Creutzfeldt-Jakob disease in a post-COVID-19 patient: did SARS-CoV-2 accelerate the neurodegeneration?

Background: Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disorder, with few months as a usual duration from onset to death. Case presentation: In this case report, a patient of Sporadic CJD (sCJD) who presented one month after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The diagnosis of this case was established after confirming findings from clinical, neurophysiology, radiological, and laboratory features of this disease. Conclusion: Putting in mind all the updated data on the pathogenesis of CJD and the immune responses to SARS-CoV-2, we can suggest that COVID-19 can lead to accelerated pathogenesis and exaggerated manifestations of this fatal neurodegenerative disease.

Post-COVID isolated subclavian artery dissection with multiple cerebral infarctions.

Background: Coronavirus disease 2019 (COVID-19) is a pandemic disease which predominantly affects the respiratory system with high critical care mortality and morbidity, yet it also causes multiple organs dysfunction in affected patients. There is a strong evidence that it increases the susceptibility of cerebrovascular strokes in such patients. Besides this prothrombotic complication, arterial dissection can be one of its mechanisms increasing the risks of stroke. Case presentation: Herein, we report a case of spontaneous isolated subclavian artery dissection in a COVID-19 patient. Sixty-one-year-old female presented with spontaneous isolated subclavian artery dissection without any traumatic events nor history of connective tissue disorders. She had left upper limb ischemia followed by cerebellar, thalamic and occipital infarctions. Whether this patient's subclavian artery dissection was triggered by exaggerated inflammatory response or arteriopathy secondary to COVID-19 remains speculative. Conclusions: Nonetheless, arterial dissection can be one of its complications, it is essential for treating physicians to be attentive for the diversity of COVID-19 clinical manifestations.

Morphometric measurements and the relationship with body weight in the Sudanese Dorcas Gazelle and Bohor Reedbuck.

The objectives were to describe the morphometric measurements and determine the best model for estimating the relationship between body weight and morphometric measurements of the two Sudanese antelopes, Dorcas Gazelle (Gazella dorcas) and Bohor Reedbuck (Redunca redunca). Twenty-four animals belonging to two Sudanese antelope species, six males and six females from each species were used. Data on body weight and body measurements were recorded from each species. Averages of body weight and morphometric traits of Bohor Reedbuck were larger than the corresponding values of Dorcas Gazelle, while the opposite was true in the case of horn thickness, which was larger in the later. Stepwise regression analysis indicated that, the best model for Dorcas Gazelle had the variables neck length, belly girth and chest height, while Bohor Reedbuck had body length, head length, neck length, tail length, chest girth and pelvic height. These variables explained 82% of the total variation in body weight of Dorcas Gazelle, and 92% of the variation of Bohor Reedbuck. These results are discussed in relation to morphometric measurements reported for antelopes elsewhere.

Sinus arrest following acute lateral medullary infarction.

Lateral medullary syndrome (LMS) is an ischemic stroke of the medulla oblongata that involves the territory of the posterior inferior cerebellar artery. LMS is often missed as the cause of autonomic dysregulation in patients with recent brain stem stroke. Due to the location of the nucleus tractus solitarius (NTS), the dorsal vagal nucleus, and the nucleus ambiguous in the lateral medulla oblongata, patients with LMS occasionally have autonomic dysregulation-associated clinical manifestations. We report a case of LMS-associated autonomic dysregulation. The case presented by recurrent syncope, requiring permanent pacemaker placement. This case shows the importance of recognizing LMS as a potential cause of life-threatening arrhythmias, heart block, and symptomatic bradycardia. Extended cardiac monitoring should be considered for patients with medullary strokes.

Potential effect of methanol leaf extracts from three Podocarpus species on experimental cryptosporidiosis.

Cryptosporidiosis causes diarrhea in both immunocompetent and immunocompromised individuals, with acute manifestations occurring particularly in children and the elderly. Up till now, there is no curative therapy for cryptosporidiosis, so discovery of new classes of drugs are of great importance. This study aimed to examine the effect of methanol leaves extracts of the three Podocarpus species; P. macrophyllus (Thunb.), P. gracilior (Pilg.) and P. elongatus (Aiton) L' Hér. ex Pers and their combination on Cryptosporidium parvum (C. parvum) in experimentally infected mice in comparison with the commercially used drug, Nitazoxanide. As well as spectrophotometric estimation of the total phenolic and flavonoid content of these extracts was done. Results revealed that treatment with these three Podocarpus extracts and their combination showed a significant reduction of the number of C. parvum oocyst shed in the stool of infected mice compared to infected control group and Nitazoxanide- infected treated group at P < 0.001. The combination of the three Podocarpus extracts was the most effective treatment showing the lowest number of oocysts shedding in comparison with other used extracts and Nitazoxanide. Histopathological inspection of sections from ilium and colon displayed signs of improvement after treatment with P. macrophyllus and P. gracilior extracts and more remarkable improvement when the three extracts were combined. It was concluded that the three Podocarpus species extracts used in this study had a promising anti-Cryptosporidium activity especially when they were combined.

