Risk factors of pediatric steroid-induced ocular hypertension.

PURPOSE: Steroid-induced ocular hypertension (SIOH) is a significant ocular complication of pediatric steroid administration. In this study, we analyzed the risk factors associated with pediatric SIOH. METHODS: We retrospectively collected data from 78 children under 20 years of age who received systemic steroids during hospitalization. The data included age, gender, primary disease, intraocular pressure (IOP) before and one month after administration, total monthly steroid dose adjusted for body weight (BW), and one-month changes in red blood cell, white blood cell, and platelet counts. A multivariate analysis was used to identify risk factors related to steroid responsiveness. RESULTS: Thirty patients (38.5%) were classified as steroid responders, and 48 as non-responders. The median IOP during the first month of steroid treatment was 24.0 mmHg (IQR; 23.0-28.3) for responders and 15.0 mmHg (IQR; 12.3-18.0) for non-responders. The Generalized Estimating Equations analysis revealed that younger age, male sex, primary disease, increase the amount of white blood cell (WBC) and total steroid dose per BW in one month were independently associated variables. The receiver operating characteristic analysis also revealed that the cutoff values for age, total monthly steroid dose, the increase amount of WBC were 11.0 years, 40.7 mg/kg and 3.40 × 10²/µl respectively. CONCLUSION: High-dose steroid administration, especially in male, younger patients, necessitates careful monitoring for IOP changes during treatment. WBC count also needs to be monitored during IOP follow-ups. KEY MESSAGES: What is known Steroid-induced ocular hypertension (SIOH) is one of the essential complications during steroid administration, but only limited analyses have been performed in children. What is new A comprehensive analysis of multiple factors was performed that are predicted to be associated with pediatric SIOH from previous literature. Younger age, male sex, primary disease, increase the amount of WBC, and higher total monthly steroid dose were extracted as risk factors of SIOH. This study can contribute to the prediction of cases in which ophthalmologic examinations are particularly important during systemic steroid administration in children.

One-year results of trabeculectomy with emphasis on the effect of patients' age.

PURPOSE: This study investigated the association between one-year surgical outcomes following trabeculectomy and age, accounting for confounding factors. STUDY DESIGN: Retrospective observational study. METHOD: Analyzing data from 305 patients undergoing initial trabeculectomy from 2019 onward, we employed three approaches to adjust variables: stratified analysis, regression analysis, and propensity score matching. Surgical success at 1-year post-surgery was defined by two criteria: achieving intraocular pressure of between 5 and 15 mmHg with a ≥ 20% reduction compared to pre-surgery levels and no additional glaucoma surgery (Criterion A); achieving intraocular pressure of between 5 and 12 mmHg with a ≥ 30% reduction compared to pre-surgery levels and no additional glaucoma surgery (Criterion B). RESULTS: Stratified analysis by age unveiled a significant increase in exfoliation glaucoma (XFG) and a trend towards shorter axial lengths with advancing age (both p < 0.0001). Older age groups were more likely to experience surgical failure in both Criterion A and B (p = 0.21, < 0.01). Univariate analysis showed age as a significant factor in surgical failure for Criterion A (p < 0.05) and a nearly significant factor for Criterion B (p = 0.12). However, this trend was not evident in multivariate analysis (p = 0.23/0.88), where XFG became a significant factor for surgical failure (both p < 0.001) in Criteria A and B. Propensity score matching revealed no significant differences in surgical success rates for Criteria A and B between younger and older patients (p = 1.00 and 0.88). CONCLUSION: Age is not a primary determinant of failure in trabeculectomy; however, the increasing incidence of XFG with aging suggests a potential for poorer outcomes.

Usage status of biologics for the chronic treatment of optic neuritis in neuromyelitis optica spectrum disorders in Japan.

