Clostridium butyricum MIYAIRI 588 contributes to the maintenance of intestinal microbiota diversity early after haematopoietic cell transplantation.

In patients undergoing haematopoietic stem-cell transplantation (HSCT), the intestinal microbiota plays an important role in prognosis, transplant outcome, and complications such as graft-versus-host disease (GVHD). Our prior research revealed that patients undergoing HSCT substantially differed from healthy controls. In this retrospective study, we showed that administering Clostridium butyricum MIYAIRI 588 (CBM588) as a live biotherapeutic agent is associated with maintaining intestinal microbiota in the early post-HSCT period. Alpha diversity, which reflects species richness, declined considerably in patients who did not receive CBM588, whereas it remained consistent in those who received CBM588. In addition, ß-diversity analysis revealed that CBM588 did not alter the gut microbiota structure at 7-21 days post-HSCT. Patients who developed GVHD showed structural changes in their microbiota from the pre-transplant period, which was noticeable on day 14 before developing GVHD. Enterococcus was significantly prevalent in patients with GVHD after HSCT, and the population of Bacteroides was maintained from the pre-HSCT period through to the post-HSCT period. Patients who received CBM588 exhibited a contrasting trend, with lower relative abundances of both genera Enterococcus and Bacteroides. These results suggest that preoperative treatment with CBM588 could potentially be beneficial in maintaining intestinal microbiota balance.

Comparative study of surgical outcomes regarding tear meniscus area and high-order aberrations between two different interventional methods for primary acquired nasolacrimal duct obstruction.

PURPOSE: To compare endonasal dacryocystorhinostomy (EN-DCR) with sheath-guided dacryoendoscopic probing and bicanalicular intubation (SG-BCI) by evaluating tear meniscus area (TMA) and total high-order aberrations (HOAs) for primary acquired nasolacrimal duct obstruction (PANDO). METHOD: We retrospectively reviewed 56 eyes of 42 patients (7 men, 35 women; age, 72.7±13.1 years) who underwent EN-DCR or SG-BCI for PANDO in Toyama University Hospital from February 2020 to June 2022. In the EN-DCR and SG-BCI groups, we measured the patency of the lacrimal passage, preoperative and postoperative TMA, and HOAs of the central 4 mm of the cornea using optical coherence tomography (AS-OCT), six months postoperatively. RESULTS: There was a positive correlation between preoperative TMA and preoperative HOAs in all cases. Postoperative patency of lacrimal passage was 100% in the EN-DCR and 80.8% in the SG-BCI group. There was a significant difference in the number of passages between the two groups (p = 0.01). Preoperative TMA and HOAs showed a significant postoperative decrease in both groups (EN-DCR group: p<0.01, p<0.01, SG-BCI group: p<0.01, p=0.03, respectively). We then calculated the rate of change of preoperative and postoperative TMA and HOAs and compared them between the two groups. The rate of change was significantly higher in the EN-DCR group than that in the SG-BCI group (TMA, p=0.03; HOAs, p=0.02). CONCLUSION: Although both EN-DCR and SG-BCI are effective for PANDO, our results suggest that EN-DCR is more effective in improving TMA and HOAs.

Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation.

BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.

The biotherapeutic Clostridium butyricum MIYAIRI 588 strain potentiates enterotropism of Rorγt+Treg and PD-1 blockade efficacy.

Immune checkpoint inhibitors (ICI) have been positioned as a standard of care for patients with advanced non-small-cell lung carcinomas (NSCLC). A pilot clinical trial has reflected optimistic association between supplementation with Clostridium butyricum MIYAIRI 588 (CBM588) and ICI efficacy in NSCLC. However, it remains to be established whether this biotherapeutic strain may be sufficient to heighten the immunogenicity of the tumor draining lymph nodes to overcome resistance to ICI. Herein, we report that supplementation with CBM588 led to an improved responsiveness to antibody targeting programmed cell death protein 1 (aPD-1). This was statistically associated with a significant decrease in α-diversity of gut microbiota from CBM588-treated mice upon PD-1 blockade. At the level of the tumor-draining lymph node, such combination of treatment significantly lowered the frequency of microbiota-modulated subset of regulatory T cells that express Retinoic Orphan Receptor gamma t (Rorγt+ Treg). Specifically, this strongly immunosuppressive was negatively correlated with the abundance of bacteria that belong to the family of Ruminococcaceae. Accordingly, the colonic expression of both indoleamine 2,3-Dioxygenase 1 (IDO-1) and interleukin-10 (IL-10) were heightened in mice with greater PD-1 blockade efficacy. The CBM588-induced ability to secrete Interleukin-10 of lamina propria mononuclear cells was heightened in tumor bearers when compared with cancer-free mice. Conversely, blockade of interleukin-10 signaling preferentially enhanced the capacity of CD8+ T cells to secrete Interferon gamma when being cocultured with CBM588-primed lamina propria mononuclear cells of tumor-bearing mice. Our results demonstrate that CBM588-centered intervention can adequately improve intestinal homeostasis and efficiently overcome resistance to PD-1 blockade in mice.

