Difference in prognostic impact of lateral pelvic lymph node metastasis between pre- and post-neoadjuvant chemoradiotherapy in rectal cancer patients

Purpose@#The prognostic significance and treatment of lateral pelvic lymph node metastasis (mLPLN) in rectal cancer patients receiving neoadjuvant chemoradiotherapy (nCRT) are not well understood. In this study, we evaluated the impact of mLPLN identified in imaging modality on outcomes. @*Methods@#Between January 2008 and December 2016, 1,535 patients who underwent radical resection following nCRT were identified. The association between mLPLN and disease-free survival (DFS), overall survival (OS), local recurrencefree survival (LRFS), and pelvic recurrence-free survival (PRFS) was analyzed, along with risk factors associated with OS and DFS. @*Results@#Overall, 329 (21.4%) of the 1,535 patients experienced disease recurrence; 71 (4.6%) had local recurrence, 25 (1.6%) had pelvic recurrence, and 312 (20.3%) had distant recurrence. The pre- and post-nCRT mLPLN (–) groups had better DFS, LRFS, PRFS, and OS than the (+) groups. LPLN sampling (LPLNs) was implemented in 24.0% of the pre-nCRT mLPLN (+) group and in 28.8% of the post-nCRT mLPLN (+) group. There was no significant difference in OS and LRFS between LPLNs group and no LPLNs group in pre- and post-nCRT mLPLN (+) groups. Pre-nCRT mLPLN was associated with poor OS (hazard ratio [HR], 1.43; P = 0.009) and post-nCRT mLPLN was associated with poor DFS (HR, 1.49; P = 0.002). @*Conclusion@#Pre- and post-nCRT mLPLN (+) have different prognostic effects. Post-nCRT mLPLN appears to be more important for disease control. However, pre-nCRT mLPLN should not be disregarded when devising a treatment strategy since it is an independent risk factor for OS.

Prognostic significance of lymph node yield on oncologic outcomes according to tumor response after preoperative chemoradiotherapy in rectal cancer patients

Purpose@#This study aimed to evaluate the predictive value of lymph node yield (LNY) for survival outcomes according to tumor response after preoperative chemoradiotherapy (PCRT) in patients with rectal cancer. @*Methods@#This study was a retrospective study conducted in a tertiary center. A total of 1,240 patients with clinical stage II or III rectal cancer who underwent curative resection after PCRT between 2007 and 2016 were included. Patients were categorized into the good response group (tumor regression grade [TRG], 0–1) or poor response group (TRG, 2–3). Propensity score matching was performed for age, sex, and pathologic stage between LNY of ≥12 and LNY of <12 within tumor response group. The primary outcome was 5-year disease-free survival (DFS) and overall survival (OS). @*Results@#LNY and positive lymph nodes were inversely correlated with TRG. In good responders, 5-year DFS and 5-year OS of patients with LNY of <12 were better than those with LNY of ≥12, but there was no statistical significance. In poor responders, the LNY of <12 group had worse survival outcomes than the LNY of ≥12 group, but there was also no statistical significance. LNY of ≥12 was not associated with DFS and OS in multivariate analysis. @*Conclusion@#LNY of <12 showed contrasting outcomes between the good and poor responders in 5-year DFS and OS. LNY of 12 may not imply adequate oncologic surgery or proper staging in rectal cancer patients treated by PCRT. Furthermore, a decrease in LNY should be comprehended differently according to tumor response.

Balancing Bleeding Risk and Thromboembolic Complications in Elderly Chronic Subdural Hematoma Patients Undergoing Burr Hole Trephination : A Multicenter Retrospective Cohort Study and Literature Review

