The discriminative role of PROX-1 immunohistochemistry between venous malformation and lymphatic malformation of the deep type with no visible diagnostic surface skin lesion.

BACKGROUND: Venous malformations (VMs) are distinguished from lymphatic malformations (LMs) when specific diagnostic skin lesions are present. In the deep type, this is difficult by clinico-radiologic evaluation alone. We aimed to investigate the usefulness of lymphatic vessel endothelial cell (LEC) markers for the differential diagnosis of the deep VMs and LMs. METHODS: A retrospective study was conducted based on the medical records of patients with VMs and LMs who underwent biopsy with both D2-40 and PROX-1 immunohistochemistry. We compared the initial clinico-radiological diagnosis with the final pathological diagnosis and identified which ones showed a difference. RESULTS: From 261 patients who had VMs and LMs, 111 remained after the exclusion of those who showed definite surface diagnostic features. After pathological diagnosis with the expressions of D2-40 and PROX-1, 38 of 111 (34.2%) patients' final diagnoses were changed. Among these 38 cases, diagnosis was not changed by D2-40 positivity alone, but changed by PROX-1 positivity alone (52.6%) or by both (47.4%). The diagnostic changes were more frequent in the deep category (43.7%) than in the superficial category. CONCLUSIONS: Identifying the expression of D2-40, and especially PROX-1, in the differential diagnosis of VMs and LMs may provide important treatment guidelines and understanding their natural course.

Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Recent trends in radiotherapy use for major cancers in Korea.

BACKGROUND: Although the trend in radiotherapy in all cancer patients has been studied, changes in radiotherapy modalities for specific cancer types have not been reported. This study aimed to analyze radiotherapy patterns for major cancers in Korea in recent years. MATERIALS AND METHODS: We collected data from claims and reimbursement records of the Health and Insurance Review and Assessment Service from 2017 to 2020, according to initial diagnostic codes. The radiotherapy modalities for major cancers, such as lung, stomach, colorectal, breast and liver cancer, were analyzed. The radiotherapy modalities consisted of two-dimensional radiotherapy, three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, proton radiotherapy and stereotactic body radiotherapy. RESULTS: Overall, from 2017 to 2020, the use of two-dimensional radiotherapy and three-dimensional conformal radiotherapy decreased, and intensity-modulated radiotherapy increased. In 2017, three-dimensional conformal radiotherapy accounted for approximately half of the radiotherapy in patients for lung and colorectal cancer, which was replaced by intensity-modulated radiotherapy in 2020. In 2020, stereotactic body radiotherapy also accounted for a large proportion of radiotherapy used in liver cancer cases. Intensity-modulated radiotherapy was most used, followed by three-dimensional conformal radiotherapy and two-dimensional radiotherapy for breast cancer in 2020. Among major cancers, radiotherapy utilization for breast cancer is the highest. Compared with other cancers, the number of patients receiving radiotherapy for stomach cancer was low. CONCLUSION: The number of patients receiving radiotherapy for major cancers has increased. The use of advanced forms of radiotherapy, such as intensity-modulated radiotherapy, is rapidly increasing for major cancers. The rate of radiotherapy utilization was higher in major cancer patients than in all cancer patients.

Recurrent C3 Glomerulonephritis along with BK-Virus-Associated Nephropathy after Kidney Transplantation: A Case Report.

C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.

Hypoxia Promotes Angiogenic Effect in Extracranial Arteriovenous Malformation Endothelial Cells.

