Asian variant intravascular large B-cell lymphoma with highly suspected central nervous system involvement: A case report.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal lymphoma. In particular, the Asian variant of IVLBCL is characterized by hemophagocytic lymphohistiocytosis along with bone marrow involvement. However, central nervous system (CNS) involvement is uncommon in this variant compared to the Western variant. Here, we report a case of typical Asian variant IVLBCL with highly suspected CNS involvement and discuss the nature of the disease and its genetic aberration. CASE SUMMARY: A 67-year-old female patient complained of gradually worsening cognitive impairment. While hospitalized, she developed a high fever and showed marked bicytopenia. Intracranial imaging revealed a suspected leptomeningeal disease. Although no malignant cells were found in the cerebrospinal fluid (CSF), the protein and lactate dehydrogenase levels in CSF were increased. Bone marrow examination revealed an increased number of hemophagocytic histiocytes, and 18F-fluorodeoxyglucose (FDG) positron emission tomography with computerized tomography scan revealed increased FDG uptake in both adrenal glands, the liver, and the right ethmoid sinus. A tissue biopsy showed atypical large lymphoid cells with prominent nucleoli in the vessels, and the tumor cells were positive for CD20, BCL2, BCL6, and IRF4/MUM1. In addition, targeted sequencing identified MYD88, TET2, and PIM1 mutations. Consequently, we diagnosed the patient with the Asian variant of IVLBCL with highly suspected CNS involvement. CONCLUSION: Suspicion of IVLBCL and immediate diagnosis lead to timely treatment. Moreover, careful CNS examination at diagnosis is recommended.

A retrospective analysis of ibrutinib outcomes in relapsed or refractory mantle cell lymphoma.

Background: While treatment strategies for mantle cell lymphoma (MCL) have evolved, patients often experience disease progression and require additional treatment therapies. Ibrutinib presents a promising option for relapsed or refractory MCL (RR-MCL). This study investigated real-world treatment outcomes of ibrutinib in patients with RR-MCL. Methods: A single-center retrospective analysis investigated clinical characteristics and survival outcomes of patients with RR-MCL, treated with ibrutinib. Results: Forty-two patients were included, with 16 received rituximab and bendamustine, and 26 receiving anthracycline-based regimens as front-line treatment. During a median follow-up of 46.0 months, the response rate to ibrutinib was 69%, with 12 CRs and 8 partial responses. Disease progression (54.8%) and adverse events (11.9%) were the primary reasons for discontinuation. Median progression-free survival (PFS) and overall survival (OS) were approximately 16.4 and 50.1 months, respectively. Patients older than 70 years (P=0.044 and P=0.006), those with splenomegaly (P=0.022 and P=0.006), and those with a high-risk simplified Mantle Cell Lymphoma International Prognostic Index (sMIPI) (P＜0.001 and P＜0.001) exhibited siginificantly inferior PFS and OS. Notably, patients with a high-risk sMIPI relapsed earlier. Post-ibrutinib treatment yilded an OS of 12.2 months, while clinical trial participants demonstrated superior survival compared to those receiving chemotherapy alone. Conclusion: This study underscores the importance of considering patient characteristics before administering ibrutinib as salvage therapy. Early relapse was associated with poor outcomes, highlighting the need for novel therapeutic strategies.

Effectiveness of the COVID-19 vaccine in the Honam region of the Republic of Korea.