Impact of Therapy in Patients with Hematologic Malignancies on Seroconversion Rates After SARS-CoV-2 Vaccination.

INTRODUCTION: The leading professional organizations in the field of hematology have recommended severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) vaccination for all patients with hematologic malignancies notwithstanding efficacy concerns. Here we report a systematic literature review regarding the antibody response to SARS-CoV-2 vaccination in patients with hematologic malignancies and its key determinants. METHODS: We conducted a systematic search of original articles evaluating the seroconversion rates with SARS-CoV-2 vaccines in hematological malignancies from the PubMed database published between April 1, 2021 and December 4, 2021. Calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between patients with hematologic malignancies versus healthy control subjects used the Review Manager software, version 5.3. RESULTS: In our meta-analysis, we included 26 studies with control arms. After the first dose of vaccination, patients with hematologic malignancies had significantly lower seroconversion rates than controls (33.3% vs 74.9%; RD: -0.48%, 95% CI: -0.60%, -0.36%, P < .001). The seroconversion rates increased after the second dose, although a significant difference remained between these 2 groups (65.3% vs 97.8%; RD: -0.35%, 95% CI: -0.42%, -0.28%, P < .001). This difference in seroconversion rates was particularly pronounced for Chronic Lymphocytic Leukemia (CLL) patients (RD: -0.46%, 95% CI: -0.56, -0.37, P < .001), and for patients with B-lineage leukemia/lymphoma treated with anti-CD20 antibodies (RD: -0.70%, 95% CI: -0.88%, -0.51%, P < .001) or Bruton Tyrosine Kinase Inhibitors (BTKi; RD: -0.63%, 95% CI: -0.85%, -0.41%, P < .001). The RD was lower for patients under remission (RD: -0.10%, 95% CI: -0.18%, -0.02%, P = .01). CONCLUSION: The seroconversion rates following SARS-CoV-2 vaccination in patients with hematologic malignancies, especially in CLL patients and patients treated with anti-CD20 antibodies or BTKi, were significantly lower than the seroconversion rates in healthy control subjects. Effective strategies capable of improving vaccine efficacy in these vulnerable patient populations are urgently needed.

Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.

BACKGROUND AND PURPOSE: The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients. METHODS: Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation. RESULTS: Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block. CONCLUSION: This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.

The burden of polypharmacy and drug-drug interactions in older cancer patients treated with immunotherapy.

INTRODUCTION: Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. METHODS: A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. RESULTS: The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). CONCLUSION: In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

Rhino-orbito-cerebral mucormycosis during the COVID-19 third wave in 2021: an Egyptian preliminary report from a single tertiary hospital.

COVID-19 is a pandemic disease which predominantly affects the respiratory system with high critical care mortality and morbidity; however, it also causes multi-organ dysfunction in a subset of patients. Although causality between COVID-19 and mucormycosis remains unclear, many factors including glucocorticoids, worsening of blood glucose control, and viral-induced lymphopenia have been attributed to cause mucormycosis in patients with COVID-19. In COVID-19 patients, especially those who need oxygen support, inflammatory and cytokine storm or usage of steroids make the immune system weak. This may pave the way for opportunistic infections including mucormycosis. We report fourteen cases of COVID-19 infection, who developed rhino-orbito-cerebral mucormycosis, during treatment. Early recognition of this life-threatening infection is the key to allow for optimal treatment and improved outcomes.