Arteriovenous malformation (AVM) is characterized by high-flow blood vessels connecting arteries and veins without capillaries. This disease shows increased angiogenesis and a pathophysiological hypoxic environment in proximal tissues. Here, we analyzed the effects of hypoxia on angiogenesis in the endothelial cells (ECs) of AVM and normal tissues. ECs from human normal and AVM tissues were evaluated using immunocytochemistry with CD31. In vitro tube formation under hypoxia was tested in both ECs using Matrigel. The relative expression of angiogenesis-related genes was measured using real-time PCR. Under normoxia, CD31 was significantly higher in AVM ECs (79.23 ± 0.65%) than in normal ECs (74.15 ± 0.70%). Similar results were observed under hypoxia in AVM ECs (63.85 ± 1.84%) and normal ECs (60.52 ± 0.51%). In the tube formation test under normoxic and hypoxic conditions, the junction count and total vessel length were significantly greater in AVM ECs than normal ECs. Under both normoxia and hypoxia, the angiogenesis-related gene FSTL1 showed a significantly higher expression in AVM ECs than in normal ECs. Under hypoxia, CSPG4 expression was significantly lower in AVM ECs than in normal ECs. Accordingly, the angiogenic effect was increased in AVM ECs compared with that in normal ECs. These results provide a basic knowledge for an AVM treatment strategy.

Oscillatory shear stress promotes angiogenic effects in arteriovenous malformations endothelial cells.

BACKGROUND: Vascular endothelial cells (ECs) are subject to continuous shear stress due to blood circulation. Mechanical stress due to high shear flow can also cause arteriovenous malformation (AVM) when ECs respond hyper-sensitively to shear flow. This study was conducted to test the hypothesis that angiogenesis could be promoted in response to mechanical stress via regulation of pro-angiogenic factors in AVM cells. METHODS: ECs were extracted from the tissue samples from six AVM patients and six normal patients. Shear stress at 7 dynes/cm2 were applied for 24 h. Before and after application of shear stress to each group, RT-PCR was performed to access the expression levels of angiopoietin2(AGP2), aquaporin1(AQP1) and TGFßR1. Immunofluorescences was also performed to evaluate the level of protein expressions. RESULTS: In both normal and AVM tissues, AGP2 and TGFßR1 under the shear stress showed increased expression in the ECs compared to the non-sheared samples. When AVMs and normal arterial vasculature were compared, the expression levels of both AGP2 and TGFßR1 in AVMs were higher when compared to normal arterial vasculature with or without shear stress. Immunofluorescence-based protein analysis also confirmed shear-induced AGP2 and TGFßR1 in both samples of normal and AVM patients. CONCLUSIONS: AVMs exhibited higher sensitivity to shear stress by producing higher expressions of some marked genes and proteins that regulate the endothelial functions upon exposure to shear stress. While the physiological mechanism for AVMs remain elusive, our study shows the plausibility of physical stress imposed by the shearing flow can cause the occurrence of AVMs.

Recurrence and risk factors of posterior communicating artery aneurysms after endovascular treatment.

BACKGROUND: Endovascular treatment (EVT) of posterior communicating artery aneurysms (PcomA) is challenging because of posterior communicating artery (Pcom) architecture. Additionally, these aneurysms have a high risk of recanalization compared with those located elsewhere. METHODS: The radiographic findings of 171 patients treated with EVT at two institutions were retrospectively reviewed. Univariate and multivariate analyses were performed, and subgroup analyses were performed based on Pcom characteristics. RESULTS: Recanalization of PcomAs occurred in 53 patients (30.9%). Seven patients (4.0%) were retreated (six endovascularly and one with microsurgical clipping). The mean follow-up duration was 27.7 months (range: 3.5-78.6). The maximum diameter (odds ratio [OR] 1.23, P = .006, 95% CI 1.07-1.44), a Raymond-Roy classification of grade II or III (OR 2.26, P = .03, 95% CI 1.08-4.82), and the presence of reinforcement (balloon or/and stent, OR 0.44, P = .03, 95% CI 0.20-0.91) were associated with recanalization using multivariate logistic regression. Significant differences were found in maximum aneurysm diameter (P = .03) between normal- and fetal-type Pcoms on analysis of variance. CONCLUSIONS: The recanalization rate of PcomAs after EVT was 30.9%; the retreatment rate was 4.0%. Maximum diameter, Raymond-Roy classification, and presence of reinforcement were significantly associated with recanalization but not associated with fetal-type Pcom. Aneurysm size was larger in patients with a fetal-type Pcom than in those with a normal Pcom. Pcom size was not related to recanalization rate.

Recurrence and retreatment of anterior communicating artery aneurysms after endovascular treatment: a retrospective study.

