Mono- and combinational drug therapies for global viral pandemic preparedness.

Broadly effective antiviral therapies must be developed to be ready for clinical trials, which should begin soon after the emergence of new life-threatening viruses. Here, we pave the way towards this goal by reviewing conserved druggable virus-host interactions, mechanisms of action, immunomodulatory properties of available broad-spectrum antivirals (BSAs), routes of BSA delivery, and interactions of BSAs with other antivirals. Based on the review, we concluded that the range of indications of BSAs can be expanded, and new pan- and cross-viral mono- and combinational therapies can be developed. We have also developed a new scoring algorithm that can help identify the most promising few of the thousands of potential BSAs and BSA-containing drug cocktails (BCCs) to prioritize their development during the critical period between the identification of a new virus and the development of virus-specific vaccines, drugs, and therapeutic antibodies.

Diffuse Leptomeningeal Glioneuronal Tumour with 9-Year Follow-Up: Case Report and Review of the Literature.

In 2016, the World Health Organisation Classification (WHO) of Tumours was updated with diffuse leptomeningeal glioneuronal tumour (DLGNT) as a provisional unit of mixed neuronal and glial tumours. Here, we report a DLGNT that has been re-diagnosed with the updated WHO classification, with clinical features, imaging, and histopathological findings and a 9-year follow-up. A 16-year-old girl presented with headache, vomiting, and vertigo. Magnetic resonance imaging (MRI) demonstrated a hyperintense mass with heterogenous enhancement in the right cerebellopontine angle and internal auditory canal. No leptomeningeal involvement was seen. The histological examination revealed neoplastic tissue of moderate cellularity formed mostly by oligodendrocyte-like cells. Follow-up MRI scans demonstrated cystic lesions in the subarachnoid spaces in the brain with vivid leptomeningeal enhancement. Later spread of the tumour was found in the spinal canal. On demand biopsy samples were re-examined, and pathological diagnosis was identified as DLGNT. In contrast to most reported DLGNTs, the tumour described in this manuscript did not present with diffuse leptomeningeal spread, but later presented with leptomeningeal involvement in the brain and spinal cord. Our case expands the spectrum of radiological features, provides a long-term clinical and radiological follow-up, and highlights the major role of molecular genetic testing in unusual cases.

Atypical Teratoid/Rhabdoid Tumor After In Vitro Fertilization: Illustrative Case Report and Systematic Literature Review.

OBJECTIVE: In vitro fertilization (IVF) is increasingly used for the treatment of infertile couples worldwide. The association between IVF and cancer risk in offspring is conflicting. We present a case of atypical teratoid/rhabdoid tumor (AT/RT) in a girl conceived by IVF and present results of systematic review of literature of primary intracranial neoplasms diagnosed in children conceived by IVF. METHODS: A systematic review of literature was conducted on April 12, 2017, to identify previously published reports of intracranial brain tumors in patients conceived after IVF. RESULTS: A 21-month-old girl born after IVF and uneventful pregnancy presented with progressive nausea, vomiting, irritability, and right-side weakness. Magnetic resonance imaging demonstrated large heterogeneous contrast enhancing left frontotemporoparietal tumor. The operation was aborted due to asystole after subtotal tumor removal. The patient passed away on postoperative day 3. Histologic examination demonstrated AT/RT. We identified 7 previously published case reports of intracranial neoplasms in children conceived by IVF. Patient age at brain tumor diagnosis ranged from 31st week of gestation to 3 years of age. The most common histological diagnosis was AT/RT (3 cases), followed by glioblastoma multiforme, gliosarcoma, medulloblastoma, craniopharyngioma, and choroid plexus papilloma. Three of five operated patients died during perioperative period. Outcomes were dismal in 7 patients. CONCLUSIONS: IVF-associated brain tumors are usually malignant and associated with high mortality. Future studies investigating possible causal relationship between IVF and brain tumor risk are encouraged.

Extended pterional approach for initial surgical management of craniopharyngiomas: a case series.

