Outcomes of mitral valve transcatheter edge-to-edge repair for patients with hemodynamic instability: A systematic review and meta-analysis.

BACKGROUND: The outcomes after mitral valve transcatheter edge-to-edge repair (M-TEER) for the patients with severe mitral regurgitation (MR) in hemodynamically unstable conditions, such as cardiogenic shock, still remain unclear. We aimed to integrate previous publications regarding M-TEER indicated for life-threatening conditions and indirectly particularly compared the short-term outcomes thereof, with that of other treatments. METHODS: We systematically searched the PubMed, Cochrane, and MEDLINE databases for studies from inception to June 2023, regarding M-TEER in patients with hemodynamic instability and severe MR. The primary outcomes analyzed included the in-hospital and 30-day mortality rates, and peri-procedural complications. RESULTS: Of the initial 820 publications, we conducted a meta-analysis of a total of 25 studies. The relative risk of moderate-to-severe or severe MR was 0.13 (95 % confidence interval [CI]: 0.10-0.18, I2 = 45.2 %). The pooled in-hospital and 30-day mortality rates were 11.8 % (95 % CI: 8.7-15.9, I2 = 96.4 %) and 14.1 % (95 % CI: 10.9-18.3, I2 = 35.5 %), respectively. The 30-day mortality rate was statistically significantly correlated with the residual moderate-to-severe or severe MR, as per the meta-regression analysis (coefficient ß = 3.48 [95 % CI: 0.99-5.97], p = 0.006). Regarding peri-procedural complications, the pooled rates of a stroke or transient ischemic attack, life-threatening or major bleeding, acute kidney injury, and peri-procedural mitral valve surgery were 2.3 % (95 % CI: 1.9-2.6), 7.6 % (95 % CI: 6.8-8.5), 32.9 % (95 % CI: 31.6-34.3), and 1.0 % (95 % CI: 0.8-1.3), respectively. CONCLUSIONS: This meta-analysis demonstrates that the relatively higher rates of procedural complications were observed, nevertheless, M-TEER can potentially provide favorable short-term outcomes even in hemodynamically unstable patients. PROSPERO REGISTRATION NUMBER: CRD42023468946.

Can EUS-FNA cytology reliably classify gastric submucosal spindle cell tumors?

BACKGROUND: Cytological diagnosis using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for gastric submucosal spindle cell tumors, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas, is challenging because of their similar morphological characteristics. OBJECTIVE AND MATERIALS: To clarify the cytological differential points, we reviewed the EUS-FNA cytology specimens of GISTs (37 cases), leiomyomas (11 cases), and schwannomas (4 cases). METHOD: Twelve cytomorphological features were evaluated: lymphocytes, crushed nuclei, naked spindle nuclei, mast cell, length of the streaming arrangement, cellularity, nuclei at the cluster margin (nuclei located at the periphery of the cell cluster), peripheral feathering (loosely aggregated cells at the margin of a cell cluster tended to taper like feathers), metachromasia, wavy nuclei, fishhook-type nuclei, and anisonucleosis. RESULTS: Among these features, lymphocytes, naked spindle nuclei, length of the streaming arrangement, cellularity, nuclei at the cluster margins, peripheral feathering, and anisonucleosis were statistically significant for differentiation. Based on these findings, we developed an algorithm for cytodiagnosis. The algorithm was taught to four cytologists, and the interobserver agreement and correct diagnosis rates were compared before and after education, which showed a significant improvement. DISCUSSION: The histological types of gastric submucosal spindle cell tumors can be estimated using this algorithm for EUS-FNA cytology. Furthermore, this algorithm can be applied for cytological diagnosis at bedside during rapid on-site evaluation.

Effect of blood volume change related to intensity of intradialytic aerobic exercise on hemodialysis adequacy: a pilot study.