BACKGROUND: Surgical treatment of anterior communicating artery (Acom) aneurysm is challenging due to anatomic complexity. We aimed to describe our experiences with endovascular treatment (EVT) of Acom aneurysms, and to evaluate the incidence and risk factors of recurrence and retreatment. METHODS: The study comprised 260 patients who were treated at a single center between January 2010 and December 2018. Patients who had EVT, including stent-assisted coiling of Acom aneurysms, were included. All medical records were retrospectively reviewed. The incidence and risk factors of recurrence and retreatment were evaluated. Univariate and multivariate analysis were conducted. RESULTS: Recurrence of Acom aneurysms occurred in 38 (14.6%) patients. Mean follow-up duration was 27 months (range 1-110). Multivariate logistic regression indicated that ruptured aneurysm (odds ratio [OR] 3.55, P = 0.001), dome direction (anterior) (OR 3.86, P = 0.002), maximal diameter (OR 1.19, P = 0.02), and mean age (OR 0.96, P = 0.02) were independent risk factors for aneurysm recurrence. Of 38 cases of recurrence, 10 (3.8%) patients underwent retreatment. Ruptured aneurysm (OR 14.7, P = 0.004), maximal diameter (OR 1.56, P = 0.02), inflow angle (OR 1.04, P = 0.03), and Raymond-Roy classes II and III (OR 6.19, P = 0.03) showed significant relation to retreatment in multivariate logistic regression analysis. CONCLUSIONS: In our study, recurrence rate of Acom aneurysms after EVT was 14.6%. Rupture, anterior dome direction, maximal diameter, and mean age were significantly associated with recurrence. Retreatment rate of recurrent Acom aneurysms after EVT was 3.8%. Patients with Acom aneurysms with large inflow, rupture, large size, or incomplete occlusion may be at a high risk of retreatment of recurring aneurysm.

Comparison of frontal alpha asymmetry among schizophrenia patients, major depressive disorder patients, and healthy controls.

BACKGROUND: Electroencephalography (EEG) frontal alpha asymmetry (FAA) has been observed in several psychiatric disorders. Dominance in left or right frontal alpha activity remains inconsistent in patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls. This study compared FAA among patients with MDD and schizophrenia, and healthy controls. METHODS: We recruited 20 patients with MDD, 18 patients with schizophrenia, and 16 healthy individuals. The EEG alpha frequency ranged from 8 Hz to 12 Hz. FAA was expressed as the difference between absolute power values of right and left hemisphere electrodes in the alpha frequency range (common-log-transformed frontal right- and left-hemisphere electrodes: F4-F3, F8-F7, FP2-FP1, AF4-AF3, F6-F5, and F2-F1). Hamilton depression and anxiety rating scales were evaluated in patients with MDD. Positive and negative syndrome scales were evaluated in patients with schizophrenia. RESULTS: Patients with schizophrenia showed significantly lower left FAA than healthy controls (F4-F3, schizophrenia vs. healthy controls: - 0.10 ± 0.04 vs. -0.05 ± 0.05). There were no significant differences in FAA between patients with schizophrenia and MDD as well as between patients with MDD and healthy controls. CONCLUSIONS: The present study suggests that FAA indicates a relatively lower activation of left frontal electrodes in schizophrenia. The left-lateralized FAA could be a neuropathological attribute in patients with schizophrenia, but a lack of sample size and information such as medication and duration of illness might obscure the interpretation and generalization of our findings. Thus, further studies to verify the findings would be warranted.

Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients.

BACKGROUND: Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C0) and dose with renal transplant outcomes and adverse events. METHODS: This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C0 of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections. RESULTS: No differences in MPA C0 and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C0 was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C0 ≥ 3.5 µg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24-11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27-27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15-12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR. CONCLUSION: Either a higher MPA C0 or dose is associated with an increased risk of cytopenia, but neither a lower MPA C0 nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.

Comparative outcomes of vascular access in patients older than 70 years with end-stage renal disease.

