The potential role of formononetin in cancer treatment: An updated review.

Currently, cancer is one of the main research topics, due to its high incidence and drug resistance to existing anti-cancer drugs. Formononetin, a natural product with phytoestrogenic properties and diverse biological functions, has attracted the attention of researchers working on anticancer drugs. Formononetin emerges as an intriguing bioactive substance compared to other isoflavones as it exhibits potent chemotherapeutic activity with less toxicity. Formononetin effectively plays a significant role in inhibiting cell proliferation, invasion, and metastatic abilities of cancer cells by targeting major signaling pathways at the junction of interconnected pathways. It also induces apoptosis and cell cycle arrest by modulating mediator proteins. It causes upregulation of key factors such as p-AKT, p38, p21, and p53 and downregulation of NF-κB. Furthermore, formononetin regulates the neoplastic microenvironment by inactivating the ERK1/2 pathway and lamin A/C signaling and has been reported to inactivate JAK/STAT, PKB or AKT, and mitogen-activated protein kinase pathways and to suppress cell migration, invasion, and angiogenesis in human cancer cells. To assist researchers in further exploring formononetin as a potential anticancer therapeutic candidate, this review focuses on both in vitro and in vivo proof of concept studies, patents, and clinical trials pertinent to formononetin's anticancer properties. Overall, this review discusses formononetin from a comprehensive perspective to highlight its potential benefits as an anticancer agent.

The role of NF-κB in breast cancer initiation, growth, metastasis, and resistance to chemotherapy.

Breast cancer (BC) is the second most fatal disease and is the prime cause of cancer allied female deaths. BC is caused by aberrant tumor suppressor genes and oncogenes regulated by transcription factors (TFs) like NF-κB. NF-κB is a pro-inflammatory TF that crucially alters the expressions of various genes associated with inflammation, cell progression, metastasis, and apoptosis and modulates a network of genes that underlie tumorigenesis. Herein, we focus on NF-κB signaling pathways, its regulators, and the rationale for targeting NF-κB. This review also includes TFs that maintain NF-κB crosstalk and their roles in promoting angiogenesis and metastasis. In addition, we discuss the importance of combination therapies, resistance to treatment, and potential novel therapeutic strategies including nanomedicine that targets NF-κB.

Carbohydrate antigen 19-9 plus carcinoembryonic antigen for prognosis in colorectal cancer: An observational study.

AIM: Carcinoembryonic antigen (CEA) is a primary prognostic marker and can detect colorectal cancer (CRC) recurrence; however, it has low sensitivity. Carbohydrate antigen 19-9 (CA 19-9) can be used as a supplemental tumour marker along with CEA. The purpose of this study was to determine whether preoperative CA 19-9 added to CEA helped predict long-term prognosis and whether follow-up CA 19-9 added to CEA had additional benefits in diagnosing the recurrence of CRC. METHOD: We retrospectively assessed patients who underwent surgery for primary CRC between January 2004 and December 2015 at Seoul National University Hospital. Data on demographics, preoperative and follow-up CEA and CA 19-9 levels, recurrence and survival were obtained and analysed with respect to tumour marker levels to ascertain their prognostic and diagnostic values. RESULTS: A total of 4972 and 1530 patients were included to analyse preoperative and follow-up tumour marker levels, respectively. The 5-year relapse-free survival rates were 72.2% ± 0.8%, 52.5% ± 2.2%, 55.5% ± 3.2% and 32.1% ± 2.3% in the normal CEA and CA 19-9, high CEA, high CA 19-9, and high CEA and high CA 19-9 groups, respectively (all P < 0.001). Patients whose elevated CEA or CA 19-9 levels reduced to normal levels had better survival outcomes than those with postoperatively elevated levels. Elevated follow-up CA 19-9 and CEA levels were related to higher incidences of distant metastasis (CA 19-9, 14.0% vs. 23.1%, P = 0.004; CEA, 12.6% vs. 30.1%, P < 0.001) but not to local recurrence. Combined follow-up CEA and CA 19-9 increased the sensitivity for recurrence to 31.4%, with a 5% difference from the sensitivity of CEA alone. In the subgroup with high preoperative CA 19-9 levels, sensitivity increased by 18.2% overall. CONCLUSION: CA 19-9 is a valuable prognostic and diagnostic marker for CRC when used adjunctively with CEA and can be a supplementary marker with CEA to improve sensitivity, especially with elevated preoperative CA 19-9.

