Immunolocalization of CD80 and CD86 in Non-Small Cell Lung Carcinoma: CD80 as a Potent Prognostic Factor

It has been demonstrated that tumor cells express programed cell death protein 1 (PD-L1) to escape T lymphocytes that express programed cell protein 1 (PD-1), and PD-1/PD-L1 immune checkpoint inhibitors have been regarded in lung cancer patients. CD80 and CD86 are members of B7 superfamily which regulates T lymphocyte activation and tolerance. However, immunolocalization of CD80 and CD86 has not been examined in the lung carcinoma tissues and their clinical significance remains unknown. Therefore, to clarify clinical significance of CD80 and CD86, we immunolocalized these in 75 non-small cell lung carcinomas (NSCLC) in this study. Immunoreactivities of CD80 and CD86 were mainly detected in tumor-infiltrating macrophages. Immunohistochemical CD80 status was high in 56% of NSCLC, and it was positively associated with stage, pathological T factor, distant metastasis, histological type and PD-L1 status. Moreover, multivariate analysis turned out that the CD80 status was an independent worse prognostic factor. CD86 status was high in 53% of the cases, but it was not significantly associated with any clinicopathological parameters. These findings suggest that CD80 is a potent worse prognostic factor possibly in association with escape from immune attack in NSCLC.     

Pharmacokinetic characteristics of amiodarone in long-term oral therapy in Japanese population

To evaluate the pharmacokinetic properties and an optimum dose schedule of amiodarone in long-term oral therapy, serum concentrations of amiodarone and its metabolite, desethylamiodarone, were monitored from 345 Japanese inpatients who received amiodarone therapy for a variety of cardiac arrhythmias. Serum amiodarone and desethylamiodarone concentrations were determined by high performance liquid chromatography system. It was observed that the amiodarone and desethylamiodarone concentrations gradually increased with time. The frequency distribution in the amiodarone clearance of 245 subjects, who received fixed maintenance amiodarone therapy for at least 6 months, was nearly a unimodal one. The variation in the ratio of desetylamiodarone to amiodarone concentration in serum was very small. Although no differences in age, dose, dose duration, amiodarone or desethyamiodarone concentration or ratio were observed between men and women: however, the mean amiodarone clearance of women was significantly higer than that of men. The laboratory data were mostly within normal values and no significant relations were observed between serum amiodarone concentration and clinical laboratory data. These results suggest that the individual variation in pharmacokinetics of amiodarone is comparatively small, which might be sufficient to decide that the maintenance dose was the same one (200 mg/d) in long-term oral amiodarone therapy.     

Editorial Commentary: Socket or Knock It? Considerations in Patellar Fixation During Medial Patellofemoral Ligament Reconstruction

The medial patellofemoral ligament (MPFL) is the primary static stabilizer to lateral patellar translation, and reconstruction of this ligament has been shown to be successful in reducing dislocation rates and improving functional outcomes in the treatment of patellar instability. Recent studies have warned that complication rates after MPFL reconstruction can be as high as 25%, with patellar fracture being one of the most catastrophic complications that can occur after this procedure. While the use of a bone socket versus cortical fixation on the patella does not appear to influence outcomes, surgeons should take into account the factors of graft and tunnel positioning, graft length/tension, and the need for concurrent procedures in each individual patient when performing this procedure. Any violation of the patella, whether as a socket or for anchor placement, should avoid the anterior cortex and maintain an adequate bony bridge that should be modified according to the patient's anatomy. The optimal technique for MPFL reconstruction continues to evolve, and further studies are needed to identify the ideal type and position of patellar fixation to minimize risks of complications and optimize surgical outcomes when performing MPFL reconstruction in the treatment of patellar instability.     

The impact of sarcopenia on short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer

Journal of Gastroenterology - Sarcopenia prevalence has increased in proportion to the aging population in Japan. We aimed to investigate the association between sarcopenia and clinical outcomes...     

Long-Term Outcomes of Japanese Type 2 Diabetic Patients With Biopsy-Proven Diabetic Nephropathy

OBJECTIVE

We evaluated the structural-functional relationships and the prognostic factors for renal events, cardiovascular events, and all-cause mortality in type 2 diabetic patients with biopsy-proven diabetic nephropathy.