OBJECTIVE: The advantage of arteriovenous fistulas (AVFs) in older patients requiring dialysis is controversial. We reviewed our vascular access experience in patients ≥70 years of age (older group) compared with younger patients. METHODS: We analyzed consecutive patients who underwent access surgery between 2013 and 2016. Primary success (PS) and primary patency (PP) data were analyzed between the older and younger groups before and after propensity score matching of the patients' characteristics and access composition. PS was defined as the achievement of access function that was amenable to two sessions of successful cannulation without early occlusion or maturation failure requiring revision. PP was defined as the time with uninterrupted patency without intervention. RESULTS: A total of 594 consecutive accesses were created among 563 patients, of whom 119 were allocated into each group after propensity score matching. In the whole cohort, 193 accesses (32.5%) were performed in older patients. AVFs were performed in 130 (67.4%) older patients and 293 (73.1%) younger patients. Regarding AVFs, the PS rate (83.6% in the older group vs 94.3% in the younger group; P = .001) and the overall PP at 6 and 12 months (73.1% and 57.1%, respectively, in the older group vs 86.7% and 77.7%, respectively, in the younger group; P = .009) were lower in the older group than in the younger group. However, no differences were found in the PS and PP rates for arteriovenous grafts between groups. Regarding the AVF location, the PS rate for forearm AVFs was significantly lower in the older group than in the younger group (76% vs 93%; P < .001); however, the PS rate of the upper arm was not different between the groups (94% vs 97%; P = .425). In the patients with PS, the PP rate of AVFs was similar between the two groups. In the older group with forearm AVFs, the median diameter of the radial artery was larger in the patients with PS than in the patients without PS (2.20 mm with PS vs 2.00 mm without PS; P = .008). The propensity score matching results demonstrated similar trends for the whole cohort, with lower PS (P = .042) and PP rates (P = .023) for AVF in the older group. CONCLUSIONS: The outcomes after AVF were poorer in the older group than in the younger group, which was primarily due to unsatisfactory outcomes in patients with forearm AVFs. Thus, stricter criteria, especially regarding the radial artery diameter, should be applied for forearm AVFs in older patients, and additional research is necessary to delineate the risk factors for primary failure.

Comparison of radiotherapy infrastructure between Korea and Japan.

BACKGROUND: Patterns of cancer incidence and radiotherapy use are similar in Korea and Japan, with differences in radiotherapy infrastructure. METHODS: The authors surveyed the megavoltage machines in 91 radiotherapy centers in Korea and published data in Japan. The number of megavoltage machines per center was used as an indicator of the fragmentation of radiotherapy services using four as the threshold, and the number of megavoltage machines per million people was compared. The practice pattern of intensity-modulated radiation therapy was analyzed. RESULTS: There were 91 centers in Korea and 825 in Japan. The number of megavoltage machines per center was 1.3 in Japan and 2.3 in Korea. Radiotherapy infrastructure showed fragmentation in Korea and hyperfragmentation in Japan. In Japan, 75% of radiotherapy centers operated with one megavoltage machine, whereas in Korea, 47% megavoltage machines per center was 3.2 in Seoul, while that in the non-capital area was 1.8, constituting a mixed pattern of centralization and fragmentation. In Japan, megavoltage machines per center in Tokyo, Kanagawa and Osaka, was 1.5, 1.3 and 1.2, respectively, indicating no concentration in the metropolis. The number of megavoltage machines per million in Korea was 4.0, whereas that in Seoul was 8.7, constituting capital concentration. In Japan, the number of megavoltage machines per million was 8.7, whereas in Tokyo, Kanagawa and Osaka, it was is 9.3, 6.3 and 9.0, showing uniform distribution. intensity-modulated radiation therapy utilization is increasing, accounting for 15% and 23% of radiotherapy patients in Japan and Korea, respectively. CONCLUSIONS: The fragmentation of radiotherapy services in Korea and Japan might affect radiotherapy quality.

Unsuccessful reduction of high-frequency alpha activity during cognitive activation in schizophrenia.