Clinical Outcomes in Older Patients Aged over 75 Years Who Underwent Early Surgical Treatment for Pyogenic Vertebral Osteomyelitis.

Older patients with pyogenic vertebral osteomyelitis (PVO) usually have more medical comorbidities compared with younger patients, and present with advanced infections from different causative organisms. To aid surgical decision-making, we compared surgical outcomes of older patients with PVO to those who underwent nonoperative treatment. We identified the risk factors for adverse post-operative outcomes, and analyzed the clinical risks from further spinal instrumentation. This retrospective comparative study included 439 patients aged ≥75 years with PVO. Multivariable analysis was performed to compare treatment outcomes among three groups: 194, 130, and 115 patients in the non-operative, non-instrumented, and instrumented groups, respectively. The risk factors for adverse outcomes after surgical treatment were evaluated using a logistic regression model, and the estimates of the multivariable models were internally validated using bootstrap samples. Recurrence and mortality of these patients were closely associated with neurologic deficits, and increased surgical invasiveness, resulting from additional spinal instrumentation, did not increase the risk of recurrence or mortality. We propose that surgical treatment for these patients should focus on improving neurologic deficits through immediate and sufficient removal of abscesses. Spinal instrumentation can be performed if indicated, within reasonable clinical risk.

Plant-derived angiogenin fusion protein's cytoprotective effect on trabecular meshwork damage induced by Benzalkonium chloride in mice.

BACKGROUND: Benzalkonium chloride (BAK), commonly used in glaucoma treatment, is an eye drop preservative with dose-dependent toxicity. Previous studies have observed the multi-functional benefits of angiogenin (ANG) against glaucoma. In our study, we evaluated ANG's cytoprotective effect on the trabecular meshwork (TM) damage induced by BAK. Additionally, we developed a plant-derived ANG fusion protein and evaluated its effect on TM structure and function. METHODS: We synthesized plant-derived ANG (ANG-FcK) by fuzing immunoglobulin G's Fc region and KDEL to conventional recombinant human ANG (Rh-ANG) purified from transgenic tobacco plants. We established a mouse model using BAK to look for degenerative changes in the TM, and to evaluate the protective effects of ANG-FcK and Rh-ANG. Intraocular pressure (IOP) was measured for 4 weeks and ultrastructural changes, deposition of fluorescent microbeads, type I and IV collagen, fibronectin, laminin and α-SMA expression were analyzed after the mice were euthanized. RESULTS: TM structural and functional degeneration were induced by 0.1% BAK instillation in mice. ANG co-treatment preserved TM outflow function, which we measured using IOP and a microbead tracer. ANG prevented phenotypic and ultrastructure changes, and that protective effect might be related to the anti-fibrosis mechanism. We observed a similar cytoprotective effect in the BAK-induced degenerative TM mouse model, suggesting that plant-derived ANG-FcK could be a promising glaucoma treatment.

What Is the Effect of the Ulnar-Plus Variance on the Outcomes of Arthroscopic Repair of the Peripheral Ulnar-Side Triangular Fibrocartilage Complex Tear?

PURPOSE: To compare the outcomes of arthroscopic repair of peripheral ulnar-side triangular fibrocartilage complex (TFCC) tears between patients with and without ulnar-plus variance (UPV) and to identify factors associated with index surgery failure in these patients. METHODS: We retrospectively analyzed 50 consecutive patients who underwent arthroscopic repair of peripheral ulnar-side TFCC tears from June 2014 to February 2018. We selected patients who were aged at least 18 years and underwent arthroscopic repair of peripheral ulnar-side TFCC tears. We excluded those with a fractured or dislocated wrist, ulnar impaction syndrome, degenerative or inflammatory arthritis of the wrist, or neurologic conditions that affect upper-extremity function, as well as those who received less than 12 months' follow-up. We evaluated the patients with a visual analog scale for pain in 3 domains (overall, with hard work, and at rest), the Patient-rated Wrist Evaluation, range of motion, and grip strength. Clinical outcomes and arthroscopic findings were compared between patients with and without UPV (UPV group and non-UPV group, respectively). We calculated the relative risk and 95% confidence interval for younger age (<30 years), sex, UPV, and coexisting degenerative central TFCC tear (type 2 tear) to determine the risk factors for arthroscopic repair failure. RESULTS: No significant differences were noted between the 2 groups regarding visual analog scale pain and Patient-rated Wrist Evaluation scores and rates of excellent or improved outcomes (P > .05). Arthroscopic repair failure was found in 4 patients. A coexisting type 2 TFCC tear was the only significant risk factor (relative risk, 49.5; 95% confidence interval, 2.94-83.96; P = .007) for arthroscopic repair failure. CONCLUSIONS: UPV did not significantly affect the outcomes of arthroscopic repair of peripheral ulnar-side TFCC tears. However, coexisting type 2 TFCC tears significantly increased the risk of index surgery failure in these patients. LEVEL OF EVIDENCE: Level IV, prognostic study.