PURPOSE: Intradialytic exercise may improve dialysis efficiency; however, the association between changes in blood volume (BV) related to exercise intensity and solute removal kinetics remains unknown. We herein investigated the relationship between changes in BV with exercise and removal of solute molecules during hemodialysis. METHODS: Each of the 21 hemodialysis patients underwent cardiopulmonary exercise test to measure anaerobic threshold (AT). According to the exercise intensity, patients were classified into two groups, the low group (n = 12), whose intensity was below the AT, and the high group (n = 9), whose intensity was at the AT level. Each patient completed two trial arms of resting and discontinuous exercise dialysis sessions in a randomized manner. RESULTS: The change in BV with the exercise dialysis session in the high group decreased during exercise (p = 0.028) and remained decreased after exercise (p = 0.016), compared with the low group. In the low group, compared with routine sessions, the removal of potassium (p = 0.030), phosphate (p = 0.024), and urea nitrogen (p = 0.065) increased during exercise, but the total removal of these solutes did not change. In the high group, the removal of phosphate (p < 0.001) and urea nitrogen (p = 0.018) after exercise and even total phosphate (p = 0.027) decreased. CONCLUSION: These findings suggest that the removal of small solute molecules is improved during exercise in intradialytic low-intensity exercise with no change in BV, and decreased after exercise in high-intensity exercise with a decrease in BV. CLINICAL TRIALS REGISTRY: Trial retrospectively registered at the UMIN Clinical Trials Registry: study number UMIN000038629 (Registration date: September 7, 2019).

Drug-induced lenticular opacity and accumulation of cholesterol-related substances in the lens cortex of dogs.

TP0446131, developed as an antidepressant agent, was found to cause lenticular opacity in a 13-week repeated-dose study in dogs. Histopathologically, the lenticular opacity was observed as a degeneration of the lens fibers, characterized by irregularity in the ordered arrangement of the fibers which is necessary to maintain the transparency of the lens, and was considered to manifest clinically as cataract. To evaluate the development mechanism of the lenticular opacity, the chemical constituents of the lens, which is known to be associated with the development of cataract, were examined. The results of liquid chromatography-tandem mass spectrometry analysis revealed an increase in the amplitudes of 3 unknown peaks in a dose- and time-dependent manner in the lens, with no remarkable changes in the other chemical components tested. In addition, the content of cholesterol, alterations of which have been reported to be associated with cataract, remained unchanged. The mass spectral data and chromatographic behavior of the 3 peaks indicated that these peaks corresponded to sterol-related substances, and that one of them was 7-dehydrocholesterol, a precursor of cholesterol biosynthesis. This finding suggested that TP0446131 exerts some effects on the cholesterol biosynthesis pathway, which could be involved in the development of the cataracts. Furthermore, increases in the levels of these sterol-related substances were also detected in the serum, and were, in fact, noted prior to the onset of the cataract, suggesting the possibility that these substances in the serum could be used as potential safety biomarkers for predicting the onset of cataract induced by TP0446131.

Paradoxical Embolism of Stroke-Related Patent Foramen Ovale in a Nonagenarian Woman.

There are few clinical reports of elderly patients with paradoxical embolism in the current literature. Herein, we describe the case of a nonagenarian patient with paradoxical embolism of stroke-related patent foramen ovale (PFO). A 95-year-old woman was admitted to our hospital because of dysarthria. Her medical history included cerebral infarction, hypertension, and dyslipidemia. Magnetic resonance imaging performed in the emergency room revealed cerebral infarction of the left temporal lobe. After hospitalization in the neurosurgery department, we performed further clinical investigations to diagnose the type of stroke. There was no significant stenosis with plaque of the carotid and cerebral arteries, and there were no sources of cardiac embolism or an episode of atrial arrhythmia. Transesophageal echocardiography (TEE) showed PFO with separation and the Eustachian valve. In addition, spontaneous bidirectional shunt flow through the PFO was detected by TEE with the patient at rest. Ultrasonography of the leg vein revealed a thrombus in the deep vein. Therefore, she was diagnosed as having paradoxical embolism of stroke-related PFO and prescribed a direct oral anticoagulant (DOAC). This very rare case in which stroke-related PFO was diagnosed in a nonagenarian patient demonstrates that PFO is the cause of paradoxical embolism of stroke regardless of age.

Predictors of early restenosis after intracardiac echocardiography guided antegrade balloon aortic valvuloplasty in high-risk or inoperable patients.