PURPOSE: To investigate the usage status of biologics for the chronic treatment of optic neuritis including neuromyelitis optica spectrum disorders in Japan. DESIGN: Multicenter retrospective case series. METHODS: Patients diagnosed with anti-aquaporin 4 antibody (AQP4-Ab) positive optic neuritis and had been initiated on biologics (satralizumab, eculizumab, and inebilizumab) between January 2020 and August 2022 were identified at 30 facilities in Japan. These patients were investigated regarding changes in oral steroid doses, optic neuritis relapse, and adverse events after initiation of biologics. RESULTS: Eighty-eight patients with AQP4-Ab positive optic neuritis initiated on biologics were included. Satralizumab was the most common biologic used (79 patients), followed by eculizumab (6 patients) and inebilizumab (3 patients). In the satralizumab group, during the observation period (10.0±7.0 months) until February 2023, the oral steroid dose was reduced significantly from 13.8 ± 8.6 mg/day at the time of initiation to 5.3 ± 4.8 mg/day (p < 0.001). No relapse of optic neuritis was observed in 76 of 79 patients (96.2%) after initiation of satralizumab. Furthermore, in 15 patients who succeeded in discontinuing steroids during 8.5 ± 5.8 months after initiation of satralizumab, no relapse of optic neuritis was observed throughout the observation period. Adverse events occurred in 7 patients with satralizumab and 2 patients with eculizumab, but no serious infections were observed. CONCLUSIONS: Satralizumab was the most commonly used biologic for AQP4-Ab positive optic neuritis in Japan. This study demonstrates the efficacy and safety of satralizumab in preventing the relapse of optic neuritis.

Postnatal weight loss and neurodevelopmental outcomes at age 3 years in extremely preterm infants: a cohort study.

BACKGROUND: Previous research has suggested a correlation between postnatal maximum weight loss (MWL) and both neonatal mortality and morbidities in extremely preterm infants. However, the relationship between MWL and neurodevelopmental outcomes remains underexplored. METHODS: In a single-center, retrospective cohort study at Okayama Medical Center, we evaluated data from extremely preterm infants admitted to the neonatal intensive care unit from 2010 to 2020. Infants who died within the first 10 days of life were excluded. MWL in the first 10 days was the main exposure, categorized into three groups: >15%, 5-15%, and < 5%. The primary outcome evaluated was the occurrence of death or neurodevelopmental impairment (NDI) at age 3 years, defined as developmental impairments (developmental quotient [DQ] < 85), cerebral palsy, hearing impairments, or visual impairments. Data analysis involved robust Poisson regression, adjusted for perinatal confounders, with a restricted cubic spline function to examine the dose-response relationship. We also conducted a sensitivity analysis using a DQ of < 70 to define developmental impairment. RESULTS: Among 135 infants assessed for neurodevelopmental outcomes, 40 were in the > 15% MWL group, 71 in the 5-15% group, and 24 in the < 5% group. Median gestational ages and birth weights were 25.9 weeks and 821 g for > 15% MWL; 26.1 weeks and 818 g for 5-15% MWL; and 26.0 weeks and 734 g for < 5% MWL. Compared with the 5-15% MWL group, the < 5% group exhibited a higher risk of death or NDI at age 3 years (62.8% vs. 80.8%, risk ratio [RR] 1.36, 95% confidence interval [CI] 1.04-1.79) and NDI alone (59.2% vs. 79.2%, RR 1.43, 95% CI 1.06-1.94). Furthermore, higher risks of developmental impairment were also noted in the > 15% (RR 1.32, 95% CI 1.00-1.75) and < 5% (RR 1.46, 95% CI 1.08-1.98) groups. These associations were confirmed by spline analyses. In contrast, the associations between MWL and neurodevelopmental outcomes using a DQ of < 70 were not apparent. CONCLUSIONS: MWL within the first 10 days of life may be associated with increased risks of NDI and developmental impairments by age 3 years in extremely preterm infants.

Impact of Sigmoid Sinus Anatomy on Assessing the Feasibility of the Retrofacial Access to the Entire Jugular Fossa Before Surgery.