Analysis of Cervical Spine Alignment and its Relationship with Other Spinopelvic Parameters After Laminoplasty in Patients with Degenerative Cervical Myelopathy.

For patients with kyphosis of the cervical spine, laminoplasty is usually incapable of improving neurological symptoms as it worsens kyphotic alignment. Thus, laminoplasty is not recommended in the presence of kyphotic alignment. Nevertheless, laminoplasty may be selected for myelopathy due to multiple-segment intervertebral disc herniation or ossification of posterior longitudinal ligament despite kyphotic alignment. This study examined whether cervical alignment influences surgical outcomes. Cervical alignment before the surgery was classified into lordosis and non-lordosis, and the non-lordosis group was subclassified into reducible and non-reducible groups to determine the change in cervical alignment before and after the surgery and to analyze its relationship with spinopelvic parameters. The lordosis group showed an increase in upper cervical motion (C0-2 Range of Motion (ROM), C0-2ROM/C0-7ROM) after surgery, while the non-lordosis group exhibited a decrease in C2-7ROM and C0-7ROM. The C0-2ROM was maintained without any reduction in the reducible group, while there was no significant change in cervical alignment and ROM of the non-reducible group. None of these changes showed significant association with the spinopelvic parameters of other sites. However, having a non-reducible type non-lordosis is not a proper indication for laminoplasty, as it does not change the alignment after surgery. Therefore, cervical alignment and reducibility should be identified before surgery.

Sagittal alignment based on inflection point and its differences according to age groups.

PURPOSE: We have always used the standard anatomical landmark vertebrae to measure the sagittal alignment. Instead, scoliosis has been evaluated by the end vertebrae in the coronal plane. There have been clinical studies to investigate sagittal alignment on the end vertebrae of inflection points (IPs). The purpose is to determine sagittal alignment based on IPs and to elucidate the changes while considering age groups. METHODS: We identified the most titled vertebrae in the sagittal plane to define the end vertebrae of S1, thoracolumbar and cervicothoracic IPs and to measure the Cobb angles of sacral slope, functional lumbar, thoracic, cervical segment between them, and the McGregor's line, and the IP distances from the C2 plumb line to the point bisecting the upper end plate of the IPs, in addition to S1. RESULTS: The most common thoracolumbar and cervicothoracic IPs were L2 and T1, respectively. However, the next most common cervicothoracic IP changed from T2 in the youngest to C7 in the oldest age group. The sagittal angles decreased at the sacral slope and functional lumbar segment but not the functional thoracic segment and functional cervical segment. Similarly, the distance increased at the C2 sagittal vertical axis (SVA) distance to S1 and thoracolumbar IP distance but not at the cervicothoracic IP distance. There was no difference in the pelvic incidence among age groups. CONCLUSION: The sagittal Cobb angles based on the IPs decreased at the sacral slope and functional lumbar segment in the older adults. Consequently, the C2 SVA distance to S1 and thoracolumbar IP distance increased.

Expression and In Vitro Function of Anti-Breast Cancer Llama-Based Single Domain Antibody VHH Expressed in Tobacco Plants.

