Predictive factors for development of the no-reflow phenomenon in patients with reperfused anterior wall acute myocardial infarction

OBJECTIVES: We sought to elucidate the clinical factors related to the development of no-reflow phenomenon after successful coronary reperfusion in patients with an acute myocardial infarction (AMI). BACKGROUND: Myocardial contrast echocardiography revealed that the no-reflow phenomenon is observed in some patients with a reperfused AMI, and those patients usually have poor functional and clinical outcomes. It is still unknown what clinical factors are related to the development of the no-reflow phenomenon. METHODS: Myocardial contrast echocardiography was performed 15 min after successful coronary reperfusion therapy in 199 patients with an anterior wall AMI who underwent successful coronary reperfusion with primary coronary angioplasty within 24 h after the onset of AMI. Multiple logistic regression analysis was used to identify independent predictors of the no-reflow phenomenon. RESULTS: Seventy-nine patients showed the no-reflow phenomenon. Univariate analysis indicated that pre-infarction angina within 48 h before symptom onset, Killip class, Thrombolysis in Myocardial Infarction flow grade 0 on the initial coronary angiogram, the number of abnormal Q-waves and the wall motion score (WMS) on the echocardiogram obtained at hospital admission are related to the no-reflow phenomenon. Multivariate logistic regression analysis revealed that all of these factors, except for Killip class, are independent predictive factors of the no-reflow phenomenon. CONCLUSIONS: Development of the no-reflow phenomenon is related to the severity of myocardial damage (number of Q-waves), the size of the risk area (WMS) and the occlusion status of infarct-related artery. In addition, ischemic preconditioning (pre-infarction angina) seems to be the factor that attenuates the no-reflow phenomenon.     

Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma

OBJECTIVE: Recent epidemiological studies indicate that there is reduced risk of all digestive carcinomas in patients who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. Cyclooxygenase (COX) is a target enzyme for NSAIDs. We investigated the role of two isoforms, COX-1 and COX-2, in the development and metastasis of gastric carcinoma. METHODS: Fifteen gastric carcinoma tissue specimens and accompanying adjacent mucosa specimens were obtained from surgical resections. COX-1 and COX-2 protein expression were evaluated using Western blotting analysis, and their relative band densities were semi quantified using standard densitometry scanning techniques. RESULTS: Compared with paired noncancerous specimens, COX-2 was overexpressed in 10 of 15 carcinoma tissue specimens (66.7%). Overall, COX-2 levels in carcinoma tissue were significantly higher. Two early carcinomas (confined to the mucosa and submucosa) and three of 13 advanced carcinomas (extended below the submucosa into the muscular wall) had weak or similar COX-2 expression in paired tissue specimens. COX-2 overexpression in tumors significantly correlated with tumor invasion into the lymphatic vessels in the gastric wall and metastasis to the lymph nodes. Furthermore, the stage grouping in the TNM classification significantly correlated with COX-2 overexpression. In contrast, COX-2 overexpression did not correlate with histopathological grading, surface size, and venous vessel invasion of the tumors. COX-1 levels were similar between paired tissues. CONCLUSION: COX-2 overexpression might enhance lymphatic invasion and metastasis in patients with gastric carcinoma, implicating a poor prognosis. Therefore, the use of COX-2-specific inhibitor to suppress lymphatic metastasis in humans should be investigated.     

Plasma fibrinogen levels as an independent indicator of severity of coronary atherosclerosis

The relationship between plasma fibrinogen levels and the severity of coronary atherosclerosis was examined in 229 patients, aged 25-82 years (162 men and 67 women), undergoing coronary angiography. Severity of coronary atherosclerosis was assessed in terms of the number of vessels with a 75% or greater stenosis and Gensini's severity score. Fibrinogen levels increased progressively with the severity of coronary atherosclerosis, determined by both the number of involved vessels and Gensini's severity score in men, and the relationships were statistically significant. Similar patterns were noted among women, but the trends were not statistically significant. The association was evident even after adjustment for age, hypertension, total cholesterol, cigarette smoking, alcohol intake, high density lipoprotein cholesterol and body mass index. These results provide evidence that in the Japanese also plasma fibrinogen levels can serve as an independent indicator of the progression of coronary atherosclerosis.     

Deracemization of 1-phenylethanols in a one-pot process combining Mn-driven oxidation with enzymatic reduction utilizing a compartmentalization technique

Racemic 1-phenylethanols were converted into enantiopure (R)-1-phenylethanols via a chemoenzymatic process in which manganese oxide driven oxidation was coupled with enzymatic biotransformation by compartmentalization of the reactions, although the two reactions conducted under mixed conditions are not compatible due to enzyme deactivation by Mn ions. Achiral 1-phenylethanol is oxidized to produce acetophenone in the interior chamber of a polydimethylsiloxane thimble. The acetophenone passes through the membrane into the exterior chamber where enantioselective biotransformation takes place to produce (R)-1-phenylethanol with an enantioselectivity of >99% ee and with 96% yield. The developed sequential reaction could be applied to the deracemization of a wide range of methyl- and chloro-substituted 1-phenylethanols (up to 93%, >99% ee). In addition, this method was applied to the selective hydroxylation of ethylbenzene to afford chiral 1-phenylethanol.

PDMS thimble was the key to combining incompatible reactions to achieve deracemization of 1-phenylethanols in high yield with high optical yield.     

