BET inhibitors rescue anti-PD1 resistance by enhancing TCF7 accessibility in leukemia-derived terminally exhausted CD8+ T cells.

Many acute myeloid leukemia (AML) patients exhibit hallmarks of immune exhaustion, such as increased myeloid-derived suppressor cells, suppressive regulatory T cells and dysfunctional T cells. Similarly, we have identified the same immune-related features, including exhausted CD8+ T cells (TEx) in a mouse model of AML. Here we show that inhibitors that target bromodomain and extra-terminal domain (BET) proteins affect tumor-intrinsic factors but also rescue T cell exhaustion and ICB resistance. Ex vivo treatment of cells from AML mice and AML patients with BET inhibitors (BETi) reversed CD8+ T cell exhaustion by restoring proliferative capacity and expansion of the more functional precursor-exhausted T cells. This reversal was enhanced by combined BETi and anti-PD1 treatment. BETi synergized with anti-PD1 in vivo, resulting in the reduction of circulating leukemia cells, enrichment of CD8+ T cells in the bone marrow, and increase in expression of Tcf7, Slamf6, and Cxcr5 in CD8+ T cells. Finally, we profiled the epigenomes of in vivo JQ1-treated AML-derived CD8+ T cells by single-cell ATAC-seq and found that JQ1 increases Tcf7 accessibility specifically in Tex cells, suggesting that BETi likely acts mechanistically by relieving repression of progenitor programs in Tex CD8+ T cells and maintaining a pool of anti-PD1 responsive CD8+ T cells.

Integrative analysis of drug response and clinical outcome in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity with genomic, transcriptomic, and clinical annotations for a large cohort of AML patients, which facilitated discovery of functional genomic correlates. Here, we present a dataset that has been harmonized with our initial report to yield a cumulative cohort of 805 patients (942 specimens). We show strong cross-cohort concordance and identify features of drug response. Further, deconvoluting transcriptomic data shows that drug sensitivity is governed broadly by AML cell differentiation state, sometimes conditionally affecting other correlates of response. Finally, modeling of clinical outcome reveals a single gene, PEAR1, to be among the strongest predictors of patient survival, especially for young patients. Collectively, this report expands a large functional genomic resource, offers avenues for mechanistic exploration and drug development, and reveals tools for predicting outcome in AML.

Electrocardiographic Manifestations in Patients with COVID-19: Daegu in South Korea.

BACKGROUND AND OBJECTIVES: As the coronavirus disease 2019 (COVID-19) spreads worldwide, cardiac injury in patients infected with COVID-19 becomes a significant concern. Thus, this study investigates the impact of several electrocardiogram (ECG) parameters and disease severity in COVID-19 patients. METHODS: Seven medical centers in Daegu admitted 822 patients with COVID-19 between February and April 2020. This study examined 267 patients among them who underwent an ECG test and evaluated their biochemical parameters like C-reactive protein (CRP), log N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), cardiac enzyme, and ECG parameters (heart rate, PR interval, QRS interval, T inversion, QT interval, and Tpe [the interval between peak to end in a T wave]). RESULTS: Those patients were divided into 3 groups of mild (100 patients), moderate (89 patients), and severe (78 patients) according to clinical severity score. The level of CRP, log NT-proBNP, and creatinine kinase-myocardial band were significantly increased in severe patients. Meanwhile, severe patients exhibited prolonged QT intervals (QTc) and Tpe (Tpe-c) compared to mild or moderate patients. Moreover, deceased patients (58; 21.7%) showed increased dispersion of QTc and Tpe-c compared with surviving patients (78.2±41.1 vs. 40.8±24.6 ms and 60.2±37.3 vs. 40.8±24.5 ms, both p<0.05, respectively). The QTc dispersion of more than 56.1 ms could predict the mortality in multivariate analysis (odd ratio, 11.55; 95% confidence interval, 3.746-42.306). CONCLUSIONS: COVID-19 infections could involve cardiac injuries, especially cardiac repolarization abnormalities. A prolonged QTc dispersion could be an independent predictable factor of mortality.

Effectiveness of a new cardiac risk scoring model reclassified by QRS fragmentation as a predictor of postoperative cardiac event in patients with severe renal dysfunction.

