Effectiveness and safety of normoxic allogenic umbilical cord mesenchymal stem cells administered as adjunctive treatment in patients with severe COVID-19.

Inflammatory response in COVID-19 contributes greatly to disease severity. Mesenchymal Stem Cells (MSCs) have the potential to alleviate inflammation and reduce mortality and length of stay in COVID-19 patients. We investigated the safety and effectiveness of normoxic-allogenic umbilical cord (NA-UC)-MSCs as an adjunctive treatment in severe COVID-19 patients. A double-blind, multicentric, randomized, placebo-controlled trial involving severe COVID-19 patients was performed from January to June 2021 in three major hospitals across Java, Indonesia. Eligible participants (n = 42) were randomly assigned to two groups (1:1), namely the intervention (n = 21) and control (n = 21) groups. UC-MSCs dose was 1 × 106 /kg body weight on day D0, D3, and D6. The primary outcome was the duration of hospitalization. Meanwhile, the secondary outcomes were radiographical progression (Brixia score), respiratory and oxygenation parameters, and inflammatory markers, in addition to the safety profile of NA-UC-MSCs. NA-UC-MSCs administration did not affect the length of hospital stay of severe COVID-19 patients, nor did it improve the Brixia score or mMRC dyspnoea scale better than placebo. Nevertheless, NA-UC-MSCs led to a better recuperation in oxygenation index (120.80 ± 72.70 baseline vs. 309.63 ± 319.30 D + 22, p = 0.038) and oxygen saturation (97.24 ± 4.10% vs. 96.19 ± 3.75% in placebo, p = 0.028). Additionally, compared to the placebo group, the treatment group had a significantly smaller increase in PCT level at D + 22 (1.43 vs. 12.76, p = 0.011). No adverse effects, including serious ones, were recorded until D + 91. NA-UC-MSCs therapy is a very safe adjunct for COVID-19 patients. It improves the oxygenation profile and carries potential to suppress inflammation.

Amniotic band syndrome with CNS involvement: a pediatric neurosurgeon's dilemma-a case series and literature review.

BACKGROUND: Amniotic band syndrome (ABS) is a rare congenital disease characterized by a broad spectrum of congenital anomalies resulting from the strangulated developing organ(s) by the detached fibrous amniotic band. The prevalence of CNS involvement in ABS is rare, but the mortality rate in these cases is high, while morbidity among the surviving patients is inevitable. CASE REPORT: Three-month-old male, 9-month-old female, and newborn female babies were presented with head lump(s), severe facial cleft, syndactyly, and finger amputation. The patient's head imaging confirmed meningoencephalocele as the cause of the head lump in 2 patients; meanwhile, a porencephalic cyst was identified as the origin of head lumps in the other patient. VP shunt placement surgery was performed as the initial management in 2 patients, while one patient directly underwent meningoencephalocele resection surgery. Craniofacial and limb reconstructions were planned as the follow-up management in all cases. Unfortunately, one patient died of complications from suspected aspiration, while another never returned for follow-up treatment. CONCLUSION: Here, we report 3 ABS cases with CNS involvement. Despite the severe disfigurement and disability, the inexistence of fatal malformation might lead to long-term survival. The treatment of malformation(s) that might predispose to another fatal condition and surgery(-ies) to improve functional outcomes and patient's social acceptability should be prioritized in managing the surviving ABS patients.

Application of rhBMP in spinal fusion surgery: any correlation of cancer incidence? A systematic review and meta-analysis.

PURPOSE: Safety concerns regarding the application of bone morphogenetic proteins (BMPs) have been highlighted in recent years. It is noted that both BMP and their receptors being identified as a trigger for cancer growth. Here, we aimed to determine the safety and efficacy of BMP for spinal fusion surgery. METHODS: We conducted this systematic review on topics of spinal fusion surgery with rhBMP application from three database (PubMed, EuropePMC, and Clinicaltrials.gov) with MeSH phrases such as "rh-BMP," "rhBMP," "spine surgery," "spinal arthrodesis," and "spinal fusion" were searched (using the Boolean operators "and" and "or"). Our research includes all articles, as long as published in English language. In the face of disagreement between the two reviewers, we discussed it together until all authors reached a consensus. The primary key outcome of our study is the incidence of cancer following rhBMP implantation. RESULTS: Our study included a total of 8 unique studies (n = 37,682). The mean follow-up varies among all studies, with the longest follow-up is 66 months. Our meta-analysis showed that exposure to rhBMP in spinal surgery did increase the risk of cancers (RR 1.85, 95%CI [1.05, 3.24], p = 0.03). CONCLUSIONS: Our study found that rhBMP was not associated with the increased risk of cancer incidence within the rhBMP cohort. Still, we did face several limitations, in which further studies are needed to confirm the result of our meta-analysis.

