Circulating endothelial cells and endothelial progenitor cells as potential predictors of acute GVHD after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Acute graft-versus-host disease (aGVHD) is a major cause of treatment-related mortality after allogeneic hematopoietic stem cell transplantation. Endothelial cell damage may trigger the initiation of aGVHD. METHODS: Endothelial damage and repair were evaluated by counting circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in 17 allogeneic hematopoietic stem cell transplantation patients at pre-conditioning, day 0, day 7, day 14, day 30, and day 60 by multicolor flow cytometry. Von Willebrand factor activity was simultaneously measured. RESULTS: Eight patients developed aGVHD and were compared to non-aGVHD patients. Patients' characteristics were not different, except for previous treatment courses. There was no difference in von Willebrand factor activity between the two groups. Both CEC and EPC counts were decreased on day 7 and day 14 and then increased thereafter. The CEC count on day 7 was significantly lower in the aGVHD group than in the non-aGVHD group (p = .0401). Restoration of the EPC count on day 60 was significantly suppressed in the aGVHD group (p = .0464). The CEC count on day 7 could predict aGVHD development (AUC 0.8214, p = .0372). CONCLUSION: The present results showed that CEC count on day 7 could be a predictor of aGVHD.

Schizophyllum commune sinusitis after allogeneic bone marrow transplantation for myelodysplastic syndrome: A case report and literature review.

Sinusitis is a serious infectious complication of allogeneic hematopoietic stem cell transplantation. Schizophyllum commune (S commune) is a common basidiomycete fungus that is rarely involved in human disease. We report herein a case of S commune sinusitis after allogeneic bone marrow transplantation. A 66-year-old man with myelodysplastic syndrome underwent allogeneic bone marrow transplantation and developed maxillary and ethmoid sinusitis. The sinusitis did not improve with liposomal amphotericin B after neutrophil engraftment, so we considered that surgical intervention was needed for the recovery of sinusitis. Endoscopic sinus surgery was performed. In the debridement tissue of paranasal mucosa, filamentous fungal elements were observed. Moreover, genetic analysis of the tissue revealed the presence of S commune. Schizophyllum commune should be recognized as a fungal pathogen that causes sinusitis after allogeneic hematopoietic stem cell transplantation. This case suggests the effectiveness of prompt surgical intervention with liposomal amphotericin B treatment for S commune sinusitis and the usefulness of genetic diagnosis for cases under antifungal treatment. (160 words).

Intestinal Behçet's Disease with Primary Myelofibrosis Involving Trisomy 8.

Behçet's disease (BD) is a disorder characterized by systemic inflammation of multiple organs, including the intestines. Several studies have reported a relationship between myelodysplastic syndrome and BD, and trisomy 8 was frequently seen, especially in intestinal BD. However, the association of BD with primary myelofibrosis (PMF) has not been well documented. A 58-year-old Japanese female was diagnosed with PMF in 2014. The symptoms of PMF resolved with ruxolitinib. However, she developed fever and intestinal perforation due to multiple ulcers in the terminal ileum in 2017. Intestinal perforation recurred 1 month later, and the dose of ruxolitinib was tapered. After discontinuation of ruxolitinib, she presented with recurrent oral aphthous ulcers and uveitis. Subsequently, intestinal perforation recurred, and she was diagnosed with intestinal BD. Trisomy 8 was identified in her peripheral blood. She underwent steroid therapy, azathioprine, and infliximab. This case suggests relationships between PMF, trisomy 8, and BD.

Upshaw-Schulman syndrome diagnosed during pregnancy complicated by reversible cerebral vasoconstriction syndrome.

