Potential antiaging activity of secretome gel of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) in UV-induced mice models.

Objectives: Skin aging is a degenerative process that can be induced by UV irradiation. UV radiation can produce reactive oxidate stress which causes premature aging. This study aims to examine the antiaging potential of secretome gel (SC) from human Wharton Jelly Mesenchymal Stem Cells (hWJ-MSCs) in a UVB-induced mice model. Materials and Methods: The secretome was obtained from hWJ-MSCs and made in gel form. Male mice were radiated by UVB for 15 min twice daily for 14 days. The gel was topically applied to the mice's dorsal skin. Two treatments of secretome gel: secretome 1 is applied once and secretome 2 is applied twice daily after UVB radiation. TGF-ß1, IL-10, and IL-18 gene expression was determined using RT-PCR. Hematoxylin Eosin staining was used to observe the inflammation and collagen density of skin tissue. An immunohistochemistry assay was used to analyze the protein expression of P53, COL4A1, MMP-2, and MMP-13. The data were statistically analyzed using the ANOVA test followed by the Tukey post hoc test (P<0.05). Results: UVB induction caused loss of collagen, increasing inflammation and high expression of aging mediators. SC increased the gene expression of TGF-ß1 and IL-10 and decreased IL-18 gene expression. Histopathological tests showed that SG increased collagen density, lowered inflammation, and repaired cell damage in skin tissue. Immunohistochemistry test showed that SC decreased MMP-2, MMP-13, and P53 expression, in contrast, increased COL4A1. Conclusion: The secretome gel of hWJ-MSCs showed antiaging activities with potential for preventing and curing skin aging.

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.

Combine Approach of Proximal Fibula Osteotomy (PFO) Followed by Intra-Articular Dextrose Prolotherapy in Severe Medial Knee Osteoarthritis.

Background: Knee osteoarthritis (OA) is a chronic and progressive degenerative disease. It resulted from mechanical and chemical disorders that damage the joint and the underlying bone. The management of knee OA is challenging due to poor self-regeneration of connective tissues. Surgical treatment with prolotherapy approaches was conducted to treat medial compartment knee OA. Aim: To know the injection frequency to reach a 50% improvement in VAS score and WOMAC index. Methods: Six patients who suffered from late-stage medial compartment knee OA underwent PFO followed by twelve sessions of intra-articular dextrose prolotherapy. The subjective pain score, visual analog scale (VAS), was assessed based on the patient subjectiveness before and after treatment. Patients marked the score from 0 to 10 cm to describe the current pain state. The functional index, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index used to evaluate the Patient's clinical symptoms. It ranges from 0 to 96 points consisting of three main sections: pain (total 20 points), stiffness (total: eight points), and physical function disability (total 68 points). Higher scores indicate severe symptoms and function. Results: Four patients showed pain relief and functional improvement with more than 50% scores of VAS and WOMAC after the treatment. Two patients received more than twelve doses of intra-articular dextrose prolotherapy due to a lack of progress. Conclusion: This study provides clinical evidence for a new treatment strategy for advanced knee OA. This combined therapy improves the patient's daily activity function and postpones the need for total knee arthroplasty (TKA).

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.

Interleukins Profiling in Umbilical Cord Mesenchymal Stem Cell-Derived Secretome.

Background: Umbilical cord mesenchymal stem cells (UC-MSCs)-derived secretome is currently used in regenerative therapy. MSCs are believed to secrete a wide spectrum of bioactive molecules which give paracrine effects in immunomodulation and regenerative capacities. One group that was found in secretome is interleukins (ILs), a cytokine that plays an essential role in the process of proliferation, differentiation, maturation, migration, and adhesion of immune cells. However, as there are many types of ILs, the profile of ILs in the UC-MSCs-derived secretome has been limitedly reported. Therefore, in this study, we would like to profile and detect the interleukin concentration secreted by UC-MSCs. Methods: UC-MSCs-derived secretome was collected from UC-MSCs passage 5 after 24- and 48-hour incubation (n=9). Secretome was filtered using 0.2 µm and stored at -80°C for further detection. All samples were normalized before the interleukin (IL-2, IL-4, IL-6, IL-9, IL-10, IL-12, IL-17A) detection using a MACSPlex Cytokine Kit. Results: The IL-6 has the highest concentration among other interleukins in both groups and increases significantly (p<0.003) after incubation for 48 hours. The pro-inflammatory factors are decreasing while anti-inflammatory factors are increasing after 48-hour incubation. Discussion: Our studies show that the UC-MSCs secrete pro- and anti-inflammatory interleukins. The concentration of anti-inflammatory interleukins shows to be increasing, while the pro-inflammatory interleukins are decreasing within the longer incubation time, but this not be applicable for IL-10 and IL-6. IL-6 has the highest concentration among other ILs. These results may provide important clues regarding when is the right time for secretome to be used in therapy patients, because all the molecules in the secretome can lead to many clinical manifestations.