Low-cost and open-source three-dimensional (3D) printing in neurosurgery: A pilot experiment using direct drive modification to produce multi-material neuroanatomical models.

BACKGROUND: 3-dimensional (3D) printing carries a genuine potential for pre-operative planning in neurosurgery. Entry-level 3D printers offer practicality in low resource settings, but are often limited by the range of filament materials as well as the capability of open-source segmentation software. OBJECTIVE: We intended to demonstrate that 3D printing of neuroanatomical structures is possible using an entry-level 3D printer equipped with the direct drive (DD) modification, which supported flexible filaments, with the models segmented using an open-source software. METHODS: A DD system was installed onto the Ender 3 Pro printer. An attempt to print neurosurgical models using a low-cost 3D printer was conducted, where four patient-based neuroanatomical models were printed: skull base-vasculature, skull base-tumour, cervical spine, and ventricular system. The results were discussed and compared to similar endeavours in past literature. RESULTS: Although DD installation was challenging and led to vibration and longer print time, which ultimately warranted an inferior printing speed, DD system enabled the printing with thermoplastic polyurethane (TPU), a versatile elastomer; in addition to producing equal amount of detail to those printed with high-end printers and advanced image segmentation software. Fitting the frame well, changing infill type, and avoiding warping and stringing will improve print quality with the DD system. CONCLUSION: 3D printing with entry-level 3D printers equipped with DD system has been proven to be a reliable way of accurately reproducing patient-specific neuroanatomical constructs. Follow-up studies are necessary to implement 3D printing for neurosurgical planning in low-resource settings.

Massive subgaleal hematoma: a potentially fatal rare entity-a case-based review.

BACKGROUND: Massive subgaleal hematoma is defined as profuse bleeding in the subgaleal layer of the scalp, causing excessive accumulation of hematoma, thus progressively increasing the size of head circumference. If not immediately diagnosed and managed carefully, continuous bleeding will lead to hematoma enlargement, impairing the functions of surrounding organ(s) and general homeostasis. In severe cases, subgaleal hematoma could lead to severe morbidity or even death. CASE REPORT: We describe the case of an 11-year-old girl with a history of microcephaly and intellectual disability, presented with massive soft tissue swelling on more than half of her cranial circumference, accompanied with intermittent fever, anemia, and leukocytosis. The initial cerebral CT scan identified a mixed density extracranial lesion with multilobulated cystic appearance. The initial effort to aspirate the mass by a needle failed, and the patient was initially diagnosed with Pott's puffy tumor. Intraoperative findings confirmed the presence of massive subgaleal hematoma, and complete removal of the hematoma was achieved. The post-surgical period was uneventful, and the patient was discharged without any complications. CONCLUSION: Massive subgaleal hematoma should be considered in cases where children's head circumference increases rapidly, with or without a clear history of trauma and the presence of any possible risk factors. Missed diagnosis and inappropriate therapy could lead to unfavorable outcome. Hence, it is important for any clinicians to be familiar with this entity, so timely diagnosis and treatment can be made.

Basic and clinical research publications of Indonesian neurosurgeons: Where are we?