Antegrade balloon aortic valvuloplasty (BAV) may be more effective than retrograde BAV. However, early restenosis is found inconstantly within three months after BAV. To evaluate the factor of ER after intracardiac echocardiogram (ICE) guided Antegrade BAV, fifty patients with severe aortic stenosis (AS) underwent BAV procedures with ICE. ER was defined as mean aortic valve pressure gradient (PG) >40 mmHg. During one-year follow-up period, 6 patients died and 2 patients underwent aortic valve replacement. ER was present in 13 patients (26%) at three months after BAV. Procedural, clinical, and hemodynamic data were collected. The mean age of the patient population was 85.4 ± 7.6 years; the mean STS score and EuroSCORE were 7.8 ± 1.1 and 14.6 ± 4.1, respectively. The mean aortic valve PG decreased from 63.4 ± 19.8 to 28.5 ± 10.1 mmHg (p < 0.0001). Baseline characteristics were similar between the two groups. There is no significant difference of mean aortic valve PG immediate after BAV(ER; 29 ± 8.8 mmHg, nonER; 21 ± 6.1 mmHg, p = ns). Univariate analysis showed patients with ER group had significantly higher rate of left ventricular hypertrophy, pulmonary hypertension, and high mean aortic valve PG at admission. Multivariate analysis revealed high mean aortic valve PG at admission as independent predictors of ER. Antegrade BAV may be effective for severe AS. Left ventricular hypertrophy, pulmonary hypertension and high mean PG were predictor of early restenosis. Early intervention should be considered for these patients.

Effects of reduced food intake for 4 weeks on physiological parameters in toxicity studies in dogs.

This study sought to clarify the effects of reduced feeding on physiological parameters in dogs to enable appropriate evaluations of the safety and toxicity of test compounds. We measured alkaline phosphatase isozymes and the circulating blood volume, as well as clinical signs, body weight, hematology, blood chemistry, electrocardiography, organ weight, and histopathology, in male beagle dogs fed a diet consisting of 300 g/day or 150 g/day for 4 weeks. There were no abnormal clinical signs in any of the dogs. In the 150-g/day feeding group, a decreased alkaline phosphatase 3 suggesting effects on the bone and a decreased circulating blood volume associated with body weight loss were observed. Additionally, the following changes were also observed in the 150-g/day group: a decrease in body weight; hematologic changes including decreases in white blood cells, neutrophils, red blood cells, hemoglobin, hematocrit and reticulocytes; blood chemical changes including decreases in aspartate aminotransferase, lactate dehydrogenase and calcium and an increase in the creatinine at week 1 or thereafter; electrocardiographic changes including a decrease in the heart rate, a prolonged QRS duration and the occurrence of a second-degree atrioventricular block at week 3 or thereafter; and pathological changes including decreases in the weights of the liver and thymus, a decrease in hepatocyte rarefaction, and thymic atrophy. These results provide useful information for assessing the safety of compounds in toxicological studies, enabling direct treatment effects and secondary changes caused by decreased food intake to be distinguished.

Effects of reduced food intake on the parameters of toxicity evaluation in dogs.

It is crucial to evaluate the variations in the toxicity parameters in experimental animals during the development of new drugs. Reduced food intake has been reported to have an impact on the toxicity parameters in rats; however, there are few reports of such studies in dogs. The aim of this study was to clarify the effects of reduced food intake on the general toxicity parameters and their reversibility in dogs. Male beagle dogs were fed 300 g/day of diet for 12 weeks in the control group, and 150 g/day for the first 8 weeks and 200 g/day for the subsequent 4 weeks in the low feeding group. During the following 4-week recovery period, the amount of feeding was set at 300 g/day. There were no clinical changes in any of the dogs. The low feeding group showed a body weight loss of 9.0%, 16.7% and 14.3% relative to the pre-test values at Week 4, 8 and 12, respectively. The following changes from the pre-test values and/or the control group in the examined parameters were observed in this group: decreased heart rate, prolonged PR interval on the ECG, decreased leukocyte count, and increased serum free fatty acid and γ-glutamyl transpeptidase levels. Significant changes of these parameters were not observed any more during the recovery period. This fact supports biological or physiological reaction to reduced food intake. These results are considered to represent useful information for toxicologists to distinguish between the direct effects of drugs and the changes attributable to reduced food intake.

[Alcohol related problem in the workplace: trial of a screening and brief intervention program for risky drinking in the workplace, via the Internet].