Upshaw-Schulman syndrome (USS) is an inherited type of thrombotic thrombocytopenic purpura (TTP) that is extremely rare, but often diagnosed during pregnancy. Reversible cerebral vasoconstriction syndrome (RCVS) is the transient stenosis of several cerebral arteries that is frequently diagnosed post-partum. We describe a 28-year-old woman with USS complicated by RCVS after delivery that was treated by plasma exchange with a good outcome. She was referred to our hospital with thunderclap headache, anemia and thrombocytopenia that occurred immediately postpartum. She was diagnosed with TTP and multiple cerebral infarctions. Plasma exchange promptly improved her symptoms on hospital day 3. Moreover, multiple stenoses of cerebral arteries indicating RCVS were resolved. Since her sister also had an episode of thrombocytopenia during pregnancy, inherited TTP was suspected and genetic analyses confirmed USS. Pregnancy is a risk for not only TTP, but also RCVS. Endothelial damage might be an underlining cause and vasospasm after delivery is a trigger of RCVS. Plasma exchange was effective against both TTP and RCVS.

Optical coherence tomography findings of falciform retinal detachment complicated with persistent fetal vasculature.

BACKGROUND: Falciform retinal detachment (FRD) usually causes pronounced retinal wrinkles, and the prognosis of visual function is poor. In this present study, we report a rare case of FRD in which optical coherence tomography (OCT) findings revealed a relatively good visual function. CASE PRESENTATION: This study involved a 22-year-old female who had previously been diagnosed with FRD at 2 years of age, and who presented with microphthalmus in both eyes with pronounced retinal folds from the optic disc to the inferior-temporal side. Based on the clinical findings, we diagnosed it as persistent fetal vasculature (PFV). We found the visual function in her left eye to be relatively poor, yet from 6 to 22 years of age, the corrected visual acuity in that eye remained at 0.08. Although a nystagmus was present, Goldman perimetry showed a relatively wider visual field than expected. Optical coherence tomography (OCT) findings revealed that the retinal layer structure near the FRD was relatively well maintained, except for the temporal peripheral region. CONCLUSIONS: Our findings reveal that OCT examination can be considered useful for predicting the visual function in cases of FRD.

A case of proliferative diabetic retinopathy in which scintillating particles appeared in the intravitreal cavity after laser photocoagulation.

BACKGROUND: To report a case of proliferative diabetic retinopathy (PDR) exhibiting the appearance of scintillating particles presumed to be crystallin inside the intravitreal cavity after laser photocoagulation. CASE PRESENTATION: A 56-year-old male patient presented at our outpatient clinic after becoming aware of decreased vision in his right eye. Ocular examination performed at the patient's initial visit revealed a massive preretinal macular hemorrhage due to PDR in his right eye. Fundus fluorescein angiography revealed extensive retinal non-perfusion areas and neovascularization in both eyes. However, no opacity was observed in the intravitreal cavity of his left eye. Vitreous surgery was performed on the patient's right eye after ultrasonic phacoemulsification aspiration and intraocular lens implantation. Post surgery, the corrected VA in that eye improved from 0.1 to 1.0. In correlation with the treatment performed on the patient's right eye, we began panretinal photocoagulation on his left eye. Examination performed prior to the patient's third session of panretinal photocoagulation revealed a large number of scintillating particles in the posterior vitreous gel in front of the retina. Examination via slit-lamp microscopy revealed that the particles were of varied hues, and closely resembled a 'Christmas tree' cataract. No posterior vitreous detachment was observed, and since these particles were situated as if captured in the posterior vitreous gel, no eye-movement-associated mobility of the particles was observed. Since the cloudiness was not severe enough to interfere with photocoagulation, additional photocoagulation was performed, and the patient is currently under observation. Six months have now passed since the fourth photocoagulation procedure was performed, and there has been no change in the state of the particles. Optical coherence tomography imaging revealed no change before and after the panretinal photocoagulation. The corrected VA in his left eye has remained at 1.0 during the postoperative follow-up period. CONCLUSIONS: We speculate that the production of crystallin in the retina in this case was triggered by the photocoagulation procedure performed for diabetic retinopathy.

Identification of a drug-response gene in multiple myeloma through longitudinal single-cell transcriptome sequencing.

