumulative survival rate in patients with DNM was significantly worse than that in patients without DNM after LDLT (P = .049). CONCLUSION: The survival rate of patients with DNM was lower than that of those without DNM. A pre-LT smoking history is a risk factor for DNM. R0 resection is effective for improving the prognosis of patients with DNM. Regular cancer screening is important for detecting DNM early after LDLT.

Synthesis, Characterization, and Evaluation of the Adsorption Behavior of Cellulose-Graft-Poly(Acrylonitrile-co-Acrylic Acid) and Cellulose-Graft-Poly(Acrylonitrile-co-Styrene) towards Ni(II) and Cu(II) Heavy Metals.

In this study, the synthesis and characterization of grafted cellulose fiber with binary monomers mixture obtained using a KMnO4/citric acid redox initiator were investigated. Acrylonitrile (AN) was graft copolymerized with acrylic acid (AA) and styrene (Sty) at different monomer ratios with evaluating percent graft yield (GY%). Cell-g-P(AN-co-AA) and Cell-g-P(AN-co-Sty) were characterized by SEM, FT-IR, 13C CP MAS NMR, TGA, and XRD. An AN monomer was used as principle-acceptor monomer, and GY% increases with AN ratio up to 60% of total monomers mixture volume. The adsorption behaviors of Cell-g-P(AN-co-AA) and Cell-g-P(AN-co-Sty) were studied for the adsorption of Ni(II) and Cu(II) metal ions from aqueous solution. Optimal adsorption conditions were determined, including 8 h contact time, temperature of 30 °C, and pH 5.5. Cell-g-P(AN-co-AA) showed maximum adsorption capacity of 435.07 mg/g and 375.48 mg/g for Ni(II) and Cu(II), respectively, whereas Cell-g-P(AN-co-Sty) showed a maximum adsorption capacity of 379.2 mg/g and 349.68 mg/g for Ni(II) and Cu(II), respectively. Additionally, adsorption equilibrium isotherms were studied, and the results were consistent with the Langmuir model. The Langmuir model's high determinant coefficient (R2) predicted monolayer sorption of metal ions. Consequently, Cell-g-P(AN-co-AA) and Cell-g-P(AN-co-Sty) prepared by a KMnO4/citric acid initiator were found to be efficient adsorbents for heavy metals from wastewater as an affordable and adequate alternative.

Direct visualization of ribosomes in the cell-free system revealed the functional evolution of aminoglycoside.

The rapid emergence of multi-drug-resistant bacteria has raised a serious public health concern. Therefore, new antibiotic developments have been highly desired. Here, we propose a new method to visualize antibiotic actions on translating ribosomes in the cell-free system under macromolecular crowding conditions by cryo-electron microscopy, designated as the DARC method: the Direct visualization of Antibiotic binding on Ribosomes in the Cell-free translation system. This new method allows for acquiring a more comprehensive understanding of the mode of action of antibiotics on the translation inhibition without ribosome purification. Furthermore, with the direct link to biochemical analysis at the same condition as cryo-EM observation, we revealed the evolution of 2-DOS aminoglycosides from dibekacin (DBK) to arbekacin (ABK) by acquiring the synthetic tailored anchoring motif to lead to stronger binding affinity to ribosomes. Our cryo-EM structures of DBK and ABK bound ribosomes in the cell-free environment clearly depicted a synthetic tailored γ-amino-α-hydroxybutyryl (HABA) motif formed additional interactions with the ribosome enhancing antibiotic bindings. This new approach would be valuable for understanding the function of antibiotics for more efficient drug development.

[Two cases of anti-nuclear matrix protein 2 antibody-positive dermatomyositis sine dermatitis with severe diffuse subcutaneous edema and dysphagia].

Case 1 involved a 68-year-old woman who was admitted to our hospital because of muscle weakness, diffuse subcutaneous edema, dysphagia, and an elevated serum creatine kinase level that had worsened within the previous month. Case 2 involved a 78-year-old woman who was admitted to our hospital because of muscle weakness, bilateral shoulder pain, diffuse subcutaneous edema, and dysphagia that had gradually worsened during the past 5 months. Both patients showed severe diffuse subcutaneous edema and dysphagia and underwent enteral tube feeding. Although they had no skin lesions consistent with dermatomyositis, muscle biopsies showed myxovirus resistance protein A (MxA) expansion, and blood tests showed positivity for anti-nuclear matrix protein 2 (anti-NXP-2) antibody. Therefore, both presents were diagnosed with anti-NXP-2 antibody-positive dermatomyositis sine dermatitis (DMSD). Anti-NXP-2 antibody-positive dermatomyositis has been reported to be closely associated with DMSD, severe edema and dysphagia. Differential diagnosis for patients who develop myositis with severe subcutaneous edema and dysphagia should include anti-NXP-2 antibody-positive dermatomyositis, and it is important to consider measurement of anti-NXP-2 antibody.