AIM: Treatment of craniopharyngiomas remains challenging. The aim of this study was to evaluate results of initial surgical management of craniopharyngiomas via the extended pterional approach. MATERIAL AND METHODS: Nineteen patients (10 female; median age of 23 years; ranging from 10 months to 67 years) undergone initial surgery for craniopharyngiomas through the extended pterional approach. Data were retrospectively collected by reviewing medical records, operative reports and imaging results. RESULTS: The median size of craniopharyngiomas was 3.2 cm (range 1.3 - 4.8). Visual deterioration (n=12) and headache (n=10) were the most common symptoms on admission. After surgery, one patient died due to medical complications, 12 patients developed diabetes insipidus and eight patients developed anterior pituitary dysfunction. Median follow-up period was 9 years (range 2 - 13). Patients with progression of craniopharyngioma (n=5) when compared to patients without progression of craniopharyngioma (n=14) were significantly younger at the time of surgery, had less visual deterioration before surgery and had higher rates of not changed vision after surgery. Children had larger craniopharyngiomas when compared to adults. CONCLUSION: Initial surgery for craniopharyngioma via the extended pterional approach is a safe and effective treatment option with low postoperative mortality, and acceptable postoperative morbidity and recurrence rate.

Introduction of novel semiquantitative evaluation of (99m)Tc-MIBI SPECT before and after treatment of glioma.

BACKGROUND AND OBJECTIVE. There is a need for objective semiquantitative indexes for the evaluation of results of single-photon emission tomography (SPECT) in patients with brain glioma. The aim of this study was to validate the total size index (TSI) and total intensity index (TII) based on technetium-99m-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT scans to discriminate the patients with high-grade glioma versus low-grade glioma and to evaluate the changes of viable glioma tissue by the means of TSI and TII after surgery and after radiation treatment. MATERIAL AND METHODS. Thirty-two patients (mean age, 55 years [SD, 18]; 20 men) underwent a (99m)Tc-MIBI-SPECT scan before surgery. Of these patients, 27 underwent a postoperative (99m)Tc-MIBI-SPECT scan and 7 patients with grade IV glioma underwent a third (99m)Tc-MIBI-SPECT scan after radiation treatment. TII that corresponds to the area and intensity of tracer uptake and TSI that corresponds to the area of tracer uptake were calculated before surgery, after surgery, and after radiation treatment. RESULTS. The TII and TSI were found to be valid in discriminating the patients with high-grade versus low-grade glioma with optimal cutoff values of 3.0 and 2.5, respectively. Glioma grade correlated with the preoperative TSI score (r=0.76, P<0.001) and preoperative TII score (r=0.64, P<0.001). There was a significant decrease in the TII and TSI after surgery in patients with grade IV glioma. After radiation treatment, there was a significant increase in the TII in patients with grade IV glioma. CONCLUSIONS. TSI and TII were found to be reliable in discriminating the patients with high-grade versus low-grade glioma and allowed for the semiquantitative evaluation of change in viable glioma tissue after surgery and after radiation treatment in patients with grade IV glioma.

Management of cerebrospinal fluid leak after surgical removal of pituitary adenomas.

OBJECTIVES: The aim of the study was to evaluate the frequency and the causes of the intra- and postoperative cerebrospinal fluid (CSF) leaks and to discuss the sella closure methods. METHODS: During the period from 1995 to 2005, 313 patients underwent 356 transsphenoidal operations for pituitary adenoma. Microadenoma was found in 80 (22.5%) cases, and in 276 (77.5%) cases, macroadenoma was removed. Two different methods to close the sella were used. The first one consisted packing the sella turcica and sphenoidal sinus with autologous fat and restoring the defect of sella turcica with autologous bone. In more resent practice, the regenerated oxidized cellulose (Surgicel) and collagen sponge with human fibrin (TachoSil) were used to cover the sella membrane defect, followed by packing the sella with autologous fat and covering the dural defect with Surgicel and TachoSil. RESULTS: Adenoma was totally removed in 198 (55.6%) cases out of 356. Microadenoma was totally removed in 91.3% and macroadenoma in 45.3% of cases, respectively. Postoperative complications were noted in 40 (11.2%) patients. Two (0.6%) patients died after surgery. Intraoperative CSF leakage was observed in 58 (16.3%) cases. Postoperative CSF leakages were observed in 3 cases, when the method of packing the sella with just autologous fat was used, whereas in 29 cases when the sella fat packing was used together with Surgicel and TachoSil to cover the sella membrane and dural defects, no postoperative CSF leakages were observed. CONCLUSIONS: The technique of covering the sella membrane and dural defects with Surgicel and TachoSil in the presence of intraoperative CSF leakage appeared to be the most reliable one, as no postoperative CSF leakage applying this technique has been observed.