Novel rapid method for identifying and quantifying pathogenic bacteria within four hours of blood collection.

Sepsis is life-threatening organ dysfunction and is considered a major cause of health loss. However, since the current biomarkers of sepsis reflect the host's immune response to microorganisms, they would inevitably cause a time-lag. This means that there is still no truly reliable biomarker of sepsis. In the present study, we developed a novel method for identifying and quantifying unknown pathogenic bacteria within four hours of sample collection. The most important point of this study is that the novel method can be used to determine the number of bacteria in a sample as a novel biomarker of infectious diseases. Indeed, based on the number of bacteria, we were able to accurately estimate the severity of microbial infection. Furthermore, using the time-dependent changes in the number of bacteria, we were able to monitor the therapeutic effect accurately. The rapid identification and quantification of bacteria may change our approach to medical care.

Inhibition of retinal ischemia-reperfusion injury in rats by inhalation of low-concentration hydrogen gas.

PURPOSE: To investigate the inhibitory effect of hydrogen gas inhalation on retinal ischemia reperfusion (I/R) injury using a rat model. METHODS: Six-week-old male Sprague-Dawley rats were used. A 27G needle connected by a tube to a saline bottle placed 200 cm above the eye was inserted into the anterior eye chamber to create a rat retinal I/R model. In the ischemia-plus-hydrogen-gas group (H2( +) group), the ischemia time was set to 90 min, and 1.8% hydrogen was added to the air delivered by the anesthesia mask simultaneously with the start of ischemia. In the non-hydrogen-treatment ischemia group (H2( -) group), I/R injury was created similarly, but only air was inhaled. ERGs were measured; after removal of the eyes, the retina was examined for histological, immunostaining, and molecular biological analyses. RESULTS: The mean thickness of the inner retinal layer in the H2( +) group was 107.2 ± 16.0 µm (n = 5), significantly greater than that in the H2( -) group (60.8 ± 6.7 µm). Immunostaining for Iba1 in the H2( -) group showed increased numbers of microglia and microglial infiltration into the subretinal space, while there was no increase in microglia in the H2( +) group. B-wave amplitudes in the H2( +) group were significantly higher than in the H2( -) group. In the membrane antibody array, levels of interleukin-6, monocyte chemotactic protein 1, and tumor necrosis factor alpha were significantly lower in the H2( +) group than in the H2( -) group. CONCLUSION: Inhalation of 1.8% hydrogen gas inhibited the induction of inflammation, morphological/structural changes, and glial cell increase caused by retinal I/R injury.

INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.

PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan. METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors. RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset. CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

Lower eyelid position before and after blepharoptosis repair.

PURPOSE: This study aimed to examine the changes in lower eyelid position after blepharoptosis surgery and the factors that influence the outcome. METHODS: We conducted a retrospective study of 155 eyes of 89 patients who underwent blepharoptosis surgery between June 2019 and October 2022. The margin reflex distance (MRD)-1 and MRD-2 were examined preoperatively and 3 months postoperatively in two groups: one with lower scleral show (LSS) (n = 37) and one without LSS (n = 118). The clinical characteristics of the two groups were compared. RESULTS: Both the LSS and non-LSS groups showed significant postoperative improvement in MRD-1 scores (p < .01, p < .01, respectively). MRD-2 was significantly reduced in the LSS group, while it remained unchanged in the non-LSS group (p < .01, p = .27, respectively). There were no significant differences between the two groups in age, sex, history of hard contact lens use, preoperative levator function, use of topical steroids, history of endophthalmic surgery, or history of filtration surgery; however, the LSS group significantly used prostaglandin analogs (PGAs) (p = .03). Postoperatively, MRD-2 decreased in 13 eyes (35.1%) and was maintained in 24 eyes (64.9%) in the LSS group and was maintained in all eyes in the non-LSS group. In the LSS group, we also examined the association between postoperative MRD-2 reduction and the use of PGAs and found that more patients with MRD-2 reduction used PGAs (p = .02). CONCLUSION: Lower scleral show in PGAs-associated blepharoptosis is expected to improve after blepharoptosis surgery.