BACKGROUND AND OBJECTIVES: The jugular fossa (JF) is a challenging area for surgical approaches because of its complex anatomy and proximity to neurovascular structures. The study evaluates the feasibility of the neuronavigated microsurgical transmastoid extended infralabyrinthine extradural retrofacial approach (mTEIER-A) in human head specimens for accessing the entire intraosseous JF in relation to the position of the sigmoid sinus (SS), horizontal angle of attack, and size of the SS. METHODS: The mTEIER-A was performed on human head specimens. Before dissection, the position of the SS, horizontal angle of attack, and size of the SS were measured on tilted axial high resolution computed tomography scans; after dissection, access to the lateral aspect of the JF on dissected human head specimens and on postoperative high-resolution computed tomography scans was examined. The position of the SS was classified relative to a predefined reference line, and the feasibility of retrofacial access was documented. RESULTS: SS positions located medial to the reference line (P1) and horizontal angles >12.5° significantly enhance retrofacial access to the lateral aspect of the JF, whereas the size of the SS has a limited impact. CONCLUSION: Depending on the position of the SS and the horizontal angle of access, mTEIER-A provides sufficient retrofacial access to the lateral aspect of the JF. These findings emphasize the need for precise preoperative planning and suggest that mTEIER-A could minimize the need for more invasive approaches, potentially reducing related morbidity. Further clinical studies are recommended to validate these findings.

The Surgical Outcomes of Modified Intraocular Lens Suturing with Forceps-Assisted Haptics Extraction: A Clinical and Basic Evaluation.

Background/Objectives: Postoperative intraocular lens (IOL) tilt is a risk associated with IOL scleral fixation. However, the cause of IOL tilt during IOL suturing remains unclear. Therefore, this study aimed to evaluate the surgical outcomes of a modified IOL suturing technique and investigate the factors contributing to postoperative IOL tilt and decentration. Methods: We included 25 eyes of 22 patients who underwent IOL suturing between April 2018 and February 2020. A modified IOL suturing technique that decreased the need for intraocular suture manipulation was used. Factors contributing to IOL tilt and decentration were investigated using an intraoperative optical coherence tomography (iOCT) system. Results: The mean postoperative best-corrected visual acuity improved from 0.15 ± 0.45 to -0.02 ± 0.19 (p = 0.02). The mean IOL tilt angle at the last visit after surgery was 1.84 ± 1.28 degrees. The present study reveals that the distance of the scleral puncture site from the corneal limbus had a stronger effect on IOL tilt; meanwhile, the suture position of the haptics had a greater effect on IOL decentration. Conclusions: The modified IOL suturing technique, which avoids intraocular suture handling, had favorable surgical outcomes with improved postoperative visual acuity and controlled IOL tilt and decentration. Accurate surgical techniques and careful measurement of distances during surgery are crucial for preventing postoperative IOL tilt and decentration.

Comparison of Single-Treatment Efficacy of Bevacizumab and Ranibizumab for Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a significant cause of blindness in infants. Appropriate therapeutic intervention is essential because retinal detachment due to the progression of ROP is critical to visual function. The intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents has been increasingly applied to inhibit the development and progression of ROP. In this study, we compared the efficacy of single intravitreal bevacizumab (IVB) and ranibizumab (IVR) injections for the treatment of ROP. METHODS: A total of 39 eyes in 21 patients with severe ROP and IVB (15 eyes of 8 patients) and IVR (24 eyes of 13 patients) were retrospectively reviewed. Patient background, the severity of ROP, and the percentage of cases in which ROP regressed without additional treatment were compared between the two groups. RESULTS: Patient background and ROP severity were not significantly different between the two groups. Recurrence was observed in one eye of one patient in the IVB group, and thirteen eyes in seven patients in the IVR group required additional laser photocoagulation, which was significantly different in the two groups (p < 0.01, Fisher's exact test). In the IVR group, two eyes of two patients underwent vitreous surgery. CONCLUSION: Compared with IVR, IVB is likely to control the severity of ROP with a single treatment.