BACKGROUND: It is difficult to evaluate the risk of patients with severe renal dysfunction before surgery due to various limitations despite high postoperative cardiac events. This study aimed to investigate the value of a newly reclassified Revised Cardiac Risk Index (RCRI) that incorporates QRS fragmentation (fQRS) as a predictor of postoperative cardiac events in patients with severe renal dysfunction. METHODS: Among the patients with severe renal dysfunction, 256 consecutive patients who underwent both a nuclear stress test and noncardiac surgery were evaluated. We reclassified RCRI as fragmented RCRI (FRCRI) by integrating fQRS on electrocardiography. We defined postoperative major adverse cardiac event (MACE) as a composite of cardiac death, nonfatal myocardial infarction, and pulmonary edema. RESULTS: Twenty-eight patients (10.9%) developed postoperative MACE, and this was significantly frequent in patients with myocardial perfusion defect (41.4% vs. 28.0%, p = 0.031). fQRS was observed 84 (32.8%) patients, and it was proven to be an independent predictor of postoperative MACE after adjusting for the RCRI (odds ratio 3.279, 95% confidence interval (CI) 1.419-7.580, p = 0.005). Moreover, fQRS had an incremental prognostic value for the RCRI (chi-square = 7.8, p = 0.005), and to the combination of RCRI and age (chi-square = 9.1, p = 0.003). The area under curve for predicting postoperative MACE significantly increased from 0.612 for RCRI to 0.667 for FRCRI (p = 0.027) and 23 patients (32.4%) originally classified as RCRI 2 were reclassified as FRCRI 3. CONCLUSIONS: A newly reclassified FRCRI that incorporates fQRS, is a valuable predictor of postoperative MACE in patients with severe renal dysfunction undergoing noncardiac surgery.

Pathogenesis of Human Immunodeficiency Virus-Mycobacterium tuberculosis Co-Infection.

Given that infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death amongst individuals living with HIV, understanding the complex mechanisms by which Mtb exacerbates HIV infection may lead to improved treatment options or adjuvant therapies. While it is well-understood how HIV compromises the immune system and leaves the host vulnerable to opportunistic infections such as Mtb, less is known about the interplay of disease once active Mtb is established. This review explores how glutathione (GSH) depletion, T cell exhaustion, granuloma formation, and TNF-α upregulation, as a result of Mtb infection, leads to an increase in HIV disease severity. This review also examines the difficulties of treating coinfected patients and suggests further research on the clinical use of GSH supplementation.

Clinical Impact of Implantable Cardioverter-Defibrillator Therapy and Mortality Prediction Model for Effective Primary Prevention in Korean Patients.

BACKGROUND: Studies on the efficacy of implantable cardioverter-defibrillator (ICD) therapy for primary prevention in Asian patients are relatively lacking compared to those for secondary prevention. Also, it is important to stratify which patients will benefit from ICD therapy for primary prevention. METHODS: Of 483 consecutive patients who received new implantation of ICD in 9 centers in Korea, 305 patients with reduced left ventricular systolic function and/or documented ventricular fibrillation/tachycardia were enrolled and divided into primary (n = 167) and secondary prevention groups (n = 138). RESULTS: During mean follow-up duration of 2.6 ± 1.6 years, appropriate ICD therapy occurred in 78 patients (25.6%), and appropriate ICD shock and anti-tachycardia pacing occurred in 15.1% and 15.1% of patients, respectively. Appropriate ICD shock rate was not different between the two groups (primary 12% vs. secondary 18.8%, P = 0.118). However, appropriate ICD therapy rate including shock and anti-tachycardia pacing was significantly higher (primary 18% vs. secondary 34.8%, P = 0.001) in the secondary prevention group. Type of prevention and etiology, appropriate and inappropriate ICD shock did not affect all-cause death. High levels of N-terminal pro-B-type natriuretic peptide, New York Heart Association functional class, low levels of estimated glomerular filtration ratio, and body mass index were associated with death before appropriate ICD shock in the primary prevention group. When patients were categorized in 5 risk score groups according to the sum of values defined by each cut-off level, significant differences in death rate before appropriate ICD shock were observed among risk 0 (0%), 1 (3.6%), 2 (3%), 3 (26.5%), and 4 (40%) (P < 0.001). CONCLUSION: In this multicenter regional registry, the frequency of appropriate ICD therapy is not low in the primary prevention group. In addition, combination of poor prognostic factors of heart failure is useful in risk stratification of patients who are not benefiting from ICD therapy for primary prevention.

Role of Carotid Artery Stenting in Prevention of Stroke for Asymptomatic Carotid Stenosis: Bayesian Cross-Design and Network Meta-Analyses.