Overexpression of human epidermal growth factor receptor type 2 (HER2) is considered as a prognostic factor of breast cancer, which is positively associated with recurrence when cancer metastasizes to the lymph nodes. Here, we expressed the single variable domain on a heavy chain (VHH) form of anti-HER2 camelid single domain antibody in tobacco plants and compared its in vitro anticancer activities with the anti-HER2 full size antibody. The gene expression cassette containing anti-HER2 camelid single domain antibody VHH fused to human IgG Fc region with KDEL endoplasmic reticulum (ER) (VHH-FcK) was transferred into the tobacco plant via the Agrobacterium-mediated transformation. The transformants were screened with polymerase chain reaction and Western blot analyses. Enzyme-linked immunosorbent assay (ELISA) confirmed the binding of the purified anti-HER2 VHH-FcK to the HER2-positive breast cancer cell line, SK-BR-3. Migration assay results confirmed anticancer activity of the plant-derived anticancer camelid single chain antibody. Taken together, we confirmed the possibility of using anti-HER2 VHH-FcK as a therapeutic anticancer agent, which can be expressed and assembled and purified from a plant expression system as an alternative antibody production system.

Natural History of Gastric Cancer: Observational Study of Gastric Cancer Patients Not Treated During Follow-Up.

BACKGROUND: Understanding the natural progression of untreated gastric cancer is critical for determining the disease prognosis as well as treatment options and timing. The aim of this study is to analyze the natural history of gastric cancer. PATIENTS AND METHODS: We included patients with gastric cancer who had not received any treatment and were staged using endoscopy/endoscopic ultrasonography and computed tomography on at least two follow-up visits during intervals of nontreatment. Tumor volumes were also measured in addition to the staging. Survival of each stage at diagnosis was also analyzed. RESULTS: A total of 101 patients were included. The mean follow-up period was 35.1 ± 34.4 months. The gastric cancer doubling time was 11.8 months for T1 and 6.2 months for T4. The progression time from early gastric cancer to advanced gastric cancer was 34 months. It decreased as the stages advanced: from 34 months between tumor-nodes-metastasis stage I and II to 1.8 months between stage III and IV. No variable was identified as a risk factor for cancer progression. The 5-year survival rates of untreated patients were 46.2% in stage I and 0% in stage II, stage III, and stage IV. CONCLUSIONS: The progression and doubling times of gastric cancer shorten as the stages advance. Objective data reported in this study can be a critical factor in determining treatment timing and screening interval.

Outcomes of additional instrumentation in elderly patients with pyogenic vertebral osteomyelitis and previous spinal instrumentation.

BACKGROUND CONTEXT: In patients with pyogenic vertebral osteomyelitis (PVO) and previous instrumentation requiring surgical treatment, a decision must be made between a less-invasive noninstrumented surgery, including retaining the previous instrumentation, or a more invasive additional instrumented surgery involving the complete removal of the infected tissue and firm restabilization. PURPOSE: To evaluate the clinical outcomes of using additional instrumentation in patients with PVO and previous instrumentation and determine the significant risk factors related to recurrent infection. STUDY DESIGN/SETTING: Retrospective cohort study (case control study). PATIENT SAMPLE: PVO patients with previous instrumentation. OUTCOME MEASURES: Recurrence of PVO and mortality. METHODS: Patients were divided into two groups (instrumented or noninstrumented) according to the presence or absence of additional instrumentation. The baseline characteristics, infection profile, and treatment outcomes were compared between the two groups, and a multivariate logistic regression analysis was performed to identify the risk factors for infection recurrence. RESULTS: A total of 187 postoperative patients with PVO and previous spinal instrumentation were included. There were no significant differences in the baseline characteristics except the presence of a titanium cage. Surgery for additional instrumentation in patients with PVO and previous instrumentation showed similar rates of infection recurrence and mortality compared with noninstrumented surgery despite a larger number of involved vertebral levels and greater incidence of epidural abscesses. However, instrumented patients with PVO and previous instrumentation who experienced infection recurrence had worse clinical outcomes than those of the noninstrumented patients with PVO. Severe medical comorbidities, the presence of a psoas abscess, and methicillin-resistant Staphylococcus aureus infection were associated with a higher risk of infection recurrence. CONCLUSIONS: Surgery for additional instrumentation in patients with PVO and previous instrumentation showed similar rates of infection recurrence and mortality to those who underwent noninstrumented surgery despite a larger number of involved vertebral levels and an increased frequency of epidural abscesses.

Optimal Nitrogen Incorporation in Nickel Silicide for Thermally Stable Contact Formation.

