Ryul Kim

Acute suppression of TGF-ß with local, sustained release of tranilast against the formation of fibrous capsules around silicone implants

We propose the acute, local suppression of transforming growth factor beta (TGF-ß), a major profibrotic cytokine, to reduce fibrosis around silicone implants. To this end, we prepared silicone implants that were able to release tranilast, a TGF-ß inhibitor, in a sustained manner for 5 days or 15 days. We performed histologic and immunohistochemical analyses for 12 weeks after the implantation of the implants in living rats. The capsule thicknesses and collagen densities significantly decreased compared with those around the non-treated silicone implants. Notably, early suppression of TGF-ß affected the fibrogenesis that actually occurs at the late stage of wound healing. This change may be ascribed to the decrease in monocyte recruitment mediated by early TGF-ß during the acute inflammatory reaction. Thus, a significant decrease in differentiated macrophages was observed along with a decrease in the quantity of TGF-ß and fibroblasts during the subsequent inflammation stage; these changes led to a diminished fibrotic capsule formation.

Nonmotor Effects of Conventional and Transdermal Dopaminergic Therapies in Parkinson's Disease

Nonmotor symptoms (NMS) are an integral component of Parkinsons disease (PD). Because the burden and range of NMS are key determinants of quality of life for patients and caregivers, their management is a crucial issue in clinical practice. Although a range of NMS have a dopaminergic pathophysiological basis, this fact is underrecognized, and thus, they are often regarded as dopamine unresponsive symptoms. However, substantial evidence indicates that many NMS respond to oral and transdermal dopaminergic therapies. In contrast, certain NMS are exacerbated or even precipitated by dopaminergic drugs and these unwanted effects may be seriously dangerous. Therefore, a dopaminergic strategy for NMS should be based on a consideration of the benefits vs the risks in individual patients with PD.

Validation of the Conversion between the Mini-Mental State Examination and Montreal Cognitive assessment in Korean Patients with Parkinson’s Disease

Objective Two conversion tables between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) have recently been established for Parkinson’s disease (PD). This study aimed to validate them in Korean patients with PD and to evaluate whether they could be influenced by educational level. Methods A total of 391 patients with PD who undertook both the Korean MMSE and the Korean MoCA during the same session were retrospectively assessed. The mean, median, and root mean squared error (RMSE) of the difference between the true and converted MMSE scores and the intraclass correlation coefficient (ICC) were calculated according to educational level (6 or fewer years, 7–12 years, or 13 or more years). Results Both conversions had a median value of 0, with a small mean and RMSE of differences, and a high correlation between the true and converted MMSE scores. In the classification according to educational level, all groups had roughly similar values of the median, mean, RMSE, and ICC both within and between the conversions. Conclusion Our findings suggest that both MMSE-MoCA conversion tables are useful instruments for transforming MoCA scores into converted MMSE scores in Korean patients with PD, regardless of educational level. These will greatly enhance the utility of the existing cognitive data from the Korean PD population in clinical and research settings.

The limited role of serum galactomannan assay in screening for invasive pulmonary aspergillosis in allogeneic stem cell transplantation recipients on micafungin prophylaxis: a retrospective study

Background We evaluated the outcomes of serum galactomannan (GM) assay for the screening of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients while on primary antifungal prophylaxis (PAP). Methods This study included patients with hematologic disorders who underwent alloHSCT from January 2013 to November 2015. Patients received routine PAP with fluconazole before 2014 and micafungin after 2014; serum GM tests were performed and retrospectively analyzed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum GM tests for detection of probable/proven IPA were evaluated. The serial change of serum GM levels was illustrated on a time series plot. Results A total of 136 alloHSCT recipients at Seoul National University Hospital were included in the study. Fluconazole was administered in 72 patients for PAP, while micafungin was administered in the remaining 64 patients. The overall sensitivity, specificity, and NPV of serum GM assays were 95.8% (95% confidence interval [CI] 78.9–99.9%), 93.8% (95% CI 91.7–95.5%), and 99.8% (95% CI 99.1–100.0%), respectively. However, the PPV of GM tests was relatively low at 35.4% (95% CI 23.9–48.2%). The serial change in serum GM levels differed according to the antifungal agents used. With effective PAP using micafungin, serial serum GM levels showed zero order kinetics during the neutropenic period. Conclusion Although the serum GM assay is a sensitive and specific test for detecting IPA in alloHSCT recipients, its role for routine surveillance in an era of effective PAP with micafungin is limited.