Mutations of CYP1B1 and FOXC1 genes for childhood glaucoma in Japanese individuals.

PURPOSE: To explore the frequency and positions of genetic mutations in CYP1B1 and FOXC1 in a Japanese population. STUDY DESIGN: Molecular genetic analysis. METHODS: Genomic DNA was extracted from 31 Japanese patients with childhood glaucoma (CG) from 29 families. We examined the CYP1B, FOXC1, and MYOC genes using Sanger sequencing and whole-exome sequencing (WES). RESULTS: For CYP1B1, we identified 9 families that harbored novel mutations, p.A202T, p.D274E, p.Q340*, and p.V420G; the remaining mutations had been previously reported. When mapped to the CYP1B1 protein structure, all mutations appeared to influence the enzymatic activity of CYP1B1 by provoking structural deformity. Five patients were homozygotes or compound heterozygotes, supporting the recessive inheritance of the CYP1B1 mutations in CG. In contrast, four patients were heterozygous for the CYP1B1 mutation, suggesting the presence of regulatory region mutations or strong modifiers. For the FOXC1 gene, we identified 3 novel mutations, p.Q23fs, p.Q70R, and p.E163*, all of which were identified in a heterozygous state. No mutation was found in the MYOC gene in these CG patients. All individuals with CYP1B1 and FOXC1 mutations were severely affected by early-onset CG. In the CYP1B1-, FOXC1-, and MYOC-negative families, we also searched for variants in the other candidate genes reported for CG through WES, but could not find any mutations in these genes. CONCLUSIONS: Our analyses of 29 CG families revealed 9 families with point mutations in the CYP1B1 gene, and four of those patients appeared to be heterozygotes, suggesting the presence of complex pathogenic mechanisms. FOXC1 appears to be another major causal gene of CG, indicating that panel sequencing of CYP1B1 and FOXC1 will be useful for diagnosis of CG in Japanese individuals.

Removal of Subinternal Limiting Membrane Hemorrhage Secondary to Valsalva Retinopathy Using a Fovea-Sparing Internal Limiting Membrane Fissure Creation Technique.

Introduction: Valsalva retinopathy can cause submacular hemorrhage (SMH), which may lead to visual disturbances. SMH can extend into the subinternal limiting membrane (ILM) and vitreous spaces, sometimes occurring concomitantly with full-thickness macular holes (FTMHs). Herein, we describe a case in which sub-ILM hemorrhage was removed without peeling the ILM of the central fovea, thus preserving the foveal ILM. Case Presentation: A 48-year-old female patient developed rapid-onset bilateral visual impairment due to SMH secondary to Valsalva retinopathy. The SMH predominantly consisted of sub-ILM hemorrhage. However, detailed observation was challenging due to the dense sub-ILM hemorrhage in the left eye. Initial best-corrected visual acuity (BCVA) in the right and left eyes were 1.2 and 0.03, respectively. Intravitreal tissue plasminogen activator (tPA) and sulfur hexafluoride (SF6) gas injections were initially administered to displace the SMH in the left eye; however, the SMH could not be successfully displaced. A vitrectomy was then performed. Intraoperatively, an ILM fissure beyond the foveal region was created using ILM forceps. The balanced salt solution was sprayed onto the ILM, and the sub-ILM hemorrhage was drained into the vitreous cavity from the ILM fissure. The surgery successfully displaced the sub-ILM hemorrhage while preserving the foveal ILM. No postoperative complications were observed. Visual acuity remained at 1.2 in the right eye and improved to 1.2 in the left eye 6 months postoperatively. Conclusion: Removing foveal sub-ILM hemorrhage without peeling the foveal ILM can be a viable treatment option to preserve the foveal ILM.

Combination of reduced post-transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft-versus-host disease in human leukocyte antigen-haploidentical peripheral blood stem-cell transplantation.