Objective@#: Chronic subdural hematoma (CSDH) patients using antithrombotic agents (AT) at high risk for cardiovascular disease are increasing. The authors aimed to analyze the factors influencing outcome by targeting patients using AT and to establish a desirable treatment strategy. @*Methods@#: A retrospective analysis was performed on data from 462 patients who underwent burr hole trephination (BHT) surgery for CSDH at five hospitals from March 2010 to June 2021. Outcomes included incidence of postoperative acute bleeding, recurrence rate, and morbidity or mortality rate. Patients were divided into the following four groups based on their history of AT use : no AT. Only antiplatelet agents (AP), only anticoagulants (AC), both of AP and AC. In addition, a concurrent literature review was conducted alongside our cohort study. @*Results@#: Of 462 patients, 119 (119/462, 25.76%) were using AT. AP prescription did not significantly delay surgery (p=0.318), but AC prescription led to a significant increase in the time interval from admission to operation (p=0.048). After BHT, AP or AC intake significantly increased the period required for an in-dwelling drain (p=0.026 and p=0.037). The use of AC was significantly related to acute bleeding (p=0.044), while the use of AP was not (p=0.808). Use of AP or AC had no significant effect on CSDH recurrence (p=0.517 and p=1.000) or reoperation (p=0.924 and p=1.000). Morbidity was not statistically correlated with use of either AP or AC (p=0.795 and p=0.557, respectively), and there was no significant correlation with mortality for use of these medications (p=0.470 and p=1.000). @*Conclusion@#: Elderly CSDH patients may benefit from maintenance of AT therapy during BHT due to reduced thromboembolic risk. However, the use of AC necessitates individualized due to potential postoperative bleeding. Careful post-operative monitoring could mitigate prognosis and recurrence impacts.

External Validation of the eCura System for Undifferentiated-Type Early Gastric Cancer with Noncurative Endoscopic Resection

Background/Aims@#The eCura system, a scoring model for stratifying the lymph node metastasis risk after noncurative endoscopic resection for early gastric cancer (EGC), has been internally validated, primarily for differentiated-type EGC. We aimed to externally validate this model for undifferentiated-type EGC. @*Methods@#This multicenter, retrospective cohort study included 634 patients who underwent additional surgery (radical surgery group, n=270) or were followed up without additional treatment (no additional treatment group, n=364) after noncurative endoscopic resection for undifferentiated-type EGC between 2005 and 2015. The lymph node metastasis and survival rates were compared according to the risk categories. @*Results@#For the radical surgery group, the lymph node metastasis rates were 2.6%, 10.9%, and 14.8% for the low-, intermediate-, and high-risk eCura categories, respectively (p for trend=0.003). For the low-, intermediate-, and high-risk categories in the no additional treatment group, the overall survival (92.7%, 68.9%, and 80.0% at 5 years, respectively, p<0.001) and cancer-specific survival rates (99.7%, 94.7%, and 80.0% at 5 years, respectively, p<0.001) differed significantly. In the multivariate analysis, the hazard ratios (95% confidence interval) in the no additional treatment group relative to the radical surgery group were 3.18 (1.41 to 7.17; p=0.005) for overall mortality and 2.60 (0.46 to 14.66; p=0.280) for cancer-specific mortality in the intermediate-tohigh risk category. No such differences were noted in the low-risk category. @*Conclusions@#The eCura system can be applied to undifferentiated-type EGC. Close follow-up without additional treatment might be considered for low-risk patients, while additional surgery is recommended for intermediate- and high-risk patients.

Mitochondrial Ribosomal Protein L14 Promotes Cell Growth and Invasion by Modulating Reactive Oxygen Species in Thyroid Cancer

Objectives@#. The mitochondrial ribosomal protein L14 (MRPL14) is encoded by a nuclear gene and participates in mitochondrial protein translation. In this study, we aimed to investigate the role of MRPL14 in thyroid cancer. @*Methods@#. We investigated the association between MRPL14 expression and clinicopathological features using The Cancer Genome Atlas (TCGA) and Chungnam National University Hospital (CNUH) databases. Functional studies of MRPL14, including proliferation, migration, invasion, mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production, were performed in papillary thyroid cancer (PTC) cell lines (B-CPAP and KTC-1). @*Results@#. Based on the TCGA dataset, PTC tissues lost mitochondrial integrity and showed dysregulated expression of overall mitoribosomal proteins (MRPs) compared with normal thyroid tissues. Of 78 MRPs, MRPL14 was highly expressed in thyroid cancer tissues. MRPL14 overexpression was significantly associated with advanced tumor stage, extrathyroidal extension, and lymph node metastasis. MRPL14 increased cell proliferation of thyroid cancer and promoted cell migration via epithelial-mesenchymal transition-related proteins. Moreover, MRPL14 knockdown reduced the expression of oxidative phosphorylation complex IV (MTCO1) and increased the accumulation of ROS. Cotreatment with a ROS scavenger restored cell proliferation and migration, which had been reduced by MRPL14 knockdown, implying that ROS functions as a key regulator of the oncogenic effects of MRPL14 in thyroid cancer cells. @*Conclusion@#. Our findings indicate that MRPL14 may promote cell growth, migration, and invasion by modulating ROS in thyroid cancer cells.

Can clinicopathologic high-risk features in T3N0 colon cancer be reliable prognostic factors?

