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1.
Acta Neurochir (Wien) ; 166(1): 288, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980421

ABSTRACT

PURPOSE: Postoperative management following elective cranial surgery, particularly after biopsy procedures, varies significantly across neurosurgical centres. Routine postoperative head CT scans, traditionally performed to detect complications such as intracranial bleeding or cerebral oedema, lack substantial evidence supporting their necessity. METHODS: This study is a retrospective cohort analysis conducted at a regional neurosurgical department of 236 patients who underwent brain biopsies between 2018 and 2022. Patient data, including demographics, surgical details, and postoperative outcomes, were collected and analysed. The outcomes investigated were the incidence and impact of postoperative CT scans on time to discharge, management changes, and the influence of preoperative anticoagulation. RESULTS: Out of 236 patients, 205 (86.86%) underwent postoperative CT scans. There was no significant relationship between postoperative hematoma, as detected on a CT scan, and neurological deficit (p = 0.443), or between preoperative anticoagulation and postoperative bleeding on CT scans (p = 0.464). Patients who had postoperative CT scans had a significantly longer length of stay (LOS) compared to those who did not (p < 0.001). Intraoperative bleeding was a predictor of hematoma on postoperative CT (p = 0.017) but not of postoperative neurological deficit. The routine postoperative CT scan showed limited predictive value for symptomatic deficits, with a positive predictive value of 6.67% and a negative predictive value of 96.88%. CONCLUSIONS: Routine postoperative CT scans after brain biopsies do not significantly impact management or improve patient outcomes but are associated with longer hospital stays. CT scans should be reserved for patients showing clinical signs of complications rather than used as a routine procedure after a brain biopsy.


Subject(s)
Brain , Tomography, X-Ray Computed , Humans , Male , Retrospective Studies , Female , Middle Aged , Adult , Biopsy/methods , Biopsy/adverse effects , Aged , Brain/pathology , Brain/diagnostic imaging , Brain/surgery , Postoperative Complications , Cohort Studies , Postoperative Care/methods , Length of Stay , Neurosurgical Procedures/methods , Neurosurgical Procedures/adverse effects
2.
J Surg Case Rep ; 2024(1): rjae004, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38283413

ABSTRACT

Cranial suture diastases are an uncommon clinical entity, with post craniotomy diastases being a previously undescribed finding in literature to our best knowledge. Herein, we report a case of a 28-year-old adult who underwent a second-stage low-grade glioma surgery 7 months after initial surgery. This study presents coronal suture diastases adjacent to the previously performed craniotomy. After literature and pathophysiology review, we found it to be unique and that the craniotomy can resemble the mechanical stress of trauma.

3.
Bioorg Chem ; 110: 104794, 2021 05.
Article in English | MEDLINE | ID: mdl-33735711

ABSTRACT

A new series of 1,3,4-thiadiazolo-adamantane derivatives were synthesized through molecular hybridization approach, then used as starting material to synthesize chloro and cyano acetamide-thiadiazole derivatives 2, 3. The newly designed compounds 1-3 were treated with different reagents to design 5-adamantyl thiadiazole derivatives 4-17 and evaluate their in vitro anti-proliferative activity against three cancer cell lines (MCF-7, HepG-2 and A549). Doxorubicin was used as a positive control. The most promising compounds 5, 6, 10a, 10b, 14b, 14c, and 17 showed up-regulation for BAX and down-regulation of Bcl-2, these findings proved their role as hopeful apoptotic inducers. In addition, the inhibitory activity against both wild EGFRWT and mutant EGFRL858R-TK for these derivatives revealed that compounds 5, 14c, and 17 have IC50 value ranging from 85 nM to 71.5 nM against wild EGFRWT and 37.85-41.19 nM against the mutant type, Lapatinib was used as a reference standard with IC50 values of 31.8 nM and 39.53 nM, respectively. The most potent derivatives were subjected to further evaluation against double mutant EGFR L858R/T790M and showed good IC50 values between (0.27-0.78 nM) compared to Lapatinib (0.18 nM) and Erlotinib (0.21 nM). Among them, thiazolo-thiadiazole adamantane derivative 17 exhibited the strongest inhibitory activity to the EGFR. Molecular docking studies were performed inside the active site of EGFR (1M17), and binding energy scores ranged between (-19.19 to -22.07 Kcal/mol) compared to Erlotinib (-19.10 Kcal/mol). Furthermore, oral bioavailability beside some pharmacokinetics properties of these derivatives were also investigated in this research work.


Subject(s)
Adamantane/pharmacology , Antineoplastic Agents/pharmacology , Drug Development , Protein Kinase Inhibitors/pharmacology , Thiadiazoles/pharmacology , Tubulin Modulators/pharmacology , Adamantane/chemical synthesis , Adamantane/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Humans , Molecular Docking Simulation , Molecular Structure , Polymerization/drug effects , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Structure-Activity Relationship , Thiadiazoles/chemistry , Tubulin/metabolism , Tubulin Modulators/chemical synthesis , Tubulin Modulators/chemistry
4.
Bioorg Chem ; 85: 399-412, 2019 04.
Article in English | MEDLINE | ID: mdl-30665034

ABSTRACT

Reaction of 5-morphilinosulfonylisatin (1) with acetophenones (2a-e) afforded 3-hydroxy-3-substituted-2-oxoindoles 3a-e, when treated with acetic acid the expected 3-phenacylidene-2-oxoindoles 4a-d and 4-hydroxy-5'-(morpholinosulfonyl) spiro [chromene-2, 3'-indolin]-2'-one 6 were obtained. Isatin derivative (1) was stirred with cyano derivatives to produce the arylidines (7a-c), while under reflux condition, it gave pyrrolo[2,3-b]indoles (8, 9). Moreover, istain (1) reacted with pyrazolo-5-one or 3-substituted phenol in presence of malononitrile to afford spiroxindole derivatives (10a,b) and (11a,b). Also, compounds (10a,b) and (11a,b) were obtained through cyclization of (7a) with pyrazolo-5-one or 3-substituted phenol. The obtained compounds were identified by IR, 1H NMR, 13C NMR and elemental analysis. Anticancer activity against three cancer cell lines (HepG-2, HCT-116 and MCF-7) were evaluated using sulforhodamine B assay method. Compounds 4b, 4c, 7a, 7c and 9 showed broad spectrum anticancer activity on the three tested cell lines with IC50 values less than 10 µM. Cell cycle analysis was performed for the most promising derivatives, compounds 4b and 7c arrested HepG-2 cells at G2-M phase, while compounds 7a and 9 accumulated cells at G0-G1 phase, all of them induced apoptosis at priG1 phase in the range of (11.32-19.17%). Additionally compounds 4b, 7a and 9 showed more potent activity against EGFR than Lapatinib, their IC50 values are from 0.019 to 0.026 µM while IC50 of Lapatinib is 0.028 µM. Molecular docking studies were conducted to investigate the binding mode, amino acid interactions and free binding energy of these potent derivatives.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Indoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/metabolism , Binding Sites , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Design , Drug Screening Assays, Antitumor , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/chemistry , ErbB Receptors/metabolism , G1 Phase Cell Cycle Checkpoints/drug effects , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Indoles/chemical synthesis , Indoles/metabolism , Lapatinib/pharmacology , Molecular Docking Simulation , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/metabolism
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