Background: With changes in European and the US academia and education systems, research has become a measurement to define academic productivity, as it is a crucial component in the process of becoming a well-trained neurosurgeon. In this recent study, we aimed to reveal the current status and challenges facing neurosurgical research in Indonesia. Methods: An open-access PubMed MEDLINE database search was performed to reveal all articles published by Indonesian Neurosurgeons from 1980 to July 2021. The detail was extracted to the following parameters: academia center or city of the study, year of publication, study type, topic, journal, institution and Q status, first author, article citation, international collaboration, and the working field. These data were processed and examined. Results: During 1980 and July 2021, a total of 242 PubMed-indexed papers were published from Indonesia. The number of publications started increasing significantly from 2010 to 2021, with an average of 19 papers per year since 2010. Most of the studies came from Bandung (22.7%), with Universitas Padjadjaran as the center of the study. According to the paper type, the majority of the articles were basic and clinical research (45.5%). The most common study type was case reports (33.5%). Neurotrauma (21.9%) was the most frequent topic followed by neuro-oncology (21.07%) and spine trauma (11.98%). Conclusion: Published articles in the neurosurgery field in Indonesia has shown a higher, promising trend. Despite many challenges faced in the process, there was significant progress in the past few decades compared to the previous ones. A comprehensive deliberate plan and multidisciplinary effort that focuses on overcoming the problems regarding defining academic productivity is needed for further improvement of neurosurgical care in Indonesia.

Lumbar interlaminar epidural steroid injections for chronic low back- and lower extremity-pain in Sjogren's syndrome: A case report.

INTRODUCTION AND IMPORTANCE: Peripheral nervous system involvement is very common in Sjogren's syndrome (SS); however, polyradiculopathy has been reported rarely in association with SS, and predominantly chronic forms have been described. Here, we reported a case from our Neurosurgery Department in Intan Medika KIM Hospital, Bangka Island, Pangkalpinang, Indonesia; as Academic Health System of Universitas Padjadjaran. CASE PRESENTATION: A 32-year-old woman, diagnosed with Sjogren's syndrome that was characterized by anti-nuclear, anti-Ro, anti-La and anti dsDNA-antibodies positives since 3 years ago; consulted to our department for a chronic low back with a radicular pain in both lower limbs from the gluteal area to both feet together with numbness, hyperstesis and allodynia. The pain was evaluated by the visual analogue scale (VAS) score of 8; we then performed cervico-lumbal computed tomography (CT) scan that demonstrated multiple protruded discs of the cervical- and lumbar-spine. CLINICAL DISCUSSION: Pain was treated with lumbar interlaminar epidural steroid injections as a safe technique that allows relieving patient symptoms; after 10 min, the patient experienced an improvement in her pain with reduced scores to 0-1 in VAS, as well as a significant improvement on her quality of life later on. CONCLUSION: The use of lumbar interlaminar epidural steroid injections for an alternative therapeutic for neuropathic pain in SS gives a satisfactory result in terms of improvement of pain as well as a significant improvement on patients' quality of life.

The use of modified glove-like abdominal flap for reconstruction of contracture following burns of dorsal hand and fingers: A case report.

INTRODUCTION AND IMPORTANCE: Burn contracture has been a challenge for its acquired functional disabilities and deformities. Surgical reconstruction poses a significant challenge for optimal aesthetic and functional improvement. Super thin abdominal skin pedicle flap can be used, but it has only one pedicle from one site of abdomen and needs tissue expander for a larger defect. The use of modified glove-like abdominal flap has been stated to be an option mainly for the use on acute hand burn. In this study, application of the modified glove-like abdominal flap was applied to contracture of dorsal hand and fingers. CASE PRESENTATION: A 39-year-old male patient with severe contracted hand, eight-month post-burn injury presented at outpatient clinic Santosa Central Hospital in 2017. Multiple series of surgeries were performed on this patient, consisting of released contracture, defect closure using a modified "glove-like" thin abdominal flap, and flap separation. CLINICAL DISCUSSION: Abdominal flap has been the commonly used technique but has the disadvantage of being bulky. Glove-like abdominal flap, a subcutaneous layer plane flap, can be performed simply, safely, and briefly. It has been published mainly for reconstruction for acute burn hand injuries, not for burn hand contracture. CONCLUSION: The use of modified glove abdominal flap technique for reconstruction in hand burn contracture gives a satisfactory result in terms of functional and aesthetic outcome and can be an option in reconstruction in contracted dorsal hand and fingers.

Production of Inflammatory Mediators in Conditioned Medium of Adipose Tissue-Derived Mesenchymal Stem Cells (ATMSC)-Treated Fresh Frozen Plasma.