BACKGROUND AND OBJECTIVES: There is insufficient evidence regarding the optimal treatment for asymptomatic carotid stenosis. METHODS: Bayesian cross-design and network meta-analyses were performed to compare the safety and efficacy among carotid artery stenting (CAS), carotid endarterectomy (CEA), and medical treatment (MT). We identified 18 studies (4 randomized controlled trials [RCTs] and 14 nonrandomized, comparative studies [NRCSs]) comparing CAS with CEA, and 4 RCTs comparing CEA with MT from MEDLINE, Cochrane Library, and Embase databases. RESULTS: The risk for periprocedural stroke tended to increase in CAS, compared to CEA (odds ratio [OR], 1.86; 95% credible interval [CrI], 0.62-4.54). However, estimates for periprocedural myocardial infarction (MI) were quite heterogeneous in RCTs and NRCSs. Despite a trend of decreased risk with CAS in RCTs (OR, 0.70; 95% CrI, 0.27-1.24), the risk was similar in NRCSs (OR, 1.02; 95% CrI, 0.87-1.18). In indirect comparisons of MT and CAS, MT showed a tendency to have a higher risk for the composite of periprocedural death, stroke, MI, or nonperiprocedural ipsilateral stroke (OR, 1.30; 95% CrI, 0.74-2.73). Analyses of study characteristics showed that CEA-versus-MT studies took place about 10-year earlier than CEA-versus-CAS studies. CONCLUSIONS: A similar risk for periprocedural MI between CEA and CAS in NRCSs suggested that concerns about periprocedural MI accompanied by CEA might not matter in real-world practice when preoperative evaluation and management are working. Maybe the benefits of CAS over MT have been overestimated considering advances in medical therapy within10-year gap between CEA-versus-MT and CEA-versus-CAS studies.

One-stage nipple and breast reconstruction using a deep inferior epigastric perforator flap after a skin-sparing mastectomy.

BACKGROUND: Nipple reconstruction is usually performed as a delayed procedure in patients with breast cancer who undergo skin-sparing mastectomy and breast reconstruction surgery using a deep inferior epigastric perforator (DIEP) flap. The authors designed this study to evaluate the utility of breast reconstruction based on a DIEP flap and immediate nipple reconstruction. METHODS: A retrospective review was conducted of all patients who underwent breast reconstruction performed by a single plastic surgeon from October 2016 to June 2018. Through a questionnaire and chart review, we compared surgical. RESULTS: and complications in cases of single-stage nipple reconstruction after skin-sparing mastectomy (n=17) with patients who underwent delayed nipple reconstruction after skin-sparing mastectomy, modified radical mastectomy, or simple mastectomy (n=7). RESULTS: In a subjective analysis using clinical photos, the immediate nipple reconstruction group had higher scores than their counterparts in an evaluation of the nipple-areolar complex (NAC) (NAC placement, 3.34 vs. 3.04; nipple projection, 3.05 vs. 3.03; nipple size, 3.30 vs. 3.29). No significant differences between the groups were found in terms of complications. CONCLUSIONS: Simultaneous nipple reconstruction is a reliable surgical method with economic advantages. No differences were found in terms of outcomes and complications in comparison to delayed reconstruction. Therefore, surgeons can consider simultaneous nipple reconstruction without particular concerns about asymmetry or necrosis.

Influence of Pd Doping on Electrical and Thermal Properties of n-Type Cu0.008Bi2Te2.7Se0.3 Alloys.

Doping is known as an effective way to modify both electrical and thermal transport properties of thermoelectric alloys to enhance their energy conversion efficiency. In this project, we report the effect of Pd doping on the electrical and thermal properties of n-type Cu0.008Bi2Te2.7Se0.3 alloys. Pd doping was found to increase the electrical conductivity along with the electron carrier concentration. As a result, the effective mass and power factors also increased upon the Pd doping. While the bipolar thermal conductivity was reduced with the Pd doping due to the increased carrier concentration, the contribution of Pd to point defect phonon scattering on the lattice thermal conductivity was found to be very small. Consequently, Pd doping resulted in an enhanced thermoelectric figure of merit, zT, at a high temperature, due to the enhanced power factor and the reduced bipolar thermal conductivity.

Serum levels of carbohydrate antigen 125 in combination with N-terminal pro-brain natriuretic peptide in patients with acute decompensated heart failure.

