Effect of decompressive hemicraniectomy in patients with acute middle cerebral artery infarction

Background/aim: We aimed to determine in which cases this procedure may be more effective based on the data of patients who underwent decompressive hemicraniectomy (DHC). Material and methods: Overall, 47 patients who underwent DHC due to acute middle cerebral artery (MCA) infarction between January 2014 and january 2019 were retrospectively investigated. These patients were divided into two groups: those who died after DHC (Group A) and those who survived DHC (Group B). The groups were compared in terms of various parameters. We investigated whether the patient's modified Rankin scale (mRS) status changed depending on age (> 60 and < 60 years). Results: The median age of all patients was 65 (37­80) years; groups A and B had median ages of 66.5 (37­80) and 61 (44­79) years (p = 0.111), respectively; 55.3% patients were male. The elapsed times until hospitalization after the onset of symptoms were 4.5 and 3 h in groups A and B, respectively (p = 0.014). The median GCS score at the time of admission was 7 (5­12) and 10 (8­14) in groups A and B, respectively (p = 0.0001). At the time of admission, 63.3% patients in group A had anisocoria, whereas no patient in group B had anisocoria (p = 0.0001). In postoperative period, 40% patients in group A and all patients in group B received AC/AA treatment. The survival of patients aged < 60 and > 60 years who underwent DHC for MCA infraction was 61.5% and 26.5%, respectively (p = 0,041). The median mRS of patients < 60 and > 60 years were 4 (1­6) and 6 (1­6), respectively (p = 0.018). Conclusion: Age, DHC timing, and elapsed time until hospitalization or access to treatment directly affect the functional outcome and survival in MCA-infarcted patients who underwent DHC. In patients in whom the medical treatment fails, early DHC administration will increase survival without waiting for neurological worsening once herniation is detected radiologically.

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

INTRODUCTION: To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS). METHODS: Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP < 10 mg/L and albumin > 35 g/L; GPS-1: CRP < 10 mg/L and albumin < 35 g/L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes. RESULTS: A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001). CONCLUSIONS: The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.

Mortality Factors in Crush Syndrome.

BACKGROUND: Crush Syndrome is a major cause of morbidity and mortality following large-scale catastrophic earthquakes. Since there are no randomized controlled studies on Crush Syndrome, knowledge on this subject is limited to expert experience. The primary objective is to analyze the epidemiological and demographic characteristics, clinical outcomes, and mortality factors of earthquake victims after the Pazarcik and Elbistan earthquakes on February 6, 2023. METHODS: This cross-sectional and observational retrospective study evaluated 610 earthquake victims who presented to our center between February 6 and April 30, 2023. Among these patients, 128 with Crush Syndrome were included in the study. Patient information was gathered from hospital records during their stay and from national registries upon referral. The primary outcome was to identify risk factors for mortality. Demographic and laboratory data were analyzed by acute kidney injury (AKI) stages; mortality-affecting factors were identified through regression analysis. RESULTS: Of the 128 Crush Syndrome patients (100 adults, 28 children), 64 were female. The AKI rate was 32.8%. Among patients with AKI, the frequency of hemodialysis requirement was 69%, and the mortality rate was 14.2%. The overall mortality rate for patients with Crush Syndrome was 4.6%, compared to 3.9% (19/482) in earthquake victims without Crush Syndrome (p=0.705). Notably, low systolic blood pressure at admission was the only factor significantly affecting mortality in Crush Syndrome patients (Hazard Ratio [HR]: 1.088, p=0.021, 95% Confidence Interval [CI]). CONCLUSION: Our study highlights low systolic blood pressure upon admission as a significant risk factor for increased mortality in Crush Syndrome patients. This finding may contribute to the literature by emphasizing the importance of monitoring blood pressure under rubble and administering more aggressive fluid therapy to patients with low systolic blood pressure.

Comparison of E-selectin and the other inflammatory markers in lumbar disc herniation: a new promising therapeutical window for radicular pain.