BACKGROUND: In 2021, the effectiveness of the COVID-19 vaccine was analyzed among people living in the Honam region (Gwangju, Jeollanam-do, Jeollabuk-do, and Jeju) of the Republic of Korea. And we investigated changes in the dominant virus strain. METHODS: This study used the data provided by the Korean Ministry of the Interior and Safety for individuals ≥12 years old in the Honam region, and the Integrated Disease and Health Management System of the Korea Centers for Disease Control and Prevention for COVID-19-vaccinated individuals as of December 31, 2021. Statistical analyzes were performed using IBM SPSS ver. 23.0. The occurrence of confirmed cases by vaccination status, the relative risk, and vaccine effectiveness by vaccine type were calculated. RESULTS: In 2021, the COVID-19 vaccination rate in Honam was 88.6%. The overall vaccine effectiveness (after 2 and 3 doses) was 98.7% (p<0.001). and the breakthrough infection rate was 0.16%. From week 21 to week 27 of 2021 (June 27 to July 3), the genome sequencing results were mostly alpha variants. The Delta variant emerged as the dominant variant after 27 weeks and the Omicron variant was found at 50 weeks (December 5-11). CONCLUSION: Vaccine effectiveness changed with the outbreak of new variants of the virus as well as over time as antibody levels decreased. that the prevention effectiveness of vaccination in Honam was >98%, and the effect among persons who received 2 doses was >90% regardless of the vaccine type. Although vaccine effectiveness decreased because of reduced antibody levels over time (as observed in breakthrough infections), receiving a booster dose restored the neutralizing antibody levels.

Real-World Data Analysis of Survival Outcomes and Central Nervous System Relapses in Testicular Diffuse Large B Cell Lymphoma.

Background: Primary testicular lymphoma is a rare type of non-Hodgkin lymphoma, mostly of the diffuse large B cell lymphoma (DLBCL). Although a consensus on standard treatment has been established, unresolved issues remain, such as recurrence in the central nervous system (CNS). Methods: We retrospectively analyzed the clinical characteristics and survival outcomes of 65 testicular DLBCL patients according to clinical settings and treatment modalities. Results: The median age of the patients in our study was 65 years, and two-thirds of them had disease limited to one testis. There was no right or left lateralization of testicular involvement. Over a median follow-up of 53.9 months (95% confidence interval 34.0-73.7 months), patients with stage I disease and a low international prognostic index score showed better survival outcomes than those in other categories. Orchiectomy, six cycles of chemotherapy, and radiation therapy (RT) to the contralateral testis demonstrated survival benefits, whereas CNS prophylaxis therapy did not reduce CNS recurrence. During the follow-up period, the survival curves showed continuous decline, mostly due to disease progression. CNS recurrence was observed in 15% of patients, and parenchymal involvement was dominant. However, no factors were associated with CNS recurrence in our analyses. Although our molecular analyses were performed in a small number of patients, MYD88, CD79B, and PIM1 mutations were frequent. Conclusion: In our study, treatment with orchiectomy, six cycles of immunochemotherapy, and contralateral RT was effective. However, because CNS prophylaxis is an essential part of testicular DLBCL management, better treatment strategies than intrathecal therapy are required.

Survival Outcomes of Patients with Follicular Lymphoma after Relapse or Progression: A Single-Center Real-World Data Analysis.

Background: Follicular lymphoma (FL) is considered incurable because remission and relapse are common. Although various salvage treatment options have been proposed, there is no consensus on treatment strategy for FL patients who failed primary treatment. Methods: This single-center study analyzed postevent overall survival (OS) among 70 patients who experienced relapse or progression after rituximab-containing immunochemotherapy according to type of salvage treatment and nature of relapse or progression. Results: Of 70 patients, 42 experienced progression of disease within 24 months (POD24), and six showed disease progression during first-line treatment. Large-cell transformation was found in nine patients with POD24. At the median follow-up of 104 months (95% CI: 90-118 months), POD24 patients experienced significantly worse OS than patients without POD24, and postevent OS was not satisfactory after conventional salvage chemotherapy because the majority of patients relapsed or progressed. However, autologous stem cell transplantation (ASCT) after the first relapse resulted in survival prolongation in patients with POD24. Half of the patients (34/67, 51%) participated in at least one clinical trial during treatment after first relapse, and patients participating in at least one clinical trial irrespective of line of treatment tended to experience better survival. Conclusions: Relapsed or refractory FL patients showed various clinical courses and treatment outcomes according to relapse or progression. Consolidation treatment with ASCT and active participation to clinical trials might prolong survival duration, especially in POD24 cases.