BACKGROUND Inflammation is the body's first response to an illness that causes irritation or infection. Inflammation is tightly correlated with aging, which is a progressive degenerative process. Conditioned medium (CM) from adipose tissue-derived mesenchymal stem cells (CM-ATMSCs) has been shown to stimulate collagen synthesis and dermal fibroblast migration, as well as reduce wrinkles and improve wound healing. This study aimed to observe the production of inflammatory modulators - interleukin (IL)-1alpha, IL-6, IL-10, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) - in CM-ATMSCs treated with fresh frozen plasma (FFP) at passages 3 (P3), 7, 11, and 15. MATERIAL AND METHODS ATMSCs P3 were obtained from liposuction of female donors, and the CM from ATMSCs was collected. Measurement of these cytokines was performed with ELISA. RESULTS At many passages, IL-6, a proinflammatory modulator, was discovered to be the most powerful modulator among FFP- and non-FFP-treated cells. However, CM-ATMSCs treated with FFP and in the late passage have significant differences (P<0.05) compared to non-FFP treatments and in other passages in their effects on secretion of inflammatory modulators. CONCLUSIONS In conclusion, CM-ATMSC has the potential to secrete proinflammatory modulators.

Infected open depressed skull fracture complicated with tetanus grade I in an unimmunized child: a rare case report with literature review.

BACKGROUND: Tetanus is a rare disease caused by Clostridium tetani, which produces tetanolysin and tetanospasmin. In 2018, there were only approximately ten tetanus cases reported in Indonesia. Despite widespread vaccination, especially in low-middle-income countries, tetanus still occurs (mostly in adults) due to the lack of immunization related to religious tenets, cultural belief, or inaccessibility to medical care. In addition, tetanus in the pediatric population shows features which are quite distinct from the adult group. CASE PRESENTATION: We report a case of a 7-year-old girl presented to our institution with a history of falling 10 days prior to admission, with only skin laceration on her forehead. For 1 day prior to admission, the patient looked drowsy and difficult to be awakened, accompanied with stiffness of her jaw; we diagnosed her as an unimmunized child with an open depressed skull fracture of her frontal bone and wound infection complicated with "lockjaw." Perioperative management of this rare case is reported and discussed. CONCLUSION: The pediatric intensive care of such patients requires halting further toxin production, neutralization of circulating toxin, and control of the clinical manifestation induced by the toxin that has already gained access to the central nervous system. The basic tenets of anesthetic care in such case must be well-managed and planned prior to surgery.

Delayed definitive treatment of life-threatening neurosurgery patient with suspected coronavirus disease 2019 infection in the midst of pandemic: Report of two cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has affected global health system; in the context of the COVID-19 pandemic, both surgeon and anesthesiologist often dealt with emergency situation, optimal timing of surgery and safety protocol in hospital setting must be implemented with many facets for both patients and health-care providers. CASE DESCRIPTION: We reported two cases. Case#1 - A 16-year-old male was referred to our hospital, due to a decreased of consciousness following a motor vehicle accident. Head CT scan revealed an epidural hemorrhage on the left temporoparietal. The patient was suspected for having COVID-19 from the reactivity of his serum against SARS-CoV-2 antigen. Procedures for the confirmation of COVID-19 and surgical preparation caused 12 h delayed from the admission. Nevertheless, the patient was deteriorated clinically before he was transported to the operating room and died after 6 cycles of cardiopulmonary resuscitation. Case#2 - A 25-year-old male was referred to RSHS, due to a decreased of consciousness, diagnosed as bilateral proximal shunt exposed with suspected COVID-19; delay occurred due to unavailability of negative pressure intensive unit for postoperative care. This caused 5760 h (4 days) delayed for bilateral shunt removal and temporary extraventricular drainage. CONCLUSION: Optimal timing of surgery, a good safety, and health protocol during pandemic in emergency setting are an obligation to protect health providers and patients. A decision-making plan must be organized precisely to maintain alertness, achieve the highest possible standard of care, and outcome in emergency surgical cases. Lack of monitoring must be abated to avoid fatality for patient, especially in emergency surgery setting.

Analysis of Mutant Isocitrate Dehydrogenase 1 Immunoexpression, Ki-67 and Programmed Death Ligand 1 in Diffuse Astrocytic Tumours : Study of Single Center in Bandung, Indonesia.