Potential effect of methanol leaf extracts from three Podocarpus species on experimental cryptosporidiosis

@#Cryptosporidiosis causes diarrhea in both immunocompetent and immunocompromised individuals, with acute manifestations occurring particularly in children and the elderly. Up till now, there is no curative therapy for cryptosporidiosis, so discovery of new classes of drugs are of great importance. This study aimed to examine the effect of methanol leaves extracts of the three Podocarpus species; P. macrophyllus (Thunb.), P. gracilior (Pilg.) and P. elongatus (Aiton) L’ Hér. ex Pers and their combination on Cryptosporidium parvum (C. parvum) in experimentally infected mice in comparison with the commercially used drug, Nitazoxanide. As well as spectrophotometric estimation of the total phenolic and flavonoid content of these extracts was done. Results revealed that treatment with these three Podocarpus extracts and their combination showed a significant reduction of the number of C. parvum oocyst shed in the stool of infected mice compared to infected control group and Nitazoxanideinfected treated group at P < 0.001. The combination of the three Podocarpus extracts was the most effective treatment showing the lowest number of oocysts shedding in comparison with other used extracts and Nitazoxanide. Histopathological inspection of sections from ilium and colon displayed signs of improvement after treatment with P. macrophyllus and P. gracilior extracts and more remarkable improvement when the three extracts were combined. It was concluded that the three Podocarpus species extracts used in this study had a promising anti-Cryptosporidium activity especially when they were combined.

Antibody Responses to COVID-19 Vaccination in Cancer: A Systematic Review.

INTRODUCTION: After the results of phase III vaccine studies became available, the leading oncology societies recommended two doses of COVID-19 vaccination to all patients with cancer with no specific recommendation for tumor type and active treatments. However, the data on the COVID-19 vaccine efficacy in cancer patients is limited due to exclusion of cancer patients from most vaccine clinical trials. Therefore, we systemically reviewed the available evidence evaluating the antibody responses in cancer patients. METHODS: We conducted a systematic search from the Pubmed database and calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between cancer patients and controls using the Review Manager software, version 5.3. RESULTS: Our systematic search retrieved a total 27 studies and we included 17 studies with control arms in the analyses. Cancer patients had significantly lower seroconversion rates (37.3%) than controls (74.1%) (RD: -0.44, 95% CI: -0.52, -0.35, p<0.001) with first vaccine dose. After two doses, the seroconversion rates were 99.6% in control arm and 78.3% in cancer patients (RD: -0.19, 95% CI: -0.28, -0.10, p<0.001). The difference in seroconversion rates was more pronounced patients with hematologic malignancies (72.6%) (RD: -0.25, 95% CI: -0.27, -0.22, p<0.001) than patients with solid tumors (91.6%) (RD: -0.09, 95% CI: -0.13, -0.04, p<0.003) and patients in remission (RD: -0.10, 95% CI: -0.14, -0.06, p<0.001). CONCLUSION: In conclusion, COVID-19 vaccine seroconversion rates were significantly lower in patients with hematological malignancies and patients under active treatment. Further research focusing on the approaches to improve vaccine efficacy and exploration of novel treatment options is urgently needed for these patients.

Lower prognostic nutritional index is associated with poorer survival in patients receiving immune checkpoint inhibitors.

Aim: Blood-based biomarkers like prognostic nutritional index (PNI) are readily available biomarkers for immunotherapy efficacy, although the data are limited. So, we aimed to evaluate the association between PNI and overall survival (OS) in immunotherapy-treated patients. Materials & methods: For this retrospective cohort study, data of 150 immunotherapy-treated advanced cancer patients were evaluated. The association between clinical factors and OS was evaluated with multivariate Cox-regression analyses. Results: After a median follow-up of 8.5 months, 94 patients died. The median OS was 11.07 months. The low PNI (hazard ratio [HR]: 2.065; p = 0.001), high lactate dehydrogenase (HR: 2.515; p = 0.001) and poor Eastern Cooperative Oncology Group (ECOG) status (HR: 2.164; p = 0.009) was associated with poorer OS in multivariate analyses. Conclusion: In our experience, survival with immunotherapy was impaired in patients with lower PNI and higher lactate dehydrogenase levels and poorer ECOG status.

Borderzone Infarction and Small Vessel Disease in a Sample of Egyptian Stroke Patients: Differences and Similarities.

BACKGROUND: The anatomical location of white matter hyperintense lesions in small vessel disease are apparently similar to those of borderzone infarction. The objective of this study is to find clinical and radiological points of differentiation between the two vascular disorders in a sample of Egyptian patients which might have an impact on primary and secondary prevention. METHODS: Ischemic stroke patients with white matter lesions were categorized into two groups: small vessel disease and borderzone infarctions. NIHSS was done on admission. Risk factor profile was reported, and investigations done including: HbA1C, lipid profile, CRP, ECG, echocardiography, carotid duplex, brain MRI, MRA and MR perfusion study. RESULTS: 46 patients completed the study, 29 with SVD and 17 with BZI. Smoking, hypertension and recurrent stroke were more common in borderzone infarctions, but only diabetes was significantly higher (p = 0.047). Limb shaking was more observed in borderzone infarctions (p = 0.049). Radiologically: lacunar pattern was observed more in small vessel disease, while rosary pattern was more in borderzone infarctions (p = 0.04). FLAIR symmetrical lesions and microbleeds were more significant in small vessel disease (p = <0.001; 0.048, respectively). Perfusion study time to peak denoted evidence of significant hypoperfusion in all regions of interest in borderzone infarctions. CONCLUSION: Limb shaking, retinal claudication or syncope, with MRI showing rosary pattern of white matter hyperintensity, few microbleeds and markedly impaired perfusion favor the diagnosis of borderzone infarctions. On the other hand, presence of lacunae, FLAIR showing symmetrical WMH and microbleeds with minimal or no perfusion deficit suggests the diagnosis of small vessel disease.

