Preservation of renal function by thyroid hormone replacement therapy in chronic kidney disease patients with subclinical hypothyroidism

Context: Subclinical hypothyroidism is not a rare condition, but the use of thyroid hormone to treat subclinical hypothyroidism is an issue of debate. Objective: This study was undertaken to investigate the impact of thyroid hormone therapy on the changes in estimated glomerular filtration rate (eGFR) in subclinical hypothyroidism patients with stage 2-4 chronic kidney disease. Patients: A total of 309 patients were included in the final analysis. Main Outcome Measure: The changes in eGFR over time were compared between patients with and without thyroid hormone replacement therapy using a linear mixed model. Kaplan-Meier curves were constructed to determine the effect of thyroid hormone on renal outcome, a reduction of eGFR by 50%, or end-stage renal disease. The independent prognostic value of subclinical hypothyroidism treatment for renal outcome was ascertained by multivariate Cox regression analysis. Results: Among the 309 patients, 180 (58.3%) took thyroid hormone (treatment group), whereas 129 (41.7%) did not (nontreatment group). During the mean follow-up duration of 34.8 ± 24.3 months, the overall rate of decline in eGFR was significantly greater in the nontreatment group compared to the treatment group (-5.93 ± 1.65 vs. -2.11 ± 1.12 ml/min/yr/1.73 m(2); P = 0.04). Moreover, a linear mixed model revealed that there was a significant difference in the rates of eGFR decline over time between the two groups (P < 0.01). Kaplan-Meier analysis also showed that renal event-free survival was significantly lower in the nontreatment group (P < 0.01). In multivariate Cox regression analysis, thyroid hormone replacement therapy was found to be an independent predictor of renal outcome (hazard ratio, 0.28; 95% CI, 0.12-0.68; P = 0.01). Conclusion: Thyroid hormone therapy not only preserved renal function better, but was also an independent predictor of renal outcome in chronic kidney disease patients with subclinical hypothyroidism.     

Disseminated cutaneous and visceral Kaposi sarcoma in a woman with rheumatoid arthritis receiving leflunomide

Kaposi sarcoma (KS) is a vascular neoplasm mainly affecting the skin of the limbs that has previously been associated with rheumatoid arthritis (RA). When compared with the RA patients treated with corticosteroids and immunosuppressive drugs, the reported number of KS in RA patients was very rare. Although the exact mechanisms of developing KS in RA patients are unclear, some drugs which include corticosteroid have been suggested as an etiological factor in previous case reports of RA and KS. We report, here in, another case of KS associated with the initiation of leflunomide in a patient with RA.     

ISN/RPS 2003 class II mesangial proliferative lupus nephritis: a comparison between cases that progressed to class III or IV and cases that did not

Lupus nephritis (LN) class II has generally been considered a mild form of LN with a good response to treatment. Although the number was small, there have also been reports on later progression to class III or IV, resulting in poor renal and patient outcome. This study aims to review cases of LN class II to analyze differences between cases that progressed to class III or IV and cases that did not. We retrospectively analyzed 15 cases of LN class II among 277 cases of biopsy-proven lupus nephritis diagnosed in a tertiary medical center over about 14?years. Among the 15 patients, 5 patients progressed to class III or IV. Biopsy specimens were reviewed by a pathologist according to the ISN/RPS 2003 classification. Response to treatment was evaluated at 6?months after treatment. On fluorescence microscopy (IF), there was significantly higher degree of deposition in the glomeruli of IgM, IgA and C4 in the progression group than in the non-progression group. At 6?months after treatment, there was a trend toward higher rates of complete remission in the non-progression group (90%) compared with those in the progression group (40%, p?=?0.077). Five of the 15 cases of ISN/RPS 2003 class II glomerulonephritis progressed to class III or IV over a mean of 5?years. The degree of immune-complex deposition for IgM, IgA and C4 in the glomeruli was significantly higher in the progression group.     

Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study

Objective We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug‐naïve type 2 diabetic patients. Design, Patients, and Measurements In this 52‐week treatment study, 150 patients (mean age, 54·9 ± 12·5 years) with type 2 diabetes and HbA1c of 7·0–10% were treated with sitagliptin 100 mg once and metformin 500 mg twice daily. To assess the predictive parameters for therapeutic efficacy, a multivariate regression analysis was performed with baseline fasting glucose, insulin, C‐peptide, and glucagon levels, homoeostasis model assessment‐insulin resistance (HOMA‐IR) and β‐cell function (HOMA‐B), insulinogenic index (IGI, defined as 30–0 min insulin/30–0 min glucose), and area under the curve for glucose, insulin, and C‐peptide obtained after 75‐g oral glucose tolerance test. Results After 52 weeks, mean HbA1c levels and fasting and postload 2‐h glucose were significantly decreased from 8·7 ± 1·4% to 7·2 ± 1·3%, 9·2 ± 3·0 to 7·2 ± 1·8 mm , and 17·5 ± 5·1 to 10·9 ± 3·6 mm , respectively (P < 0·01). HOMA‐B and IGI increased significantly from 50·3 ± 33·5 to 75·1 ± 32·8 and from 11·3 ± 1·3 to 35·0 ± 6·3 at 52 weeks, respectively (P < 0·01). Multivariate regression analysis indicated that the reduction in HbA1c was significantly associated with high baseline HbA1c, low IGI, and short duration of diabetes after adjusting for age, sex, body mass index, blood pressure, triglycerides, creatinine, high‐sensitivity CRP, glucagon, C‐peptide, HOMA‐B, and HOMA‐IR. No severe adverse events were observed. Conclusion These results suggest that drug‐naïve type 2 diabetic patients with low β‐cell function would benefit the most from early initial combination therapy of sitagliptin and metformin.     

Postmorbid learning of saxophone playing in a patient with frontotemporal dementia

Some patients with frontotemporal dementia (FTD) show an artistic enhancement of musical abilities. However, no patients with FTD, to date, have been reported to be able to learn how to play a musical instrument after disease onset. Herein we describe a patient (J. K.) who had never played any musical instruments premorbidly, but who learned to play the saxophone after being diagnosed with a behavioral variant of FTD. He mastered a repertoire that consisted of 10 pieces of Korean folk songs over a period of three years. Furthermore, his saxophone skills were high enough to outperform other students in his class.     

Prevalence of Disc Degeneration in Asymptomatic Korean Subjects. Part 2 : Cervical Spine

Objective

Similar to back pain, neck pain has recently shown to have increasing prevalence. Magnetic resonance imaging (MRI) is useful in identifying the causes of neck pain. However, MRI shows not only pathological lesions but also physiological changes at the same time, and there are few Korean data. The authors have attempted to analyze the prevalence of disc degeneration in highly selective asymptomatic Korean subjects using MRI.

Methods

We performed 3 T MRI sagittal scans from C2 to T1 on 102 asymptomatic subjects (50 men and 52 women) who visited our hospital between the ages of 14 and 82 years (mean age 46.3 years). All images were read independently by three observers (two neurosurgeons and one neuroradiologist) who were not given any information about the subjects. We classified grading for cervical disc herniation (HN), annular fissure (AF), and nucleus degeneration (ND), using disc degeneration classification.

Results

The prevalence of HN, AF, and ND were 81.0%, 85.9%, and 95.4%, respectively. High prevalence of HN, AF, and ND was shown compared to previous literature.

Conclusion

In asymptomatic Korean subjects, the abnormal findings of 3 T MRI showed a high prevalence in HN, AF, and ND. Several factors might play important roles in these results, such as population-specific characters, MRI field strength, and disc degeneration grading system.     

Effect of the Refrigerator Storage Time on the Potency of Botox for Human Extensor Digitorum Brevis Muscle Paralysis

Background and Purpose

It is recommended that Botox be used within 5 hours of reconstitution, which results in substantial quantities being discarded. This is not only uneconomic, but also inconvenient for treating patients. The aim of this study was to determine the potencies of Botox used within 2 hours of reconstitution with unpreserved saline, the same Botox refrigerated (at +4℃) 72 hours after reconstitution, and during the next 4 consecutive weeks (weeks 1, 2, 3, and 4). This comparison was used to determine the length of refrigeration time during which reconstituted Botox will maintain the same efficacy as freshly reconstituted toxin.

Methods

Individual paralysis rates in the extensor digitorum brevis (EDB) compound muscle action potential (CMAP) amplitude and area were measured 1 week after injecting fresh reconstituted 2.5 MU of Botox on one side of the foot, and when the same quantity of Botox that had been refrigerated for a designated time (i.e., 72 h, or 1, 2, 3, or 4 weeks) into the other side of the foot. The EDB CMAP amplitude and area at 12 and 16 weeks postinjection were also measured to compare the efficacy durations in all five comparative groups.