BACKGROUND/AIMS: Carbohydrate antigen 125 (CA-125) is an emerging prognostic biomarker for heart failure. We aimed to test the long-term prognostic value of CA-125 in combination with N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with acute decompensated heart failure (ADHF). METHODS: This observational study included a total of 413 patients (64.1 ± 15.6 yearold, 214 men) with ADHF. All-cause mortality during the 2-year follow-up was investigated for the prognosis. RESULTS: During the follow-up (mean follow-up, 591 ± 233 days), 109 deaths (26.0%) were recorded. In the multivariable analysis model, CA-125 was an independent factor associated with all-cause mortality (log CA-125: hazard ratio, 1.23; 95% confidence interval, 1.02 to 1.48; p = 0.030) together with age, sex, New York Heart Association class, ß-blocker, and NT-proBNP. The Kaplan-Meier survival analysis demonstrated that the group with both low marker levels showed the best 2-year survival (87.9%) followed by the group with low NT-proBNP and high CA-125 (76.1%), high NT-proBNP and low CA-125 (64.7%) and high NT-proBNP and high CA-125 levels (54.3%) (p < 0.001). Addition of CA-125 in combination with NT-proBNP and established risk factors further increased the predictive power for mortality in patients with ADHF. CONCLUSION: CA-125 was an independent factor associated with all-cause mortality in patients with ADHF. Combination of CA-125 with NT-proBNP significantly improved the prediction of mortality in patients with ADHF.

Extension block and direct pinning methods for mallet fracture: A comparative study.

BACKGROUND: Mallet fracture can easily occur during sports activities or in daily life; however, the principles and methods of treatment for such fractures remain debated. Among the surgical treatments, various methods of closed reduction have been proposed. We treated patients with the extension block method (EBM) and the direct pinning method (DPM), and then compared the results. We assessed differences in range of motion and measurements of finger movement after surgery. METHODS: A total of 41 patients who underwent surgery from August 2013 to September 2015 were evaluated retrospectively. Among them, 21 patients were treated with the EBM and 20 patients were treated with the DPM. We then compared extensor lag, range of motion, and outcomes according to Crawford's criteria between before surgery and at 6 to 8 months postoperatively. RESULTS: The postoperative extensor lag improvement was 4.28° and 10.73°, and the postoperative arc of motion was 55.76° and 61.17° in the EBM and DPM groups, respectively. The Crawford assessment showed no statistically significant difference between the groups, although the score in the DPM group was higher than that in the EBM group (3.5 vs. 3.1). CONCLUSIONS: As closed reduction methods for the treatment of mallet fracture, both the EBM and DPM showed good results. However, the DPM proved to be superior to the EBM in that it produced greater improvements in extensor lag and range of motion.

Rare experience of keloidal dermatofibroma of forehead.

Dermatofibromas most commonly occur on limbs and rarely occur on the face. Dermatofibroma occurring on the face is associated with unusual clinicopathologic features and a more aggressive clinical course in comparison to typical cases. Additionally, the most common subtype found in previous studies was benign fibrous histiocytoma, with the keloid type being very rare (about 1% of reported cases). The aim of this study was to present our experience with a keloidal dermatofibroma of the face, which is usually missed clinically, and to discuss the treatment of a keloidal dermatofibroma in this location.

Nasogastric tube insertion using airway tube exchanger in anesthetized and intubated patients.

BACKGROUND: A nasogastric tube (NGT) is commonly inserted into patients undergoing abdominal surgery to decompress the stomach during or after surgery. However, for anatomic reasons, the insertion of NGTs into anesthetized and intubated patients may be challenging. We hypothesized that the use of a tube exchanger for NGT insertion could increase the success rate and reduce complications. METHODS: One hundred adult patients, aged 20-70 years, who were scheduled for gastrointestinal surgeries with general anesthesia and NGT insertion were enrolled in our study. The patients were randomly allocated to the tube-exchanger group or the control group. The number of attempts, the time required for successful NGT insertion, and the complications were noted for each patient. RESULTS: In the tube-exchanger group, the success rate of NGT insertion on the first attempt was 92%, which is significantly higher than 68%, the rate in the control group (P = 0.007). The time required for successful NGT insertion in the tube-exchanger group was 18.5 ± 8.2 seconds, which is significantly shorter than the control group, 75.1 ± 9.8 seconds (P < 0.001). Complications such as laryngeal bleeding and the kinking and knotting of the NGT occurred less often in the tube-exchanger group. CONCLUSIONS: There were many advantages in using a tube-exchanger as a guide to inserting NGTs in anesthetized and intubated patients. Compared to the conventional technique, the use of a tube-exchanger resulted in a higher the success rate of insertion on the first attempt, a shorter procedure time, and fewer complications.