Genetic Analysis of HPIV3 That Emerged during the SARS-CoV-2 Pandemic in Gwangju, South Korea.

Community mitigation measures taken owing to the COVID-19 pandemic have caused a decrease in the number of respiratory viruses, including the human parainfluenza virus type 3 (HPIV3), and a delay in their occurrence. HPIV3 was rarely detected as a consequence of monitoring respiratory viral pathogens in Gwangju, Korea, in 2020; however, it resurfaced as a delayed outbreak and peaked in September-October 2021. To understand the genetic characteristics of the reemerging virus, antigenic gene sequences and evolutionary analyses of the hemagglutinin-neuraminidase (HN) and fusion (F) genes were performed for 129 HPIV3 pathogens prevalent in Gwangju from 2018 to 2021. Unlike the prevalence of various HPIV3 strains in 2018-2019, the prevalence of HPIV3 by strains with reduced diversity was confirmed in 2021. It could be inferred that this decrease in genetic diversity was due to the restriction of inflow from other regions at home and abroad following the community mitigation measures and the spread within the region. The HPIV3 that emerged in 2021 consisted of HN coding regions that were 100% consistent with the sequence identified in Saitama, Japan, in 2018, and F coding regions exhibiting 99.6% homology to a sequence identified in India in 2017, among the ranks reported to the National Center for Biotechnology Information. The emergence of a new lineage in a community can lead to a mass outbreak by collapsing the collective immunity of the existing acquired area; therefore, continuous monitoring is necessary.

Comprehensive comparison of international prognostic indexes for follicular helper T-cell lymphoma.

In 2016, World Health Organization classification of lymphoid neoplasms separated firmly-follicular helper (Tfh) cell origin lymphomas from peripheral T-cell lymphoma-not specified (PTCL-NOS) based on their unique immunogenic characteristics. Generally, Tfh cell origin lymphoma, which has an approximately 25% incidence, is classified into three categories: angioimmunoblastic T-cell lymphoma (AITL), follicular peripheral T-cell lymphoma (F-PTCL), and nodal peripheral T-cell lymphoma with a T-follicular helper phenotype (nodal PTCL with Tfh cell phenotype). Their prognosis has been estimated using four traditional prognostic tools for T-cell lymphoid malignancies: the international prognostic index (IPI), the prognostic index for peripheral T-cell lymphoma unspecified (PIT), the modified PIT (mPIT) and the international T-cell lymphoma project index. In addition, the AITL score that reflects AITL characteristics well has been introduced recently. However, there are no clear guidelines for evaluating the prognosis of Tfh cell lymphoma. Thus, we performed a comparative analysis to determine which of these five indexes is most suitable for Tfh cell lymphoma. We evaluated the accuracy of classification according to risk score and predicted survival rate. Based on review by lymphoma pathology experts, we enrolled 198 patients diagnosed with Tfh cell lymphoma in this retrospective study. AITL was the most common subtype (n = 168), followed by F-PTCL (n = 21) and nodal PTCL with Tfh cell phenotype (n = 9). The median progression-free survival and overall survival with front-line treatment was 0.8 years (95% confidence interval [CI], 0.6-1.1 years) and 2.9 years (95% CI, 1.6-4.2 years), respectively. The AITL score showed better differentiation than other scoring systems in terms of classification according to risk score. However, for predicting PFS (concordance-index [C-index], IPI vs. PIT vs. modified PIT vs. international T-cell lymphoma project index vs. AITL score; 0.617 vs. 0.605 vs. 0.576 vs. 0.591 vs. 0.592) and OS (C-index, IPI vs. PIT vs. modified PIT vs. international T-cell lymphoma project index vs. AITL score; 0.663 vs. 0.651 vs. 0.612 vs. 0.672 vs. 0.583), the IPI, and the international T-cell lymphoma project index showed better performance. In conclusion, there are unmet needs to develop a prognostic index for Tfh cell lymphoma because its characteristics differ from PTCL-NOS. Although the AITL score reflects Tfh cell-origin lymphoma characteristics well and clearly shows their power of classification according to risk score, there are concerns about accurate prediction of survival outcomes. Therefore, it seems too early to settle on a single scoring system in Tfh cell origin lymphoma. In the future, along with classification, a more effective tool for survival prediction needs to be developed that reflects the specific characteristics of T-cell lymphoma.