Cutting-edge regenerative therapy for Hirschsprung disease and its allied disorders.

Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management. Thus, regenerative therapy has come to light as a potential form of treatment involving regeneration of the enteric nervous system, mesenchyme, and smooth muscle in affected areas. We review the cutting-edge regenerative therapeutic approaches for managing HSCR and AD-HSCR, including the use of enteric nervous system progenitor cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells as cell sources, the recipient intestine's microenvironment, and transplantation methods. Perspectives on the future of these treatments are also discussed.

Cytotoxic Lesions of the Corpus Callosum (CLOCC) Suggesting Exacerbation by Heterogeneous COVID-19 Booster Vaccination.

Cytotoxic lesions of the corpus callosum (CLOCC) is a disease entity associated with reversible lesions of the corpus callosum on magnetic resonance imaging (MRI). CLOCC is caused by a variety of etiologies, but CLOCC after vaccination is extremely rare. Four prior cases of CLOCC after the first dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have been reported; these were localized to the splenium and showed early clinical and neuroradiological recovery. We experienced an unusual case in which a heterogeneous COVID-19 booster vaccination caused rather severe CLOCC damage. A 74-year-old Japanese woman presented with ataxia, high fever, and hearing loss several days after her third vaccination against COVID-19. This booster was an mRNA-1273 while her first and second vaccinations were both BNT162b2 type. SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis was negative, but serum SARS-CoV-2 S-IgG antibodies were elevated. Her cerebrospinal fluid (CSF) showed an elevated cell count and high levels of protein and interleukin-6 (IL-6). Brain MRI showed CLOCC spreading throughout the body of the corpus callosum. After the exclusion of other potential causes, the diagnosis of vaccination-related CLOCC was made. Six months later, recovery of clinical and MRI findings remained incomplete. It was suggested that the patient's CLOCC might have been caused by the increase in CSF IL-6 due to an enhanced immune response from the heterogeneous vaccination, resulting in more severe damage to the corpus callosum than usual.

Synthesis of novobiocin derivatives and evaluation of their antigonococcal activity and pharmacokinetics.

Gonorrhea has become a serious problem because the number of infected people is increasing and the multi-drug resistance of the causative bacteria, Neisseria gonorrhoeae, is progressing. To develop novel drugs against resistant N. gonorrhoeae, we focused on the antibiotic novobiocin (1). This natural product has a different mechanism of action from existing drugs for gonorrhea, which may make it effective against resistant strains. Actually, it was applied to resistant N. gonorrhoeae, and moderate antibacterial activity was confirmed. Based on this result, we investigated the development of an antigonococcal drug with 1 as the lead compound. The pharmacophore is thought to be the noviose sugar moiety, especially around the 3'-position, so we derivatized this part in order to improve antibacterial activity. As a result, we found that 5 with an methylpyrrole ester structure have a very potent antibacterial activity. This derivative also showed excellent antigonococcal activity against resistant strains in vitro, however it has poor water solubility and pharmacokinetics because it is the acidic lipid-soluble compound. Therefore, we considered introduction of a basic substituent into the molecule would result in an amphoteric compound with improved water solubility, and we investigated further derivatization. As a result of synthesizing various derivatives, we found 47 containing imidazole with strong antigonococcal activity and greatly improved water solubility. This derivative has also improved metabolism and blood concentration in vivo, and is expected to be orally absorbed. Based on these results, we believe that 47 is a very promising anti-gonococcal lead compound and has great potential for further development.

A rare case of pyosalpinx in adolescent girl with Hirschsprung's disease who underwent transvaginal ultrasound-guided drainage.

BACKGROUND: Hydrosalpinx and pyosalpinx are rare gynecologic problems during adolescence, especially in girls without a history of sexual activity. They are even rarer in women with Hirschsprung's disease (HD). We herein report a case of pyosalpinx in an adolescent girl with HD treated by transvaginal ultrasound-guided drainage. CASE PRESENTATION: The present patient was a 12-year-old girl (weight 83 kg; height 159 cm; body mass index 32.8 kg/m2). She had undergone five laparotomies for long-segment HD by 2 years. Her menarche had occurred at 10 years. She was admitted with lower abdominal and anal pain. Computed tomography (CT), magnetic resonance imaging (MRI), and transvaginal ultrasound showed left pyosalpinx and abdominal abscess. Surgical drainage was necessary; however, she had a history of polysurgery and was severely obese, so laparotomy was considered to carry a high risk. Transvaginal ultrasound was deemed more likely to reach the abscess safely. Therefore, she was treated with transvaginal ultrasound-guided drainage by a gynecologist skilled in the procedure. She was discharged home after 52 days. One year and nine months after discharge, there was no reformation of either the abscess or pyosalpinx. CONCLUSIONS: Adolescent girls with HD are at risk of developing hydrosalpinx. Depending on the defecation status, pyosalpinx may also develop. As a less-invasive surgical treatment, transvaginal ultrasound-guided drainage can avoid laparotomy. Collaboration with a gynecologist is essential for the diagnosis and treatment of this clinical condition. Pediatric surgeons should communicate with gynecologists for such cases beginning around puberty for continuous follow-up.