This report describes the effect of a screening and brief intervention via the Internet (6-month Total health Management Program: TMP, a kind of life evolution program), for improvement of alcohol related problem in the workplace. At a certain company, 2,096 employees were screened.using AUDIT-C and CAGE via the Internet (electronic screening). From those screened, 17 risky drinkers were picked up. The classification of "risky drinker" was determined based on employees scoring over six points on AUDIT-C and over two points on_ AGE. These employees were then called to one-day practical seminar program (including the program of food education, music therapy, aro-atherapy, body conditioning etc.). After which, during 6 months, they were followed up via e-mail every month. After the 6-month follow up, their results of AUDIT-C were significantly decreased. Additionally, aside from the frequency of drinking at bedtime, maximum alcohol consumption per day was also significantly decreased. The Visual Analogue Scale for anxiety captured the initial screen and then again after follow-up was reduced significantly. Moreover, quality-of-life index for sleep and dinner were both significantly improved as well..These results suggest that the SBI (screening and brief intervention: TMP) is effective for reducing drinking behavior, can be used to effectively elevate quality of life.

Aberrant Activation of Heat Shock Protein 60/65 Reactive T Cells in Patients with Behcet's Disease.

Behcet's disease (BD) is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. We found that heat shock proteins (HSPs) reactive T cells were prevalent in patients with BD. Here, we summarize current findings on HSP reactive T cells and their contribution to the pathogenesis in patients with BD.

Clinical and histologic resolution of poststreptococcal glomerulonephritis with large subendothelial deposits and kidney failure.

A 16-year-old male adolescent who had fallen and scratched his knee developed cold-like symptoms. Gross hematuria, oliguria, and peripheral edema appeared about 2 weeks after his fall. Tests showed hypocomplementemia, increased antistreptolysin O titers, and severe kidney failure with hematuria/proteinuria. Kidney biopsy showed endocapillary proliferative glomerulonephritis visible using light microscopy and deposits of complement C3 on capillary walls, detectable using immunofluorescence microscopy. Although these findings suggested that he had acute poststreptococcal glomerulonephritis (APSGN), electron microscopy failed to detect subepithelial humps, a feature typical of APSGN; instead, massive electron-dense deposits were visible in the subendothelial space. A second biopsy performed 3 months later showed mesangial cell proliferation without endocapillary proliferation using light microscopy and the disappearance of subendothelial electron-dense deposits in electron micrographs, suggesting that APSGN had resolved. Glomerular deposition of nephritis-associated plasmin receptor, a nephritogenic streptococcal antigen, was observed in the first biopsy specimen, but not the second. The patient required 4 hemodialysis treatments, and within 1 year of supportive therapy only, kidney function and urinalysis had normalized. This is an interesting case of APSGN presenting with acute kidney injury and atypical massive subendothelial deposits, but no subepithelial deposits on electron microscopy, a pattern resembling that in membranoproliferative glomerulonephritis type I.

Mobile and accurate detection system for infection by the 2009 pandemic influenza A (H1N1) virus with a pocket-warmer reverse-transcriptase loop-mediated isothermal amplification.

The 2009 pandemic H1N1 influenza A virus spread quickly worldwide in 2009. Since most of the fatal cases were reported in developing countries, rapid and accurate diagnosis methods that are usable in poorly equipped laboratories are necessary. In this study, a mobile detection system for the 2009 H1N1 influenza A virus was developed using a reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) kit with a disposable pocket-warmer as a heating device (designated as pwRT-LAMP). The pwRT-LAMP can detect as few as 100 copies of the virus--which is nearly as sensitive as real-time reverse-transcription polymerase chain reaction (RT-PCR)--and does not cross-react with RNA of seasonal influenza viruses. To evaluate the usefulness of the pwRT-LAMP system, nasal swab samples were collected from 56 patients with flu-like symptoms and were tested. Real-time RT-PCR confirmed that the 2009 H1N1 influenza A virus was present in 27 of the 56 samples. Of these 27 positive samples, QuickVue Influenza A+B immunochromatography detected the virus in only 11 samples (11/27; 40.7%), whereas the pwRT-LAMP system detected the virus in 26 of the 56 samples (26/27 of the positive samples; 96.3%). These findings indicate that the mobile pwRT-LAMP system is an accurate diagnostic system for the 2009 H1N1 influenza A virus, and has great potential utility in diagnosing future influenza pandemics.

A successfully treated case of hyperosmolar hyperglycemic state complicated with rhabdomyolysis, acute kidney injury, and ischemic colitis.

A 48-year-old Japanese male was admitted to our hospital due to hyperosmolar hyperglycemic state (HHS), combined with rhabdomyolysis and acute kidney injury. His blood sugar levels were gradually decreased by fluid resuscitation and insulin infusion; however, his renal function worsened, and he developed bloody stools. He required continuous hemodiafiltration to improve his hemodynamics. As colonoscopy revealed longitudinal ulcers, ischemic colitis was diagnosed. We treated him conservatively at first, but when we found the ulceration of the sigmoid colon had penetrated the mesenterium, colectomy was indicated. After surgery, his general condition improved. Careful monitoring of complications related to HHS is important.