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.

Epidemiological Pattern of Traumatic Brain Injury in the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

BACKGROUND: Although the incidence of traumatic brain injury (TBI) has decreased since the beginning of the coronavirus disease 2019 (COVID-19) pandemic and severe acute respiratory syndrome coronavirus 2 is still evolving, the number of TBI cases has still greatly increased in multiple countries. In the present systematic review and meta-analysis, we evaluated the epidemiological characteristics of patients with TBI before and during the COVID-19 pandemic. METHODS: We conducted a systematic literature search of original studies, short reports, and research letters from databases on studies that contained data about the severity, mortality, presence of neurological deficits, radiological diagnosis, cause of injury, and type of management of TBI during a specified period within the pandemic compared with before the pandemic. RESULTS: A total of 18,490 subjects from 13 studies were included in the present study. The results of the meta-analysis showed a higher TBI mortality rate during the COVID-19 pandemic in the low-to-middle income countries (odds ratio, 1.65; 95% confidence interval, 1.12-2.41; P < 0.05; I2 = 40.8%; P = 0.18). The proportion of subdural hemorrhage was decreased, and the proportion of subarachnoid hemorrhage was increased in low- to middle-income and high-income countries, respectively. The proportion of assaults as the cause of TBI had increased during the pandemic (odds ratio, 1.40; 95% confidence interval, 1.06-1.86; P = 0.02; I2 = 20.8%; P = 0.28). We did not find any significant differences in the incidence of surgical intervention for TBI during the pandemic. CONCLUSIONS: Our results have indicated that during the COVID-19 pandemic, the TBI mortality rate had increased in low- to middle-income countries. The rate of assault as the cause of TBI had also increased during the pandemic.

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.

Potency of Mesenchymal Stem Cell and Its Secretome in Treating COVID-19.

Abstract: The COVID-19 disease, which is caused by the novel coronavirus, SARS-CoV-2, has affected the world by increasing the mortality rate in 2020. Currently, there is no definite treatment for COVID-19 patients. Several clinical trials have been proposed to overcome this disease and many are still under investigation. In this review, we will be focusing on the potency of mesenchymal stem cells (MSCs) and MSC-derived secretome for treating COVID-19 patients. Fever, cough, headache, dizziness, and fatigue are the common clinical manifestations in COVID-19 patients. In mild and severe cases, cytokines are released hyper-actively which causes a cytokine storm leading to acute respiratory distress syndrome (ARDS). In order to maintain the lung microenvironment in COVID-19 patients, MSCs are used as cell-based therapy approaches as they can act as cell managers which accelerate the immune system to prevent the cytokine storm and promote endogenous repair. Besides, MSCs have shown minimal expression of ACE2 or TMPRSS2, and hence, MSCs are free from SARS-CoV-2 infection. Numerous clinical studies have started worldwide and demonstrated that MSCs have great potential for ARDS treatment in COVID-19 patients. Preliminary data have shown that MSCs and MSC-derived secretome appear to be promising in the treatment of COVID-19. Lay Summary: The COVID-19 disease is an infection disease which affects the world in 2020. Currently, there is no definite treatment for COVID-19 patients. However, several clinical trials have been proposed to overcome this disease and one of them is using mesenchymal stem cells (MSCs) and MSC-derived secretome for treating COVID-19 patients. During the infection, cytokines are released hyper-actively which causes a cytokine storm. MSCs play an important role in maintaining the lung microenvironment in COVID-19 patients. They can act as cell managers which accelerate the immune system to prevent the cytokine storm and promote the endogenous repair. Therefore, it is important to explore the clinical trial in the world for treating the COVID-19 disease using MSCs and MSC-derived secretome.