Parameters of a basic ophthalmic examination that can ensure proper timing of corneal crosslinking in patients with keratoconus.

BACKGROUND: By the time patients with keratoconus are referred to specialists for treatment, the disease-related thinning of their corneas has already made them ineligible (< 400 µm) for corneal crosslinking (CXL). PURPOSE: To find basic ophthalmic examination parameters that can ensure proper timing of referral for CXL. METHODS: We reviewed cases referred to Toyama University Hospital for the treatment of keratoconus from August 2011 to May 2021 to identify the frequency of contraindication due to minimal corneal thickness (MCT) < 400 µm at first visit. We performed a receiver operator characteristic (ROC) analysis of basic exam parameters (uncorrected distance visual acuity, corrected distance visual acuity, corrected distance visual acuity with hard contact lens, sphericity, cylindricity, and/or corneal astigmatism) potentially predicting eligibility for CXL. For those with an area under the curve (AUC) > 0.8, we determined cut-off values and calculated sensitivity and specificity. RESULTS: Analyses included 66 eyes of 38 Japanese patients aged 25.0 ± 7.1 yrs (range 12-38 yrs) (56 male eyes and 10 female eyes). Thirty percent of the patients had an MCT < 400 µm. The AUC for uncorrected distance visual acuity (UCDVA) was 0.85. A cut-off value of 1.22 (converted to decimal visual acuity: ≥ 0.06) yielded 87% sensitivity and 75% specificity. The AUC for corrected distance visual acuity (CDVA) was 0.90. A cut-off of 0.52 (converted to decimal visual acuity: ≥ 0.3) yielded 89% sensitivity and 75% specificity. CONCLUSIONS: It is advisable to refer patients with keratoconus to a specialized facility for CXL when either of the following conditions is present: (i) UCDVA (decimal visual acuity) ≥ 0.06 or (ii) CDVA (decimal visual acuity) ≥ 0.3.

Macular vessel density in central retinal artery occlusion with retinal arterial cannulation.

To characterize and compare macular vessel density in central retinal artery occlusion (CRAO) eyes with retinal arterial cannulation and CRAO eyes with standard treatment. This study was Cross-sectional, observational study. Twenty-two eyes with nonarteric CRAO which underwent retinal arterial cannulation and 19 eyes with nonarteric CRAO with standard treatment were included. Optical coherent tomography angiography (OCTA)-based macular vessel density and visual acuity were examined. The dynamic ranged-based normalized rates of vessel density was compared within each group at the first visit to the clinic and 7 days after the onset. Macular vessel density in cannulation group was significantly better at 7 days after the onset than that at the first visit (3.73 ± 3.02 mm-1 vs. 7.89 ± 1.02 mm-1, P = 0.0001), while there wasn't significant improvement of macular vessel density in standard treatment group at 7 days after the onset (2.13 ± 1.62 mm-1 vs. 2.89 ± 0.22 mm-1, P = 0.067). At one month after the onset, mean LogMAR visual acuity in CRAO eyes with cannulation significantly improved compared with that at the first visit after the onset (1.678 vs. 0.979, P = 0.00012). Macular vessel density loss in CRAO eyes was improved by retinal arterial cannulation. Early intervention of retinal arterial cannulation is useful for minimizing visual impairment in CRAO eyes.

A Novel Method for Quantifying Plant Morphological Characteristics Using Normal Vectors and Local Curvature Data via 3D Modelling-A Case Study in Leaf Lettuce.