Results

Ninety-four volunteers were divided into five groups according to the refrigerator storage time of the second Botox injection. The paralysis of the EDBs was significant for each injection of Botox, both fresh and refrigerated, with no statistically significant differences between them, regardless of the refrigeration time. There was a tendency toward increased CMAP amplitude and area at 12 or 16 weeks postinjection (p<0.0001). The duration of effective muscle paralysis did not differ significantly throughout the 16-week follow-up period between all five groups.

Conclusions

The potency of reconstituted Botox is not degraded by subsequent refrigeration for 4 weeks. However, there are definite concerns regarding its sterility, and hence its safety, since multiple withdrawals from the same vial over long periods can introduce bacterial contamination.     

Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus

Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are nonspecific, and include abdominal discomfort, mild hepatomegaly, and transaminase elevation. In this report we describe three cases of patients presenting serum transaminase elevation and hepatomegaly with a history of poorly controlled type I DM. All of the cases showed sudden elevation of transaminase to more than 30 times the upper normal range (like in acute hepatitis) followed by sustained fluctuation (like in relapsing hepatitis). However, the patients did not show any symptom or sign of acute hepatitis. We therefore performed a liver biopsy to confirm the cause of liver enzyme elevation, which revealed GH. Clinicians should be aware of GH so as to prevent diagnostic delay and misdiagnosis, and have sufficient insight into GH; this will be aided by the present report of three cases along with a literature review.     

Role of radical surgery in patients with stage IV gallbladder cancer

Objectives

The role of surgery in stage IV gallbladder (GB) cancer is not well established. This study analyses prognostic factors in patients with stage IV GB cancer following surgical resection with the aim of identifying a subgroup of patients who might benefit from surgical resection.

Methods

Clinicopathological details were analysed for 94 patients who were surgically treated for stage IV GB cancer at Seoul National University Hospital.

Results

Median survival was 8 months in patients with either stage IVa or IVb disease. Sixteen patients (17.0%) underwent resection with curative intent, which increased overall survival over that in patients undergoing palliative surgery (P < 0.001). No survival benefit was seen following surgery with curative intent in patients with stage IVa disease (P = 0.764). Surgery with curative intent resulted in a survival benefit in patients with stage IVb disease, patients with an isolated liver metastasis near the GB bed (median survival: 31 months vs. 9 months; P < 0.001) and patients with limited numbers of peritoneal implantations (median survival: 20 months vs. 6 months; P = 0.002). Preoperative serum carcinoembryonic antigen (CEA) (P = 0.018), surgery with curative intent (P = 0.045) and adjuvant chemotherapy (P = 0.002) were independent prognostic factors in patients with stage IV GB cancer.

Conclusions

Surgery in combination with systemic chemotherapy may be beneficial in carefully selected patients with stage IVb GB cancer.     

BRAF V600E Mutation Analysis in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-time PCR

Background

Activating somatic mutation of the BRAF ^V600E has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (32–87 %) in different series by different methods. The BRAF ^V600E mutation is associated with various clinicopathological parameters. The mutation is an important factor for the management of the PTC patients. The objective of this study was to detect the BRAF ^V600E mutation in PTCs by peptide nucleic acid (PNA) clamp real-time PCR and to analyze the results with clinicopathological parameters.

Methods

We performed genetic analysis of BRAF ^V600E by PNA clamp real-time PCR in 211 PTCs in Korea, stratified by clinicopathological parameters.

Results

The BRAF ^V600E mutation was detected in 90 % of PTC cases, and it occurred significantly more often in female patients than in male patients (p = 0.001). The clinicopathological parameters of age, tumor size, and disease stage were not associated with the BRAF ^V600E mutation, while extrathyroid invasion (p = 0.031), lymph nodal metastasis (p = 0.002), and tumor multiplicity (p = 0.020) were.

Conclusions

The prevalence (90 %) of the BRAF ^V600E mutation in this study is the highest ever reported, confirming the key role of this mutation in PTC tumorigenesis. The BRAF ^V600E mutation was associated with aggressive clinical behaviors including extrathyroid invasion, lymph nodal metastasis and tumor multifocality. The PNA clamp real-time PCR method for the BRAF ^V600E mutation detection is sensitive and is applicable in a clinical setting.