Modified FOLFIRINOX as a Second-Line Treatment for Patients with Gemcitabine-Failed Advanced Biliary Tract Cancer: A Prospective Multicenter Phase II Study.

BACKGROUND: After the publication of the ABC-02 trial, gemcitabine and cisplatin combination therapy (GP) became the standard first-line treatment for advanced biliary tract cancer (BTC). Despite GP therapy, most patients suffer from disease progression. The ABC-06 trial recommended FOLFOX as a second-line treatment, but its efficacy was modest. In this phase II study, we looked at the efficacy and safety of a second-line modified dose of FOLFIRINOX (mFOLFIRINOX) for patients who had failed first-line gemcitabine-based treatment. METHODS: From January 2020 to January 2021, 34 patients with advanced BTC who failed first-line gemcitabine-based chemotherapy were enrolled. We evaluated the clinical efficacy and safety outcomes of mFOLFIRINOX. RESULTS: With a median follow-up duration of 13.4 months, the median progression-free survival and overall survival was 2.8 months (95% confidence interval (CI): 1.6-4.0 months) and 6.2 months (95% CI: 5.0-7.4 months), respectively. The objective response rate was 14.7% with no complete response. The disease control rate was 61.7%, with a disease control duration of 4.2 months. Due to the rapid progression of the disease, approximately half of all patients received less than three cycles of treatment. The most common type of adverse event (AEs) was hematopoietic AEs. The incidence of non-hematopoietic AEs was relatively low. CONCLUSIONS: The efficacy of mFOLFIRINOX as a second-line treatment in advanced BTC patients after the failure of gemcitabine-based first-line treatment was replicated, albeit with slightly shorter survival results compared to previous studies. Long-term administration of mFOLFIRINOX with toxicity management might offer a survival benefit.

Bevacizumab plus irinotecan with or without gamma knife radiosurgery after failure of concurrent chemo-radiotherapy for high-grade glioma.

INTRODUCTION: Concurrent chemo-radiotherapy (CCRT) with temozolomide (TMZ) is a standard first-line treatment for high-grade glioma. However, if CCRT with TMZ treatment fails, second-line treatment options have limited value. Bevacizumab plus irinotecan is the only available treatment option for such patients. The role of gamma knife radiosurgery (GKS) in patients with high-grade gliomas is not well-established. In this study, we evaluated the efficacy and safety of bevacizumab plus irinotecan with or without GKS in the treatment of high-grade glioma patients who progressed after initially being treated with CCRT with TMZ. METHODS: We collected clinical data of patients with biopsy-proven high-grade glioma (glioblastoma multiforme (GBM) or anaplastic astrocytoma) who were treated at Samsung Medical Center from January 2015 to December 2020, retrospectively. We evaluated the overall survival (OS), progression-free survival (PFS), and safety of bevacizumab plus irinotecan with or without GKS. RESULTS: In total, 203 patients were diagnosed with high-grade glioma, including GBM and anaplastic astrocytoma. The median OS was 8.73 months (95% confidence interval [CI]: 7.27-10.18), and the median PFS was 4.36 months (95% CI: 3.75-4.97). Sixty-eight (33.4%) patients underwent GKS prior to bevacizumab plus irinotecan treatment, which led to a significantly prolonged OS (10.13 months, 95% CI: 8.65-11.60 vs. 8.26 months, 95% CI: 7.01-9.51, p = 0.012). The most common adverse events of any grade were neutropenia (36.9%) and thrombocytopenia (22.6%). However, the incidence of adverse events in patients who underwent GKS prior to bevacizumab plus irinotecan was not different compared with those in patients who did not undergo GKS. CONCLUSIONS: Bevacizumab plus irinotecan was well-tolerated and moderately effective in patients with high-grade gliomas. The addition of GKS prior to bevacizumab plus irinotecan led to a significant OS benefit with a manageable safety profile. GKS prior to bevacizumab plus irinotecan can therefore be considered a potential treatment option for these patients.