Despite recent therapeutic advances for multiple myeloma (MM), relapse is very common. Here, we conducted longitudinal single-cell transcriptome sequencing (scRNA-seq) of MM cells from a patient with relapsed MM, treated with multiple anti-myeloma drugs. We observed five subclusters of MM cells, which appeared and/or disappeared in response to the therapeutic pressure, and identified cluster 3 which emerged during lenalidomide treatment and disappeared after proteasome inhibitor (PI) treatment. Among the differentially expressed genes in cluster 3, we found a candidate drug-response gene; pellino E3 ubiquitin-protein ligase family member 2 (PELI2), which is responsible for PI-induced cell death in in vitro assay. Kaplan-Meier survival analysis of database revealed that higher expression of PELI2 is associated with a better prognosis. Our integrated strategy combining longitudinal scRNA-seq analysis, in vitro functional assay, and database analysis would facilitate the understanding of clonal dynamics of MM in response to anti-myeloma drugs and identification of drug-response genes.

Rapid decrease in eGFR with concomitant use of tyrosine kinase inhibitors and renin-aldosterone-angiotensin system inhibitors in patients with chronic myelogenous leukemia.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). However, TKI-related chronic renal toxicity has been reported, particularly in patients with hypertension. We assessed whether incidental use of specific types of antihypertensive drugs, including renin-aldosterone-angiotensin system inhibitors (RAASis), affects the change in estimated glomerular filtration rate (eGFR) during TKI treatment. We retrospectively analyzed all eGFR measurements during TKI treatment for 142 CML patients at Kyushu University Hospital, estimating the rate of eGFR change using a mixed-effects model. Overall, a significant interaction was found between the type of antihypertensive medication used and the yearly change in eGFR (P < 0.01), with RAASi users exhibiting the most rapid decrease in eGFR (- 5.5%/year). The analysis by TKI used showed that the interaction was significant only in imatinib and bosutinib users (P < 0.01 and P = 0.04, respectively). The yearly rate of eGFR decrease was the most notable in RAASi users, at - 5.7 (- 6.6, - 4.9) and - 10.1 (- 12.3, - 7.9) for imatinib and bosutinib users, respectively. Our findings indicate that eGFR should be carefully monitored in patients taking these TKIs.

Intraocular gas dynamics after 20-gauge and 23-gauge vitrectomy with sulfur hexafluoride gas tamponade.

PURPOSE: The purpose of this study was to evaluate the intraocular gas dynamics after 23-gauge transconjunctival sutureless vitrectomy (TSV) as compared with 20-gauge pars plana vitrectomy (PPV). METHODS: A consecutive series of 290 eyes that experienced 20-gauge or 23-gauge vitrectomy with 25% sulfur hexafluoride (SF6) gas tamponade were retrospectively reviewed. Intraocular gas bubble size on postoperative Day 1 and Gas50, the interval to dissipate to a 50% gas fill, were evaluated. RESULTS: The mean intraocular bubble size on postoperative Day 1 was 92.0 ± 8.3% in the 20-gauge PPV cases and 83.8 ± 13.7% in the 23-gauge TSV cases (P < 0.001). The mean Gas50 was 8.6 ± 1.6 days in the 20-gauge PPV cases and 6.6 ± 2.2 days in the 23-gauge TSV cases (P < 0.001). Thorough peripheral vitrectomy and 23-gauge TSV were significantly associated with Gas50 ≤ 4 days (odds ratio, 4.62 and 16.8; P = 0.036 and P = 0.007, respectively). Among thoroughly vitrectomized eyes, 13 eyes treated with 23-gauge PPV with intraoperative suture placement at the sclerotomy sites had gas longevity comparative to those with 20-gauge PPV. CONCLUSION: Eyes treated with 23-gauge TSV tend to have earlier gas disappearance or incomplete gas fill. Intraoperative suture placement would be a solution.

A case of relapsing polychondritis associated with auricular cartilage infiltration of immunoglobulin G4-positive plasma cells and lung cancer.