We evaluated the clinical impacts of the concurrent modification of post-transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)-initiation timing in 61 patients with human leukocyte antigen-haploidentical transplantation. Reduced-dose PTCy (80 mg/kg) was associated with a higher incidence of moderate-to-severe chronic graft-versus-host disease (GVHD) than standard-dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early-initiation Tac (day -1) increased moderate-to-severe chronic GVHD than standard-initiation Tac (day 5) in the reduced-dose PTCy group (p = 0.032), whereas Tac-initiation timing did not impact chronic GVHD in the standard-dose PTCy group. These data indicate that the combination of reduced-dose PTCy and early-initiation Tac can amplify chronic GVHD.

Assessment of Obesity as Risk Factor of Lumbar Disc Surgery: Retrospective Analysis of 598 Cases and Simulated Surgery on 3D-Printed Models.

(1) Background: Obesity poses known risks in surgery, including a prolonged operation time and postoperative complications. Given the rising obesity rates and frequent lumbar disc surgeries, understanding these risks is crucial. This study aims to assess the impact of obesity on operation duration and postoperative complications in lumbar disc prolapse surgery. (2) Methods: We retrospectively analyzed 598 patients with monosegmental disc herniation, correlating their body mass index (BMI) as a surrogate parameter for obesity with operation time. Excluding complex cases (multi-segmental herniations or recurrent herniations), complication rates and hospital stays were recorded. Simulated surgeries on 3D-printed models of varying obesity levels examined operation times and instrument suitability. (3) Results: Of these patients, 438 patients had a BMI of <30, and 160 patients had a BMI of ≥30. Complication rates showed no significant differences between groups. Linear regression analysis failed to establish a sole dependency of operation time on BMI, with R2 = 0.039 for the normal-weight group (BMI < 30) and R2 = 0.059 for the obese group (BMI ≥ 30). The simulation operations on the 3D-printed models of varying degrees of obesity showed a significant increase in the simulated operation time with higher levels of obesity. A geometrically inadequate set of surgical instruments was assumed to be a significant factor in the simulated increase in operating time. (4) Conclusions: While various factors influence operation time, obesity alone does not significantly increase it. However, simulated surgeries highlighted the impact of obesity, particularly on instrument limitations. Understanding these complexities is vital for optimizing surgical outcomes in obese patients.

Optimal timing of bridging annuloplasty and patch augmentation for heterotaxy syndrome associated with functional single ventricles.

OBJECTIVE: Although the challenging prognosis of functional single ventricles with common atrioventricular valves due to complex morphology and uncontrollable regurgitation by valvuloplasty has been highlighted, reports on when and how these extremely complicated atrioventricular valves should be repaired are few. This study investigated the timing and risk factors for valve intervention in these patients. METHODS: Between April 2006 and March 2023, 40 patients with heterotaxy syndrome associated with functional single ventricles underwent surgery. Valve intervention was performed in 14 of the 40 patients with moderate or severe atrioventricular valve regurgitation. RESULTS: The timing of the first valve intervention varied, with four, five, three, and two patients undergoing valve intervention before the cavopulmonary shunt, simultaneously with the cavopulmonary shunt, before total cavopulmonary connection, and simultaneously with total cavopulmonary connection, respectively. Mechanical valve replacements were performed in three patients. Among the 14 patients undergoing valve intervention, four died. Three of the four patients underwent valvuloplasty before the cavopulmonary shunt, including two who could undergo the cavopulmonary shunt but died after the procedure. Eight of the fourteen patients completed total cavopulmonary connection. The cumulative survival rate was not significantly different between the 14 patients who underwent and 26 who did not undergo intervention (hazard ratio, 2.52; 95% confidence interval, 0.56-11.24; P = 0.23). CONCLUSION: Our surgical strategies provide a chance for the next staged repair of common atrioventricular valves in patients with both heterotaxy and valvular regurgitation. Including patch augmentation, advanced valve intervention is possible at or after the cavopulmonary shunt.