Real-World Evidence of Trastuzumab, Pertuzumab, and Docetaxel Combination as a First-Line Treatment for Korean Patients with HER2-Positive Metastatic Breast Cancer.

PURPOSE: Trastuzumab has markedly improved the survival outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and dual blockade of HER2 using trastuzumab and pertuzumab in combination with taxanes (THP) has become a standard of care for HER2-positive metastatic breast cancer (MBC) worldwide since the CLEOPATRA trial. We assessed the outcomes of THP as a first-line treatment for Korean HER2-positive MBC patients in the real-world setting. MATERIALS AND METHODS: Between August 2008 and October 2020, we identified 228 HER2-positive MBC patients who received THP as a first-line palliative chemotherapy. We analyzed survival outcomes, efficacy, and adverse events of THP retrospectively. RESULTS: After a median follow-up duration of 28.7 months, median overall survival and progression-free survival were 58.3 months (95% confidence interval [CI], 36.6 to 80.0) and 19.1 months (95% CI, 16.2 to 21.9), respectively. Better survival outcomes were observed in patient who received docetaxel for more than six cycles. Patients exposed to anti-HER2 directed therapies in a perioperative setting had poor survival outcomes. The overall response rate was 86.8% with a complete response (CR) rate of 17.7%. Among responders, 16.7% of patients sustained THP over 35 months and showed better survivals and higher CR rates. Adverse events were comparable to those reported in previous studies. CONCLUSION: In a real-world context, clinical outcomes of Korean HER2-positive MBC patients treated with THP were similar to those of patients in the CLEOPATRA trial. Much longer follow-up results would be warranted.

The Modulation of Nrf-2/HO-1 Signaling Axis by Carthamus tinctorius L. Alleviates Vascular Inflammation in Human Umbilical Vein Endothelial Cells.

Carthamus tinctorius L., known as safflower, has been used in traditional treatment for cardiovascular, cerebrovascular, and diabetic vascular complications. We proposed to investigate how the ethanol extract of Carthamus tinctorius L. (ECT) can be used ethnopharmacologically and alleviate vascular inflammatory processes under cytokine stimulation in human vascular endothelial cells. Using the optimized HPLC method, six markers were simultaneously analyzed for quality control of ECT. Pretreatment with ECT (10-100 µg/mL) significantly reduced the increase of leukocyte adhesion to HUVEC by TNF-α in a dose-dependent manner. Cell adhesion molecules (CAMs) such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial cell selectin (E-selectin) are decreased by ECT. In addition, ECT significantly suppressed TNF-α-induced oxidative stress referring to reactive oxygen species (ROS) production. p65 NF-κB nuclear translocation and its activation were inhibited by ECT. Furthermore, pretreatment of ECT increased the HO-1 expression, and nuclear translocation of Nrf-2. These data suggest the potential role of ECT as a beneficial therapeutic herb in vascular inflammation via ROS/NF-kB pathway and the regulation of Nrf-2/HO-1 signaling axis is involved in its vascular protection. Thus, further study will be needed to clarify which compound is dominant for protection of vascular diseases.

Extrapulmonary tuberculosis in patients with RET fusion-positive non-small cell lung cancer treated with pralsetinib: A Korean single-centre compassionate use experience.