Risk stratification and subclinical phenotyping of dilated and/or arrhythmogenic cardiomyopathy mutation-positive relatives: CVON eDETECT consortium.

In relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy, early detection of disease onset is essential to prevent sudden cardiac death and facilitate early treatment of heart failure. However, the optimal screening interval and combination of diagnostic techniques are unknown. The clinical course of disease in index patients and their relatives is variable due to incomplete and age-dependent penetrance. Several biomarkers, electrocardiographic and imaging (echocardiographic deformation imaging and cardiac magnetic resonance imaging) techniques are promising non-invasive methods for detection of subclinical cardiomyopathy. However, these techniques need optimisation and integration into clinical practice. Furthermore, determining the optimal interval and intensity of cascade screening may require a personalised approach. To address this, the CVON-eDETECT (early detection of disease in cardiomyopathy mutation carriers) consortium aims to integrate electronic health record data from long-term follow-up, diagnostic data sets, tissue and plasma samples in a multidisciplinary biobank environment to provide personalised risk stratification for heart failure and sudden cardiac death. Adequate risk stratification may lead to personalised screening, treatment and optimal timing of implantable cardioverter defibrillator implantation. In this article, we describe non-invasive diagnostic techniques used for detection of subclinical disease in relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy.

Predictive biomarkers for immunotherapy efficacy in non-small-cell lung cancer: current status and future perspectives.

In recent years, immune checkpoint inhibitors have rapidly changed treatment paradigms and have been pivotal for the treatment of advanced NSCLC patients. However, many patients don't respond to immunotherapy, and toxicities are a concern. Mounting evidence suggests that PD-L1 expression and tumor mutational burden are useful biomarkers in NSCLC and widely used in clinical practice. Given various limitations of PD-L1 and tumor mutational burden, many candidate biomarkers have emerged. From these biomarkers, peripheral blood-based biomarkers are promising options for the prediction of immunotherapy efficacy with ease of access, repeatability and low cost. This review provides an overview of recent developments on the biomarkers in immunotherapy efficacy together with comments on future perspectives.

Prevention of DMBA-induced mammary gland tumors in mice by a dual-function inhibitor of JAK3 and EGF receptor tyrosine kinases.

Objectives: We tested the chemopreventive effect of WHI-P131 in side by side evaluation with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer model.Methods: One hundred BALB/cmice were divided into five groups. (i) Control (ii) DMBA (iii)  DMBA+ Paclitaxel (10 mg/kg) (iv)  DMBA+WHI-P131 (Janex1, 50 mg/kg of BW, i.p, three times per week) ("J") (v) DMBA+P+J. The duration of study was 25 weeks.Results: Our findings demonstrate that WHI-P131 impedes DMBA-induced carcinogenesis, reduces size, weight, and load of tumors (P < 0.001) in DMBA-challenged mice and improves their survival outcome (P < 0.01). The tumors developing despite WHI-P131 chemoprevention displayedattenuated levels of JAK3, STAT3, and NF-κB as well as increased I-κB expression (P < 0.001). Notably, these tumors exhibited significantly decreased levels of phosphorylated AKT-PI3-Kinase pathway signaling proteins p-mTOR, p-p70S6K1, and p-4E-BP1 (P < 0.001). Our findings are consistent with a model in which DMBA-induced malignant clones with low-level expression of the six signature proteins JAK3/STAT3/NF-κB/p-mTOR, p-p70S6K1/p-4E-BP1, albeit not as aggressive as their JAK3/STAT3/NF-κB overexpressing counterparts are capable of escaping chemo-preventive effects of WHI-P131.Conclusion: These insights may provide the foundation for new chemo-preventive strategies in which WHI-P131 is applied to prevent the development of aggressive forms of breast cancer.