AIMS: Electroencephalogram (EEG) alpha activity during resting state reflects the 'readiness' of an individual to respond to the environment; this includes the performance of cognitive processes. Alpha activity is reported to be attenuated in schizophrenia (SCZ). Understanding the interaction between alpha activity during rest and when cognitively engaged may provide insights into the neural circuitry, which is dysfunctional in SCZ. This study investigated the changes of alpha activity between resting state and cognitive engagement in SCZ patients. METHODS: Thirty-four SCZ patients and 29 healthy controls (HC) were recruited. EEG was performed in the resting state and during an auditory P300 task. All experimental procedures followed the relevant institutional guidelines and regulations. RESULTS: In SCZ, high-frequency alpha activity was reduced in the resting state. High-frequency alpha source density was decreased in both the resting-state and a P300 task condition in patients, compared to HC. HC, but not SCZ patients, showed a reduction in high-frequency alpha source density during the P300 task compared to the resting state. The negative correlation between high-frequency alpha source density in the resting state and positive symptoms was significant. CONCLUSIONS: High-frequency alpha activity in SCZ patients and its unsuccessful reduction during cognitive processing may be biological markers of SCZ.

Posttraumatic Symptoms and Change of Complicated Grief among Bereaved Families of the Sewol Ferry Disaster: One Year Follow-up Study.

BACKGROUND: The objective of this study was to determine whether severity and severity change of coexisting psychiatric symptoms might affect change of complicated grief (CG) regarding the Sewol ferry disaster. METHODS: Data from a cross-sectional survey were obtained 18 months (Time 1) and 30 months (Time 2) after the disaster. We ascertained sociodemographic variables and variables obtained from self-reporting questionnaires (i.e., CG, depression, anxiety, post-traumatic stress disorder [PTSD], insomnia, embitterment, and suicidal risk) among 56 bereaved family members. RESULTS: Severity of other psychiatric symptoms at Time 1 had no effect on change of CG at Time 2. However, changes in severity of PTSD over a year affected change of CG. CONCLUSION: It is important to evaluate changes in severity of PTSD and its treatment during management of CG, especially when it involves bereaved families experiencing a traumatic accident.

Comparison of Transplant Outcomes for Low-level and Standard-level Tacrolimus at Different Time Points after Kidney Transplantation.

BACKGROUND: Optimal tacrolimus (TAC) trough levels for different periods after kidney transplantation (KT) has not been definitely established. This study aimed to investigate transplant outcomes of low-level (LL) and standard-level (SL) TAC according to post-transplant period. METHODS: A total of 278 consecutive kidney transplant recipients (KTRs) receiving TAC-based immunosuppression were divided into LL and SL-TAC groups (4-7 and 7-12 ng/mL for 0-2 months, 3-6 and 6-10 ng/mL for 3-6 months, 2-5 and 5-8 ng/mL for 7-12 months, respectively) according to TAC trough level at each period. We compared estimated glomerular filtration rate (eGFR), biopsy-proven acute rejection (BPAR), de novo donor-specific antibody (dnDSA), calcineurin inhibitor (CNI) toxicity, opportunistic infection, and allograft survival. RESULTS: SL-TAC group showed significantly higher mean eGFR at 0-2 months than LL-TAC group (72.1 ± 20.3 vs. 64.2 ± 22.7 mL/min/1.73m2; P = 0.003). Incidence of BPAR at 7-12 months was significantly lower in SL-TAC group than in LL-TAC group (0.0% vs. 3.9%; P = 0.039). Patients with persistent SL-TAC lasting 12 months showed higher eGFR at 7-12 months than those with persistent LL-TAC (65.5 ± 13.0 vs. 57.9 ± 13.9 mL/min/1.73m2; P = 0.007). No significant differences in dnDSA, CNI toxicity, serious infections, or allograft survival were observed. CONCLUSIONS: Maintenance of proper TAC trough level after 6 months could reduce BPAR without adverse drug toxicities in KTRs. Moreover, persistent SL-TAC during the first year after KT might have a beneficial effect on a trend for a lower incidence of dnDSA and better renal allograft function.

Bereaved families are still embittered after the Sewol ferry accident in Korea: A follow-up study 18 and 30months after the disaster.

