Effects of FCGRIIIa‐158V/F polymorphism on antibody‐dependent cellular cytotoxicity activity of adalimumab

The associations between the efficacy of IgG reagents and the FCGRIIIa‐158V/F polymorphism (rs396991) have been investigated. Although the genotype frequencies in healthy Japanese have been reported, those have varied, as one study reported that the proportions of V/V, V/F, and F/F were 59.1%, 38.6%, and 2.3%, respectively, while another study found that they were 4%, 44%, and 52%, respectively. However, there are no known investigations of the association between the antibody‐dependent cellular cytotoxicity (ADCC) activity of adalimumab (ADA), an IgG reagent, in combination with FcγRIIIa and the polymorphism. In this study, we analyzed healthy Japanese to clarify genotype frequency using a direct sequence method. In addition, we examined the association between the ADA‐mediated ADCC activity and the polymorphism. Our results showed that the frequencies of the V/V, V/F, and F/F genotypes in healthy Japanese were 9.2%, 39.8%, and 51.0%, respectively. The average activity of ADA‐mediated ADCC was 25.0%, 19.0%, and 13.3% in the V/V, V/F, and F/F genotypes, respectively. Then, the ADCC activity of V/V was significantly higher than that of F/F (p < 0.05) in therapeutic concentration. The differences in therapeutic effect of ADA among individuals can be explained, in part, by ADCC activity via the FCGRIIIa‐158V/F polymorphism.     

Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST

OBJECTIVE: The purpose of this article is to review cancer- and therapy-specific tumor response assessment criteria used in clinical trials and in practice, with illustrative case examples, and to discuss future directions toward "personalized" tumor response assessment. CONCLUSION: Although Response Evaluation Criteria in Solid Tumors will remain as the primary generalized criteria for response assessment, newer cancer- and therapy-specific criteria will play an important role in providing state-of-the-art response assessment of tumor following molecular targeted therapy and will contribute to personalized cancer care in the era of molecular medicine.     

Characteristics and treatment strategies of mitral regurgitation associated with undifferentiated papillary muscle

Purpose

In this report we review our experience of operations on mitral regurgitation associated with abnormal papillary muscles/chordae tendineae of the mitral valves and discussed the clinical characteristics, operative findings, and treatment strategies.

Methods

Undifferentiated papillary muscle was defined as a hypoplastic chordae tendineae with anomalous formation of papillary muscles attached to the mitral valves directly. Consecutive 87 patients undergoing surgery for mitral regurgitation at our institution were reviewed and 6 of them had undifferentiated papillary muscle.

Results

The underlying mechanism of regurgitation was prolapse at the center of the anterior leaflet in 3 cases and tethering, a wide area of myxomatous degeneration, and annular dilatation in one case, respectively. Five patients underwent mitral valve plasty and 1 patient received replacement. Anomalous formation of chordae tendineae was corrected by resection and suture with transplantation at the tip of the leaflet to which abnormal chordae were attached in 2 cases, while resection and suture with chordal shortening was performed in 1 case, and chordal reconstruction using artificial chordae was employed in 2 cases. There was no operative death, and postoperative echocardiography showed no residual regurgitation in any of the cases.

Conclusions

Mitral regurgitation associated with undifferentiated papillary muscle resulted from prolapse or tethering and impaired flexibility of leaflets. It was possible to successfully treat the patients by mitral valve plasty unless complex congenital cardiac malformation coexisted. Detailed examinations of attached papillary muscle by echocardiography and intraoperative inspection are necessary and surgical techniques should be selected appropriately in each case.

     

Severe laryngeal edema caused by Pseudoterranova species: A case report

Rationale:Severe laryngeal edema can cause upper airway obstruction, which is fatal. Pseudoterranova, an uncommon nematode of the family Anisakidae, predominantly invades the stomach after ingestion of the nematodes in raw or undercooked marine fish. There have been a few reports of development of severe laryngeal edema caused by the nematode invading the base of the tongue.Patient concerns:A 69-year-old Japanese woman complained of stuffy and scratchy throat for 8 hours and reported eating sashimi, fresh slices of raw jacopever, 4 days before the first visit.Diagnosis:Endoscopy revealed a white-yellowish wriggling worm at the left side of the base of the tongue and severe edema of the larynx.Interventions:The worm was extracted using endoscopic forceps. The patient was hospitalized and treated with intravenous injection of an antibiotic and steroid.Outcomes:The symptoms and laryngeal edema disappeared the next day. The worm was identified as a 4th-stage larva of Pseudoterranova spp based on morphologic features. The serum Anisakis-specific IgE antibody level was high, at 38.6 UA/mL.Lessons:Clinicians should be aware of the possibility of severe laryngeal edema due to invasion by anisakid nematodes in the pharyngolaryngeal area in cases involving previous ingestion of raw or uncooked marine fish.     