Purpose@#The purpose of this study was to assess the reliability and prognostic significance of the high-risk feature (HRF) in patients with T3N0 colon cancer. @*Methods@#We included 1,205 patients with pT3N0 colon cancer treated with curative radical resection between 2012 and 2016. HRF was defined as lymphovascular invasion, perineural invasion, poorly/undifferentiated histology, margin involvement, and preoperative obstruction. We investigated the relationships between the number and type of HRF and recurrence-free survival (RFS) and overall survival (OS), as well as the effect of adjuvant treatment. @*Results@#A total of 751 of the patients (62.3%) had more than 1 HRF and 515 of the patients (42.7%) underwent adjuvant treatment. Patients who had more than 2 HRFs had a significantly worse 5-year RFS and OS compared to patients who had neither HRF nor even one HRF. According to the findings of the multivariate analysis, the presence of multiple HRFs was a risk factor for a lower RFS and OS. When the quantity and type of HRF were taken into consideration in the multivariate analysis, adjuvant chemotherapy was not found to be linked with RFS or OS in patients with pT3N0 colon cancer. @*Conclusion@#In the present study, adjuvant treatment based on the current guideline of treatment indication was unable to enhance the prognosis of patients with pT3N0 colon cancer. The role of adjuvant treatment in T3N0 colon cancer must be examined with the HRF count in mind.

SARS-CoV-2 variants show temperature-dependent enhancedpolymerase activity in the upper respiratory tract and high transmissibility

With the convergent global emergence of SARS-CoV-2 variants of concern (VOC), a precise comparison study of viral fitness and transmission characteristics is necessary for the prediction of dominant VOCs and the development of suitable countermeasures. While airway temperature plays important roles in the fitness and transmissibility of respiratory tract viruses, it has not been well studied with SARS-CoV-2. Here we demonstrate that natural temperature differences between the upper (33{degrees}C) and lower (37{degrees}C) respiratory tract have profound effects on SARS-CoV-2 replication and transmission. Specifically, SARS-COV-2 variants containing the P323L or P323L/G671S mutation in the NSP12 RNA-dependent RNA polymerase (RdRp) exhibited enhanced RdRp enzymatic activity at 33{degrees}C compared to 37{degrees}C and high transmissibility in ferrets. MicroScale Thermophoresis demonstrated that the NSP12 P323L or P323L/G671S mutation stabilized the NSP12-NSP7-NSP8 complex interaction. Furthermore, reverse genetics-derived SARS-CoV-2 variants containing the NSP12 P323L or P323L/G671S mutation displayed enhanced replication at 33{degrees}C, and high transmission in ferrets. This suggests that the evolutionarily forced NSP12 P323L and P323L/G671S mutations of recent SARS-CoV-2 VOC strains are associated with increases of the RdRp complex stability and enzymatic activity, promoting the high transmissibility.

Expression of Toll-Like Receptor Messenger Ribonucleic Acid in the Distal Facial Nerve After Facial Nerve Injury / 대한이비인후과학회지

Background and Objectives@#This study aimed to evaluate whether Toll-like receptors (TLRs) messenger ribonucleic acid (mRNA) were expressed in the facial nerve after incurring a crush or an injury of the facial nerve.Materials and Method An adult Sprague-Dawley underwent a crush or injury of the unilateral facial nerve. The crush or injury was incurred by a cutting at the midpoint between the facial nerve trunk and its branch. The whisker movement of vibrissae muscle was examined 4 and 14 days after injury. Real-time polymerase chain reaction was performed for the normal facial nerve taken from the left side and the damaged nerve taken from the right side. @*Results@#On the 4th day of injury, the expression of TLR 9, 13 mRNA was significantly lower in the crush and injured groups than in the control group (p<0.05). On the 14th day of injury, the expression of TLR 2 mRNA was significantly higher in the injured group than in the control group (p<0.05). @*Conclusion@#The expressions of TLR 9, 13 mRNA in the distal facial nerve after injury in the crush and injured groups were significantly lower than that in the control group, but the expression of TLR 2 mRNA in the injured group was significantly higher. Therefore, TLRs may be involved in facial nerve damage and regeneration.