STUDY DESIGN: Histopathologic and immunohistochemical analysis of the herniated disc specimens obtained from 50 patients who had unilateral persistent radicular pain or unilateral radicular motor paresis. OBJECTIVE: The aim of this study was to investigate the prevalence of inflammatory cells in lumbar disc herniations (LDH) and compare the prevalence of leukocyte adhesion protein "E-selectin" with other inflammatory cells such as T cells, B cells, and macrophages. SUMMARY OF BACKGROUND: Studies on inflammatory cells and biochemical mediators of inflammation have suggested that these factors may play an important role in pathophysiology of radicular pain, and the medical therapy was formed against to block these cells and inflammatory cytokines. METHODS: The herniated disc specimens obtained from 50 patients who had unilateral persistent radicular pain or unilateral radicular motor paresis were microscopically examined after staining with monoclonal antibodies of CD20, CD45, CD68, and E-selectin. Relative risk assessment of the straight-leg raising (SLR) test positivity or negativity with CD20, CD45, CD68, and E-selectin staining was investigated. RESULTS: Our data emphasize that, the cases with positive SLR test had higher rates of immunostaining with E-selectin and CD45. There were no statistically significant relationship between SLR positivity and CD20 and CD68. CONCLUSIONS: We suggest that E-selectin is as valuable as the other well-known inflammatory markers in the pathogenesis of LDH. In our opinion, beside the well-known nonsteroidal anti-inflammatory drugs, antagonists targeting E-selectin can be potentially effective therapeutics for controlling inflammation in LDH.

Significance of the Cerebellopontine Cistern Cross-Sectional Area and Trigeminal Nerve Anatomy in Trigeminal Neuralgia: An Anatomical Study Using Magnetic Resonance Imaging.

AIM: To evaluate the relationship between trigeminal neuralgia (TN) and potential magnetic resonance imaging (MRI)-related measurements in patients with TN. MATERIAL AND METHODS: Retrospective analysis of 104 patients with TN was performed. MRI studies of 98 healthy controls were included in the study to compare the parameters with TN patients’ measurements. MRI measurements of cerebellopontine cistern (CPC) cross-sectional area, trigeminal-pontine angle (TPA) width, and trigeminal nerve cisternal segment length and thickness were assessed on both symptomatic and asymptomatic sides using 1.5T MRI with constructive interference in steady-state sequences. The images were interpreted by two radiologists blinded to the affected sides of the patients. RESULTS: There were significant differences between the symptomatic and asymptomatic sides in terms of mean trigeminal nerve length (8.8 ± 2.34 mm vs. 9.39 ± 2.29 mm; respectively, p=0.001) and thickness (20.9 ± 9.6 mm2 vs. 25 ± 9.98 mm2, respectively; p < 0.001). The median cerebellopontine cistern cross-sectional area was considerably lower on the symptomatic side compared with the asymptomatic side [201 mm2 (interquartile range=93) vs. 224.5 mm2 (interquartile range=77), respectively; p < 0.001]. There were no significant differences between the trigeminal-pontine angle width on either side (38.32 ± 10.38 vs. 38.78 ± 10.9, respectively; p=0.679). There were no statistically significant differences between the right and left sides regarding these parameters in the control group. CONCLUSION: Smaller CPC cross-sectional area, trigeminal nerve length, and trigeminal nerve thickness on MRI were demonstrated to commonly exist on the symptomatic side in patients with TN. We suggest that this narrow space may increase the risk of vascular compression on the nerve.

Is topical tissue plasminogen activator application effective on prevention of post-laminectomy epidural fibrosis? An experimental study.

OBJECTIVE: Impaired fibrinolytic activity has been shown to be associated with poor outcome after lumbar disc surgery. The purpose of this study was to determine the efficacy of topical tissue plasminogen activator (t-PA) in preventing epidural fibrosis in rats. METHODS: L4-L5 laminectomy was performed under surgical microscope in 40 rats. Animals received either normal saline (control; n=20) or 0.5 mg/kg t-PA (n=20), topically to the operative sites. All animals were killed 1, 2, 4 and 6 weeks after surgery. Fibrosis, inflammation, necrosis and abscess formation were evaluated histopathologically. RESULTS: The results showed that 6 weeks after surgery, inhibition in formation of epidural fibrosis was noted in both control and treatment animals. We found no significant differences in inflammation, tissue necrosis and abscess formation between groups. CONCLUSION: A meticulous microsurgical technique with careful hemostasis seems to be an effective and adequate method for prevention of epidural fibrosis.