Factors associated with enlargement of chorioretinal atrophy after intravitreal bevacizumab for myopic choroidal neovascularization

Purpose

To determine the factors significantly associated with an enlargement of the area of a chorioretinal atrophy (ChRA) after intravitreal bevacizumab (IVB) to treat myopic choroidal neovascularization (mCNV).

Methods

The medical charts of 27 eyes with a mCNV that had received IVB were reviewed. The ophthalmic examinations included measurements of the best-corrected visual acuity, visual fields with the Humphrey 10-2 Field Analyzer, fluorescein angiography, and indocyanine green angiography. The area of the mCNV and the chorioretinal atrophy (ChRA) were measured on the FA images.

Results

Eyes with an enlargement of the ChRA had significantly larger mCNVs at the baseline, a greater reduction in the size of the mCNV, a higher incidence of subretinal hemorrhage, longer duration of follow-up, received more injections of IVB, and had a greater decrease of retinal sensitivity (P?≤?0.041). Multiple regression analyses showed that the factors most significantly associated with an enlargement of the ChRA were the CNV size at baseline, the number of IVB injections, and the duration of the follow-up period (P?Conclusions Our findings showed that eyes with a larger CNV at the baseline and longer follow-up period had a greater risk of developing a ChRA like non-treatment, even if IVB treatment was performed for mCNV.     

Eosinophil infiltration in the heart with free-wall rupture following acute myocardial infarction: a case report

A 90-year-old woman was referred to us due to acute extensive anterior myocardial infarction with cardiogenic shock. Echocardiography revealed akinesis of infarct region, associated with wall thinning. She was treated with catecholamines and diuretics because her hemodynamics were classified in Forrester subset IV. On the ninth day after the onset of infarction, she died of free-wall rupture. The postmortem histological study demonstrated eosinophil infiltration in the area of rupture, which may have been a pathological factor.     

Ultrasonic tissue characterization in patients with dilated cardiomyopathy: comparison with findings from right ventricular endomyocardial biopsy

Aim: The clinical usefulness of integrated backscatter (IB) imaging was compared with right ventricular endomyocardial biopsy for assessing myocardial damage in patients with dilated cardiomyopathy (DCM). Methods: We examined 15 patients with DCM and 20 healthy controls. In addition to the conventional M-mode echocardiographic parameters, we determined the cyclic variation in IB values (CV-IB) obtained from parasternal short axis views of the left ventricle just under the transducer for both the interventricular septum (IVS) and the left ventricular posterior wall (PW). The per cent fibrosis area (%) and the transverse diameter of myocytes (m) were measured in right ventricular endomyocardial biopsy specimens by computer image analysis. To analyze the relationship between pathological findings and CV-IB, we divided patients into four subgroups on the basis of the pathological characteristics of endomyocardial biopsy specimens as follows: degeneration dominant group (n=5), fibrosis dominant group (n=5), dilated phase hypertrophic cardiomyopathy (n=2), and mixed type (n=3). Results: CV-IB in the IVS and the PW was lower in patients with DCM (8.8 ± 2.9, 8.3 ± 2.7dB, respectively) than in normal subjects (14.4 ± 2.9, 13.6 ± 2.6dB, respectively). Biopsy findings showed a mean per cent fibrosis area of 24.0 ± 12.3%, and a mean myocyte diameter of 14.3 ± 2.9m in patients with DCM. CV-IB was correlated with both of these findings: per cent fibrosis area (r=–0.56 in IVS, r=–0.56 in PW) and myocyte diameter (r=0.67 in IVS, r=0.71 in PW). CV-IB was decreased in all DCM subgroups compared with normal subjects, but there was no significant difference between subgroups. Conclusions: CV-IB was correlated with both the extent of fibrosis in myocardial tissue and the myocyte diameter. These findings suggest that ultrasonic tissue characterization is a good indicator of the severity of fibrosis and myocyte atrophy in patients with DCM.