A 79-year-old man was diagnosed with relapsing polychondritis, from symptoms of bilateral auricular deformity and pigmentation, polyarthralgia, and audiovestibular damage, and from histological examination of the left auricular cartilage. The left auricular cartilage biopsy specimen revealed cartilage destruction with infiltration of plasmacytes expressing IgG4. This case suggests that IgG4 may be involved in the pathogenesis and etiology of relapsing polychondritis.

Transformation of follicular lymphoma to double-hit lymphoma during adjuvant chemotherapy for concurrent ovarian carcinoma.

The frequency of multiple primary malignant neoplasms (MPMN) is increasing due to population aging. Since consensus guidelines for the treatment of MPMN are lacking, treatment strategies are determined by disease status on a per-patient basis. In this report, we describe a case of MPMN with follicular lymphoma (FL) grade 1 that transformed to double-hit lymphoma during adjuvant chemotherapy for concurrent ovarian carcinoma. A 64-year-old woman was diagnosed with MPMN of FL and endometrioid carcinoma by staging laparotomy and lymph node biopsy. She received four cycles of adjuvant chemotherapy (carboplatin and paclitaxel) for endometrioid carcinoma, but during chemotherapy, the FL grade 1 transformed to double-hit lymphoma. We speculate that adjuvant chemotherapy for endometrioid carcinoma may have triggered the transformation of FL in the present case.

Familial exudative vitreoretinopathy complicated with full thickness macular hole: A case report.

RATIONALE: To report a case of familial exudative vitreoretinopathy (FEVR) complicated with full-thickness macular hole (FTMH). PATIENT CONCERNS: A 39-year-old male presented after becoming aware of metamorphopsia in his left eye. DIAGNOSES: Fundus examination showed a retinal avascular area, retinal vascular abnormality, and yellow exudation at the peripheral retina in both eyes. Optical coherence tomography findings revealed impending MH (IMH) due to posterior vitreous detachment (PVD) in his left eye. Despite of the occurrence of spontaneous complete PVD, an FTMH developed at 4 months after the onset of IMH. INTERVENTIONS: To treat the FTMH, vitreous surgery was performed. Intraoperative findings revealed that the thick posterior vitreous membrane (PVM) had no adhesions with the edge of the FTMH. However, a thin epiretinal membrane (ERM) was observed around the MH. OUTCOMES: Postoperatively, the FTMH was closed, and the patient's corrected visual acuity improved from (0.4) to (0.8). LESSONS: In this present case, an IMH developed via traction by a thick PVM, characteristic of FEVR, with FTMH then developing via traction by a thin ERM. Our findings reveal that it is vital to fully understand these anatomical features before performing vitreous surgery for FTMH complicated with FEVR.

Case Report of a Family Affected by Stickler Syndrome in Which Rhegmatogenous Retinal Detachment Occurred in Five Eyes of Three Siblings.

PURPOSE: Stickler syndrome is an autosomal dominant inherited disorder that is well known to be highly associated with the development of rhegmatogenous retinal detachment. In this study, we report the case of a family affected by Stickler syndrome in which rhegmatogenous retinal detachment developed in 5 eyes of 3 siblings. CASE SERIES: For treatment, we performed vitreous surgery on 1 eye of the eldest son, and bilateral scleral buckling surgery on the 2 younger children. A good postoperative outcome was obtained on the 4 eyes that underwent scleral buckling surgery, yet the prognosis was poor on the 1 eye that underwent vitrectomy due to redetachment of the retina and corneal complication. Since vitreous surgery was quite difficult due to strong vitreoretinal adhesion, we created an artificial posterior vitreous detachment via the bimanual technique combined with encircling. For the scleral buckling surgery, broad scleral extrusion was needed to seal multiple retinal breaks. CONCLUSIONS: The findings of this study showed a high prevalence of rhegmatogenous retinal detachment in a single family with Stickler syndrome. In these cases, scleral buckling surgery was effective for treating the detached retina, and some prophylactic treatment, such as laser photocoagulation to prevent the occurrence of rhegmatogenous retinal detachment, should be considered for such cases in the future.

A Case of Retinal Detachment with Unique Optical Coherence Tomography Findings after Gamma Knife® Radiosurgery Treatment for Choroidal Melanoma.