An unusual cause of low back pain: paravertebral muscle metastases of lung cancer.

Paravertebral muscle metastasis is an extremely rare cause of low back pain. Lipomas, haemangiomas, hibernomas and liposarcomas should be considered first in the aetiology of paravertebral muscle masses. Schwannoma, neurofibroma, ganglioneuroma and paraganglioneuromas that show contiguous spread should also be included in the differential diagnosis. Haematogenous metastases are most frequently caused by lung cancers. Lung cancers typically metastasize to liver, brain, bone, kidney, and adrenal glands. They rarely metastasize to skeletal muscles due to metabolism, high tissue pressure and blood flow of muscles. Our case was a 48-year-old male who had been smoking 40 cigarettes per day and presented to our clinic with low back pain and a mass in the lower back region. The mass in his lower back region was excised and histopathological examination confirmed metastasis of a neuroendocrine tumour. Further examinations revealed the lung as the primary source of the metastasis.

A rare but fatal case of granulomatous amebic encephalitis with brain abscess: the first case reported from Turkey.

The incidence of protozoal and helminthic infestations of the central nervous system (CNS) is less than 1%, but these infestations tend to follow a fatal course. They are more common among children, the elderly and immunocompromised individuals. CNS infections due to Entamoeba histolytica have been known for a long time. In recent years, especially in developing countries, there has been an increase in CNS infections due to free-living amebas (FLAs). Acute CNS infection due to Naegleria fowleri, which ends in death within 2-7 days, is termed primary amebic meningoencephalitis (PAM); subacute or chronic CNS infections due to Acanthamoeba spp, Balamuthia mandrillaris, and Sappinia diploidea, which occasionally cause cerebral abscess, are termed granulomatous amebic encephalitis (GAE). This paper presents a case of GAE with abscess formation in a 75-year-old male patient.

Spontaneous primary intraventricular hemorrhage in adults: clinical data, etiology and outcome.

AIM: Primary intraventricular hemorrhage (PIVH), bleeding in the ventricular system without a recognizable parenchymal component, is a rare neurological disorder. The purpose of this study was to identify clinical features, risk factors, etiology and outcome of patients with PIVH. MATERIAL AND METHODS: We retrospectively reviewed the clinical data, complementary examinations, outcome and computed tomography (CT) IVH score of 24 patients in our hospital from 2004 to 2008. We identified 24 patients with the inclusion criteria of non-traumatic PIVH. Their mean age was 60.6+/-17.4 years (range 38-79). Fourteen patients were male and 10 were female. RESULTS: The major symptoms included headache (n=24), loss of consciousness (n=6), confusion and disorientation (n=14), nausea/vomiting (n=10). Angiography revealed vascular malformations in five patients (21%). Other possible causative factors were hypertension in 12 patients (50%) and clotting disorder in one. The aetiology remained unknown in six patients. Most PIVH patients had associated hydrocephalus (58%) and 37% of the patients required ventricular drainage. In-hospital mortality was high (41%) and a FOUR score

Treatment of Cavernous Sinus Hemangiomas with Gamma Knife Radiosurgery as a Primary and Sole Therapy.