Delayed Acute Perimyocarditis and Bilateral Facial Nerve Palsy in a Patient with COVID-19

A 41-year-old Japanese man was admitted to our hospital with acute perimyocarditis 4 weeks after coronavirus disease 2019 (COVID-19) infection. Ten days after admission, the patient showed bilateral facial nerve palsy in the course of improvement of perimyocarditis under treatment with aspirin and colchicine. After prednisolone therapy, perimyocarditis completely improved, and the facial nerve palsy gradually improved. Acute perimyocarditis and facial nerve palsy can occur even 4 weeks after contracting COVID-19.     

Real‐world outcomes of pembrolizumab monotherapy in non‐small cell lung cancer in Japan: A post‐marketing surveillance

This post‐marketing surveillance (PMS) was initiated in Japan to identify factors affecting the safety and effectiveness of pembrolizumab monotherapy in patients with advanced non‐small cell lung cancer (NSCLC) with programmed cell death ligand‐1 (PD‐L1) expression. This PMS was conducted from December 2016 to June 2019 at 717 centers across Japan. Patients with unresectable advanced/recurrent NSCLC who received pembrolizumab monotherapy as first‐line (1L) treatment for PD‐L1‐expressing tumors (Tumor Proportion Score [TPS] ≥ 50%) or second‐line or later (2L+) treatment for tumors with PD‐L1 TPS ≥ 1% were enrolled and followed up for 1 year. Of 2805 registered patients, 2740 and 2400 comprised the safety and effectiveness analysis sets, respectively. The median age (range) was 69 (27–92) years; 55.7% and 29.2% of patients experienced treatment‐related adverse events and adverse events of special interest (AEOSIs), respectively. More common AEOSIs included interstitial lung disease, endocrine disorders, liver dysfunction, colitis/severe diarrhea, infusion reactions, and severe skin disorders. The frequency of experiencing ≥2 AEOSIs was low (1L, 6.5%; 2L+, 2.8%). Most AEOSIs occurred within 150 days after initiation of pembrolizumab monotherapy. At 1‐year follow‐up, the objective response rate was 39.2% (1L, 51.5%; 2L+, 30.0%). In conclusion, the 1‐year safety and effectiveness of pembrolizumab monotherapy in patients with unresectable advanced/recurrent NSCLC as 1L treatment for tumors with PD‐L1 TPS ≥ 50% and 2L+ treatment for tumors with PD‐L1 TPS ≥ 1% were similar to those reported in phase 2/3 trials.     

Posterior Pelvic Tilt in the Standing Position Might Be Associated with Collapse Progression in Post‐Collapse Stage Osteonecrosis of the Femoral Head

ObjectiveExcessive pelvic tilt has been reported to impair the biomechanical loading of the hip joint. However, the influence of pelvic tilt in osteonecrosis of the femoral head (ONFH) remains unclear. This study aims to assess whether sagittal pelvic posture in the standing position correlates with progression of femoral head collapse in post‐collapse stage ONFH.MethodsThis is a single‐center retrospective study. We investigated 107 patients (107 hips; 73 males and 34 females; mean age, 48 years) diagnosed with Association of Research Circulation Osseous (ARCO) stage III ONFH at the first visit and who subsequently underwent surgical treatment in our institution from July 2016 to December 2020. The sagittal pelvic posture in the standing position before surgery was quantified as the angle formed by the anterior pelvic plane and the vertical z‐axis in the sagittal view (APP angle). An APP angle <0° indicated posterior pelvic tilt. Progression of femoral head collapse was calculated as collapse speed. The following factors potentially associated with collapse speed were evaluated by exploratory data analysis followed with multiple linear regression analysis: sex, age, BMI, etiology, pelvic incidence, contralateral hip condition, time interval between the first visit and surgery, size of necrotic lesion, location of necrotic lesion, and APP angle.ResultsAs ONFH progressed from ARCO stage IIIA to stage IV, APP angle decreased significantly and continuously (stage IIIA, −0.2° ± 5.5°; stage IIIB, −3.7° ± 5.8°; stage IV, −7.1° ± 6.4°). The factors significantly associated with collapse speed were size of necrotic lesion (p = 0.0079), location of necrotic lesion (p = 0.0190), and APP angle (p < 0.0001). APP angle showed a negative correlation with collapse speed (r = −0.40, p < 0.0001). After stratifying by size of necrotic lesion (<50% and ≥50% involvement) and location of necrotic lesion (JIC type C1 and C2), a significant negative correlation was observed between APP angle and collapse speed in each group (JIC type C1 with <50% involvement, r = −0.69, p < 0.0001; JIC type C1 with ≥50% involvement, r = −0.58, p = 0.0475; JIC type C2 with <50% involvement, r = −0.51, p = 0.0124; JIC type C2 with ≥50% involvement, r = −0.39, p = 0.0286).ConclusionsOur results suggest that posterior pelvic tilt in the standing position occurred as ONFH progressed from ARCO stage IIIA to stage IV, which might be associated with progression of femoral head collapse in ONFH.     

Vasospastic Angina: An Immune-related Adverse Event

A 54-year-old Japanese woman was admitted to our ward because of recurrent chest pain at rest for 2 months. She had been treated with nivolumab, an immune checkpoint inhibitor for inoperable advanced hypopharyngeal cancer for 21 months. She had no chest pain after cessation of nivolumab treatment. Cardiac catheterization confirmed the presence of vasospastic angina. Benidipine 8 mg was started, and she had no chest pain even after resuming therapy with nivolumab. Vasospastic angina is an adverse effect of nivolumab.