Costs and clinical outcomes of patients with diffuse large B-cell lymphoma in first remission: role of PET/CT surveillance

Background/Aims The role of [18F]-f luorodeoxyglucose positron emission tomography-computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) in first remission is unclear. Methods Medical costs within the first 3 years of treatment completion and clinical outcomes of 118 patients with DLBCL in first remission with and without surveillance PET/CT (PET/CT [+] group [n = 76] and PET/CT [–] group [n = 42], respectively) were retrospectively analyzed. Results In a propensity matched cohort with adjustment for International Prognostic Index risk and relapse, the PET/CT (+) group was shown to have similar medical costs as the PET/CT (–) group. Relapse-free survival (RFS) and overall survival (OS) were comparable between the two groups (median RFS not reached [NR] for both groups, p = 0.133; median OS NR, p = 0.542). Among 76 patients with surveillance PET/CT, 31 (40.8%) had findings suggestive of recurrence and 16 of these (51.6%) were later confirmed to have recurrent disease. Fifteen patients (48.4%) were confirmed to not have recurrence after follow-up CT or PET/CT evaluation (n = 10) and biopsy (n = 4). None of the patients with negative PET/CT findings had disease recurrence. Sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT for detection of recurrence were 1, 0.75, 0.52, and 1, respectively. Conclusions Surveillance PET/CT resulted in similar clinical outcomes and medical costs compared to no surveillance PET/CT. Approximately half of patients with PET/CT findings of recurrence had no recurrence after follow-up imaging and biopsy, which would not have been carried out if PET/CT had not been performed in the first place.

Expanding the Spectrum of Dopa-Responsive Dystonia (DRD) and Proposal for New Definition: DRD, DRD-plus, and DRD Look-alike

Previously, we defined DRD as a syndrome of selective nigrostriatal dopamine deficiency caused by genetic defects in the dopamine synthetic pathway without nigral cell loss. DRD-plus also has the same etiologic background with DRD, but DRD-plus patients have more severe features that are not seen in DRD because of the severity of the genetic defect. However, there have been many reports of dystonia responsive to dopaminergic drugs that do not fit into DRD or DRD-plus (genetic defects in the dopamine synthetic pathway without nigral cell loss). We reframed the concept of DRD/DRD-plus and proposed the concept of DRD look-alike to include the additional cases described above. Examples of dystonia that is responsive to dopaminergic drugs include the following: transportopathies (dopamine transporter deficiency; vesicular monoamine transporter 2 deficiency); SOX6 mutation resulting in a developmentally decreased number of nigral cells; degenerative disorders with progressive loss of nigral cells (juvenile Parkinsons disease; pallidopyramidal syndrome; spinocerebellar ataxia type 3), and disorders that are not known to affect the nigrostriatal dopaminergic system (DYT1; GLUT1 deficiency; myoclonus-dystonia; ataxia telangiectasia). This classification will help with an etiologic diagnosis as well as planning the work up and guiding the therapy.

Peripheral blood inflammatory markers in early Parkinson’s disease

The aim of this study was to characterize peripheral inflammatory markers in patients with early Parkinsons disease (PD) and to explore whether these markers contribute to motor and non-motor symptoms. We collected serum from patients with early PD (nu202f=u202f58) and from healthy control subjects (nu202f=u202f20). The following inflammatory markers were measured: interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-α, and high-sensitivity C-reactive protein. The Movement Disorders Society Unified Parkinsons Disease Rating Scale part 3 and Hoehn and Yahr stage were used to assess motor symptoms, and the Non-motor Symptoms Scale, the Cross-Cultural Smell Identification Test, the Montreal Cognitive Assessment, and the Composite Autonomic Symptom Score 31 (COMPASS-31) were used to assess non-motor symptoms. The levels of IL-1β, IL-2, and IL-6 were higher in the PD group than in the control group. However, only IL-1β among those markers remained significant after Bonferroni correction (Pu202f=u202f0.024). In the PD group, the anti-inflammatory cytokine IL-10 levels correlated positively with the COMPASS-31 score (ru202f=u202f0.277, Pu202f=u202f0.035), whereas no correlation was found between the other inflammatory marker levels and motor or non-motor symptoms. Among the domains of the COMPASS-31, the IL-10 levels correlated only with the gastrointestinal domain (ru202f=u202f0.358, Pu202f=u202f0.006). Our results suggest increased peripheral inflammation in the early stage of PD, but the role of inflammation in motor and non-motor symptoms is unclear. Although we found a correlation between IL-10 levels and gastrointestinal symptoms, this finding may simply reflect a protective response against inflammatory processes associated with the disease.

Residency Training: Bilateral facial nerve palsies after a suicide attempt by hanging

A 56-year-old woman presented with bilateral facial paralysis. Two days before, she had attempted to hang herself. Immediately after the event, her husband noted that her facial expressions had changed but it was not until 2 days later that she was brought to the hospital after she failed to improve. Examination revealed a ligature mark from the anterior neck to bilateral postauricular areas (figure 1, A) and bilateral peripheral facial palsies (figure 1, B). Brain MRI showed no hypoxic damage. Testing of the blink reflex showed bilateral efferent pathway defects (figure 2). The extratemporal segment of the facial nerve originates at the stylomastoid foramen and passes through the parotid gland.1 In our patient, compression provoked by the ligature over the extratemporal segment of the facial nerves just outside the stylomastoid foramen may have led to regional ischemia.