Nickel silicide (NiSi) is commonly used as a contact material for metal junctions but the poor thermal instability of NiSi above 600 °C has limited the further scaling down of devices and the implementation of novel schemes, such as monolithic 3-dimensional integration. This paper suggests a process to improve the thermal stability of NiSi through nitrogen incorporation during the silicidation process. The optimal level of nitrogen incorporation in NiSi reduced the nickel diffusion rate and enhanced the thermal stability by preventing the formation of a nickel disilicide phase. On the other hand, a higher level of N incorporation led to Ni3N formation, which impeded the complete transformation to NiSi. Therefore, it is essential to incorporate the optimal content of N. In this study, NiSi with 3.9% N incorporation showed superior electrical characteristics, such as the sheet resistance, junction leakage, and stable Schottky barrier height, even after high-temperature post silicidation annealing at 600 °C for 30 min.

Production of Recombinant Anti-Cancer Vaccines in Plants.

Plant expression systems have been developed to produce anti-cancer vaccines. Plants have several advantages as bioreactors for the production of subunit vaccines: they are considered safe, and may be used to produce recombinant proteins at low production cost. However, several technical issues hinder large-scale production of anti-cancer vaccines in plants. The present review covers design strategies to enhance the immunogenicity and therapeutic potency of anti-cancer vaccines, methods to increase vaccine-expressing plant biomass, and challenges facing the production of anti-cancer vaccines in plants. Specifically, the issues such as low expression levels and plant-specific glycosylation are described, along with their potential solutions.

Right iliac arterial aneurysm in a 4-year-old girl who does not have a right external iliac artery.

Pediatric arterial aneurysm is rare disease. Among them, idiopathic-congenital arterial aneurysm is extremely rare. This is a case report of right common iliac artery idiopathic aneurysm with absence of right external iliac artery. A 4-year-old girl who had been complaining of intermittent abdominal pain since 2 years prior presented with a right lower abdominal mass that had been palpable since 6 months prior. Abdominal CT revealed a 5.2 cm × 4.5 cm × 5.1 cm, right-sided, partially thrombosed, saccular, iliac artery aneurysm. She underwent to operation, aneurismal resection. A pathological examination confirmed that it was a true aneurysm, considering that all layers of the vascular wall were stretched with no deficit. The patient was discharged 3 days after the surgery without any complication. Five months passed since the surgery, and the patient is doing well without any abdominal or leg pain.

Preoperative Angiographic Criteria for Predicting Free-Flap Transfer Outcomes in Patients With Lower-Extremity Peripheral Arterial Disease.

Patients scheduled for microsurgical reconstruction of the lower leg often receive preoperative assessment of recipient vessels using angiography. However, no clear standard is available for evaluating angiographic results to predict free-flap survival outcomes. We developed angiographic criteria for predicting surgical outcome in patients with lower-extremity peripheral arterial disease based on abnormality of the anterior tibial and posterior tibial arteries. We applied the criteria to a small number of patients scheduled for microsurgical reconstruction of the lower leg. Angiographies with arterial abnormalities were classified into 3 groups: favorable free-flap survival, compromised free-flap survival, and postsurgical pedal ischemia. The study enrolled 50 patients between 2005 and 2013. In 42% of patients, arterial abnormalities were observed by angiography. Age >65 years was the strongest risk factor for development of lower-leg arterial abnormality ( P < .001). The anterior tibial and peroneal arteries were significantly more stenotic than other vessels. In the favorable free-flap survival and compromised free-flap survival groups, free-flap transfers were attempted in 7 patients but intraoperatively abandoned in 2 patients, with postoperative failure in 1 patient. In the postsurgical pedal ischemia group, free-flap transfers were attempted in 10 patients but intraoperatively abandoned in 6 patients, with postoperative failure in 3.

Postoperative Quality of Life after Total Gastrectomy Compared with Partial Gastrectomy: Longitudinal Evaluation by European Organization for Research and Treatment of Cancer-OG25 and STO22.