PURPOSE: To report a case of retinal detachment with unique optical coherence tomography (OCT) findings after Gamma Knife® (GK; Elekta Instrument AB, Stockholm, Sweden) treatment for choroidal melanoma (CM). CASE REPORT: A 48-year-old woman underwent GK therapy for CM in her right eye from the macula to the temporal side. While the tumor subsequently shrank, the patient developed radiation retinopathy, which was treated with laser photocoagulation. The tumor lesions later subsided; however, her visual acuity (VA) decreased 8 years after the initial treatment. Although the tumor lesions in the right eye had become scarred, a bullous retinal detachment with fixed folds occurred in the superior-nasal quadrants. OCT examination revealed a preretinal membrane, vitreoretinal traction, and an inner retinal break; however, no outer retinal break was clearly detectable. MRI scans showed no increase in tumorous lesions, and 123I-IMP SPECT imaging showed no photon accumulation. Thus, it was determined that there was no tumor activity. The corrected VA in her right eye was light perception, and it was determined that there was no indication for vitreous surgery. CONCLUSION: In this case, an inner retinal break was formed by the vitreoretinal traction around the scarred tumor and radiation retinopathy, thus suggesting the possibility of the development of a rhegmatogenous retinal detachment presumably complicated with an outer retinal break.

A Case of a Ruptured Eyeball Caused by High-Pressure Water Jets.

To report the case of a ruptured eyeball caused by high-pressure water jets. In this study, the right eye of a 49-year-old male was injured by high-pressure water jets while he was engaged in demolition work. Upon examination, remarkable hyphema and vitreous hemorrhage were observed in the injured eye. After treating the patient's right eye with vitrectomy, in addition to lens subluxation and iridodialysis, retinal detachment was observed at the nasal inferior. The edge of the retinal break was found to be incarcerated into the nasal sclera rupture wounds. The findings of this study indicate that direct exposure to high-pressure water jets can cause a rupture of the eyeball. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:451-455.].

A Case of Rhegmatogenous Retinal Detachment at Late Stage following Endogenous Bacterial Endophthalmitis.

PURPOSE: To report a case of rhegmatogenous retinal detachment in the late stage, despite the fact that it had previously been halted after intravitreal injection of an antimicrobial agent against endogenous bacterial endophthalmitis (EBE). CASE: This study involved a 62-year-old male who had previously been diagnosed with septicemia due to liver abscess and the detection of Klebsiella pneumoniae in a culture of his liver abscess, and who underwent ophthalmic examination after his conjunctival hyperemia had failed to improve. Visual acuity could not be measured due to his general condition being poor and his declining level of consciousness. Slit lamp examination revealed bilateral iritis and cataracts, and the fundus was invisible due to vitreous opacity. Ultrasonic B-mode examination showed subretinal abscess and exudative retinal detachment, leading to the diagnosis of EBE. Vitreous injections of antibiotics were administered to both of his eyes. His right eye became affected by phthisis bulbi, but the condition in his left eye subsided, leaving a scarred lesion near the macula. However, complete retinal detachment occurred in his left eye approximately 10 months after the vitreous injection. During vitreous surgery, proliferative membrane formation was observed in the posterior pole area, and an irregular retinal break was detected in the scar margin caused by the traction of the proliferative membrane. After vitreous surgery, the retina was reattached under silicone oil. CONCLUSION: In cases of EBE, even if the inflammation has previously subsided, strict follow-up examinations are necessary, since complications such as rhegmatogenous retinal detachment may occur at a late stage.

A Case of Serious Eye Injury Caused by a Mistaken Injection of Methylrosaniline Chloride During Vitreous Surgery.