BACKGROUND: Pralsetinib, an RET inhibitor, has shown a dramatic response in patients with RET fusion- or mutation-positive tumours in previous studies. As a novel target agent, however, the safety of pralsetinib remains to be determined. Herein, we present two cases of extrapulmonary tuberculosis (TB) that developed during pralsetinib therapy. METHODS: From April 2020, we administered pralsetinib to a total of 10 patients with RET fusion-positive non-small cell lung cancer under the compassionate use program. We retrospectively analysed the clinical efficacy of and adverse events related to pralsetinib therapy. RESULTS: Of the nine patients with measurable lesions, seven achieved a partial response. Additionally, one patient without measurable lesions also showed a clinical response. As of January 8, 2021, nine patients were still receiving pralsetinib therapy, while only one had discontinued pralsetinib therapy. Most adverse events were mild and manageable. However, two patients experienced extrapulmonary TB shortly after starting pralsetinib. The disease was well controlled with anti-TB medication, and the cancer lesions were managed through ongoing pralsetinib therapy. CONCLUSION: The development of TB during pralsetinib therapy is worth noting, although further large studies are required to demonstrate definitive relationship between causality and underlying mechanism.

Cutaneous T-cell lymphoma in Asian patients: a multinational, multicenter, prospective registry study in Asia.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.

Real-World, Single-Center Data for Lenalidomide Plus Rituximab in Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Transformed Follicular Lymphoma.

BACKGROUND: This study explored the efficacy of lenalidomide plus rituximab for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) including cases of secondary central nervous system (CNS) involvement and transformed follicular lymphoma (FL) in real-world context because of anti-tumor effect and blood-brain barrier permeability of lenalidomide. METHODS: Twenty-four patients including relapsed or refractory DLBCL (n = 21) including seven patients with secondary CNS involvement and transformed FL (n = 3) were retrospectively analyzed. RESULTS: Based on the best response, the complete response (CR) rate was 21% (5/24) and the overall response rate (ORR) was 38% (9/24). However, as all cases of transformed FL (n = 3) did not respond, all responders had DLBCL, and the CR and ORR rates of DLBCL were 24% (5/21) and 43% (9/21), respectively. The median number of treatment cycles was only two (range: 1-7) due to frequent occurrence of early progression, and 18 patients died and the cause of death was disease progression. The response rate was not significantly different among patients with and without secondary CNS involvement. The median post-treatment overall and progression-free survival were 7.3 and 1.8 months, respectively. Hematologic toxicities were common adverse events, but most hematologic toxicities were manageable. There were no serious infectious complications or treatment-related mortality. CONCLUSION: Lenalidomide plus rituximab might be a salvage therapy for relapsed or refractory DLBCL, especially in case of secondary CNS involvement. However, the addition of other agents should be considered to prolong the duration of response.

Non-Polio Enteroviruses from Acute Flaccid Paralysis Surveillance in Korea, 2012-2019.

The risk of polio importation and re-emergence persists since epidemic polio still occurs in some countries, and the resurgence of polio occurring almost 20 years after polio eradication was declared in Asia has been reported. We analyzed the results of acute flaccid paralysis (AFP) surveillance in Korea to assess the quality of AFP surveillance and understand the etiology of non-polio enterovirus (NPEV)-associated central nervous system diseases in a polio-free area. We investigated 637 AFP patients under 15 years of age whose cases were confirmed during 2012-2019 by virus isolation, real-time reverse transcription polymerase chain reaction, and VP1 gene sequencing. Among the 637 AFP cases, NPEV was detected in 213 (33.4%) patients, with the majority observed in EV-A71, with 54.9% of NPEV positives. EV-A71 has been shown to play a role as a major causative agent in most neurological diseases except for Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM), and meningitis. This study provides information on the AFP surveillance situation in Korea and highlights the polio eradication stage in the monitoring and characterization of NPEV against the outbreak of neurological infectious diseases such as polio.

Detection and Isolation of SARS-CoV-2 in Serum, Urine, and Stool Specimens of COVID-19 Patients from the Republic of Korea.