Three-dimensional measurement is a high-throughput method that can record a large amount of information. Three-dimensional modelling of plants has the possibility to not only automate dimensional measurement, but to also enable visual assessment to be quantified, eliminating ambiguity in human judgment. In this study, we have developed new methods that could be used for the morphological analysis of plants from the information contained in 3D data. Specifically, we investigated characteristics that can be measured by scale (dimension) and/or visual assessment by humans. The latter is particularly novel in this paper. The characteristics that can be measured on a scale-related dimension were tested based on the bounding box, convex hull, column solid, and voxel. Furthermore, for characteristics that can be evaluated by visual assessment, we propose a new method using normal vectors and local curvature (LC) data. For these examinations, we used our highly accurate all-around 3D plant modelling system. The coefficient of determination between manual measurements and the scale-related methods were all above 0.9. Furthermore, the differences in LC calculated from the normal vector data allowed us to visualise and quantify the concavity and convexity of leaves. This technique revealed that there were differences in the time point at which leaf blistering began to develop among the varieties. The precise 3D model made it possible to perform quantitative measurements of lettuce size and morphological characteristics. In addition, the newly proposed LC-based analysis method made it possible to quantify the characteristics that rely on visual assessment. This research paper was able to demonstrate the following possibilities as outcomes: (1) the automation of conventional manual measurements, and (2) the elimination of variability caused by human subjectivity, thereby rendering evaluations by skilled experts unnecessary.

FFR-CT is extremely useful in detecting hemodynamically significant left-main coronary artery stenosis with right coronary artery hypoplasia: A case report.

Left main coronary artery (LMCA) stenosis in patients with coronary artery disease (CAD) is associated with a significant increase in cardiac events, and determining its contribution to ischemia is essential. Currently, several noninvasive modalities are available for the ischemic assessment of CAD. In multi-vessel disease, including LMCA disease, the accuracy of myocardial perfusion scintigraphy (MPS) for detecting myocardial ischemia can be poor. Fractional flow reserve from computed tomography (FFR-CT) has emerged as a promising noninvasive modality that can provide functional myocardial ischemia information. Herein, we describe the case of a 50-year-old woman with type 2 diabetes who presented to the hospital due to intermittent chest pain on exertion. Coronary computed tomography angiography showed right coronary artery hypoplasia, 25 % stenosis in the LMCA, and 75 % stenosis in the left anterior descending. FFR-CT identified myocardial ischemia due to LMCA stenosis, but MPS did not. Invasive coronary angiography with conventional fractional flow reserve was mostly consistent with the results of FFR-CT. Learning objective: Fractional flow reserve from computed tomography (FFR-CT), which is a novel noninvasive method, can provide absolute, not relative, functional myocardial ischemia information by applying computational fluid dynamics to coronary computed tomography angiography on a lesion-by-lesion basis. FFR-CT can be extremely useful in detecting patients with left main coronary artery stenosis with right coronary artery hypoplasia.

Use of a Backflush Needle with a Silicone Tip Cannula to Embed Lamellar Hole-Associated Epiretinal Proliferation.

PURPOSE: For the treatment of lamellar macular hole, the recent development of a lamellar hole-associated epiretinal proliferation (LHEP) embedding technique is likely to improve functional and anatomical results. However, the peeling of LHEP is often technically challenging. We have developed a new technique using a backflush needle with a silicone tip cannula that seems safer and more effective for use in LHEP embedding. METHODS: A 25-gauge vitrectomy system with an enhancing visual acuity system (D.O.R.C., Zuidland, Netherlands) was used in all cases. After core vitrectomy, triamcinolone acetonide (Wakamoto Pharmaceutical Co., Ltd., Tokyo, Japan) was used to visualize the membrane. A 25-gauge backflush needle with a silicone tip cannula was used to remove the thin preretinal membrane centripetally, leaving an LHEP on the edge of the hole. Brilliant Blue G (internal limiting membrane Blue; D.O.R.C.) was then used to stain the internal limiting membrane. RESULTS: This technique was used in six eyes with lamellar macular holes. In all cases, peeling and embedding of the LHEP was effectively performed without damaging the internal limiting membrane or causing retinal hemorrhage. No other intraoperative or postoperative complications were experienced. CONCLUSION: Using a silicone-tipped backflush needle with passive aspiration was a simple and effective technique for peeling and embedding of LHEPs in this small series.

Corneal endothelial cell loss after EX-PRESS surgery depends on site of insertion, cornea or trabecular meshwork.