OBJECTIVE: Diffuse astrocytic tumour (DAT) is a diffuse infiltrative astrocytoma tumour accompanied by molecular parameters such as the presence or absence of isocitrate dehydrogenase (IDH) gene mutations. Ki-67 is a marker for DAT proliferation, while programmed death ligand 1 (PD-L1) indicates an immune evasion mechanism. This study aimed to analyze the correlation among mutant IDH1 R132H, Ki-67, and PD-L1 immunoexpression in the DAT. METHODS: A cross-sectional study was carried out on 30 paraffin blocks of DAT cases. Paraffin block samples consist of grade II (n=14), grade III (n=8), and grade IV (n=8). In this study, the immunohistochemistry-staining of mutant IDH1 R132H, Ki-67, and PD-L1 were carried out to determine the frequency of DAT with IDH1 mutations. RESULTS: Our study shown the frequency of IDH1 mutations in grade II 50.0% (7/14), grade III 37.5% (3/8), and grade IV 12.5% (1/8). Our study also showed a difference in Ki-67 and PD-L1 expression between each the degree of DAT histopathology (p=0.0001 and p=0.002, respectively). There was an association between both mutant IDH1 R132H, and Ki-67 with PD-L1 expression in DAT (p=0.0087 and p=0.0049, respectively). CONCLUSION: DAT with the mutant IDH1 is frequently observed in grade II and small number of grade III. The expression of wild type IDH1, Ki-67, and PD-L1 were found to be higher in high grade DAT (grade III and grade IV). There is a correlation between each of mutant IDH1 status and Ki-67 with PD-L1 expression in DAT.

A rare cystic lymphoplasmacyte-rich meningioma: A case report and review of the literature.

BACKGROUND: Meningiomas are common central nervous system neoplasms, accounts for 30% of all primary intracranial neoplasms; the occurrence of meningiomas with cystic lesions is an exceptionally rare. Lymphoplasmacyte-rich meningioma (LPRM) is a rare pathological entity belong to the World Health Organization Grade I meningiomas. LPRM is characterized by abundant lymphoplasmacytic infiltrates which over-shadow the underlying meningothelial component. CASE DESCRIPTION: A 42-year-old male was admitted to our hospital with a chronic headache for about 3 weeks prior to admission. His symptoms worsen, and subsequently, he experienced left extremities weakness about 1 week before admission. His brain magnetic resonance imaging revealed an irregular and heterogeneously enhancing solid lesion with intratumoral cystic changes at the temporal lobe. A gross total resection was performed; pathological examination revealed a cystic LPRM. CONCLUSION: This rare variant of meningioma is a benign tumor entity featured with massive inflammatory cell infiltration and often less proportion of meningothelial elements. Surgical resection remains the treatment of choice. This is the first report regarding cystic LPRM from Indonesia; we also summarized relevant literature upto-date, May 2020, reported LPRM cases.

Effect of interleukins (IL-2, IL-15, IL-18) on receptors activation and cytotoxic activity of natural killer cells in breast cancer cell.

INTRODUCTION: Breast cancer is one of the leading cause of cancer deaths in women. Metastasis in BC is caused by immunosurveillance deficiency, such NK cell maturation, low NK activity and decreasing cytotoxicity. This study was performed to improve activating receptors and cytotoxicity of NK cells using interleukins (ILs). METHODS: Human recombinant IL-2, -15, and -18 were used to induce NK cells. We measured the activating and inhibiting receptors, proliferation activity of NK cells, and the cytotoxicity of NK cells on BC cells (MCF7). The effects of ILs were tested on the NK cell receptors CD314, CD158a and CD107a with flowcytometry, proliferation at various incubation times with 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and concentrations of TNF-α and IFN-γ by NK cells with ELISA. RESULTS: ILs increased NK cell receptor levels (CD314, CD158a, and CD107a) at 24 hours of incubation. ILs increased NK cell viability, which increased with longer incubation. Moreover, ILs-induced NK cells inhibited proliferation in MCF7 cells, as well as increased TNF-α, IFN-γ, PRF1 and GzmB secretion. CONCLUSION: IL-2, IL-15, and IL-18 improved activating receptors and proliferation of NK cells. IL-induced NK cells increased TNF-α, IFN-γ, PRF1 and GzmB secretion and cytotoxic activity on BC cells. High NK cell numbers increased BC cell growth inhibition.