DISCREPANCY BETWEEN FUNDUS AUTOFLUORESCENCE ABNORMALITY AND VISUAL FIELD LOSS IN BIETTI CRYSTALLINE DYSTROPHY.

PURPOSE: The aim of this study was to explore the potential benefits of retinal pigment epithelium replacement therapy in patients with Bietti crystalline dystrophy (BCD) by assessing the disease pathology with the distinctive relationship between fundus autofluorescence (FAF) abnormality and visual field defect. METHODS: Sixteen eyes from 16 patients with BCD and 16 eyes from 16 patients with RHO-associated retinitis pigmentosa were included. Fundus autofluorescence, optical coherence tomography, and Goldmann perimetry results were retrospectively reviewed and assessed using image analyses. RESULTS: In patients with BCD, the FAF abnormality area was not correlated with the overall visual field defect area and median overall visual field defect area (57.5%) was smaller than FAF abnormality area (98.5%). By contrast, the ellipsoid zone width was significantly correlated with the central visual field area (r = 0.806, P < 0.001). In patients with RHO-associated retinitis pigmentosa, the FAF abnormality area and ellipsoid zone width were significantly correlated with the overall visual field defect area (r = 0.833, P < 0.001) and central visual field area (r = 0.887, P < 0.001), respectively. CONCLUSION: The FAF abnormality shown in patients with BCD involves retinal pigment epithelium degeneration without complete loss of photoreceptors or visual function. These results suggest that patients with BCD are good candidates for retinal pigment epithelium replacement therapy for preservation of residual visual function.

Extended Long-Term Outcome After Conservative Decompressive Microsurgery and Routine Adjuvant Fractionated Stereotactic Radiotherapy for Symptomatic Cavernous Sinus Meningiomas.

BACKGROUND AND OBJECTIVES: Cavernous sinus meningiomas (CSM) pose one of the most difficult to treat subgroup of skull base meningiomas. The purpose of this study was to evaluate the efficacy of an interdisciplinary treatment approach for symptomatic CSM which incorporated conservative function preserving microsurgery and routine adjuvant fractionated stereotactic radiotherapy (FSRT). METHODS: A homogenous group of patients with symptomatic primary CSM with extracavernous extension was treated between 2005 and 2012. All patients were available for a minimum follow-up of 5 years. Clinical follow-up included detailed examination of oculomotor deficits, visual status, and endocrinologic function. Radiologic follow-up was conducted by tumor volumetry. RESULTS: Overall, 23 patients were included in this study (78.3% women; median age 58 years). Diplopia was the most common presenting symptom, followed by headache and visual disturbances. Surgical morbidity was low (3/23; 13%). FSRT was applied after a median of 2 months after surgery. At a median clinical follow-up of 113 months, 70.45% of the presenting symptoms had improved, 25% remained unchanged, and in 2 cases (4.54%), worsening occurred. Overall tumor regression was evident in 19/21 World Health Organization 1 and in 1/2 of World Health Organization 2 CSM, respectively, at a median radiological follow-up of 103 months. CONCLUSION: Our findings demonstrate the efficacy of an interdisciplinary treatment approach for symptomatic primary CSM with extracavernous extension with decompression of neurovascular elements followed by FSRT. Precise preoperative planning and intraoperative decision making in combination with routine postoperative radiotherapy can achieve excellent tumor control, improve neurologic function, and minimize long-term morbidity.

Association between mean airway pressure during high-frequency oscillatory ventilation and pulmonary air leak in extremely preterm infants during the first week of life.