PURPOSE: Previously, we reported that the Ex-press® shunt (EXP) was associated with more rapid reduction in corneal endothelial cells when inserted into the cornea rather than the trabecular meshwork (TM). We compared the reduction rate of corneal endothelial cells between the corneal insertion group and TM insertion group. METHODS: This was a retrospective study. We included patients who had undergone EXP surgery and were followed for > 5 years. We analyzed the corneal endothelial cell density (ECD) before and after EXP implantation. RESULTS: We included 25 patients in the corneal insertion group and 53 patients in the TM insertion group. One patient in the corneal insertion group developed bullous keratopathy. The ECD decreased significantly more rapidly in the corneal insertion group (p < 0.0001), in whom the mean ECD decreased from 2227 ± 443 to 1415 ± 573 cells/mm2 at 5 years with a mean 5-year survival rate of 64.9 ± 21.9%. By contrast, in the TM insertion group, the mean ECD decreased from 2356 ± 364 to 2124 ± 579 cells/mm2 at 5 years, and the mean 5-year survival rate was 89.3 ± 18.0%. The decrease rate of ECD was calculated as 8.3%/year in the corneal insertion group and 2.2%/year in the TM insertion group. CONCLUSIONS: Insertion into cornea is a risk factor for rapid ECD loss. The EXP should be inserted into the TM to preserve the corneal endothelial cells.

Saccade Analysis in Patients With Orbital-Wall Fractures Without Diplopia.

PURPOSE: This study aimed to analyze saccades in patients with orbital-wall fractures with little or no ocular motor impairment. METHODS: We included 7 eyes of 7 patients with unoperated orbital-wall fractures (3 cases of orbital-floor fractures and 4 cases of medial orbital-wall fractures) with mild or no diplopia who presented to our hospital between August 2019 and March 2021. Eye movements were assessed at the first visit and after 1 month using the Hess area ratio according to the Hess screen test, binocular single vision (BSV) scores (total 59 points) obtained using Goldman perimetry, and maximum velocity and amplitude of saccades within 15 degrees obtained using an eye tracker system. RESULTS: Hess area ratio and BSV scores at the first visit and after 1 month were 88.6±8.2% and 97.4±3.6% and 49.6±8.5 points and 53.5±6.6 points, respectively, with no significant change (Hess area ratio, P =0.06; BSV, P =0.44). Next, the authors compared the velocity and amplitude of the saccades between the first visit and 1 month later and found no significant changes in any of the 4 directions (adduction, abduction, upgaze, and downgaze). Similarly, no significant differences were observed between the velocity and amplitude of the saccades between the injured and noninjured eyes, both at the first visit and after 1 month. CONCLUSIONS: In patients with orbital-wall fractures with little or no eye movement impairment, eye tracker-based saccade analysis showed that the saccade velocity and amplitude did not change during the natural course of healing of the fracture.

Improvement of the loss of corneal endothelial cells by relocating the tip of the Baerveldt® implant tube from the anterior chamber to the vitreous cavity.

PURPOSE: It has been reported that corneal endothelial cells (CEC) decrease faster when the tip of the Baerveldt glaucoma implant (BGI) tube is inserted into the anterior chamber than into the vitreous cavity. We investigated whether surgically relocating the tip of the BGI tube from the anterior chamber to the vitreous cavity could reduce CEC loss. PATIENTS AND METHODS: This was a single facility retrospective cohort study. The inclusion criteria were the CEC density less than 1500 cells/mm2 and the CEC reduction ratio was greater than 10%/year. The subjects were 11 consecutive patients that could be followed > 12 months after relocation surgery. All patients were undergone vitrectomy, and the tip of tube was inserted into the vitreous cavity from the anterior chamber. We compared the intraocular pressure (IOP), reduction slope of CEC density and annual reduction rate of CEC density before and after relocation surgery. We calculated the annual reduction ratio in comparison with the preoperative CEC density (%/year). RESULTS: The mean of period between the Baeveldt with anterior chamber insertion surgery and the relocation surgery was 33.8 ± 15.0 months. The mean of follow-up after relocation surgery was 21.8 ± 9.8 months. The relocation surgery did not significantly change IOP (p = 0.974). The mean preoperative and postoperative IOP were 13.1 ± 4.5 and 13.6 ± 4.3 mmHg. The reduction ratio of the CEC density was 15.4 ± 6.7 (%/year) before relocation surgery and significantly slower at 8.3 ± 6.5 (%/year) after relocation surgery (p = 0.024). Two patients resulted in bullous keratopathy after relocation surgery. CONCLUSIONS: Relocating the tip of BGI tube from the anterior chamber to the vitreous cavity could reduce CEC loss.

Comparison of the results of Ex-PRESS® surgery for primary open-angle glaucoma between high and low preoperative intraocular pressure.