AIM: To evaluate the effectiveness of Gamma Knife radiosurgery (GKRS) as the primary and only therapy for the treatment of cavernous sinus hemangiomas (CSH) and to report the tumor volume dynamics, course of symptoms, and complications after stereotactic radiosurgery. MATERIAL AND METHODS: A total of 10 CSH patients were treated with GKRS using a median margin dose of 14.2Gy (range 13-16Gy). The median follow-up period was 42 months (range 12-85 months). Tumor volumes were calculated from magnetic resonance images before treatment and compared with those after treatment. RESULTS: Prior to the treatment, all patients complained of headache and retro-orbital pain, and six patients complained of diplopia due to abducens nerve paralysis. Within six months of treatment, all patients declared some improvement in headache and retro-orbital pain, and abducens nerve paralysis recovered fully in all six patients. At the first-year follow-up, at least 74% decrease in tumor volume was noted with average tumor volume reduction of 90.2% in all treated patients. Tumors less than 6 cm3 in volume nearly disappeared at 24 months. No tumor progression, re-growth, or radiation-induced adverse effects were noted in our patients. CONCLUSION: Characteristic radiological features that enable identification of CSH avert the need for an open biopsy for diagnosis. Under suitable circumstances, GKRS may be considered as the primary and only therapy for CSH. GKRS has favorable outcomes in the treatment of CSH, demonstrating good tumor shrinkage, symptom recovery, and low incidence of side effects.

Ultrastructure protection and attenuation of lipid peroxidation after blockade of presynaptic release of glutamate by lamotrigine in experimental spinal cord injury.

OBJECT: Lamotrigine is an antiepileptic drug that inhibits presynaptic voltage-gated sodium channels and reduces the presynaptic release of glutamate in pathological states. Neuroprotective effects of this drug have already been demonstrated in cerebral ischemia models. The aim of the present study was to determine the effects of presynaptic glutamate release inhibition on experimental spinal cord injury (SCI). METHODS: A total of 66 adult Wistar rats were randomly allocated into 6 groups. Group I was the control group used to obtain normal blood samples and spinal cord specimens. Spinal cord injury was introduced by using the extradural clip compression technique, but no medication was given to Group II (trauma group) rats. Group III was treated with vehicle, and the same amount of dimethyl sulfoxide used in treatment groups was administered to these rats. A dose of 50 mg/kg lamotrigine was administered intraperitoneally to Group IV (pretreatment), Group V (peritreatment), and Group VI (posttreatment) rats 30 minutes before, during, and 30 minutes after SCI, respectively. Oxidative stress parameters and transmission electron microscopic findings were examined. RESULTS: Blockade of presynaptic release of glutamate by lamotrigine treatment yielded protective effects on the spinal cord ultrastructure even when administered after the SCI, but it prevented oxidative stress only when it was administered before or during the SCI. CONCLUSIONS: Currently, no available agent has been identified, that can block all the glutamate receptors at the same time. To prevent excitotoxicity in SCI, inhibiting glutamate release from the presynaptic buttons instead of blocking the postsynaptic glutamate receptors seems to be a more rational approach. Further research, such as neurobehavioral assessment, is warranted to demonstrate the probable neuroprotective effects of presynaptic glutamate release inhibition in SCI.

A non-bleeding complex intracerebral giant aneurysm case: case report.

An intracranial aneurysm with a diameter larger than 25 mm is considered a giant aneurysm (GA), and represent about 3-5% of all aneurysms. They are divided into two forms, specifically saccular and fusiform. Fusiform aneurysms are rare, making up only 1% of all intracranial aneurysms. They frequently involve the internal carotid artery (ICA) or the basilar or vertebral arteries, and rarely bleed. Treatment of huge aneurysms that have not bled is still controversial. Unlike the saccular huge aneurysms that lead to death of 80% of the patients few years after diagnosis, fusiform huge aneurysms, particularly those presenting with mass effect, have a better prognosis. In this manuscript, we discuss the infrequently seen intracranial fusiform giant aneurysms in light of the pertinent literature.

Endovascular treatment of primary infectious aneurysm in childhood: a case report.