Aprosamine Derivatives Active against Multidrug-Resistant Gram-Negative Bacteria.

Novel aprosamine derivatives were synthesized for the development of aminoglycoside antibiotics active against multidrug-resistant Gram-negative bacteria. The synthesis of aprosamine derivatives involved glycosylation at the C-8' position and subsequent modification (epimerization and deoxygenation at the C-5 position and 1-N-acylation) of the 2-deoxystreptamine moiety. All 8'-ß-glycosylated aprosamine derivatives (3a-h) showed excellent antibacterial activity against carbapenem-resistant Enterobacteriaceae and 16S ribosomal RNA methyltransferase-producing multidrug-resistant Gram-negative bacteria compared to the clinical drug, arbekacin. The antibacterial activity of 5-epi (6a-d) and 5-deoxy derivatives (8a,b and 8h) of ß-glycosylated aprosamine was further enhanced. On the other hand, the derivatives (10a,b and 10h) in which the amino group at the C-1 position was acylated with (S)-4-amino-2-hydroxybutyric acid showed excellent activity (MICs 0.25-0.5 µg/mL) against resistant bacteria that produce the aminoglycoside-modifying enzyme, aminoglycoside 3-N-acetyltransferase IV, which induces high resistance against parent apramycin (MIC > 64 µg/mL). In particular, 8b and 8h showed approximately 2- to 8-fold antibacterial activity against carbapenem-resistant Enterobacteriaceae and 8- to 16-fold antibacterial activity against resistant Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, compared to apramycin. Our results showed that aprosamine derivatives have immense potential in the development of therapeutic agents for multidrug-resistant bacteria.

The Volume of Intestinal Decompression can Predict the Necessity of Surgical Intervention for Adhesive Small Bowel Obstruction.

BACKGROUND: There is no standard timing for switching to surgical management for children with adhesive small bowel obstruction (ASBO) who initially receive conservative treatment. We hypothesized that an increased gastrointestinal drainage volume may indicate the need for surgical intervention. METHODS: The study population included 150 episodes in the patients less than 20 years of age who received treatment for ASBO in our department from January 2008 to August 2019. Patients were divided into two groups: the successful conservative treatment group (CT) and the eventual surgical treatment group (ST). Following the analysis of all episodes (Study 1), we limited our analysis to only first ASBO episodes (Study 2). We retrospectively reviewed their medical records. RESULTS: There were statistically significant differences in the volume on the 2nd day in both Study 1 (9.1 ml/kg vs. 18.7 ml/kg; p < 0.01) and study 2 (8.1 ml/kg vs. 19.7 ml/kg; p < 0.01). The cut-off value was the same for both Study 1 and Study 2 (11.7 ml/kg). CONCLUSIONS: The gastrointestinal drainage volume on the 2nd day in ST was significantly larger than that in CT. Accordingly, we considered that the drainage volume may predict eventual surgical intervention for children with ASBO who initially receive conservative treatment. LEVEL OF EVIDENCE: Level IV.

A Case of Oculopharyngeal Muscular Dystrophy Caused by a Novel PABPN1 c.34G > T (p.Gly12Trp) Point Mutation without Polyalanine Expansion.

Immediately after the initial methionine codon, the PABPN1 gene encodes a stretch of 10 alanines, 1 glycine, and 2 alanines. Oculopharyngeal muscular dystrophy (OPMD) is caused by the expansion of the first 10 alanine stretches. The only exception is the missense mutation of glycine at the 12th residue into alanine, which elongates the stretch to 13 alanines by connecting the first and second stretch with the addition of one alanine in between, indicating that the expansion or elongation of the alanine stretch results in OPMD. We report a 77-year-old man with the novel missense mutation c.34G > T (p.Gly12Trp) in PABPN1 gene whose clinicopathological findings were compatible with OPMD. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness. Magnetic resonance imaging revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Immunohistochemistry studies of the muscle biopsy sample revealed PABPN1-posibive aggregates in the myonuclei which have been reported to be specific to OPMD. This is the first OPMD case caused by neither the expansion nor the elongation of alanine stretch. The present case suggests that OPMD may be caused not only by triplet repeats but also by point mutations.

AeiA is a novel autophagy-related protein that promotes peroxisome degradation by pexophagy in Aspergillus oryzae.