OBJECTIVES: Coronavirus Disease-19 (COVID-19) is a respiratory infection characterized by the main symptoms of pneumonia and fever. It is caused by the novel coronavirus severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), which is known to spread via respiratory droplets. We aimed to determine the rate and likelihood of SARS-CoV-2 transmission from COVID-19 patients through non-respiratory routes. METHODS: Serum, urine, and stool samples were collected from 74 hospitalized patients diagnosed with COVID-19 based on the detection of SARS-CoV-2 in respiratory samples. The SARS-CoV-2 RNA genome was extracted from each specimen and real-time reverse transcription polymerase chain reaction performed. CaCo-2 cells were inoculated with the specimens containing the SARS-COV-2 genome, and subcultured for virus isolation. After culturing, viral replication in the cell supernatant was assessed. RESULTS: Of the samples collected from 74 COVID-19 patients, SARS-CoV-2 was detected in 15 serum, urine, or stool samples. The virus detection rate in the serum, urine, and stool samples were 2.8% (9/323), 0.8% (2/247), and 10.1% (13/129), and the mean viral load was 1,210 ± 1,861, 79 ± 30, and 3,176 ± 7,208 copy/µL, respectively. However, the SARS-CoV-2 was not isolated by the culture method from the samples that tested positive for the SARS-CoV-2 gene. CONCLUSION: While the virus remained detectable in the respiratory samples of COVID-19 patients for several days after hospitalization, its detection in the serum, urine, and stool samples was intermittent. Since the virus could not be isolated from the SARS-COV-2-positive samples, the risk of viral transmission via stool and urine is expected to be low.

Pain control and early wound healing effect using sitz bath with ozonised water after haemorrhoidectomy.

OBJECTIVE: Studies have shown that ozone in an aqueous state on a scar, because of its antibacterial effect, aids wound-healing. This study aimed to compare the pain control effect, based on the time to wound healing, of using a sitz bath with ozonised water with that of using a sitz bath with ordinary tap water in patients who have had a haemorrhoidectomy. METHOD: Patients were divided into two equal-sized groups: Group O used a sitz bath with ozonised water after haemorrhoidectomy and patients in Group T used a sitz bath with ordinary tap water. Different concentrations (1ppm, 2ppm and 4ppm) of ozonized water were tested to determine their bactericidal activities. Pain levels were measured using the Visual Analogue Scale (ranging from 0-10 where 0 is 'no pain' and 10 is 'unbearable pain'), on days two, three and seven. Cohort analysis was retrospectively performed on the prospectively randomised collected data for this study. RESULTS: A total of 80 patients participated in the study. No case showed any signs of bacterial growth. On postoperative day seven, patients in Group O showed a significantly lower pain level than those in Group T (1.35±0.48 versus 2.40±0.9; p<0.001). The time needed for anus scars to be completely healed was significantly shorter for Group O than that for Group T (2.75±0.63 weeks versus 3.85±0.80 weeks; p<0.001). CONCLUSION: The results of this study showed that using a sitz bath with ozonised water reduced pain and accelerated healing in patients who have had a haemorrhoidectomy.

Long-term compensation of renal function after donor nephrectomy.