Developmental outcomes in children from cryopreserved embryos compared to their siblings from fresh embryo transfers: a case series.

OBJECTIVE: This study aimed to evaluate the developmental outcomes in children from cryopreserved embryos, with minimum influences of interparental variation that would cause potential bias. Hence we examined siblings, in which the older sibs were from fresh embryo transfers, while the younger sibs were from cryopreserved embryos. METHODS: Three pairs of siblings were evaluated. All routine prenatal and neonatal evaluation were performed, while personal-social, language, fine and gross motor evaluation were all evaluated by the Denver Developmental Screening Test (DDST)-II. Wechsler Preschool and Primary Scale of Intelligence (WPPSI) test was used to measure the Intelligent Quotient (IQ) in 5 of 6 children. RESULTS: Standard prenatal measurements of all children suggested uneventful pregnancies, followed by uneventful deliveries. DDST-II results showed that the aspects of personal-social, language, fine and gross motor in every child are as expected according to their ages. Results from WPPSI tests suggest that 5 of 6 evaluated children acquired average to high-average intelligences. CONCLUSIONS: The results suggest that the developmental outcomes in children from cryopreserved embryos have no significant differences with the outcomes in children from fresh embryo transfers.

Delayed subaponeurotic fluid collection on an infant's head: Underreported case and review of the literature.

BACKGROUND: Delayed subaponeurotic fluid collection (DSFC) is a relatively uncommon problem, probably under reported soft swelling in the scalp which usually develops in infancy that occurs weeks to months after birth. Although the exact etiology remains unclear, several theories have been postulated such as (i) cerebrospinal fluids (CSF) leak from microfractures of the skull and (ii) disrupted lymphatic drainage, gradually liquefying subaponeurotic bleeding. Here, we reported typical clinical findings of DSFC and analysis of the fluid aspirate from our patient. To the best of our knowledge, this is the first case reported from Asia, particularly from Indonesia. CASE DESCRIPTION: A healthy 2-month-old girl infant presented with 2 weeks history of occipital painless fluctuant scalp mass with no swelling. She was born at term from a nulliparous mother; by emergency cesarean delivery following failed induction of labor. There was no history of scalp injury at birth nor recent head trauma; ultrasonography showed translucent fluid in subaponeurotic or subgaleal space. The fluid collection was noted to be fluctuant, free-flowing across suture lines, without discoloration or bruising; when placed supine, the fluid collected at her midocciput. A diagnostic tap confirmed the presence of serosanguinous CSF led to a diagnosis of DSFC. CONCLUSION: Herein, we reported the first DSFC case from Indonesia. With no previous experience of the condition, a definitive diagnosis was possible through a very carefully physical examination and history taking, along with a good communication among the neurosurgeon, pediatrician, and the clinical pathologist.

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.

Short tandem repeat near hypoxia response element (HRE) instead of HRE genetic variants in promoter calcitonin receptor-like receptor (CRLR) gene as risk factor in severe preeclampsia: a preliminary study.

OBJECTIVE: Calcitonin receptor-like receptor (CRLR) regulates vasoconstriction and dilatation; the expression increases during hypoxia via activation of hypoxia response element (HRE) in CRLR gene promoter region. Variant in HRE, as well short tandem repeat (STR) variants near HRE in CRLR alters the gene expression. This study focused on a case-control study to investigate the expression of genetic typing CLRL promoter variant in pregnant women with severe preeclampsia and normal pregnancies, we also tried to describe interesting findings of the genetic expression in anemic patients in the severe preeclampsia group. Our aimed to observe the correlation of CRLR gene promoter variant and anemia in severe preeclampsia. RESULTS: There was no nucleotide variant in HRE; CACA box prior to HRE varied in length (15-24); CACA box with length > 20 was used as cut off point. Hb was lower in CACA box length ≥ 21 (10.33 ± 1.57) vs. < 21 (11.01 ± 1.67; p = 0.391). CACA box polymorphism and anemia were correlated in severe preeclampsia (p = 0.005) OR 0.038 (CI 0.003-0.544); not in normal (p = 0.069).

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.