RESEARCH DESIGN AND METHODS

Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy (n = 260) were enrolled. Patients were stratified by albuminuria (proteinuria) and estimated glomerular filtration rate (eGFR) at the time of renal biopsy. The outcomes were the first occurrence of renal events (requirement of dialysis or a 50% decline in eGFR from baseline), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, coronary interventions, or nonfatal stroke), and all-cause mortality.

RESULTS

The factors associated with albuminuria (proteinuria) regardless of eGFR were hematuria, diabetic retinopathy, low hemoglobin, and glomerular lesions. The factors associated with low eGFR regardless of albuminuria (proteinuria) were age and diffuse, nodular, tubulointerstitial, and vascular lesions. The glomerular, tubulointerstitial, and vascular lesions in patients with normoalbuminuria (normal proteinuria) and low eGFR were more advanced compared to those in patients with normoalbuminuria (normal proteinuria) and maintained eGFR. In addition, compared to patients with micro-/macroalbuminuria (mild/severe proteinuria) and low eGFR, their tubulointerstitial and vascular lesions were similar or more advanced in contrast to glomerular lesions. The mean follow-up period was 8.1 years. There were 118 renal events, 62 cardiovascular events, and 45 deaths. The pathological determinants were glomerular lesions, interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis for renal events, arteriosclerosis for cardiovascular events, and IFTA for all-cause mortality. The major clinical determinant for renal events and all-cause mortality was macroalbuminuria (severe proteinuria).

CONCLUSIONS

Our study suggests that the characteristic pathological lesions as well as macroalbuminuria (severe proteinuria) were closely related to the long-term outcomes of biopsy-proven diabetic nephropathy in type 2 diabetes.Diabetic nephropathy occurs in 20–40% of patients with diabetes (1). The prevalence of diabetic nephropathy is increasing in proportion to the increase in prevalence of diabetes, and it has been predicted to continue to increase in future (2). Diabetes is a risk factor of cardiovascular disease and death, and diabetic nephropathy further increases these risks (3). In addition, diabetic nephropathy is the leading cause of end-stage renal disease requiring dialysis or transplantation in developed countries (4–6).In recent years, many clinical studies have suggested strict glycemic control and blood pressure management by use of appropriate medication to suppress the onset and progression of diabetic nephropathy. Thus, it is important to identify patients at risk in the early stages to improve prognosis in patients with diabetic nephropathy (1). Albuminuria and glomerular filtration rate (GFR) are recommended for use as clinical markers of diabetic nephropathy (1,7–9). On the other hand, selection of pathological markers is complicated because a variety of renal lesions can be found in diabetic nephropathy in addition to factors such as obesity, hypertension, dyslipidemia, and aging, which are frequently complicated in type 2 diabetes, causing a wide variety of pathological changes (10).We previously reported on the clinical factors related to the development and progression of renal lesions in diabetic nephropathy by the evaluation of serial renal biopsies or autopsy (11). In this report, we demonstrated a significant relationship between the progression of diabetic glomerulosclerosis and clinical factors such as the control of blood glucose, type of diabetes, age at onset, type of treatment, and degree of obesity.After this study, we conducted a long-term retrospective study to evaluate the structural-functional relationships and the predictive impacts of clinicopathological parameters for renal events, cardiovascular events, and all-cause mortality among Japanese patients with biopsy-proven diabetic nephropathy in type 2 diabetes.     

Transverse stiffness: a method for estimation of myocardial wall stress

Determination of regional ventricular wall stress would allow quantification of both regional contractile state and its interplay with global function. Current methods for quantifying regional stress include mathematical modelling and measurements with strain gauges. Both methods are difficult to validate. We hypothesized that transverse stiffness (i.e., the ratio of indentation stress to strain as the ventricular wall is indented in the direction perpendicular to the wall) would be proportional to the stresses in the plane of the wall and could be used to estimate the latter. To test this hypothesis, 6 arterially perfused canine ventricular septa were mounted in an apparatus that could exert biaxial load in the plane of the wall. A servo system maintained the central third of the septa isometric during active contractions while the septa were paced at 30-60 pulses/min. In the center of the isometric region, a probe of 7 mm diameter indented the septa while the transverse indentation stress and strain were measured. For values of peak systolic in-plane stress from 0.56 to 2.6 g/mm2, the transverse stiffness varied from 1.2 to 11.7 g/mm2 and was linearly related to the in-plane wall stress in each septum (p less than 0.001, ANOVA). After cardioplegia, the transverse stiffness also correlated with passively applied wall stress for each dog (p less than 0.001). The slopes of the individual relations between transverse stiffness and wall stress from active contractions were similar to those from passively applied stress (mean +/- SEM; 1.82 +/- 0.36 versus 1.45 +/- 0.31, NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of itch-associated scratch behavior to the development of skin lesions in <Emphasis Type="Italic">Dermatophagoides farinae</Emphasis>-induced dermatitis model in NC/Nga mice