An adult with acute poststreptococcal glomerulonephritis complicated by hemolytic uremic syndrome and nephrotic syndrome.

We report the case of a 47-year-old man with the simultaneous occurrence of clinical and laboratory features consistent with acute poststreptococcal glomerulonephritis (APSGN), hemolytic uremic syndrome (HUS), and nephrotic syndrome. Acute nephritic syndrome occurred 3 weeks after having pharyngeal pain and diarrhea. He presented with edema and hypertension on admission. Laboratory evaluation showed hemolytic anemia with fragmentation, thrombocytopenia, elevated lactic dehydrogenase level, low haptoglobin level, low complement C3 level, and elevated antistreptolysin-O titer. Serum creatinine level was 1.22 mg/dL (108 micromol/L), and urinalysis showed marked proteinuria, with protein of 8.7 g/d, and hematuria. The renal biopsy specimen was characteristic of APSGN, but not HUS. Moderate expansion of the mesangial matrix, moderate proliferation of epithelial and endothelial cells, and marked infiltration of neutrophils was seen by means of light microscopy, and many subepithelial humps were seen by means of electron microscopy. Neither fibrin deposition nor evidence of thrombotic microangiopathy was found. Complement C3 deposition along the capillary wall and tubules was seen in an immunofluorescence study. The patient was administered plasma infusion at 320 mL/d and antihypertensive drugs. Serum complement C3 and haptoglobin levels returned to normal within 3 weeks. This is a rare case of the simultaneous occurrence of APSGN, HUS, and nephrotic syndrome.

Monitoring of ELISA for anti-BP180 antibodies: clinical and therapeutic analysis of steroid-treated patients with bullous pemphigoid.

We studied the precise correlation between ELISA values for BP180 NC16A and the alternations of disease activity in 5 patients with bullous pemphigoid (BP) during various treatments and tried to answer the question of how we can use ELISA to determine the timing of prednisolone (PSL) tapering. Disease activity in some patients with BP, but not in all, was poorly correlated with ELISA values in short-term follow-up. However, all patients showed a good correlation of disease activity with ELISA values as a whole in long-term follow-up. Three patients with typical BP showed rapid and good responses to PSL for erosion and blister formation. Their ELISA values gradually decreased to 40% of initial values during PSL therapy after four weeks. Two patients with the vesicular type of BP did not show rapid and good responses to PSL for erosion and blister formation. In the cases with the vesicular type of BP, diaphenylsulfone in addition to PSL dramatically improved the clinical symptoms including erosion and blister formation, even though the ELISA values were as high as those before treatment. Relapses did not occur with the tapering of PSL dosage when the ELISA values decreased to 40% of initial values, although they were still not within the normal range.

Characterization and expression analysis of genes encoding phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxylase kinase of Lotus japonicus, a model legume.

Phosphoenolpyruvate carboxylases (PEPCs), one form of which in each legume species plays a central role in the carbon metabolism in symbiotic root nodules, are activated through phosphorylation of a conserved residue by a specific protein kinase (PEPC-PK). We characterized the cDNAs for two PEPC isoforms of Lotus japonicus, an amide-translocating legume that forms determinate nodules. One gene encodes a nodule-enhanced form, which is more closely related to the PEPCs in amide-type indeterminate nodules than those in ureide-type determinate nodules. The other gene is expressed in shoots and roots at a low level. Both forms have the putative phosphorylation site, Ser11. We also isolated a cDNA and the corresponding genomic DNA for PEPC-PK of L. japonicus. The recombinant PEPC-PK protein expressed in Escherichia coli phosphorylated recombinant maize C4-form PEPC efficiently in vitro. The level of mRNA for PEPC-PK was high in root nodules, and those in shoots and roots were also significant. In situ hybridization revealed that the expression patterns of the transcripts for PEPC and PEPC-PK were similar in mature root nodules, but were different in emerging nodules. When L. japonicus seedlings were subjected to prolonged darkness and subsequent illumination, the activity of PEPC-PK and the mRNA levels of both PEPC and PEPC-PK in nodules decreased and then recovered, suggesting that they are regulated according to the amounts of photosynthates transported from shoots.