Infectious aneurysms constitute 4% of all intracranial aneurysms. The microorganisms responsible are most commonly streptococcus viridans, staphylococcus aureus and combined bacterial infections. Nonetheless, cases with no reproduction in their cultures are rather frequent. A 6-year-old patient admitted with complaints of sudden headache, nausea, vomiting and high temperature. Intracerebral hematoma and saccular aneurysm located at the distal posterior cerebral artery were diagnosed as a result of the laboratory investigations and neuroradiological examinations. Infectious aneurysm was considered due to the clinical findings, morphology and location of the aneurysm. Although the causative microorganism was detected in blood culture, no focus could be detected. The aneurysm was hindered by endovascular intervention. In this manuscript, we discuss the infrequently seen childhood infectious aneurysm in the light of the pertinent literature.

A rare case of massive NF1 with invasion of entire spinal axis by neurofibromas: case report.

Neurofibromatosis type-1 (NF1) is a type of phakomatosis inherited in an autosomal dominant fashion. Also called 'von Recklinghausen disease' or 'peripheral neurofibromatosis', it comprises 90% of all neurofibromatosis (NF) cases. It is characterized by multiple peripheral nerve sheath tumors of benign character called neurofibromas. Surgical intervention is indicated when myelopathy and motor losses develop in the case of paraspinal neurofibromas, which are frequently localized to the cervical and lumbar regions. The level of surgical intervention required should be carefully considered and should take into account neurophysiological tests of paraspinal neurofibroma cases that allow estimation of the risk that the neurofibromas will invade the complete spinal axis. The best results are obtained with patients showing minimal neurological deficits during the pre-operative period. Little improvement may be expected from the patients who develop complete transection syndrome during the postoperative period. In the present paper, we discuss an NF1 case in which paraspinal neurofibromas were observed along the complete spinal axis of a 32-year-old male patient who arrived at the clinic reporting increasingly intense pins and needles and weakness. We discuss the patient's diagnosis, treatment, and prognosis, and relate this case to the literature.

Multiple Extraneural Metastases of Anaplastic Oligodendroglioma.

Oligodendrogliomas (ODGs) is a diffuse glial tumor that constitutes 4.2% of all brain tumors. Extraneural metastases, sometimes seen in glioblastoma multiforme, are extremely rare in ODG. In this report, we present a 63-year-old male patient who was diagnosed with Grade 3 ODG and had an intracranial mass resected in our clinic 4 years ago. The subject now presented with low back pain and was found to have widespread metastases. The prolongation of patient survival by current treatment regimens has revealed a growing number of ODG patients with metastases. We believe that back pain complaints in patients with ODG should be viewed as an indicator of metastasis.

Effect of gabapentin on primary surgical treatment of experimental sciatic nerve injury in rats.

BACKGROUND: The aim of our study is to minimize the morbidity related to nerve injury by determining the protective effects of gabapentin in experimental sciatic nerve injury and end-to-end anastomosis model in rats and to guide clinical studies on this subject. METHODS: In our study, 40 adult male Sprague-Dawley rats were randomly divided into the following five groups: I: Only surgical intervention was applied; II: The sciatic nerve was cut properly and was repaired by end-to-end anastomosis. No additional procedure was performed; III: A single dose of gabapentin at 30 mg/kg was given after anastomosis; IV: 30 mg/kg gabapentin was given for 3 days after anastomosis; and V: 30 mg/kg gabapentin was given for 7 days after anastomosis. The experiment was terminated with high-dose thiopental (50 mg/kg) 60 days after the surgical intervention. The right sciatic nerve was taken from all animals. The obtained sections were examined immunohistopathologically. RESULTS: Immunohistochemical properties and Schwann cell proliferation were found to be statistically significantly lower in the control group than in the other groups. Schwann cell proliferation was higher in Group 3 than in Group 5. Immunohistochemical changes were significantly lower in Group 4 than in Group 3. Axonal degeneration was also higher in Group 4 than in Group 3. CONCLUSION: Gabapentin promotes neurological recovery histopathologically in peripheral nerve injury due to its neuroprotective properties. Our study results show that gabapentin can be used as an adjunctive therapy to primary surgical treatment after peripheral nerve injury.

The effects of infusion of perineural pregabalin in the experimentally created sciatic nerve anastomosis in rats.