Detection of endometriosis using immunocytochemistry of P450 Aromatase expressions in eutopic endometrial cells obtained from menstrual sloughing: a diagnostic study.

OBJECTIVE: To explore the possibility of a new diagnostic approach of endometriosis based on immunocytochemistry scoring of Aromatase P450 expressions in endometrial cells collected from menstrual sloughing. This is a case control study. Immuncytochemistry scores vs. histopathological examination in one tertiary- and secondary-level hospital in Bandung; two secondary level hospital in Garut and Sumedang, West Java, Indonesia. Thirty-five patients with and without endometriosis were enrolled. All subjects had diagnostic procedures for endometriosis suspicion, with addition menstrual blood samples for cytopathological examination. The specimens were sent for immunocytochemistry assessment of P450 Aromatase expressions (ICAPEC). The previous procedure resulted in cut-off point of histo score (H-score), sensitivity, specificity, (+) and (-) ICAPEC predictive value. RESULTS: The P450 Aromatase expression in endometrial cells of women with endometriosis was significantly stronger than without one. The cut-off point of H-scores to detect endometriosis was > 4. By this criteria, H-score had 94.6% sensitivity, 90.9% specificity, 92% positive predictive value and 93% negative predictive value. Immunocytochemistry scoring of Aromatase P450 expression in endometrial cells (ICAPEC) derived from menstrual blood specimen was a good candidate as alternatives approach in diagnostic procedure of endometriosis. Application and evaluation in clinical practice would provide the economically benefit in diagnostic procedure.

Identification of Periostin as a Potential Biomarker in Gliomas by Database Mining.

BACKGROUND: Bioinformatics analysis integrating microenvironmental factors and single cell analysis segregated the glioblastoma (GBM) subtype into 3 subtypes: proneural, classic, and mesenchymal. Mesenchymal GBM tends to have the worst survival but benefits from aggressive treatment protocols. Therefore, it is clinically meaningful to identify relevant biomarkers to distinguish the mesenchymal subtype. Moreover, in developing nations with limited resources, rigorous examinations are costly and inefficient for patient care. METHODS: In this study, we analyzed The Cancer Genome Atlas (TCGA)-Glioblastoma and TCGA-Low-Grade Glioma RNA sequencing (RNAseq) cohorts and confirmed that the mesenchymal subtype was associated with the worst prognosis. RESULTS: We identified periostin (POSTN) as a mesenchymal subtype biomarker with prognostic value across histologic grades and confirmed the reliability of POSTN by gene expression meta-analysis combining TCGA, Chinese Glioma Genome Atlas (CGGA) and REMBRANDT (Repository for Molecular Brain Neoplasia Data) GBM cohorts (hazard ratio, 1.71 [range, 1.47-2.07], n = 693) and LGG cohorts (hazard ratio, 2.55 [range, 1.61-4.05], n = 1226). CONCLUSIONS: By using available online glioma databases, our study provided an insight into the expression of POSTN as an independent predictor for patients with glioma (GBM and LGG) and could be useful for diagnostic simplification to identify high-risk groups.

Correlation between the skull base fracture and the incidence of intracranial hemorrhage in patients with traumatic brain injury.