Recently, we have reported that the pathophysiological features of dermatitis induced by the repeated application with Dermatophagoides farinae (Df) extract ointment in NC/Nga mice were similar to those observed in the patients with atopic dermatitis. In the present study, we first examined whether the application of Df in other mouse strains could induce dermatitis. The repeated application of Df body (Dfb) ointment to the barrier-disrupted back of ICR, C57BL/6, and Balb/c mice did not cause any apparent skin lesions, although transient increase in serum immunoglobulin E (IgE) levels during antigen application was observed. On the other hand, in NC/Nga mice, dermatitis scores and serum IgE levels increased remarkably, and then these changes sustained for at least 10 days after stopping of antigen elicitation. Using NC/Nga mice, we investigated the contribution of scratching behavior to the development and maintenance of Dfb-induced dermatitis. In correlation with the increase in scratching behavior, erythema, hemorrhage, edema, scarring, erosion and excoriation were observed. Cutting off the hind toenails of mice exhibiting chronic skin lesions dramatically alleviated the dermatitis. From these findings, the onset of skin lesions and its chronically sustained course in Dfb-induced dermatitis in NC/Nga mice were closely associated with increased scratching behavior.     

A case of Wolff-Parkinson-White syndrome presenting spontaneous mutual frequent transition between atrioventricular reciprocating tachycardia and atrioventricular nodal re-entrant tachycardia

Atrioventricular reciprocating tachycardia (AVRT) and atrioventricular nodal re-entrant tachycardia (AVNRT) can coexist and present unidirectional transition (from AVRT to AVNRT, or from AVNRT to AVRT) in a single patient. Actually, such cases have already been reported previously. However, a case with spontaneous bidirectional transition of both tachycardias during supraventricular tachycardia has never been reported. This article describes a case with spontaneous, mutual, and frequent transition between AVRT and AVNRT.     

Assessment of abnormal left atrial relaxation by transesophageal pulsed doppler echocardiography of pulmonary venous flow velocity

Background: Several studies on left ventricular relaxation have been undertaken in the past: however, left atrial (LA) relaxation has not been fully evaluated. Hypothesis: The purpose of this study was to assess abnormalities in LA relaxation by evaluating pulmonary venous flow velocity and interatrial septal motion using transesophageal echocardiography. Methods: The subjects were 56 untreated patients in sinus rhythm, including 25 with previous myocardial infarction, 9 with hypertrophic cardiomyopathy, 11 with dilated cardiomyopathy, as well as 11 with chest pain syndrome as controls. Peak first systolic velocity (PVS₁), peak atrial systolic velocity (PVA), and their time-velocity integrals (PVS₁-I and PVA-I, respectively) were calculated from the pulmonary venous flow velocity. Results: The PVS₁ and PVS₁-I correlated negatively with the maximum LA dimension and mean pulmonary capillary wedge pressure, and correlated positively with the amplitude of the interatrial septal motion during LA relaxation and percent fractional LA relaxation. The PVA and PVA-I did not correlate with the mean pulmonary capillary wedge pressure. There was a weak positive correlation between PVA and PVS₁, and a close positive correlation between the ratio of PVA to PVS₁ and mean pulmonary capillary wedge pressure. Multiple regression analysis indicated that the PVS₁ was most closely related to percent fractional LA relaxation, followed by mean pulmonary capillary wedge pressure. Conclusion: The PVS₁ determined from the pulmonary venous flow velocity is closely related to parameters of LA relaxation which may be determined by transesophageal M-mode echocardiography, and the ratio of PVA to PVS₁ is useful for noninvasive evaluation of LA pressure..