PURPOSE: To compare surgical outcomes of Ex-PRESS® (EXP) surgery for primary open-angle glaucoma (POAG) between low preoperative intraocular pressure (IOP) and high preoperative IOP. METHODS: This was a retrospective non-randomized study. Seventy-nine POAG patients who underwent EXP surgery and were followed for > 3 years were included. Patients with a preoperative IOP of ≦ 16 mmHg and > 16 mmHg with tolerant glaucoma medications were defined as the low IOP group and the high IOP group, respectively. We compared the surgical outcomes, postoperative IOP and number of glaucoma medications. Success was defined as a postoperative IOP of ≦ 15 mmHg and a reduction of > 20% from the preoperative IOP to the postoperative IOP. RESULTS: EXP surgeries significantly decreased IOPs from 13.2 ± 2.0 to 9.1 ± 2.9 mmHg in the low IOP group (p < 0.001), and from 22.5 ± 4.8 to 12.5 ± 4.0 mmHg in the high IOP group (p < 0.001). The mean postoperative IOP was significantly low in the low IOP group at 3 years (p = 0.0008). Success rates compared using the Kaplan-Meier survival curve were not significantly different (p = 0.449). CONCLUSIONS: EXP surgery was useful for POAG patients with a low preoperative IOP.

Differences in clinical and echocardiographic features and outcomes between atrial functional mitral regurgitation patients with and without posterior mitral leaflet bending.

BACKGROUND: Posterior mitral leaflet (PML) bending is a cause of atrial functional mitral regurgitation (AFMR). We aimed to investigate differences in clinical and echocardiographic features and outcomes between AFMR patients with and without PML bending. METHODS: We retrospectively examined 118 AFMR patients with atrial fibrillation (AF), mild or greater MR without degenerative mitral valve changes, and left ventricular ejection fraction ≥50 %. Patients were classified by the presence of PML bending: PML bending (n=24) and no PML bending (n=94). PML bending was defined as PML-to-anterior mitral leaflet angle ratio ≥3.1 calculated using receiver operating characteristics analysis for eccentric MR jet toward left atrial posterior wall. The study endpoint was a composite of cardiac death, admission for heart failure, and mitral valve surgery. RESULTS: Overall, a total of 88 patients (75 %) had mild MR. There were no between-group differences in clinical and echocardiographic characteristics including AF duration and cardiac cavities size except for the length of inward bending of the left ventricular posterobasal wall and the mitral annular area. The 36-month event-free survival for the composite endpoint was significantly lower in the PML bending group (63 % vs. 78 %; Log-rank p=0.047). In multivariate analysis, PML bending was also associated with the composite outcome. CONCLUSIONS: AFMR patients with PML bending may have worse outcomes than those without PML bending despite similar clinical features.

Clopidogrel Use in CYP2C19 Loss-of-Function Carriers With High Bleeding Risk After Percutaneous Coronary Intervention.

BACKGROUND: It is not known whether clopidogrel use in cytochrome P450 (CYP) 2C19 loss-of-function (LOF) carriers with high bleeding risk (HBR) contributes to adverse outcomes after percutaneous coronary intervention (PCI).Methods and Results: This retrospective observational study included 618 consecutive patients with available CYP2C19 polymorphism information who underwent PCI between September 2014 and August 2021. Patients with HBR (319 [52%] met the Academic Research Consortium definition) were divided into 2 groups according to P2Y12inhibitor action, namely decreased (i.e., clopidogrel in CYP2C19 LOF carriers) and retained (i.e., clopidogrel in CYP2C19 LOF non-carriers or prasugrel regardless of CYP2C19 polymorphisms), and clinical outcomes at 1 year were compared using inverse probability-weighted Cox proportional hazard regression. The primary ischemic outcome (a composite of cardiovascular death, myocardial infarction, or ischemic stroke) was significantly higher in the decreased than retained group (10.2% vs. 3.0%; adjusted hazard ratio [aHR] 2.78; 95% confidence interval [CI] 1.40-5.52; P=0.004). The primary bleeding outcome (Bleeding Academic Research Consortium 3 or 5) did not differ significantly between the decreased and retained groups (3.4% vs. 6.9%, respectively; aHR 0.48; 95% CI 0.22-1.01; P=0.054). There were no interactions between the treatment groups and HBR status in primary ischemic and bleeding outcomes. CONCLUSIONS: Among patients with HBR, clopidogrel use in CYP2C19 LOF carriers was significantly associated with increased ischemic events after PCI.