A comparison of ultrasound alone vs ultrasound with nerve stimulation guidance for continuous femoral nerve block in patients undergoing total knee arthroplasty.

STUDY OBJECTIVE: To compare analgesic efficacy of ultrasound (US) guidance alone and US guidance combined with nerve stimulation (NS) for continuous femoral nerve block (CFNB) in patients undergoing total knee arthroplasty (TKA). DESIGN: Prospective, randomized double-blind trial. SETTING: Postanesthesia care unit and general ward. PATIENTS: Fifty American Society of Anesthesiologist physical status I to II patients undergoing TKA under spinal anesthesia. INTERVENTIONS: In group A (n = 25), an 18-gauge Tuohy needle was directed at the lower mid-part of the femoral nerve, and a nonstimulating catheter was inserted through the needle under US guidance. In group B (n = 25), an 18-gauge Tuohy needle and stimulating catheter were directed to the lower part of femoral nerve under US guidance, and quadriceps muscle contraction was checked using NS. All patients received a 20-mL loading dose of 0.2% ropivacaine, a continuous infusion of 4 mL/h, and a 4-mL bolus of 0.2% ropivacaine with a lockout time of 60 minutes for patient-controlled analgesia. MEASUREMENTS: The primary outcome was resting and exercising pain quality assessed by numeric rating scale. Other outcomes included procedure time for correct catheter placement, block failure rate, patient satisfaction for postoperative pain control, total dose of local anesthetic, additional opioid requirement, and adverse effects postoperatively. MAIN RESULTS: There were no significant differences between groups in resting and exercising numeric rating scale. Procedure times were longer in group B than group A (P < .05). There were no significant differences between groups in block failure rate or other outcomes. CONCLUSIONS: US-guided CFNB was associated with similar analgesic efficacy and block failure rate and reduced procedure time compared to US with NS guidance for CFNB in patients undergoing TKA.

A Rare Case of Malignant Lymphoma Occurred at Spinal Epidural Space: A Case Report.

The sacral spinal epidural space is an uncommon site for primary malignant lymphomas, presenting with symptoms associated with cauda equina compression. Especially, lumbo-sacral epidural lymphoma has been reported to be very rare. We present a rare case of 29-year-old male with sacral spinal epidural malignant lymphoma. The patient complained of tingling sensation in his buttocks that was radiating to his calf. The neurological examination was normal. Magnetic resonance imaging (MRI) with contrast showed a well-defined extradural mass lesion at the mid L5 to mid S2 level. The lesion was iso- to hypointense on T1 and T2 weighted images and showed homogenous enhancement and a focal enhancement in the L5 vertebral body on post-contrast images. The patient underwent a L5-S2 laminectomy and subtotal excision of the lesion. Intra-operatively, the lesion was extradural and not densely adherent to the dura; the lesion was friable, not firm, fleshy, brownish and hypervascular. The histologic diagnosis was grade 2 non-Hodgkin's follicular lymphoma. Even though the primary spinal epidural non-Hodgkin's lymphoma is a very rare disease, clinicians should take it into consideration in the differential diagnosis of patients with spinal epidural tumor.

Cervical Stand-Alone Polyetheretherketone Cage versus Zero-Profile Anchored Spacer in Single-Level Anterior Cervical Discectomy and Fusion : Minimum 2-Year Assessment of Radiographic and Clinical Outcome.

OBJECTIVE: We compared the clinical and radiographic outcomes of stand-alone polyetheretherketone (PEEK) cage and Zero-Profile anchored spacer (Zero-P) for single level anterior cervical discectomy and fusion (ACDF). METHODS: We retrospectively reviewed 121 patients who underwent single level ACDF within 2 years (Jan 2011-Jan 2013) in a single institute. Total 50 patients were included for the analysis who were evaluated more than 2-year follow-up. Twenty-nine patients were allocated to the cage group (m : f=19 : 10) and 21 for Zero-P group (m : f=12 : 9). Clinical (neck disability index, visual analogue scale arm and neck) and radiographic (Cobb angle-segmental and global cervical, disc height, vertebral height) assessments were followed at pre-operative, immediate post-operative, post-3, 6, 12, and 24 month periods. RESULTS: Demographic features and the clinical outcome showed no difference between two groups. The change between final follow-up (24 months) and immediate post-op of Cobb-segmental angle (p=0.027), disc height (p=0.002), vertebral body height (p=0.033) showed statistically better outcome for the Zero-P group than the cage group, respectively. CONCLUSION: The Zero-Profile anchored spacer has some advantage after cage for maintaining segmental lordosis and lowering subsidence rate after single level anterior cervical discectomy and fusion.