Autophagy is classified into nonselective and selective autophagy, depending on the specificity of substrate degradation. In the filamentous fungus Aspergillus oryzae, selective autophagy, which includes pexophagy and mitophagy, has been observed. However, the molecular mechanism underlying selective autophagy in filamentous fungi remains unclear. Here, we identified a novel protein that interacts with the autophagy-related protein Atg8 in A. oryzae, named AoAtg8-interacting protein A (AeiA). AeiA was localized to AoAtg8-positive autophagic membrane structures and peroxisomes. Moreover, peroxisomal trafficking into the vacuole was reduced in AeiA disruptants. Taken together, AeiA is a novel selective autophagy-related protein that contributes to pexophagy in A. oryzae.

Retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab injections for diabetic macular edema.

Purpose: To describe a case of unilateral retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab (IVBr) treatments for diabetic macular edema (DME). Observations: A 68-year-old Japanese woman who had a 3-year history of insulin-dependent diabetes mellitus presented with decreased vision in the right eye (oculus dexter, OD). After two consecutive IVBr (3 mg) treatments for DME, spaced 6 weeks apart, her best corrected visual acuity improved from 20/32 to 20/28 OD, as central macular thickness (CMT) decreased from 368 µm to 253 µm on optical coherence tomography (OCT). Immediately after the 3rd IVBr, the right intraocular pressure (IOP) increased. One week later, iritis (aqueous flares: 65.0 photon count [PC]/ms) was observed, followed by localized vasculitis 2 weeks later. One month after the 3rd IVBr, extensive vasculitis and vasculitis occluding retinal arterioles were identified. Based on the history of IVBr use and clinical findings, intraocular inflammation (IOI) and subsequent retinal arterial occlusive vasculitis due to IVBr was diagnosed. Topical steroid administration (i.e., eye drops and subtenon injection) resulted in improvement of IOI after 3 months. She subsequently underwent two intravitreal aflibercept injections for DME and panretinal photocoagulation (PRP) to prevent the development of proliferative changes due to diabetic retinopathy. One year after the diagnosis of retinal arterial occlusive vasculitis, the patient had slight loss of vision (20/50) compared to baseline, due to the progression of cataracts, and OCT angiography (OCTA) showed extensive non-perfusion area on the temporal side. However, other examination findings (IOP: 16 mmHg, aqueous flares: 30.5 PC/ms, CMT: 283 µm) were stable. Conclusions and importance: Diagnosis and treatment at a relatively early stage after the onset of IOI prevented severe visual impairment in this case. Topical betamethasone eye drops reduced anterior chamber inflammation associated with IVBr; however, vascular sheathing worsened when topical drops alone was used. Occlusive retinal vasculitis, diagnosed with fluorescein angiography (FA) and OCTA, appeared to stabilize when subtenon triamcinolone injection was added to topical steroid administration. Because the central macula was not involved, severe vision loss was prevented. It is unknown if topical steroid administration would be adequate to prevent worsening of occlusive vasculitis in other cases. Although not used in this case, oral prednisone is one treatment option that may prevent severe vision loss. However, it requires monitoring of side effects, such as elevated blood glucose levels. PRP is also an option in cases where progression of proliferative changes is a concern, as was done in this case. With these considerations in mind, it is important to diagnose brolucizumab-associated IOI and subsequent retinal arterial occlusive vasculitis in DME patients early and initiate treatment to prevent severe visual impairment. Diagnosing new IOI and subsequent retinal arterial occlusive vasculitis is more difficult in DME than in neovascular age-related macular degeneration because of the inflammatory component often associated vascular occlusions. Therefore, early IOI diagnosis and follow-up using various instruments such as laser flare cell meter, wide-field color imaging, OCT/OCTA, and FA, in addition to usual comprehensive ophthalmologic examinations, is crucial.

[A case of neurosyphilis presenting as sudden onset of limbic encephalitis].

A 52-year-old male was carried to hospital by ambulance, because of an abrupt abnormal behavior and impaired consciousness. Soon after the arrival, the patient started a generalized seizure. Although the seizure was stopped by Midazolam, amnesia were observed. With meningeal irritation signs, in addition to the clinical course, the patient was thought to develop limbic encephalitis. The cause of the encephalitis was diagnosed as neurosyphilis because of the positive serum and CSF syphilis reactions, and the patient was treated with penicillin G from the first admission day on. Steroid pulse therapy was also conducted, followed by acyclovir since herpes encephalitis could not be ruled out; the brain MRI showed left-side dominant T2/FLAIR high intensity lesions in the bilateral temporal lobes and left hippocampus. With the treatment progression, the amnestic syndrome improved and the patient returned to work. Although neurosyphilis is a rare cause of acute onset limbic encephalitis, it is important to keep the possibility of this disease in mind in making a treatment plan.