This case involved a 75-year-old female with left-eye epiretinal membrane (ERM) and cataract who developed serious eye disorders during vitreous surgery due to methylrosaniline chloride (MRC) being mistakenly injected and applied to the retina instead of Brilliant Blue G during internal limiting membrane staining. Once realized, MRC was washed out with intraocular infusion solution, and ERM surgery was successfully completed. Postoperatively, a Descemet's fold and corneal edema, marked reduction in corneal endothelial cell density, and inner retina damage and visual field defect extending from the macula toward the temporal side were observed. MRC was found highly toxic to eye tissues. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:1010-1015.].

A Case of Diabetic Macular Edema with Prominent Chorioretinal Folds.

PURPOSE: To report a case of diabetic macular edema with prominent chorioretinal folds. CASE REPORT: This study involved a 55-year-old male with untreated bilateral diabetic retinopathy who had undergone cataract surgery at another clinic. Following that surgery, diabetic macular edema rapidly exacerbated, accentuating marked cystoid macular edema and radial chorioretinal folds in the macula. Investigation of his medical history revealed that in addition to diabetes, he had uncontrolled hypertension and severe diabetic nephropathy. Vitreous surgery was performed on both eyes due to a resistance to a subtenon injection of triamcinolone acetonide or intravitreal injection of an antivascular endothelial growth factor agent. After surgery, the macular edema and chorioretinal folds showed a tendency towards improvement. Thereafter, kidney transplant surgery was performed for renal failure, and a mild tendency of chorioretinal folds was observed. CONCLUSION: In the case presented in this study, we observed remarkable cystoid macular edema in the fovea centralis and theorize that distortion with the surrounding tissue might have occurred, thus leading to the formation of chorioretinal folds around the macula.

Vitrectomy for Tractional Retinal Detachment with Twin Retinal Capillary Hemangiomas in a Patient with Von Hippel-Lindau Disease: A Case Report.

PURPOSE: The purpose of this study was to report a case of Von Hippel-Lindau disease (VHL) with twin retinal capillary hemangiomas that was successfully treated by vitreous surgery for tractional retinal detachment following laser photocoagulation. CASE: A 44-year-old male presented at our university hospital after noticing decreased visual acuity in his right eye. The patient had previously undergone multiple operations for cerebellar, thoracic, and lumbar spine hemangioblastomas when he was approximately 19 years old. Upon initial examination, ocular findings revealed twin connected retinal capillary hemangiomas around the temporal upper area of the patient's right eye. The patient was subsequently diagnosed with VHL based on his medical history and current observations of the ocular fundus. Tractional retinal detachment had occurred as the result of the formation of proliferative membranes following laser photocoagulation. The patient underwent vitreous surgery to treat the tractional retinal detachment, resulting in a successful postoperative outcome. CONCLUSION: The findings of this study show the possibility that proliferative changes and tractional retinal detachment can arise following photocoagulation for retinal capillary hemangiomas in patients with VHL.

A Case of Proliferative Diabetic Retinopathy with HIV Infection in Which HAART Possibly Influenced the Prognosis of Visual Function.

BACKGROUND: We report on a patient with proliferative diabetic retinopathy (PDR) and human immunodeficiency virus (HIV) infection who exhibited extremely active PDR followed by a rapid onset of blindness in the right eye. The progression of visual disturbance in the patient's left eye was slowed after starting highly active anti-retroviral therapy (HAART), and vision in that eye was rescued after vitrectomy. CASE REPORT: A 72-year-old male developed pneumocystis carinii pneumonia stemming from an HIV infection and began HAART at the Department of Hematology, Osaka Medical College, Takatsuki City, Japan. Prior to HAART, the patient had shown rapidly progressing retinopathy in the right eye accompanied by vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma, ultimately leading to early-onset blindness. After starting HAART, the progression of the retinopathy in the left eye became slower compared to the right eye, with corrected visual acuity improving to 0.6 after vitrectomy, despite being accompanied by vitreous hemorrhage. The patient's overall condition has remained stable following the operation, and the condition of the ocular fundus in the left eye has also settled. CONCLUSION: Significant differences were found in the progression rate of PDR with HIV infection between before and after starting HAART. Our findings suggest that early administration of HAART to HIV patients with diabetic retinopathy is crucial for maintaining visual function.