Risk of continuing planned surgery after endovascular repair of subclavian artery injury: a case report.

Endovascular repair with covered stents has been widely used to treat subclavian and axillary artery injuries and has produced promising early results. The possibility of a thromboembolism occurring in cerebral arteries during an endovascular procedure should be a cause for concern. In the case of endovascular management of arterial traumas, a prompt and sufficient period for check-up of the patient's neurological signs is needed, even if it requires postponing elective intervention for the patient's safety. We report a rare case of liver transplantation immediately after endovascular repair of an iatrogenic subclavian arterial injury to describe the risk of continuing planned surgery without neurologic assessment.

Warning signals confer advantage to prey in competition with predators: bumblebees steal nests from insectivorous birds.

Aposematic (warning) signals of prey help predators to recognize the defended distasteful or poisonous prey that should be avoided. The evolution of aposematism in the context of predation has been in the center of modern ecology for a long time. But, the possible roles of aposematic signals in other ecological contexts have been largely ignored. Here we address the role of aposematic signals in competition between prey and predators. Bumblebees use visual and auditory aposematic signals to warn predators about their defenses. For 2 years, we observed competition for nestboxes between chemically defended insects, Bombus ardens (and possibly also Bombus ignitus), and cavity nesting birds (Parus minor and Poecile varius). Bumblebees settled in 16 and 9 % of nestboxes (in 2010 and 2011 breeding seasons, respectively) that contained bird nests at the advanced stage of nest building or at the stage of egg laying. Presence of bumblebees prevented the birds from continuing the breeding activities in the nestboxes, while insects took over the birds' nests (a form of kleptoparasitism). Playback experiments showed that the warning buzz by bumblebees contributed to the success in ousting the birds from their nests. This demonstrates that aposematic signals may be beneficial also in the context of resource competition.

Fabry cardiomyopathy.

Fabry disease is a progressive X-linked disorder of glycosphingolipid metabolism caused by a deficiency of the α-galactosidase lysosomal enzyme. The partial or complete deficiency of the lysosomal enzyme leads to an accumulation of neutral glycosphingolipids in the vascular endothelium and visceral tissues throughout the body. In the heart, glycosphingolipids deposition causes progressive left ventricular hypertrophy (LVH). We report a case of Fabry disease which was suspected based upon two-dimensional echocardiographic finding of LVH. A 44-year-old man was admitted to evaluation of aggravated exertional dyspnea of two weeks duration. He had been diagnosed with end-stage renal disease of unknown etiology at age 41 followed by renal transplantation that year. He had been treated with oral immunosuppressive agents. On hospital day two, transthoracic echocardiography revealed concentric LVH. Left ventricular systolic function was preserved but diastolic dysfunction was present. Fabry disease was confirmed by demonstration of a low plasma α-galactosidase A (α-Gal A) activity. Analysis of genomic DNA showed α-Gal A gene mutation. The patient was diagnosed with Fabry disease.

Familial Transthyretin Amyloidosis with Variant Asp38Ala Presenting with Orthostatic Hypotension and Chronic Diarrhea.

A 53-year-old man complained of orthostatic, non-rotating dizziness, and chronic watery diarrhea of several years duration. His nerve-conduction velocity test revealed peripheral sensory-motor polyneuropathy and he showed an autonomic function abnormality. Echocardiographic examination showed ventricular and atrial wall thickening with a granular "sparkling" appearance. Left ventricular systolic function was preserved but pseudonormal diastolic dysfunction was present. Coronary angiography showed normal coronary arteries and an endomyocardial biopsy revealed lesions consistent with cardiac amyloidosis. Colonoscopic biopsy also revealed the deposition of amyloid fibrils. Gene analysis found the transthyretin variant Asp38Ala. His son had same mutation, but three daughters did not. In conclusion, we report a case of familial transthyretin amyloidosis with Asp38Ala.