PURPOSE: A head injury (HI) may cause a skull fracture, which may or may not be associated with injury to the brain. In essence, a skull base fracture (SBF) is a linear fracture at the base of the skull. Loss of consciousness and Glasgow coma score (GCS) may vary depending on an associated intracranial pathology. The pathomechanism is believed to be caused by high energy impact directly to the mastoid and supraorbital bone or indirectly from the cranial vault. Aim of this study is to define the correlation between SBF and intracranial hemorrhage (ICH) in patients with HI. METHODS: Analysis of data obtained from a retrospective review of medical records and from a systematized database pertaining to diagnostic criteria of SBF patients based only on clinical symptoms associated with ICH caused by HI treated in the Department of Neurosurgery at Dr. Hasan Sadikin Hospital, Bandung, Indonesia from January 1, 2012 to December 31, 2017. The exclusion criteria included age less than 15 years and no head computed tomography (CT) scan examination provided. RESULTS: A total of 9006 patients were included into this study in which they were divided into 3 groups: group 1, HI with no ICH; group 2, HI with single ICH and group 3, HI with multiple ICH. In all the SBF cases, SBF at anterior fossa accounted for 69.40% of them, which were mostly accompanied with mild HI (64.70%). Severity of HI and site of SBF correlated with the existence of traumatic brain lesions on CT scan, thus these factors were able to predict whether there were traumatic brain lesions or not. Most of the patients with epidural hemorrhage (EDH) has single traumatic lesion on CT scan, whereas most of the patients with cerebral contusion (CC) has multiple traumatic lesions on CT scan. On patients with both traumatic brain injury and SBF, most of the patients with anterior fossa SBF has EDH; whereas most of the patients with middle fossa SBF were accompanied with CC. Surgery was not required for most of the patients with SBF. CONCLUSION: SBFs were strongly correlated with traumatic ICH lesions patients with anterior fossa SBF were more likely to suffer EDH whereas with middle fossa SBF were more likely to suffer CC.

Expression of the RAC1, RHOA and CXCR4 proteins and their interaction as risk factors for infiltration to the nipple areola complex in operable breast carcinoma.

BACKGROUND: Nipple areola complex (NAC) infiltration in operable breast carcinoma (OBC) is associated with local recurrence. NAC infiltration in OBC suggests that RAC1, RHOA and CXCR4 proteins are risk factors for migration and infiltration of OBC to NAC. This study aims to analyze the expression and interactions of these proteins as risk factors for NAC infiltration in OBC. MATERIALS AND METHODS: This is an analytic observational cross-sectional study coupled with a categorical comparative study in each 40 subjects of OBC with and without NAC infiltration. The immunohistochemistry performed with a cut-off point based on the result of a receiver operating characteristics (ROC). RESULTS: RAC1, p < 0.001 with POR 5.76, 95% CI: 2.06-16.08; RHOA, p < 0.001 with POR 7.00, 95% CI: 2.28-21.53; and CXCR4, p = 0.001 with POR 6.33, 95% CI 2.06-19.49. There was an interaction between RAC1 and RHOA (p < 0.001 with POR 17.14, 95% CI: 3.07-125.66); between RAC1 and CXCR4 (p < 0.001 with POR 30.93, 95% CI 3.62-686.89); between RHOA and CXCR4 (p < 0.001 with POR 10.21, 95% CI 2.19-54.17); and between the RAC1, RHOA and CXCR4 proteins (p < 0.001 with POR = 23.69, 95% CI 2.51-544.86). CONCLUSION: We conclude that the expression of the RAC1, RHOA, and CXCR4 proteins and their interactions play a role as risk factors of NAC infiltration.

Novel Chemically Synthesized, Alpha-Mangostin-Loaded Nano-Particles, Enhanced Cell Death Through Multiple Pathways Against Malignant Glioma.

Mangostin is a hydrophobic agent with potential anticancer activity. Molecular dynamics computer simulation indicated methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) and α-mangostin (α-M) have good compatibility. The α-M-loaded nano-particles acting as an anticancer agents against growth of glioma cells were prepared by self-assembly methods. In this study, the effects of α-M-loaded nano-particles, α-M/MPEG-PLA with drug loading of 15% and a mean particle size of 32 nm, on the growth of glioma cells were examined both in vitro and in vivo. The occurrence of changes in the cell signaling molecules and expression levels of various proteins related to cell death and glioma xenograft models (i.e., zebra fish, subcutaneous-mouse and orthotopic-mouse) growth following the administration of α-M/MPEG-PLA were investigated. The novel α-M/MPEG-PLA inhibited the growth of malignant glioma cells, induced cells apoptosis with cleaved caspases expression and DNA fragmentation, along with down-regulation of anti-apoptotic molecules and up-regulation of apoptotic molecules. Furthermore, decreased proliferation as well as vascularization of the tumor in vivo models were significantly achieved. A dramatic induction of programmed cell death was found in malignant glioma cells after treatment with synthetic α-M/MPEG-PLA. These results suggest that synthetic α-M/MPEG-PLA could be a promising novel anticancer agent for performing chemotherapy against malignant glioma.