Current status of the gastric cancer screening program in Korea

In 2019, gastric cancer was one of the most common cancers in Korea. As a secondary prevention strategy for gastric cancer, the cancer screening has been provided since 1999 by the National Cancer Screening Program every 2 years for adults aged ≥40 years.Current Concepts: The participation rates for gastric cancer screening program have increased from 7.4% in 2002 to 62.9% in 2019. Until 2017, either upper gastrointestinal series or endoscopy were recommended for screening method. Since 2018, endoscopy has become the preferred screening method and 89.1% of the participants underwent endoscopy in 2019. After the introduction of the screening program, the 5-year relative survival rates have markedly improved (43.9% between 1993 and 1995 vs. 77.5% between 2015 and 2019), and the proportion of early gastric cancer detection has increased (28.6% in 1995 vs. 63.6% in 2019). The risk of death from gastric cancer decreased by 47% in participants who had undergone endoscopy screening. Additionally, the gastric cancer screening program is cost-effective, and endoscopy-associated adverse events rarely occur.Discussion and Conclusion: With the implementation of the screening program, mortality due to gastric cancer has decreased owing to early detection. After the completion of ongoing clinical trials in the general population, the primary prevention strategy of Helicobacter pylori eradication should be considered to effectively reduce the incidence of gastric cancer. Further studies are also required to provide optimal screening interval according to the presence of risk factors including H. pylori infection and presence of gastric mucosal atrophy.

Clinical Characteristics and Current Managements for Patients with Chronic Subdural Hematoma : A Retrospective Multicenter Pilot Study in the Republic of Korea

Objective@#: Chronic subdural hematoma (CSDH) is a common disease in neurosurgical departments, but optimal perioperative management guidelines have not yet been established. We aimed to assess the current clinical management and outcomes for CSDH patients and identify prognostic factors for CSDH recurrence. @*Methods@#: We enrolled a total of 293 consecutive patients with CSDH who underwent burr hole craniostomy at seven institutions in 2018. Clinical and surgery-related characteristics and surgical outcomes were analyzed. The cohort included 208 men and 85 women. @*Results@#: The median patient age was 75 years. Antithrombotic agents were prescribed to 105 patients. History of head trauma was identified in 59% of patients. Two hundred twenty-seven of 293 patients (77.5%) had unilateral hematoma and 46.1% had a homogenous hematoma type. About 70% of patients underwent surgery under general anesthesia, and 74.7% underwent a single burr hole craniostomy surgery. Recurrence requiring surgery was observed in 17 of 293 patients (5.8%), with a median of 32 days to recurrence. The postoperative complication rate was 4.1%. In multivariate analysis, factors associated with CSDH recurrence were separated hematoma type (odds ratio, 3.906; p=0.017) and patient who underwent surgery under general anesthesia had less recurrence (odds ratio, 0.277; p=0.017). @*Conclusion@#: This is the first retrospective multicenter generalized cohort pilot study in the Republic of Korea as a first step towards the development of Korean clinical practice guidelines for CSDH. The type of hematoma and anesthesia was associated with CSDH recurrence. Although the detailed surgical method differs depending on the institution, the surgical treatment of CSDH was effective. Further studies may establish appropriate management guidelines to minimize CSDH recurrence.

Surgical safety in the COVID-19 era: present and future considerations

The impacts of coronavirus disease 2019 (COVID-19) have been globally paradigm shifting in all aspects. Surgeons have experienced unprecedented changes regarding operation schedules, preparations before surgery, and the precautions needed both during and after surgery. Many medical centers simultaneously reported a decrease in their numbers of surgeries, whether they were elective or emergent, or for cancerous or benign resections. However, accumulated surgical outcomes from the last 2 years of experience presented postoperative morbidity and mortality data that were comparable to the pre-pandemic era, whether in elective or urgent settings. Although COVID-19 showed a significant association with postoperative morbidity and mortality, the majority of noninfected patients could be treated successfully with stringent mitigation protocols. Initially recommended to be avoided at the start of the pandemic, minimally invasive surgery seems to be safe and feasible according to reported surgical outcomes. Numerous sets of guidelines have now been produced from medical societies and adhering to the basic precautions has been found to be practicable. It is crucial that health care systems and surgical staff remain vigilant and attentive to the ever-changing situation in this pandemic in order to provide optimal medical support to their patients.