Background: Living donors are the major source of kidneys in countries with a shortage of deceased donors. Kidney donation after careful donor selection is generally accepted as a safe procedure, but the physiologic consequences after donor nephrectomy are not fully verified. In this study we retrospectively reviewed the renal function of the residual kidney in living donors. Methods: Post-nephrectomy laboratory data of 1,175 living donors (60.7%) from 1,933 living donors who received uninephrectomy from January 1999 to December 2017 at Yonsei University, Severance Hospital, Korea were retrospectively collected. Post-nephrectomy renal function was monitored by the relative ratio of estimated glomerular filtration rate (e-GFR; pre-nephrectomy e-GFR ratio vs. post-nephrectomy e-GFR) that was calculated by the Modification of Diet in Renal Disease formula. Results: During 36.3±37.6 months of mean follow-up, two cases (0.17%, 2/1,175) of renal failure developed. The mean e-GFR decreased to 64.3±14.2 mL/min/1.73 m2 immediately after nephrectomy from 99.2±19.9 mL/min/1.73 m2 of the pre-nephrectomy e-GFR. Early decrement of e-GFR was prominent in male and obese donors (body mass index >25 kg/m2, P<0.05). The e-GFR ratio increased according to post-nephrectomy duration, and the mean increment degree of e-GFR ratio after nephrectomy calculated by linear regression analysis was 1.94% per year. Unlike the early decrement of e-GFR ratio after nephrectomy, donor factors such as degree of obesity and donor sex did not affect the late increment of e-GFR ratio after nephrectomy (P>0.05). Conclusions: Our data showed that long-term compensation of the renal function after nephrectomy occurs independently of preoperative donor characteristics.

Long-term comparison of physiologic anorectal changes and recurrence between transanal repair and transanal repair with posterior colporrhaphy in rectocele.

BACKGROUND: Rectocele is often associated with chronic constipation. Various surgical techniques have been described to repair rectoceles, but the results vary. The aim of this study was to compare the outcomes of transanal repair (TAR) and transanal repair with posterior colporrhaphy (TAR + PC). METHODS: While 44 patients underwent TAR, 49 patients underwent TAR + PC for surgical repair of rectocele. Patients were followed up 3 months post-surgery for anorectal physiological changes. From the entire cohort of patients who underwent the surgical repair, 22 patients who underwent TAR and 25 patients who underwent TAR + PC agreed to participate in the 3-year post-treatment check-up. RESULTS: Out of the 22 patients who underwent TAR, 3 patients (13.6%) scored more than 15 on the constipation scoring system (CSS), while 1 out of 25 patients who underwent TAR + PC scored more than 15 on the CSS 3 months post-treatment, which is considered as recurrence (p = 0.237). With 7 patients from the TAR group (31.8%) and 2 patients from the TAR + PC group (8.0%) showing recurrence of rectocele at 3-year post-treatment follow-up, this study found that TAR + PC had a much lower rate of recurrence than TAR. Furthermore, TAR + PC was found to be more effective than TAR in terms of rectal sensation, sensory threshold (p = 0.001), and early defecation urge (p = 0.003). CONCLUSIONS: TAR + PC can help alleviate some symptoms by restoring the rectal sensation and improving the rectovaginal septum. It can be inferred that the addition of a simple treatment method can lead to a lower rate of recurrence.

Reduced expression of pyruvate kinase in kidney proximal tubule cells is a potential mechanism of pravastatin altered glucose metabolism.

Recent studies have reported that statins are associated with increased incidence of diabetes. Although several mechanisms have been proposed, the role of the kidney's glucose metabolism upon statin treatment is still unclear. Thus, we investigated the role of pravastatin in gluconeogenesis and glycolysis. HK-2 and HepG2 cells were treated with pravastatin and cultured under either high- or normal-cholesterol conditions. In HK-2 cells treated with pravastatin under both high- and normal-cholesterol conditions, the protein expression of only pyruvate kinase isozymes L/R (PKLR) decreased in a dose-dependent manner, while the protein expression of other glucose metabolism related enzymes remained unchanged. Within the in vivo experiment, male C57BL/6 mice were fed either pravastatin-treated normal-fat diets for 2 or 4 weeks or pravastatin-treated high-fat diets for 16 weeks. Protein expression of PKLR in the kidneys from mice that consumed pravastatin-treated high-fat diets decreased significantly compared to the controls. Upon the treatments of pravastatin, only the PKLR expression decreased in lean mice. Furthermore, PKLR activity decreased significantly in the kidney after pravastatin treatments. However, there was no change in enzyme activity in the liver, suggesting that pravastatin decreased PKLR activity only in the kidney. This change may be associated with the hyperglycemic effect of statins.