Lesion-level correspondence and longitudinal properties of paramagnetic rim and slowly expanding lesions in multiple sclerosis.

BACKGROUND: Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs). OBJECTIVE: To assess the lesion-level concordance of PRLs and SELs in MS and to characterize changes in brain tissue integrity in CALs over time. METHODS: MRIs were analyzed from a substudy of AFFINITY [NCT03222973], a phase 2 trial of opicinumab in relapsing MS. Assessments included (1) identification of SELs based on longitudinal MRIs over 72 weeks, and identification of PRLs on susceptibility-weighted imaging (SWI) filtered phase images at week 72; (2) evaluation of subject-level correlation of SEL and PRL counts, volumes, and degree of lesion-level overlap between SELs and PRLs; and (3) characterization of tissue integrity over time in overlapping and non-overlapping SELs and PRLs. RESULTS: In 41 subjects, 119 chronic PRLs and 267 SELs were detected. Of 119 (39.5%) chronic PRLs, 47 co-localized with a SEL; 46/267 (17.2%) SELs co-localized with a PRL. PRLs co-localized with SELs showed expansion and worsening microstructural damage over time. SELs with and without co-localization with PRLs showed ongoing tissue damage. CONCLUSIONS: Chronic MS lesions identified as both PRL and SEL were associated with the most severe accumulation of tissue damage. TRIAL REGISTRATION: AFFINITY [NCT03222973].

Biological evaluation of indirect restorations in endodontically treated posterior teeth with deeply located proximal margins following deep margin elevation versus surgical crown lengthening: a randomized controlled trial.

OBJECTIVE: The current clinical trial was conducted to evaluate the effect of proximal indirect restorations in endodontically treated posterior teeth with deeply located margins following deep margin elevation compared to surgical crown lengthening. MATERIAL AND METHODS: Deep proximal cavities in endodontically treated posterior teeth were randomly assigned into two groups; deep margin elevation (DME) or crown lengthening (CL). The clinical attachment level (CAL), probing depth (PD), bleeding on probing (BOP), crestal bone level (CBL), and secondary caries were evaluated at the baseline, 1, 3, 6, 9, and 12 months. RESULTS: A total of 20 proximal cavities were included in the study; there was no significant difference between the two groups regarding mean CAL values at the baseline and 1 month, while there was a significant difference between the two groups in all other periods. Regarding the PD, there was no statistical significance between the two groups except at 9 and 12 months, where CL showed higher mean PD values than DME. There was no statistically significant difference in BOP or CBL between the two groups. CONCLUSIONS: DME and CL are considered clinically successful with favorable biologic responses. CLINICAL RELEVANCE: The deep margin elevation approach could provide a more conservative solution when relocating deeply seated cervical margins in a more coronal position. DME reduced the number of visits and time needed for the restoration of endodontically treated teeth. Surgical crown lengthening remains a gold standard procedure in the re-establishment of the supracrestal tissue attachment, especially in cases where cervical margins are beyond the elevation capacity.

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Modified genioglossus advancement with radiofrequency tongue base reduction for retroglossal collapse in Obstructive sleep apnea patients.

OBJECTIVE: To study the combined effect of modified genioglossus advancement (MGGA) and radiofrequency tongue base reduction (RFTBR) a long with anterolateral advancement (ALA) pharyngolplasty on OSA patients with retrolingual airway collapse. STUDY DESIGN: Prospective clinical study. SETTING: Zagazig and Benha Universities Medical Hospitals. PATIENTS AND METHODS: Twenty-one patients (21)with multilevel OSA underwent modified genioglossus advancement with radiofrequency tongue base reduction and anterolateral advancement pharyngolplasty. All patients were assessed before and 6 months after surgery by history talking, clinical examination, Epworth Sleepiness Scale evaluation fiberoptic examination during muller's maneuver, drug induced sleep endoscopy (DISE), panoramic X-ray, Cephalometry and polysomnography. RESULTS: Postoperative mean ± SD Epworth Sleepiness Scale (ESS) significantly decreased from 18.86 ± 2.03to 8.19 ± 1.86 (P-value was <0.001 95% (CI) 9.80 to 11.53).postoperative mean ± SD AHI decreased from 53.39 ± 14.10 to 26.66 ± 5.44 (P-value was <0.001 95% CI 22.37 to 32.81), postoperative mean ± SD LOS increased from 68.33 ± 9.12 to 86.0 ± 4.96 (P-value was <0.001 95% (CI) 15.24 to21.33).Based on cephalometric analysis postoperative mean ± SD PAS at mid retrolingual point in mm increased from 6.43 ± 1.25 to 11.98 ± 1.69 (P-value was <0.001 95% (CI) 4.78 to 6.32), also postoperative mean ± SD Distance between H-MP in mm decreased from 23.38 ± 1.14 to 15.17 ± 0.97 (P-value was 0.001 95% (CI) 7.66 to 8.76).The postoperative mean ± SD distance from hyoid to menton (H-me) in mm decreased from 39.47 ± 2.37to24.83 ± 2.43(P-value was 0.001 95% (CI) 7.31 to 8.41), the mean ± SD distance of genioglossus muscle advancement in mm was 14.45 ± 1.12.With a success rate defined as AHI < 20 and/or 50% reduction in AHI of the pre- operative value, the surgical success was 81%. CONCLUSION: MGGA with RFTBR along with anterolateral advancement pharyngoplasty in a single session is well tolerated and safe surgery in the treatment of multilevel OSA patients. It is effective in reducing respiratory parameters and subjective symptoms of OSA.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome-a case series and review.

INTRODUCTION: Cranial irradiation is used both prophylactically and for the treatment of brain tumors. There are various complications associated with it. The rare complication of stroke-like migraine attacks after radiation therapy (SMART) syndrome usually occurs several years after radiation therapy but is a reversible phenomenon. It usually presents with headaches, seizures, or other focal neurological deficits concerning stroke or recurrence of the underlying disease. OBJECTIVES: We aim to present two cases of SMART syndrome highlighting the typical presentation, imaging findings, and differential diagnosis. We also conducted the literature review since the early recognition of this rare delayed onset complication is crucial, given its self-limited course and to avoid misinterpretations of the cases. CONCLUSION: Our extensive review favors MRI, CT, and prolonged EEG monitoring to rule out other differentials and showed that initiation of corticosteroid therapy and antiepileptic treatment were helpful in the resolution of symptoms and prevent recurrences. Therefore, future studies should be focused on early identification and management guidelines for SMART syndrome.

The Prevalence and Predictors of Post-Stroke Depression and Anxiety During COVID-19 Pandemic.

INTRODUCTION: Stroke is associated with a rise in post-stroke depression (PSD) and anxiety (PSA). In this study, we evaluated the impact of COVID-19 pandemic on the rates of PSD and PSA. METHODS: All stroke admissions to two hospitals in Saudi Arabia during two months were prospectively evaluated for PSD and PSA. NIHSS and serum TSH assessed on admission. PSD and PSA were evaluated using Hospital Anxiety and Depression Scale (HADS). Post-stroke disability was assessed by mRS, while social support assessed by Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: Among 50 participants (28 males), clinically significant PSD was found in 36%, while PSA in 32%. PSD associated with higher NIHSS (P < 0.001); lower MSPSS (P = 0.003); higher mRS (P = 0.001); and discontinuation of rehabilitation (P = 0.02). PSA was associated with higher TSH (P = 0.01); lower MSPSS (P = 0.03); while discontinuation of rehabilitation was related to less PSA (P = 0.034). Multivariate analysis showed that NIHSS (OR: 1.58, 95% CI: 742-3.37; P = 0.01); and MSPSS score (OR: 0.66, 95% CI: 0.47-0.94; P = 0.002) were associated with PSD; while PSA was related to TSH level (OR: 8.32, 95% CI:1.42-47.23; P = 0.02), and discontinuation of rehabilitation (OR: -0.96, 95% CI: -1.90-0.02; P = 0.04). CONCLUSIONS: Our research shows that the rise in PSD is related to stroke severity and this has not changed significantly during the pandemic; however, PSA showed a noticeable peak. Social deprivation and the lacking levels of rehabilitation related significantly to both.

Possible curative role of curcumin and silymarin against nephrotoxicity induced by gamma-rays in rats.

Curcumin (CUR) and silymarin (SLM) are powerful antioxidant and anti-inflammatory compounds with beneficial protective effects against renal diseases. The purpose of this study was to evaluate the efficacy of CUR and SLM alone or in combination on radiation (IR) induced kidney injury. The results showed that CUR and SLM alone or in combination attenuated the oxidative stress denoted by a reduction in the level of malondialdehyde (MDA), hydrogen peroxide (H2O2) and advanced oxidation protein products (AOPP) along with a marked increase of glutathione GSH content and total antioxidant capacity (TAC). Additionally, a significant decrease in the level of blood urea nitrogen (BUN), creatinine, Cystatin-C (CYT-C), neutrophil gelatinase-associated lipocalin (N-GAL) and Kidney Injury Molecule-1 (Kim-1) was recorded. Moreover, the treatment resulted in a remarkable decline in the serum levels of interleukin-18(IL-18), tumor necrosis factor- alpha (TNF-α), C reactive protein (CRP), BCL2 associated X protein (Bax), Factor-related Apoptosis (FAS) and the activity of Caspase-3 associated by an increase of B-cell CLL/lymphoma 2 (Bcl2) level. The results were confirmed with the histopathological examination. Kidney of irradiated showed glomerular atrophy, massive necrotic changes of expanded tubules with hyaline cast inside some tubules and apoptotic changes were recorded in some renal tubules. While irradiated rats treated with CUR and SLM exhibited marked preservation of the cellular structure of their kidney tissue. In conclusion, the combination of CUR and SLM could be more potent than a single agent on the biochemical and histological changes of the irradiated rat renal tissue.

Differential effect of Taraxacum officinale L. (dandelion) root extract on hepatic and testicular tissues of rats exposed to ionizing radiation.

Exposure to high doses of radiation negatively impacts on human organs. Dandelion (Taraxacum officinale ) L. has been used as a traditional folk. This study was to investigate the effect of dandelion root extract (DRE) on radiation -induced hepatic and testicular tissues injury. Animals were exposed to 8.5 Gy of gamma radiation applied as a shot dose and DRE (200 mg/kg/day), was orally supplemented to rats 14 days before and after irradiation. The results showed that DRE administration attenuated oxidative stress in the liver and testis denoted by a significant reduction in the level of MDA and PCO with a marked elevation in GSH and the activity of SOD, CAT and Gpx. Moreover, DRE administration showed positive modulation in the activity of PNPase, GLDH and GSH-Ts. Additionally, these alterations were associated with a significant decrease in the activity of ALT, AST, ALP, and LDH with a marked increase of AL level. Further, elevated levels of testosterone, LH and inhibin B, as well as StAR and P450scc gene expression and Zn level with a decrease of FSH level were noticed. Also, DRE reduced the level of IL-1ß, TNF-α, and caspase-3. Also administration of DRE significance diminished the histopathological changes in the hepatic and testicular tissues, denoted by a reduction in the necrotic and degenerative changes of hepatocytes or fibrinoid necrosis of congested central vein and improving the seminiferous tubules and interstitial tissue between the tubules of the testis. In conclusion, treatment with DRE pre-irradiation is effective on both liver and testicular tissues of rats. Meanwhile, in the case of post-radiation administration, DRE was more effective on testicular tissue than liver. So we suggest that it is better to use the dandelion before exposure to radiation rather than after it.

Discriminative analysis of regional evolution of iron and myelin/calcium in deep gray matter of multiple sclerosis and healthy subjects.

BACKGROUND: Combined R2* and quantitative susceptibility (QS) has been previously used in cross-sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. PURPOSE: We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. STUDY TYPE: Longitudinal (baseline and 2-year follow-up) retrospective study. SUBJECTS: Twenty-seven relapsing-remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age-matched healthy subjects. FIELD STRENGTH/SEQUENCE: 4.7T 10-echo gradient-echo acquisition. ASSESSMENT: Automatically segmented caudate nucleus (CN), thalamus (TH), putamen (PU), globus pallidus, red nucleus (RN), substantia nigra, and dentate nucleus were retrospectively analyzed to quantify regional volumes, bulk mean R2*, and bulk mean QS. DARE utilized combined R2* and QS localized changes to compute spatial extent, mean intensity, and total changes of DGM iron and myelin/calcium over 2 years. STATISTICAL TESTS: We used mixed factorial analysis for bulk analysis, nonparametric tests for DARE (α = 0.05), and multiple regression analysis using backward elimination of DGM structures (α = 0.05, P = 0.1) to regress bulk and DARE measures with the follow-up Multiple Sclerosis Severity Score (MSSS). False detection rate correction was applied to all tests. RESULTS: Bulk analysis only detected significant (Q ≤ 0.05) interaction effects in RRMS CN QS (η = 0.45; Q = 0.004) and PU volume (η = 0.38; Q = 0.034). DARE demonstrated significant group differences in all RRMS structures, and in all PMS structures except the RN. The largest RRMS effect size was CN total R2* iron decrease (r = 0.74; Q = 0.00002), and TH mean QS myelin/calcium decrease for PMS (r = 0.70; Q = 0.002). DARE iron increase using total QS demonstrated the highest correlation with MSSS (r = 0.68; Q = 0.0005). DATA CONCLUSION: DARE enabled discriminative assessment of specific DGM changes over 2 years, where iron and myelin/calcium changes were the primary drivers in RRMS and PMS compared to age-matched controls, respectively. Specific DARE measures of MS DGM correlated with follow-up MSSS, and may reflect complex disease pathology. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

Progressive iron accumulation across multiple sclerosis phenotypes revealed by sparse classification of deep gray matter.

PURPOSE: To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls. MATERIALS AND METHODS: R2*/QS maps were computed using a 4.7T 10-echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing-remitting (RR), 40 secondary-progressive (SP), 13 primary-progressive (PP) MS patients, and 75 controls. Sparse classification for R2*/QS maps of segmented caudate nucleus (CN), putamen (PU), thalamus (TH), and globus pallidus (GP) structures produced localized maps of iron/myelin in MS patients relative to controls. Paired t-tests, with age as a covariate, were used to test for statistical significance (P ≤ 0.05). RESULTS: In addition to DGM structures found significantly different in patients compared to controls using whole region analysis, singular sparse analysis found significant results in RRMS PU R2* (P = 0.03), TH R2* (P = 0.04), CN QS (P = 0.04); in SPMS CN R2* (P = 0.04), GP R2* (P = 0.05); and in PPMS CN R2* (P = 0.04), TH QS (P = 0.04). All sparse regions were found to conform to an iron accumulation pattern of changes in R2*/QS, while none conformed to demyelination. Intersection of sparse R2*/QS regions also resulted in RRMS CN R2* becoming significant, while RRMS R2* TH and PPMS QS TH becoming insignificant. Common iron-associated volumes in MS patients and their effect size progressively increased with advanced phenotypes. CONCLUSION: A localized technique for identifying sparse regions indicative of iron or myelin in the DGM was developed. Progressive iron accumulation with advanced MS phenotypes was demonstrated, as indicated by iron-associated sparsity and effect size. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1464-1473.

Consensus Guideline on the Management of Epilepsy in Egypt: A National Delphi Consensus Study.

OBJECTIVE: In epilepsy, early diagnosis, accurate determination of epilepsy type, proper selection of antiseizure medication, and monitoring are all essential. However, despite recent therapeutic advances and conceptual reconsiderations in the classification and management of epilepsy, serious gaps are still encountered in day-to-day practice in Egypt as well as several other resource-limited countries. Premature mortality, poor quality of life, socio-economic burden, cognitive problems, poor treatment outcomes, and comorbidities are major challenges that require urgent actions to be implemented at all levels. In recognition of this, a group of Egyptian epilepsy experts met through a series of consecutive meetings to specify the main concepts concerning the diagnosis and management of epilepsy, with the ultimate goal of establishing a nationwide Egyptian consensus. METHODS: The consensus was developed through a modified Delphi methodology. A thorough review of the most recent relevant literature and international guidelines was performed to evaluate their applicability to the Egyptian situation. Afterward, several remote and live rounds were scheduled to reach a final agreement for all listed statements. RESULTS: Of 278 statements reviewed in the first round, 256 achieved ≥80% agreement. Live discussion and refinement of the 22 statements that did not reach consensus during the first round took place, followed by final live voting then consensus was achieved for all remaining statements. SIGNIFICANCE: With the implementation of these unified recommendations, we believe this will bring about substantial improvements in both the quality of care and treatment outcomes for persons with epilepsy in Egypt. PLAIN LANGUAGE SUMMARY: This work represents the efforts of a group of medical experts to reach an agreement on the best medical practice related to people with epilepsy based on previously published recommendations while taking into consideration applicable options in resource-limited countries. The publication of this document is expected to minimize many malpractice issues and pave the way for better healthcare services on both individual and governmental levels.

Endovascular treatment of cerebral sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

INTRODUCTION: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. PATIENTS AND METHODS: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. RESULTS: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). DISCUSSION AND CONCLUSION: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.

Acute mancozeb-fungicide exposure induces neuro-ethology disruption, health disorders, and immune-oxidative dysfunction in Nile tilapia (Oreochromis niloticus).

An acute exposure study of mancozeb (MAZ) fungicide was applied on Oreochromis niloticus for 96-h duration. Three hundred fish (20.50 ± 1.60 g) were assigned into six groups (50 fish/ group; 10 fish/replicate) and exposed to different six concentrations (0, 4, 8, 12, 16, and 20 mg L-1) of MAZ for 96-h. The Probit analysis program was used to compute the 96-h lethal concentration 50 (96-h LC50) of MAZ. During the exposure duration, the fish's behavior, clinical symptoms, and mortalities were recorded daily. After the exposure period was ended, the hematological, biochemical, immunological, and oxidant/antioxidant parameters were evaluated. The results of this study recorded the 96-h LC50 of MAZ for O. niloticus to be 11.49 mg L-1. Acute MAZ exposure badly affected the fish's behavior in the form of increased the breath gasping and swimming activity with aggressive mode. The exposed fish showed excessive body hemorrhages and fin rot. The survival rate of the exposed fish to MAZ was 100, 80, 66, 50, 38, and 30% in 0, 4, 8, 12, 16, and 20 mg L-1 MAZ, respectively. The hematological indices (red blood cell count, hemoglobin, packed cell volume%, and white blood cell count) were significantly decreased by increasing the MAZ exposure concentration (8-20 mg L-1). The acetylcholine esterase activity and immune indices (lysozyme, nitric oxide, immunoglobulin M, complement 3) were decreased by MAZ exposure (4-20 mg L-1). Acute MAZ exposure induced hepato-renal dysfunction and elevated stress-related parameter (cortisol) by increasing the MAZ concentration. A significant reduction in the antioxidant parameters (total antioxidant activity, catalase, and superoxide dismutase) with increasing the lipid peroxidation marker (malondialdehyde) was noticed by acute MAZ exposure (4 -20 mg L-1) in O. niloticus. Based on these outcomes, the MAZ exposure induced toxicity to the fish evident in changes in fish behavior, neurological activity, hepato-renal functioning, and immune-antioxidant responses which suggest physiological disruption.

Dural Arteriovenous Fistula Presenting as a Rapidly Progressive Thalamic Dementia: A Case Report.

Rapidly progressive dementia is an uncommon neurological presentation and usually needs extensive workup, especially for reversible causes. Dural arteriovenous fistula (DAVF) has been rarely reported as a cause of thalamic dementia, in which bilateral thalamic venous congestion and edema cause dementia that usually progresses rapidly. We present a case of a 45 years-old male who presented with rapidly progressive severe attention and memory impairment over one week. Initial work-up showed bilateral thalamic recent venous infarctions and edema. Extensive work-up revealed an intracranial DAVF with internal deep venous thrombosis. Management with endovascular treatment of DAVF followed by anticoagulation for venous thrombosis leads to improvement of the patient's clinical condition, particularly memory and attention. In conclusion, DAFV could present with thalamic rapidly progressive dementia due to bithalamic infarctions and edema. Early diagnosis and treatment will reverse the cause and improve the patient's general and cognitive conditions.

Post COVID-19 Vaccination-Associated Neurological Complications.

PURPOSE: Neurological sequelae after COVID-19 vaccination are rare. We investigated the possible pathogenesis behind the development of neurological complications within a short period after Saudi residents received a COVID-19 vaccine. PATIENTS AND METHODS: We evaluated 18 patients who recently received a COVID-19 vaccine (Comirnaty and Vaxzevria vaccines) and presented with neurological complications to the Saudi German Hospitals in Jeddah, Saudi Arabia. Neurologists assessed the patients' clinical presentation, radiological investigations, and laboratory findings. RESULTS: Three patients who received the first dose of the Vaxzevria vaccine experienced severe cerebral venous thrombosis, two of them were complicated by intracranial hemorrhage. Their laboratory investigations showed very high d-dimers and severe thrombocytopenia, which have been linked to higher mortality and poor outcome. Ischemic stroke occurred in eight cases (44.4%) with a predominance in older male patients. Three patients presented with seizures, two had optic neuritis. Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) occurred in two male patients following vaccination with Comirnaty. CONCLUSION: Neurological complications after COVID-19 vaccinations are very rare, and only a few cases have been reported worldwide. The shared pathophysiological basis between COVID-19 viral infection and COVID-19 vaccines stands behind the very rare neurological complications resulting from the hypercoagulable state triggered by the general inflammatory condition. We suspect some differences in the pathogenesis of ischemic stroke caused by COVID-19 infection and COVID-19 vaccines, which render COVID-19 vaccine-associated ischemic stroke more responsive to treatment. To date, no definitive association between the vaccine and GBS has been proven by any strong evidence, but it has recently been added as a very rare side effect of the Janssen COVID-19 vaccine. No possible links of Miller Fisher syndrome to COVID-19 vaccines have been reported before the one reported in this study.

Regional and national differences in stroke thrombolysis use and disparities in pricing, treatment availability, and coverage.

BACKGROUND: Major disparities have been reported in recombinant tissue plasminogen activator (rtPA) availability among countries of different socioeconomic status. AIMS: To characterize variability of rtPA price, its availability, and its association with and impact on each country's health expenditure (HE) resources. METHODS: We conducted a global survey to obtain information on rtPA price (50 mg vial, 2020 US Dollars) and availability. Country-specific data, including low, lower middle (LMIC), upper middle (UMIC), and high-income country (HIC) classifications, and gross domestic product (GDP) and HE, both nominally and adjusted for purchasing power parity (PPP), were obtained from World Bank Open Data. To assess the impact of rtPA cost, we computed the rtPA price as percentage of per capita GDP and HE and examined its association with the country income classification. RESULTS: rtPA is approved and available in 109 countries. We received surveys from 59 countries: 27 (46%) HIC, 20 (34%) UMIC, and 12 (20%) LMIC. Although HIC have significantly higher per capita GDP and HE compared to UMIC and LMIC (p < 0.0001), the median price of rtPA is non-significantly higher in LMICs (USD 755, interquartile range, IQR (575-1300)) compared to UMICs (USD 544, IQR (400-815)) and HICs (USD 600, IQR (526-1000)). In LMIC, rtPA cost accounts for 217.4% (IQR, 27.1-340.6%) of PPP-adjusted per capita HE, compared to 17.6% (IQR (11.2-28.7%), p < 0.0001) for HICs. CONCLUSION: We documented significant variability in rtPA availability and price among countries. Relative costs are higher in lower income countries, exceeding the available HE. Concerted efforts to improve rtPA affordability in low-income settings are necessary.

Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: a randomized controlled trial.

COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to the hepatitis C virus (HCV) in the replication process. Sofosbuvir/ledipasvir is an approved drug to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection. This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group that received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. 250 patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p<0.001). Kaplan-Meir plot showed a considerably higher cure over time in the S.L. group (Log-rank test, p=0.032). There were no deaths in the S.L. group, but there were six deaths (4.8%) in the OCH group (RR=0.08, p=0.013). Seven patients (5.6%) in the S.L. group and six patients (4.8%) in the OCH group were admitted to the intensive care unit (ICU) (RR=1.17, P=0.776). There were no significant differences between treatment groups regarding total leukocyte and neutrophils count, lymph, and urea. Sofosbuvir/ledipasvir is suggestive of being effective in treating patients with moderate COVID-19 infection. Further studies are needed to compare Sofosbuvir/ledipasvir with new treatment protocols.

Unusual Manifestation of Choroidal Metastasis as Late Presentation of Treated Lung Cancer with Floaters.

Metastatic tumors to the choroid are the most common intraocular malignancies. Choroidal metastasis from lung cancer is uncommon. Visual affection or other ocular manifestations as the initial clinical presentation of lung cancer primarily are rare. We report a case of a 71-year-old female patient presented with eye floaters in her right eye. Examination of the right eye visual acuity of 20/30 and fundoscopy revealed a pale choroidal mass superior to optic disc. Ocular coherent tomography showed subretinal fluid at the site of choroidal lesion. The patient is currently treated with radiotherapy and chemotherapy for secondary metastasizes in liver. In spite of floaters is very common nonserious symptoms in ophthalmology practice, but it should be taken seriously to rule out lifesaving condition.

Effect of Low-Dose Gamma Radiation and Lipoic Acid on High- Radiation-Dose Induced Rat Brain Injuries.

AIM: This work aims to investigate the possible radio-adaptive mechanisms induced by low-dose (LD) whole-body γ-irradiation alone or combined with alpha-lipoic acid (ALA) administration in modulating high-dose (HD) head irradiation-induced brain injury in rats. MATERIALS AND METHODS: Rats were irradiated with LD (.25 Gy) 24 hours prior HD (20 Gy), and subjected to ALA (100 mg/kg/day) 5 minutes after HD and continued for 10 days. At the end of the experiment, animals were sacrificed and brain samples were dissected for biochemical and histopathological examinations. RESULTS: HD irradiation-induced brain injury as manifested by elevation of oxidative stress, DNA damage, apoptotic, and inflammatory markers in brain tissue. Histological examination of brain sections showed marked alterations. However, LD alone or combined with ALA ameliorated the changes induced by HD. CONCLUSION: Under the present experimental conditions, LD whole-body irradiation exhibited neuroprotective activity against detrimental effects of a subsequent HD head irradiation. This effect might be due to the adaptive response induced by LD that activated the anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms in the affected animals making them able to cope with the subsequent high-dose exposure. However, the combined LD exposure and ALA supplementation produced a further modulating effect in the HD-irradiated rats.

A nano based approach to alleviate cisplatin induced nephrotoxicity.

BACKGROUND AND OBJECTIVE: Cisplatin, an effective drug against cancer, commonly induces nephrotoxicity; limiting its therapeutic efficacy and application. In this study, Cisplatin NanoComposite (Cis NC) was formulated successfully from irradiated chitosan coated Cisplatin and MgO nanoparticles (CHIT/Cis/MgO NPs) to promote cisplatin release in a more sustained manner to improve therapeutic efficacy via the reduction of its nephrotoxicity. To compare the relative induced renal toxicity of cisplatin with Cisplatin NanoComposite, histological and biochemical mechanisms underlying nephrotoxicity were investigated. METHODS: Thirty rats were equally separated to three groups, first group received saline injections and adjusted as the control group, the second group was injected intra-peritoneal with cisplatin 0.64 mg/kg b. wt./day for 6 weeks, the third group was injected intra-peritoneal with Cis NC 5.75 mg/kg b. wt. daily for 6 weeks. RESULTS: Cisplatin-induced renal functional impairment and histopathological damages in the kidney; also, cisplatin disrupted the balance of the redox system in renal tissue, stimulated the inflammatory reactions in the kidney via triggering signal transducer and activator of transcription-1 (STAT1) dependent pathways. Moreover, Cisplatin-induced activation of mammalian target of rapamycin mTOR and inactivation of AMPK/PI3K/Akt signal pathway, and was coupled with induction of p53 activity and the executioner caspase3 to induce apoptotic renal cell death. On the other hand, Cis NC exerted a minimal stimulatory effect on apoptotic and inflammatory signal cascade with negligible renal functional and morphological alterations. CONCLUSION: We postulated that Cis NC may be a valued possible drug to decrease the cytotoxicity of cisplatin thus reserves the renal function and structure.