Neurotrauma Clinical Practice Guidelines Committee of the Korean Neurotraumatology Society: A Review of a Group That Writes and Inherits the Thoughts and Will of the Society / 대한신경손상학회지

The Neurotrauma Clinical Practice Guidelines Committee of the Korean Neurotraumatology Society (KNTS-NCPGC) is developing clinical guidelines for neurotrauma in line with the capabilities of the Korean Neurotraumatology Society, which is leading pioneering development in the field of neurosurgery. From the mid-1990s, the KNTS-NCPGC has been working to develop guidelines and disseminate evidence-based medicine, including the development of Korean guidelines for the management of severe head injuries and active participation in the Clinical Practice Guidelines Committee of the Korean Academy of Medical Sciences. The KNTS-NCPGC strives to write and inherit the will of the society through the development of clinical practice guidelines, which are one of the outcomes representing professionalism and public interest and can be expressed in terms of “trust” and “best.” In this review, the history and achievements of KNTS-NCPGC, the status of the ongoing development of guidelines, and the perspectives of the committee are covered.

A Radiological Assessment of Chronic Subdural Hematomas / 대한신경손상학회지

Chronic subdural hematoma (CSDH), which generally occurs in elderly patients, is a frequently diagnosed condition in neurosurgical departments. Computed tomography (CT) and magnetic resonance imaging (MRI) are the most preferred diagnostic modalities for CSDH assessment. With early diagnosis and adequate management, CSDH may show favorable prognosis in majority of the patients; however, recurrence after surgery can occur in a significant number of patients. The recently increasing number of CSDH studies could reveal the prognostic factors affecting CSDH recurrence. Particularly, radiological characteristics regarding the internal architecture of CSDH are considered closely associated with recurrence in surgically treated CSDH patients. In this literature review, we evaluated the various diagnostic modalities of CSDH and its radiological characteristics on CT and MRI. Furthermore, we summarized the prognostic factors of recurrence for the hematoma type based on the radiological findings.

Local SARS-CoV-2 peptide-specific Immune Responses in Convalescent and Uninfected Human Lung Tissue Models

Multi-specific and long-lasting T cell immunity have been recognized as indicators for long term protection against pathogens including the novel coronavirus SARS-CoV-2, the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovering from COVID-19 (COVID-19+) are beginning to be appreciated; but little is known about lung resident memory T cells (lung TRM) in SARS-CoV-2 infection. Here, we utilize a perfused three dimensional (3D) human lung tissue model and identify pre-existing local T cell immunity against SARS-CoV-2 proteins in lung tissues. We report ex vivo maintenance of functional multi-specific IFN-{gamma} secreting lung TRM in COVID-19+ and their induction in lung tissues of vaccinated COVID-19+. Importantly, we identify SARS-CoV-2 peptide-responding B cells and IgA+ plasma cells in lung tissues of COVID-19+ in ex vivo 3D-tissue models. Our study highlights the importance of balanced and local anti-viral immune response in the lung with persistent induction of TRM and IgA+ plasma cells for future protection against SARS-CoV-2 infection. Further, our data suggest that inclusion of multiple viral antigens in vaccine approaches may broaden the functional profile of memory T cells to combat the severity of coronavirus infection.

Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant. HighlightsO_LICT-P59 significantly inhibit B.1.1.7 variant to a similar extent as to wild type virus C_LIO_LICT-P59 showed reduced potency against the B.1.351 variant in in vitro studies C_LIO_LITherapeutic dosage of CT-P59 showed in vivo neutralizing potency against B.1.351 in ferret challenge study. C_LI

Development of spike receptor-binding domain nanoparticle as a vaccine candidate against SARS-CoV-2 infection in ferrets

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19 pandemic, enters host cells via the interaction of its Receptor-Binding Domain (RBD) of Spike protein with host Angiotensin-Converting Enzyme 2 (ACE2). Therefore, RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling H. pylori-bullfrog ferritin nanoparticles as an antigen delivery. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. 16-20 months-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD-nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD-nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss and clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious viruses in nasal washes and lungs as well as viral RNA in respiratory organs. This study demonstrates the Spike RBD-nanoparticle as an effective protein vaccine candidate against SARS-CoV-2.

Long-term Outcomes of Undifferentiated-Type Early Gastric Cancer with Positive Horizontal Margins after Endoscopic Resection

Background/Aims@#This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management. @*Methods@#From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46). @*Results@#No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality. @*Conclusions@#UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Adult Diffuse Midline Glioma: Version 2021.1

Background@#There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As ‘diffuse midline glioma’ was recently defined, and there was no international guideline, trials and guidelines of ‘diffuse intrinsic pontine glioma’ or ‘brain stem glioma’ were thoroughly reviewed first. @*Results@#The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma’s protocol is recommended. @*Conclusion@#The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Antiepileptic Drug Usage of Brain Tumor: Version 2021.1

Background@#To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. @*Results@#The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. @*Conclusion@#The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.