Background: While positive pressure ventilation has been considered an important contributing factor associated with pulmonary air leaks, studies examining the association between specific ventilatory settings during acute-phase high-frequency oscillatory ventilation (HFOV) and pulmonary air leaks among extremely preterm infants are limited. Methods: This was a single-center retrospective cohort study conducted at an institution that primarily used HFOV after intubation in extremely preterm infants. We analyzed data from extremely preterm infants born between 2010 and 2021. The primary outcome was pulmonary air leakage during the first 7 days of life. The exposure variable was the maximum mean airway pressure (MAP) on HFOV during the first 7 days of life or before the onset of pulmonary air leaks. Maximum MAP was categorized into three groups: low (7-10 cmH2O), moderate (11-12 cmH2O), and high (13-15 cmH2O) MAP categories. We conducted robust Poisson regression analyses after adjustment for perinatal confounders, using the low MAP category as the reference. Results: The cohort included 171 infants (low MAP, 123; moderate MAP, 27; and high MAP, 21). The median (interquartile range) gestational age and birth weight were 25.7 (24.3-26.7), 25.7 (24.9-26.9), and 25.3 (24.3-26.6) weeks and 760 (612-878), 756 (648-962), and 734 (578-922) g for infants in the low, moderate, and high MAP categories, respectively. Compared to infants in the low MAP category, those in the high MAP category had a higher incidence of pulmonary air leaks (4.1% vs. 33.3%; adjusted risk ratio, 5.4; 95% confidence interval, 1.6-18.5). In contrast, there was no clear difference in the risk of pulmonary air leaks between the moderate and low MAP categories (3.7% vs. 4.1%; adjusted risk ratio, 0.9; 95% confidence interval, 0.1-6.1). Conclusion: Extremely preterm infants requiring high MAP (≥13 cmH2O) in acute-phase HFOV had a higher risk of pulmonary air leak during the first 7 days of life.

Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis.

Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable ulcerative colitis (UC). No previous reports have described the efficacy including histopathological evaluations and the safety of combination therapy with upadacitinib (UPA) plus intensive GMA (two sessions per week) for intractable UC showing resistance to conventional agents and adalimumab. This retrospective study evaluated the 10-week clinical and histopathological efficacy of induction combination therapy with UPA plus intensive GMA in patients with intractable UC. Among eight patients (moderate UC, n = 1; severe UC, n = 7) who received combination therapy with UPA plus intensive GMA, 50.0% had achieved clinical remission by 10 weeks. Percentages of patients with histological-endoscopic mucosal improvement and mucosal healing at 10 weeks were 62.5% and 12.5%, respectively. After excluding one patient who discontinued treatment by week 10 because of intolerance for UPA, mean full Mayo score, endoscopic subscore and C-reactive protein concentration at baseline were 11.43 ± 0.37, 3 ± 0 and 1.29 ± 0.70 mg/dL, respectively. Corresponding values at 10 weeks were 2.28 ± 0.77 (P < 0.03), 1.14 ± 0.34 (P < 0.03) and 0.03 ± 0.008 mg/dL (P < 0.05), respectively. Adverse events of herpes zoster, temporary increase in creatinine phosphokinase and anemia were observed in one patient each. One patient discontinued combination therapy at week 4 because of temporary taste abnormality due to UPA. Combination comprising UPA plus intensive GMA appears likely to achieve satisfactory induction of clinical remission and histopathological improvement for patients with intractable UC for whom conventional agents and anti-tumor necrosis factor-α antibody have failed.

Acute Noninfectious Anterior Ocular Inflammation Following Ranibizumab Biosimilar Intravitreal Injection in a Patient With Recent COVID-19 Vaccination.