Significance of intracranial pressure and cerebral perfusion pressure in severe pediatric traumatic brain injury.

The aim of the study was to evaluate outcome of children after severe traumatic brain injury treated according to intracranial pressure (ICP)-targeted protocol, to define threshold values of peak ICP and minimal cerebral perfusion pressure (CPP) for decompressive osteoplastic craniotomy, and to determine the relationship between ICP, CPP and long-term outcome in these children. All children admitted to Pediatric Intensive Care Unit of Kaunas University of Medicine Hospital after severe head injury from January 2004 to June 2006 and treated according to ICP-targeted protocol for the management of severe head trauma were prospectively included in the study. Raised ICP was defined as a level higher than 20 mmHg. Minimal CPP was considered to be at a level of 40 mmHg. Outcome was defined using Glasgow Outcome Scale (GOS) at discharge from the hospital and after 6 months. Forty-eight patients (32 boys and 16 girls) were included into the study. Favorable outcome (GOS score of 4 and 5) after 6 months was achieved in 43 (89.6%) cases. Mean peak ICP was 24.2+/-7.2 mmHg and mean minimal CPP - 53.1+/-14.7 mmHg. Decompressive craniotomy was performed in 13 cases. Threshold values of peak ICP and minimal CPP for decompressive craniotomy were 22.5 mmHg (area under the curve, 0.880) and 46.5 mmHg (area under the curve, 0.898), respectively. The differences in peak ICP and minimal CPP in groups of favorable and unfavorable outcomes were not statistically significant. Treating children after severe traumatic brain injury according to the ICP-targeted protocol for the management of severe pediatric traumatic brain injury resulted in a favorable long-term outcome.

Predictive value of scoring system in severe pediatric head injury.

OBJECTIVES: To determine the threshold values of Pediatric Index of Mortality 2 (PIM 2) score, Pediatric Trauma Score (PTS), and Glasgow Coma Scale (GCS) score for mortality in children after severe head injury and to evaluate changes in outcomes of children after severe head injury on discharge and after 6 months. MATERIAL AND METHODS: All children with severe head injury admitted to the Pediatric Intensive Care Unit of Kaunas University of Medicine Hospital, Lithuania, from January 2004 to June 2006 were prospectively included in the study. The severity of head injury was categorized according to the GCS score < or =8. As initial assessment tools, the PTS, postresuscitation GCS, and PIM 2 scores were calculated for each patient. Outcome was assessed according to Glasgow Outcome Scale on discharge and after 6 months. RESULTS: The study population consisted of 59 children with severe head injury. The group consisted of 37 (62.7%) boys and 22 (37.3%) girls; the mean age was 10.6+/-6.02. The mean GCS, PTS, and PIM 2 scores were 5.9+/-1.8, 4.8+/-2.7, and 14.0+/-19.5, respectively. In terms of overall outcome, 46 (78.0%) patients survived and 13 (22.0%) died. All three scales appeared to be significant predictors of death. Threshold values for which potential mortality in children after severe head injury increased were 10.75 for PIM 2, 3 for PTS and 5 for GCS. PIM 2 score provided the best discrimination between survivors and nonsurvivors. CONCLUSIONS: The threshold values for mortality in children after severe head trauma were PIM 2> or =10.75%, PTS< or =3 and GCS< or =5, and these values were significant risk factors of death in severely head injured children. The changes in outcome for survivals on discharge and after 6 months were statistically significant.

[Severe pediatric head injury: is there any optimal solution?]. / Sunki vaiku galvos smegenu trauma. Ar yra optimalus gydymo budas?

Traumatic brain injury in children is a worldwide problem. The incidence of trauma cases is increasing over the world, and in Lithuania it is several times higher than in the most developed European countries. The article reviews data about the most modern means of managing pediatric traumatic brain injury. The role of prehospital care, emphasizing on airway management, adequate ventilation, oxygenation, and perfusion in order to preclude secondary brain injury, which begins straight after trauma, is being noted. Establishing trauma system and patient's treatment in pediatric trauma centers, where child gets urgent and sufficient help, reduces mortality and improves outcomes. Pediatric patient's triage using patient's status scoring and trauma scoring systems is recommended. The role of intracranial pressure and cerebral perfusion pressure is crucial. Immediate management of intracranial pressure reduces mortality and improves outcomes. Techniques of intracranial pressure monitoring and management strategies of intracranial hypertension, their advantages and possible disadvantages are described.