INTRODUCTION: The Sewol ferry accident that occurred in April 2014 was one of the most tragic human-made disasters in Korean history. Due to the deaths of hundreds of children, bereaved families likely feel embittered; however, there is little extant research documenting embitterment among those who experienced the disaster. Consequently, we investigated bereaved family members' embitterment and other psychiatric symptoms 18months and 30months after the disaster. METHODS: Data from a cross-sectional survey were obtained 18months (Time 1) and 30months (Time 2) after the disaster. We ascertained socio-demographic variables and variables obtained from a self-reporting questionnaire (i.e., depression, anxiety, posttraumatic stress disorder, complicated grief, and embitterment) among 56 bereaved family members. RESULTS: Bereaved families showed substantial embitterment at Time 1 (64.3%), which increased at Time 2 (76.8%, t=1.761, p=0.084). The participants who displayed increased embitterment at Time 2 also increased in anxiety, post-traumatic stress symptoms, and complicated grief (but not depression). Furthermore, participants who displayed decreased embitterment at Time 2 also decreased in all other psychiatric symptoms. (time×group interaction in depression (F 0.644, p=0.426), anxiety (F 4.970, p=0.030), PTSD (F 10.699, p=0.002), and complicated grief (F 8.389, p=0.005)). CONCLUSIONS: Embitterment of bereaved families had not ceased after 18months and even increased 1year later. Additionally, as embitterment increased, many other psychiatric symptoms also increased, and vice versa. Our results suggest that embitterment is associated or can even influence other psychiatric symptoms; therefore, embitterment should be examined after disasters.

Characteristics and Clinical Significance of De Novo Donor-Specific Anti-HLA Antibodies after Kidney Transplantation.

BACKGROUND: The association of de novo donor-specific anti-human leukocyte antigens (HLA) antibodies (DSA) and development of antibody-mediated rejection (AMR) in kidney transplant recipients (KTRs) is still undetermined. METHODS: We prospectively screened de novo DSA in 167 KTRs during 32 months after kidney transplantation (KT). Timing of DSA detection was at 3, 6, and 12 months post-transplant and annually thereafter and when clinically indicated. DSA levels were determined by Luminex assays and expressed as mean fluorescence intensity (MFI). We evaluated the incidence, characteristics of DSA, and association between DSA and tacrolimus trough levels or AMR. RESULTS: De novo DSA developed in 16 KTRs (9.6%) and acute AMR occurred more commonly in KTRs with de novo DSA compared to KTRs without de novo DSA (18.8% vs. 0%, P < 0.001). All de novo DSA were against class II antigens. The mean number of DSA was 1.8 ± 1.2 and the average MFI of DSA was 7,399 ± 5,470. Tacrolimus trough level during the first 0-2 months after KT was an independent predictor of DSA development (hazard ratio, 0.70; 95% confidence interval, 0.50-0.99; P = 0.043). No differences were found in the number of DSA, average MFI of DSA, and tacrolimus levels during the first year between de novo DSA-positive KTRs with AMR and those without AMR. CONCLUSION: The results of our study suggest that monitoring of DSA and maintaining proper tacrolimus levels are essential to prevent AMR during the initial period after KT.

Frequency of pathogenic germline mutation in CHEK2, PALB2, MRE11, and RAD50 in patients at high risk for hereditary breast cancer.