Even in the post-coronavirus disease 2019 (COVID-19) era, it is prudent to exercise caution regarding the timing between intravitreal anti-vascular endothelial growth factor (VEGF) injections and COVID-19 vaccinations, as ocular inflammation can occur following both procedures. However, this perspective has not been sufficiently discussed thus far. Herein, we report a case of acute noninfectious anterior ocular inflammation following an intravitreal injection of ranibizumab biosimilar (RBZ BS, Senju Pharmaceuticals, Japan) in a patient recently vaccinated against COVID-19. A 74-year-old male with myopic choroidal neovascularization (CNV) in the left eye was treated with RBZ BS intravitreal injection. He received his fourth COVID-19 vaccination with messenger ribonucleic acid (mRNA)-1273 (Moderna) two days prior to his second RBZ BS intravitreal injection. He reported no systemic symptoms associated with the fourth COVID-19 vaccination. The second RBZ BS intravitreal injection was safely performed without complications. However, a few hours later, he experienced blurred vision without ocular pain in his left eye, a symptom not observed after the first injection. He visited a local ophthalmologic clinic the following day and was subsequently referred to our hospital due to anterior ocular inflammation in the left eye. His vision in the left eye was 0.3 decimal best-corrected visual acuity. Examination revealed non-granulomatous anterior ocular inflammation with 3+ cells and 2+ flare in the left eye. Anterior vitreous inflammation, keratic precipitates, or conjunctivitis was absent. Fundus examination also showed no signs of posterior inflammation. Both fluorescence angiography and indocyanine green angiography revealed staining corresponding to CNV without retinal vasculature leakage. There is nothing abnormal with the right eye based on the examination. Given that the noninfectious ocular inflammation was likely, based on the acute onset of symptoms within less than 24 hours following the RBZ BS intravitreal injection, and the presence of non-granulomatous inflammation only in the anterior segment without ocular pain, betamethasone eye drops four times daily was initiated in the left eye on the first day following the second RBZ BS intravitreal injection. Then, his ocular inflammation improved to mild by the fourth day post-injection. His eye eventually cleared, with no cells or flare in the anterior chamber at five months. Eventually, given the clinical course of good response to only topical steroid therapy, the diagnosis of noninfectious anterior ocular inflammation following RBZ BS in the case of a recent episode of COVID-19 vaccination was retrospectively confirmed. Although this case represents one of the initial instances of noninfectious ocular inflammation following RBZ BS (Senju Pharmaceuticals) administration, sterile ocular inflammation after other intravitreal anti-VEGF therapy has already been well-reported. In addition, given the recent COVID-19 vaccination, the ocular inflammation might be influenced by the vaccination, synergistically leading to vaccine-associated uveitis with similar signs and symptoms. In conclusion, to prevent such a complex situation, it is advisable to consider an adequate interval between COVID-19 vaccination and intravitreal anti-VEGF injections.

A case of pulmonary tuberculosis that developed during nivolumab and ipilimumab treatment for pulmonary adenocarcinoma that recurred two months after completion of anti-tuberculous treatment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become key agents in the treatment of non-small cell lung cancer worldwide. However, immune-related adverse events (irAEs) must be addressed to maximize the efficacy of ICIs. Mycobacterium tuberculosis (Mtb) infection is considered as a type of irAE associated with ICIs, but the underlying mechanism is not completely understood. Here, we present a case of pulmonary tuberculosis (TB) that developed during administration of nivolumab and ipilimumab for pulmonary adenocarcinoma that recurred just 2 months after completion of anti-TB treatment. CASE DESCRIPTION: A 67-year-old man with lung adenocarcinoma was referred to our hospital for chemotherapy. He was a former smoker and had been diagnosed with stage IVA (cT4N1M1a) lung adenocarcinoma. Interferon-gamma release assay (IGRA) yielded positive results at the start of treatment. One month after initiating treatment with nivolumab and ipilimumab, he presented with productive cough and Mtb complex was cultured from sputum samples. Two months after completing anti-TB treatment, recurrence of TB was observed. The series of strains were found to be identical. CONCLUSIONS: This represents the first report of pulmonary TB that developed during nivolumab and ipilimumab treatment, and recurred 2 months after completing anti-TB treatment. Physicians should be mindful of the potential for TB recurrence following the use of ICIs, particularly in patients showing positive results from IGRA.

Does 5-ALA Fluorescence Microscopy Improve Complete Resectability in Cerebral/Cerebellar Metastatic Surgery? A Retrospective Data Analysis from a Cranial Center.

(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases.