What an adult multiple sclerosis registry can tell us about pediatric onset multiple sclerosis?

BACKGROUND: Multiple Sclerosis (MS) is an immune-mediated, chronic disease of the central nervous system that affects mainly adults. However, it is increasingly recognized that MS may start in childhood resulting in a relentlessly progressive disability and cognitive impairment. Registries across the globe are reporting inconstant data about their Pediatric-Onset Multiple Sclerosis (POMS) patients. Moreover, newer lines of treatments are emerging and showing efficacy in controlling the MS disease regardless of the onset. Therefore, there is a requirement for more research into the clinical profile of POMS in different populations and ethnicities. METHODS: This study was a cross-sectional study that included MS patients who visited the MS unit at Alexandria University from January 2019 to January 2021. We analyzed their epidemiological, clinical, radiological data, and cerebrospinal fluid (CSF) results from their updated records as well as follow-up interviews. RESULTS: Annual Relapse Rate (ARR) was marginally less in POMS than AOMS (0.72 ± 0.57 vs 1.04 ± 0.78 relapse/year, P =.008). POMS patients had a bigger gap to their first relapse (40.0 ± 47.35 vs 22.71 ± 34.33 months, p= .066). The difference in relapse rate between the two groups was abolished after the exclusion of patients who had a gap of more than 5 years to their first relapse. AOMS patients were significantly more likely to start with a second-line disease-modifying treatment (DMT) than POMS patients (11.5% vs 31%, p= .04), whereas POMS patients were more likely to be escalated to the second line (34.6% vs 19.3%, p= .07). ARR had a positive and significant correlation with expanded disability status scale (EDSS) progression per year (rs(24)= .57 p=.003). A Mann-Whitney test indicated that POMS patients who had infratentorial involvement in the initial MRI brain had higher EDSS (3.08 ± 1.99) than POMS who did not (1.07 ± 0.79) U=24 P =.013. IgG index had a significant and positive correlation with annual EDSS progression rate rs (8) = 0.8 p=.001. CONCLUSION: Early disease onset does not mean a higher relapse rate when including the full spectrum of POMS and longer follow-up duration. POMS patients relapsed more on the first-line DMT and escalation should be considered early. Infratentorial involvement in the initial magnetic resonance imaging (MRI) brain and high IgG index are potential predictors for aggressive disease course in POMS.

Cardiac function in women receiving dual anti-Her2 antibodies (trastuzumab and pertuzumab) combined with chemotherapy for breast cancer.

BACKGROUND: Chemotherapy regimens containing a combination of anti-Her2 antibodies are effective but can be associated with cardiac toxicity. OBJECTIVES: We evaluate the outcome with a particular focus on the cardiac function of patients with Her2 over-expressed breast cancer receiving Chemotherapy regimens combined with Trastuzumab and Pertuzumab in routine clinical practice settings. DESIGN AND METHODS: The initial cohort of patients who started Chemotherapy regimens in combination with Trastuzumab and Pertuzumab before September 2019 in four cancer units were reviewed retrospectively. All patients had regular measurements of left ventricular ejection fraction by Doppler ultrasound. RESULTS: Sixty-seven patients were identified. Chemotherapy regimens in combination with Trastuzumab and Pertuzumab treatment were administered in the neoadjuvant and palliative settings in 28 (41.8%) and 39 (58.2%) patients, respectively. All patients underwent left ventricular ejection fraction assessment prior to starting Chemotherapy regimens in combination with Trastuzumab and Pertuzumab treatment and at 3 and 6 months later. Subsequently, left ventricular ejection fraction was measured at 9, 12, 15, 18, 21, and 24 months as long as patients are still receiving any of the treatment components. Compared to baseline, the mean left ventricular ejection fraction was not significantly different at any of the subsequent time points (range; decrease by 0.936% to increase by 1.087%: T-test P value not statistically significant for all comparisons). Trastuzumab and Pertuzumab administration was withheld temporarily for two patients due to clinically suspected cardiac toxicity which was excluded upon further investigations. In the neoadjuvant cohort, 82.3% of patients were relapse free at 3 years. The median progression-free survival was 20 months, and the median overall survival was 41 months in the palliative cohort. CONCLUSION: In this cohort describing our limited initial experience, dual anti-Her2 antibodies (Trastuzumab and Pertuzumab) combined with chemotherapy is effective and not associated with significant cardiac toxicity when the left ventricular ejection fraction is measured every 3 months. This may suggest that previous concerns about cardiotoxicity may have been overemphasized. Further studies investigating less frequent left ventricular ejection fraction monitoring may be warranted.

Patterns of Visual Task-based Functional MRI Activation in Chronic Posterior Cerebral Artery Stroke Patients.

PURPOSE: Stroke is a principal cause of disability worldwide. In motor stroke, the tools for stratification and prognostication are plentiful. Conversely, in stroke causing mainly visual and cognitive problems, there is still no gold standard modality to use. The purpose of this study was to explore the fMRI recruitment pattern in chronic posterior cerebral artery (PCA) stroke patients and to investigate fMRI as a biomarker of disability in these patients. METHODS: The study included 10 chronic PCA stroke patients and another 10 age-matched volunteer controls. The clinical presentation, cognitive state, and performance in visual perceptual skills battery (TVPS-3) were determined for both patients and control groups. Task-based fMRI scans were acquired while performing a passive visual task. Individual and group analyses of the fMRI scans as well as correlation analysis with the clinical and behavioral data were done. RESULTS: At the level of behavioral assessment there was non-selective global impairment in all visual skills subtests. On visual task-based fMRI, patients recruited more brain areas than controls. These activations were present in the ipsilesional side distributed in the ipsilesional cerebellum, dorsolateral prefrontal cortex mainly Brodmann area (BA) 9, superior parietal lobule (somatosensory associative cortex, BA 7), superior temporal gyrus (BA 22), supramarginal gyrus (BA 40), and contralesional associative visual cortex (BA 19). Spearman's rank correlation was computed to assess the relationship between the TVPS scores and the numbers of fMRI neuronal clusters in each patient above the main control activations, there was a negative correlation between the two variables, r(10) = -0.85, p ≤ 0.001. CONCLUSION: In chronic PCA stroke patients with residual visual impairments, the brain attempts to recruit more neighboring and distant functional areas for executing the impaired visual skill. This intense recruitment pattern in poorly recovering patients appears to be a sign of failed compensation. Consequently, fMRI has the potential for clinically relevant prognostic assessment in patients surviving PCA stroke; however, as this study included no longitudinal data, this potential should be further investigated in longitudinal imaging studies, with a larger cohort, and multiple time points.

Using ESN-Smartphone Application to Maximize AIS Reperfusion Therapy in Alexandria Stroke Network: A Stroke Chain of Survival Organizational Model.

Background: In developing countries like Egypt, the clinical workflow of stroke management is poorly established due to the lack of awareness of the stroke patients concerning their need of therapeutic intervention and the poor identification of facilities equipped to treat stroke. Hence, establishing a stroke system of care in developing countries that can efficiently and rapidly triage patients to the appropriate reperfusion therapy center is imperative to improving stroke management and outcomes. Aims: To evaluate a pilot experience in stroke hospital identification and expediting decision-making in AIS treatment through the Alexandria stroke network and Egyptian Stroke Network (ESN)-app. Methods: Between 2017 and 2019, seven hospitals registered themselves on the AS-Network as pilot hospitals. The ESN-application was used to detect stroke type, tele-connect stroke teams and hospitals, track triage of patients to equipped facility in real time, and streamline stroke workflow. The quality of and time required for stroke management were compared between 84 patients with acute ischemic stroke (AIS) whose treatment involved the ESN-app and 276 patients whose treatment did not. Results: During this pilot study, 360 AIS cases received reperfusion therapy, 84 of which were indicated by the ESN-app. The use of the application was associated with the significant drop in time metrics for the reperfusion AIS-patients (door-in-door-out time; 56 ± 34 min vs. 96 ± 45 min, door-to-groin puncture time; 50 ± 7 min vs. 120 ± 25 min, door-to-needle time; 55 ± 12 min vs. 78 ± 16 min with p < 0.0001). Its use was also associated with higher rates of excellent outcomes at the 90-day follow-up (without ESN-app vs. with ESN-app, 67.9 vs. 47.1%, p = 0.001) but no difference in 90-day mortality or symptomatic intracerebral hemorrhage (without ESN-app vs. with ESN-app, 9.5 vs. 11.2% and 4.8 vs. 5.1%, p > 0.05). Conclusion: Our pilot experience demonstrated that the use of the ESN-app expedited the stroke treatment workflow and facilitated tele-connection between registered stroke facilities. Additionally, its use might be associated with achieving higher rates of excellent outcomes at 90 days, where a larger scale study is needed for more confirmation.

Deciding Thrombolysis in AIS Based on Automated versus on WhatsApp Interpreted ASPECTS, a Reliability and Cost-Effectiveness Analysis in Developing System of Care.

Background: Automated ASPECTS has the potential of reducing interobserver variability in the determination of early ischemic changes. We aimed to assess the performance of an automated ASPECTS vs. ASPECTS interpreted for sent CT images on WhatsApp and to correlate these results with the outcome. Materials and Methods: Patients with anterior circulation stroke who had baseline NCCT and underwent successful IV-thrombolysis were included. NCCT-ASPECTS was assessed by two neuroradiologists, and discrepancies were resolved by agreement. Two groups of patients were included; group 1, where treatment was decided after an automated ASPECTS interpretation that was provided by RAPID software, and group 2, where patients received IV-tPA after an assessment of CT images sent on WhatsApp. Results: A total of 122 patients were included: 36 in group 1 and 86 in group 2. In group 2, the interobserver agreement for NCCT ASPECTS was moderate (κ = 0.36), as was the dichotomized data (κ = 0.44). IOA, however, improved (to κ = 0.57 and κ = 0.64) when the same CT images were interpreted on a workstation. In group 1, Automated ASPECTS showed excellent agreement (κ = 0.80) with agreement reads for workstation images. There were significantly (P < 0.001) increased odds of functional independence and fewer hemorrhagic complications with thrombolyzed patients in group 1. Conclusions: Automated ASPECTS provided by the RAPID@IschemaView ASPECTS performs at a level equal to the agreement read of expert neuroradiologists, and this performance was severely degraded when WhatsApp captured CT images used for ASPECTS assessment. In our study, we found that automated ASPECTS might predict outcomes after IV thrombolysis.

Predictive risk factors of venous thromboembolism (VTE) associated with peripherally inserted central catheters (PICC) in ambulant solid cancer patients: retrospective single Centre cohort study.

AIMS: Peripherally inserted central catheters(PICC) lines are becoming increasingly popular in solid cancer patients for the administration of chemotherapy. This study aims looking at the incidence of PICC line related and distant thromboembolism associated with these catheters and exploring risk factors. METHODS: Records were reviewed for 158 patients who underwent PICC line insertion over the two years period in the medical oncology unit, Milton Keynes University Hospital. The Incidence PICC line related Deep Venous Thrombosis (DVT) which is defined as upper extremity DVT at the site of PICC line insertion was documented after checking reports of ultrasound Doppler of all symptomatic patients to confirm the presence of thrombo-embolism and Computed Tomography(CT)scan or Computed Tomography Pulmonary Angiography (CTPA) to confirm the presence Pulmonary Embolism(PE). RESULTS: 23(13%) symptomatic patients with confirmed diagnosis by ultrasound Doppler were found to have PICC line related DVT and similar number of patients developed distant VTE, namely PE and lower limbs DVT. Average time to thrombo-embolism from the insertion of PICC line was 13 days and 51 days in distant VTE. Statistically significant results have been identified in the term of risk factors leading to VTE events during the period of PICC line insertion. CONCLUSIONS: VTE is a common complication in medical oncology patients who underwent insertion PICC line insertion for chemotherapy. Risk of distant VTE is high as well as the PICC line related DVT and the risk of the PICC line related DVT is higher in the first two weeks after PICC insertion. We concluded that high BMI,high PLTs count and Fluropyrimidine containing chemotherapy are all significant risk factors for VTE events recorded while smoking and high BMI are significantly contributing to the high rate of the PICC line related DVT.

Solitary biceps muscle metastasis from breast cancer.

Although direct muscle invasion by carcinoma is well recognised, skeletal muscle metastases are rare. Breast cancer very rarely metastasises to skeletal muscles. We present a case of breast cancer that metastasised to the biceps muscle. The woman developed breast cancer in 1990 and then developed axillary subcutaneous metastasis in 2001. In 2015, she presented with pain in the left forearm extending to the hand. Initial imaging showed no abnormalities, but the positron emission tomography-CT scanning revealed a hot spot in the left biceps muscle. Additionally, the nerve conduction study showed feature of carpal tunnel syndrome. The hot spot was deemed inconclusive in the view of normal CT and MRI scans, and the patient was treated with carpal tunnel decompression. A few months later, the patient developed a lump in the left biceps muscle, which appeared to be a metastatic lesion from her primary breast cancer. The patient was treated with radiotherapy and responded satisfactorily.

Does treatment interruption and baseline hemoglobin affect overall survival in early laryngeal cancer treated with radical radiotherapy? 10 years follow up.

PURPOSE: In this retrospective study we assessed different factors affecting the outcome of early laryngeal cancer, focusing on the impact of the pretreatment hemoglobin (Hb) level, time interval between diagnosis and start of radiotherapy, as well as treatment interruption during the course of radiotherapy. METHODS: We reviewed the hospital records, oncology database and radiotherapy treatment sheets of 88 patients with T1-T3 N0M0 squamous cell carcinoma of the larynx who had been treated with radical radiotherapy at Northamptonshire Centre for Oncology during the period from 1st January 1996 till 31st December 2002 inclusive. Patients were followed up for 10 years. RESULTS: There were no significant overall survival differences with regard to sex , stage, radiotherapy dose received, treatment interruption for 1 to 2 days , as well as the delay to start radiotherapy (mean delay 57 days). However, there was statistically significant adverse overall survival outcome with increasing age (p<0.001). On the other hand, patients with pretreatment Hb level >12 g/dl had significant statistical overall survival benefit over those with ≤12 g/dl (p=0.018). CONCLUSION: Pretreatment Hb level had a significant impact on overall survival in patients with early laryngeal carcinoma treated with radical radiotherapy. Time to start radiation treatment, treatment interruption for 1 or 2 days and different dose / fractionations did not affect the overall survival.

Radiotherapy versus stenting in treating malignant dysphagia.

The most commonly used treatments for maliganat dysphagia are stenting and radiotherapy (RT). A prospective data of 91 patients with locally advanced or metastatic esophageal cancer who has been treated with either palliative RT, stent or both. Group I had RT only, Group II had stent only and group III had both RT and stent. The median overall survival was 169, 119 and 237 in the three groups respectively. The difference between GI & III was statistically significant (P=0.01). Combinations of stent and RT may provide survival benefit in patients with malignant dysphagia. A randomized clinical trial is recommended.

Squamous cell carcinoma metastatic to cervical lymph nodes from unknown primary origin: the impact of chemoradiotherapy.

The management of cervical lymph node metastases of squamous cell carcinoma from an unknown primary site is still a therapeutic challenge. We report here our experience in treating these patients with chemoradiotherapy as a curative approach. Data from 40 patients were reviewed. In total, 20 (50%) patients underwent excisional biopsy. All patients underwent radiotherapy, which was delivered to both sides of the neck and pharyngeal mucosa (extensive field), and concurrent chemotherapy consisting of weekly cisplatin at a dose of 40 mg/m(2). The clinical stage of the cervical nodes at presentation was N1 in 25%, N2 in 60%, and N3 in 15%. Most patients (75%) developed at least grade 3 mucositis. Eight patients (20%) had grade 3 xerostomia and 18 patients (45%) required esophageal dilation for stricture. The 5-year overall survival(OS) rate of all patients was 67.5%. The 5-year OS rates of patients with N1, N2, and N3 lesions were 100%, 67%, and 41%, respectively (P = 0.046). The 5-year progression-free survival rate was 62.5%. In multivariate analysis, only N stage significantly affected OS(P = 0.022). Emergence of the occult primary was very limited (1 patient only). Our results suggest that extensive irradiation of both sides of the neck and pharyngeal mucosa with concurrent chemotherapy results in a lower emergence of primary tumor. Because the survival of patients with unknown primary is comparable to that of patients with known primary, an attempt at cure should always be made.

Hypofractionation in post-mastectomy breast cancer patients: seven-year follow-up.

To compare three fractionation schedules in post-mastectomy patients treated with radiotherapy as regard acute and early late effects as well as local recurrence rates. One hundred and seven breast cancer patients treated with modified radical mastectomy and adjuvant radiotherapy±adjuvant systemic treatments between November 2001 and July 2004 were enrolled in this study. Patients were categorized into three groups. Group A (41 patients) received conventional fractionation 50 Gy over 25 fractions. Group B (36 patients) received other fractionation regimen 45 Gy over 17 fractions. Group C (30 patients) received 40 Gy over 15 fractions. The median follow-up period was 23 months. There has been no statistical significant difference in local control (P=0.88), pain (P=0.98), telangectasis (P=0.23), fibrosis (P=0.13), arm oedema (P=0.96) or pigmentation (P=0.80) between the three groups. GII-III Erythema was significantly higher in the two hypofractionation arms compared to the control arm (P=0.001). Although acute skin reactions were higher in the hypofractionated arms, there was no significant difference in the local recurrence rates or late radiation effects. A national randomized multicentre study is recommended to explore this further.

Northampton outcome for first and second line chemotherapy in non-small cell lung cancer: 5 years data.

AIM OF THE STUDY: There is a definite improvement of progression-free survival as well as overall survival in treating patients with non-small cell lung cancer (NSCLC) with second line chemotherapy. We reviewed the use of chemotherapy in the first and second line setting at Northampton Oncology Centre with emphasis on the survival benefit. The goal of this retrospective study was to review our clinical practice in delivering multiple lines of therapy in comparison to published data worldwide. MATERIAL AND METHODS: Data were collected from patients' records and the oncology database in Northampton Oncology Centre for patients with non-small cell lung cancer patients. A total of 156 patients' records were studied. RESULTS: Out of 156 cases, 108 (69.23%) received first line chemotherapy and 48 (30.77%) received second line chemotherapy. Average survival in the first line group was 395 days (13 months) and in the second line group it was 580 days (19 months). There was a difference of 6.1 months (p = 0.04). Also in the first group average time to progression was 8.5 months and in the second group it was 10.5 months, a difference of nearly two months. CONCLUSIONS: Although we have improved the survival of patients who have metastatic NSCLC with our first line treatments, the rate of recurrence and mortality remains high. Second line chemotherapy should be offered in a selected group of patients.

The effect of the surgical margins on the outcome of patients with head and neck squamous cell carcinoma: single institution experience.

OBJECTIVE: To assess the impact of close or positive surgical margins on the outcome, and to determine whether margin status influence the recurrence rate and the overall survival for patients with head and neck cancers. METHODS: Records from 1996 to 2001 of 413 patients with primary head and neck squamous cell carcinoma (SCC) treated with surgery as the first line treatment were analysed. Of these patients, 82 were eligible for the study. Patients were followed up for 5 years. RESULTS: Patients with margins between 5-10 mm had 50% recurrence rate (RR), those with surgical margins between 1-5 mm had RR of 59% and those with positive surgical margins had RR of 90% (P=0.004). The 5-year survival rates were 54%, 39% and 10%, respectively (P=0.002). CONCLUSIONS: Unsatisfactory surgical margin is an independent risk factor for recurrence free survival as well as overall survival regardless of the other tumor and patient characteristics.