PURPOSE: This study was performed to evaluate the frequency of mutations in CHEK2, PALB2, MRE11, and RAD50 among Korean patients at high risk for hereditary breast cancer. METHODS: A total of 235 Korean patients with hereditary breast cancer who tested negative for BRCA1/2 mutation were enrolled to this study. Entire coding regions of CHEK2, PALB2, MRE11, and RAD50 were analyzed using massively parallel sequencing (MPS). Sequence variants detected by MPS were confirmed by Sanger sequencing. RESULTS: Six patients (2.5 %) were found to have pathogenic variants in CHEK2 (n = 1), PALB2 (n = 2), MRE11 (n = 1), and RAD50 (n = 2). Among the pathogenic variants, PALB2 c.2257C>T was previously reported in other studies, while CHEK2 c.1245dupC, PALB2 c.1048C>T, MRE11 c.1773_1774delAA, RAD50 c.1276C>T, and RAD50 c.3811_3813delGAA were newly identified in this study. A total of 15 missense variants were found in the four genes among 26 patients; 7 patients had a variant in CHEK2, 11 in PALB2, 2 in MRE11, and 6 in RAD50. When in silico analyses were performed to the 15 missense variants, six variants (CHEK2 c.686A>G, PALB2 c.1492G>T, PALB2 c.3054G>C, MRE11 c.140C>T, RAD50 c.1456C>T, and RAD50 c.3790C>T) were predicted to be deleterious. CONCLUSIONS: Pathogenic variants in CHEK2, PALB2, MRE11, and RAD50 were detected in a small proportion of Korean patients with features of hereditary breast cancer.

Recurrence outcomes after omission of postoperative radiotherapy following breast-conserving surgery for ductal carcinoma in situ of the breast: a multicenter, retrospective study in Korea (KROG 16-02).

PURPOSE: To evaluate the loco-regional recurrence (LRR) rate after breast-conserving surgery without postoperative radiotherapy (RT) for ductal carcinoma in situ (DCIS) of the breast. METHODS: Between 2000 and 2010, 311 DCIS patients from 9 institutions were analyzed retrospectively. The median age was 47 (range, 20-82). The median tumor size was 7 mm (range, 0.01-76). Margin width was <1 cm in 85 patients (27.3%), and nuclear grade was high in 37 patients (11.9%). Two hundred and three patients (65.3%) received tamoxifen. RESULTS: With a median follow-up of 74 months (range, 5-189), there were 11 local recurrences (invasive carcinoma in 6 and DCIS in 5) and 1 regional recurrence. The 7-year LRR rate was 3.8%. On univariate analysis, age and margin width were significant risk factors influencing LRR (p = 0.017 and 0.014, respectively). When age and margin width were combined among 211 patients whose margin width were available, the 7-year LRR rates were as follows (p < 0.001): (1) 0% in patients with age >50 years and any margin width status (n = 64), (2) 1.2% in age ≤50 years and margin width ≥1 cm (n = 93), (3) 13.1% in age ≤50 years and margin width <1 cm (n = 54). CONCLUSIONS: The LRR rate was very low in selected DCIS patients treated with breast-conserving surgery without postoperative RT. However, adjuvant RT should be considered for those with age ≤50 years and margin width <1 cm.

Parametrial Involvement on Magnetic Resonance Imaging Has No Effect on the Survival of Early-Stage Cervical Cancer Patients.

OBJECTIVES: Parametrial involvement (PMI) in patients with cervical cancer is known to be an unfavourable prognostic factor. The purpose of this study was to investigate the prognostic significance of PMI on magnetic resonance imaging (MRI) in patients with early-stage cervical cancer. METHODS: Three hundred three patients with stage IB or IIA cervical cancer treated by adjuvant radiotherapy or concurrent chemoradiotherapy following primary surgery from 2001 to 2011 were enrolled in this study. We reviewed preoperative MRI and pathologic findings and compared recurrence and survival of group defined according to PMI status. RESULTS: There were 73 patients (24.1%) with PMI based on MRI and 52 patients (17.2%) with PMI based on surgical pathology. The accuracy of MRI for detecting PMI was 77.2% (sensitivity, 53.8%; specificity, 82.1%). In all patients, pathology-based evidence of PMI had a negative effect on both 5-year disease-free survival (73.2% vs 85.3%, P = 0.048) and 5-year overall survival (76.6% vs 91.4%, P = 0.009), but PMI on MRI did not have a significant effect on survival. In subgroups defined according to PMI status on MRI and surgical pathology, subgroups with pathology-based evidence of PMI showed a trend of a lower survival rate, regardless of PMI on MRI, but without statistical significance. CONCLUSIONS: Unlike pathologic results, PMI on MRI was not associated with recurrence or survival in patients with early-stage cervical cancer.