PURPOSE: The European Organization for Research and Treatment of Cancer quality-of-life questionnaire-OG25 was developed to evaluate the quality of life in patients with stomach and esophageal cancer. The following are included in the OG25 but not in the STO22: odynophagia, choked when swallowing, weight loss, trouble eating with others, trouble swallowing saliva, trouble talking, and trouble with coughing. In this study, we evaluated the quality of life of gastrectomized patients using both, the OG25 and the STO22. MATERIALS AND METHODS: A total of 138 patients with partial gastrectomy (PG) (distal gastrectomy=91; pylorus-preserving gastrectomy= 47) and 44 patients with total gastrectomy (TG) were prospectively evaluated. Body weight and scores from the OG25 and STO22 were evaluated preoperatively and at 3 weeks, 3 months, and 6 months after surgery. RESULTS: Patients with TG had significant weight loss compared to patients with PG. At 3 months, TG was associated with worse scores for dysphagia, eating, odynophagia, trouble eating with others, trouble with taste, and weight loss on the OG25. TG was also associated with dysphagia, eating restrictions, and anxiety on the STO22. The OG25 helped differentiate between the groups with respect to weight loss, odynophagia, choked when swallowing, and trouble eating with others. The OG25 scores changed over time and were significantly different. CONCLUSIONS: The OG25 is a more sensitive and useful scale than the STO22 for evaluating the quality of life of gastrectomized patients, especially those with total gastrectomy.

Forehead Osteoma Excision by Anterior Hairline Incision with Subcutaneous Dissection.

Forehead osteomas are benign but can pose aesthetic and functional problems. These osteomas are resected via bicoronal or endoscopic approach. However, large osteomas cannot be removed via endoscopic approach, and bicoronal approach can result in damage to the supraorbital nerve with resultant numbness in the forehead. We present a new approach to resection of forehead osteomas, with access provided by an anterior hairline incision and subcutaneous dissection. Three patients underwent resection of the forehead osteoma through an anterior hairline incision. The dissection was carried in the subcutaneous plane, and the frontalis muscle and periosteum were divided parallel to the course of supraorbital nerve. The resulting bony defect was re-contoured using Medpor®. All three patients recovered without any postoperative infection or complication and symptoms. Scalp sensory was preserved. Aesthetic outcomes were satisfactory. Patients remain free of recurrence for 12 months of follow up. The anterior hair line approach with subcutaneous dissection is an effective method for removal of forehead osteoma, since it offers broad visualization and hides the scar in the hairline. In addition, the dissection in the subcutaneous plane avoids inadvertent injury to the deep nerve branches and helps to maintains scalp sensation.

Production of monoclonal antibodies in plants for cancer immunotherapy.

Plants are considered as an alternative platform for recombinant monoclonal antibody (mAb) production due to the improvement and diversification of transgenic techniques. The diversity of plant species offers a multitude of possibilities for the valorization of genetic resources. Moreover, plants can be propagated indefinitely, providing cheap biomass production on a large scale in controlled conditions. Thus, recent studies have shown the successful development of plant systems for the production of mAbs for cancer immunotherapy. However, their several limitations have to be resolved for efficient antibody production in plants.

Analysis of the risk factors for development of post-operative extradural hematoma after intracranial surgery.

OBJECTIVE: Post-operative extradural hematoma (EDH) is a relatively common complication in patients undergoing intracranial operations. The risk factors associated with the occurrence of EDH are not well described in the literature. The objective of this study was to identify the risk factors and the incidence of post-operative EDH adjacent and regional to the craniotomy or the craniectomy site. METHOD: This was a retrospective study of 24 (2.6% of total) patients who underwent extradural hematoma evacuation after primary intracranial supratentorial surgery between January 2005 and December 2011. During this period, 941 intracranial operations were performed. The control group (72 patients) was selected on the basis of having undergone the same pre-operative diagnosis and treatment within 2 months of the operations for the 24 hematoma patients. The Glasgow Coma Scale score and operation character (emergency or elective) of the hematoma and control group were individually matched to minimize pre-operative conditional bias. The ages of both groups were individually matched with similar ages within 10 years of each other to minimize age bias. RESULT: Univariate analysis showed that the significant pre-operative and intra-operative factors associated with post-operative EDH were an intra-operative blood loss of greater than 800 mL (p=0.007), maximal craniotomy length of greater than or equal to 100 mm (p=0.001), and craniotomy area of greater than or equal to 71.53 cm2 (p=0.018). In multivariate analysis, intra-operative blood loss exceeding 800 mL (median of total patients) placed a patient at significantly increased risk for post-operative EDH. CONCLUSION: The data did not examine established risk factors for post-operative hematoma, such as thrombocytopenia, anti-coagulant and anti-platelet therapy, and a history of heavy alcohol consumption and/or tobacco intake. Recognizing the limitations of the study, large intra-operative blood loss and wide craniotomy area are implicated with an increased risk of post-operative EDH after intracranial surgery.