INTRODUCTION AND OBJECT: The aim of our study was to assess the effect of perineural pregabalin administration on the success of coaptation in experimental rat sciatic nerve anastomosis by measuring the expression of anti-inflammatory cytokine TGF-ß. It is thus to provide alternative solutions to this problem which we often see in clinical practice and whose results are not satisfactory. METHODS: In our study, 40 adult, male, Sprague-Dawley rats; 5 groups were randomly assigned. Group 1: This group's sciatic nerves were dissected and the surgical site was sutured. Group 2: Rats whose sciatic nerves are sectioned transversely through the full-thickness and end-to-end anastomosis is performed and no additional procedure is performed. Group 3: Intraperitoneal administration of 30 mg / kg pregabalin for 7 days with anastomosis. Group 4: 30 mg/kg pregabalin given orally for 7 days with anastomosis. Group 5: Given 10 microliters / h pregabalin subcutaneous perineural infusion for 7 days with anastomosis. After 60 days of surgery, the experiment was terminated with high dose thiopental (50 mg/kg). The right sciatic nerves of all animals were taken and sections obtained were examined immunohistopathologically. RESULTS: Inflammation was significantly less in the 5th group than in the other groups. TGF-ß expression in Groups 3, 4, and 5 is significantly higher than Groups 1 and 2, which also supports this situation. Although the expression in group 5 was not statistically significant, the number of TGF-ß expression was higher than Groups 3 and 4. In terms of immunohistochemical properties; 1 to 3, 1 to 4, 1 to 5, 2 to 5 groups were statistically significant (p <0,05). CONCLUSIONS: In conclusion, perinural infusion of pregabalin into the anastomotic region has not been previously tried in the literature and it has been found that immunohistochemistry provides positive contributions to healing of anastomosis. More research is needed to demonstrate that this effect is superior to other methods of administration of the drug. KEY WORDS: Anastomosis, Peripheral nerve, Perineural, Pregabalin, Sciatic nerve.

Brain Metastasis Of Penile Angiosarcoma.

Angiosarcoma is a rare malignancy originating from vascular endothelial cells. Brain metastasis of aniosarcomas are uncommon up to the literature. Penile angiosarcomas are also seldom among all anjiosarcomas. A case with penile angiosarcoma with confirmed brain metastasis is aimed to be reported and contribute to the literature for similar cases.

Safety and Efficacy of Ventriculostomy Procedures under Dual Antiplatelet Therapy in Patients Treated With Stent Assisted Coiling In Subarachnoid Hemorrhage.

AIM: Stent assisted coilling (SAC) is an alternative in the treatment of ruptured aneurysms. Stenting requires the use of dual antiplatelet agents. Hydrocephaly is a complication of subarachnoid hemorrhage (SAH) requiring ventriculostomy. Antiplatelet treatment reveal a risk of hemorrhage in ventriculostomy. Anti-aggregant effect starts at least four hours after the initial doses of treatment. However, in many studies, ventriculostomy was performed before antiplatelet treatment and the hemorrhagic complications were related to the procedure. The aim of this study was to determine the risk of ventriculostomy related hemorrhage in patients with impaired thrombocyte function and to contribute to the literature. MATERIAL AND METHODS: Between 2011 and 2016, 53 patients treated with SAC due to SAH in our clinic were retrospectively evaluated. Hemorrhagic complication risks due to antiplatelet therapy related to ventriculostomy were retrospectively evaluated Results: All of the ventricular catheter procedures were performed at least 1 day after the dual therapy (in average 4,3 days after SAC). On 5 patients 1 ventriculostomy was performed, on 2 patients 2, and on 1 patient 6 ventriculostomies were performed. Although radiological hemorrhage was present on the catheter tract in 4 patients, no temporary or permanent neruologic deficit was observed. CONCLUSION: Impaired thrombocyte functions pose a risk in ventriculostomy. Also, evaluating the risk of hemorrhage before the antiplatelet treatment reaches its full effect may lead to false results. Studies with small patient groups with antiagregant therapy and impaired thrombocyte functions also contribute to the literature. Larger studies regarding this subject are needed.