Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases

An epidemiological relationship between urolithiasis and cardiovascular diseases has extensively been reported. Endothelial dysfunction is an early pathogenic event in cardiovascular diseases and has been associated with oxidative stress and low chronic inflammation in hypertension, coronary heart disease, stroke or the vascular complications of diabetes and obesity. The aim of this study is to summarize the current knowledge about the pathogenic mechanisms of urolithiasis in relation to the development of endothelial dysfunction and cardiovascular morbidities. Methods: A non-systematic review has been performed mixing the terms “urolithiasis”, “kidney stone” or “nephrolithiasis” with “cardiovascular disease”, “myocardial infarction”, “stroke”, or “endothelial dysfunction”. Results: Patients with nephrolithiasis develop a higher incidence of cardiovascular disease with a relative risk estimated between 1.20 and 1.24 and also develop a higher vascular disease risk scores. Analyses of subgroups have rendered inconclusive results regarding gender or age. Endothelial dysfunction has also been strongly associated with urolithiasis in clinical studies, although no systemic serum markers of endothelial dysfunction, inflammation or oxidative stress could be clearly related. Analysis of urine composition of lithiasic patients also detected a higher expression of proteins related to cardiovascular disease. Experimental models of hyperoxaluria have also found elevation of serum endothelial dysfunction markers. Conclusions: Endothelial dysfunction has been strongly associated with urolithiasis and based on the experimental evidence, should be considered as an intermediate and changeable feature between urolithiasis and cardiovascular diseases. Oxidative stress, a key pathogenic factor in the development of endothelial dysfunction has been also pointed out as an important factor of lithogenesis. Special attention must be paid to cardiovascular morbidities associated with urolithiasis in order to take advantage of pleiotropic effects of statins, angiotensin receptor blockers and allopurinol.

Clinical and Laboratory Findings of Viral Influenza among Children Hospitalized in Qazvin Pediatric Hospital in Iran, 2015-2020

Background: Children are one of the most important groups at risk of catching the influenza infection. The consequences of influenza in some children, especially children with chronic and underlying diseases, can be very severe and lead to hospitalization. Objective: Purpose of this research was to determine children with influenza and their clinical and laboratory findings in Qazvin children hospital between 2015 to 2020 years. Methods: In this descriptive cross-sectional study, epidemiological and clinical finding of children hospitalized due to confirmed influenza were considered. A total of 1468 children with a suspected diagnosis to influenza were included in this study. Then, based on the Real-time Polymerase Chain Reaction (PCR) a total of 229 were confirmed positive to influenza. Statistical analysis was done using software SPSS 23.0, Analysis Of Variance (ANOVA) and t-test (p≤0.05). Results: Most of patients (53.7%) were infected with influenza H1N1 type. Most comorbidity was observed with Central Nervous System (CNS) disease and febrile seizure (each one 3.10%). Highest clinical feature was fever (83.4%). Significant relationship was observed between the season (p=0.001), sore in throat (p=0.001), febrile seizure (p=0.051), muscle and joint pain (p=0.059), rhinorrhea (p=0.006) and shiver (p=0.051) and occurrence of influenza. Also 4 children had died from influenza during hospitalization. Conclusion: Children with influenza disease were found in this study. Influenza has some side effects on children health. Due to the irreversible and dangerous effects of the influenza, early diagnosis and appropriate treatment in children is important.

Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia

Background Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses. Method We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms. Results Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination. Conclusions These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.

Cell culture model system utilizing engineered A549 cells to express high levels of ACE2 and TMPRSS2 for investigating SARS-CoV-2 infection and antivirals

Novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an imminent global threat since its initial outbreak in December 2019. A simple in vitro model system using cell lines highly susceptible to SARS-CoV-2 infection are critical to facilitate the study of the virus cycle and to discover effective antivirals against the virus. Human lung alveolar A549 cells are regarded as a useful and valuable model for respiratory virus infection. However, SARS-CoV-2 uses the ACE2 as receptor for viral entry and the TMPRSS2 to prime the Spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a robust human lung epithelial cell-based model by transducing ACE2 and TMPRSS2 into A549 cells and show that the ACE2 enriched A549ACE2/TMPRSS2 cells (ACE2plus) and its single-cell-derived subclone (ACE2plusC3) are highly susceptible to SARS-CoV-2 infection. These engineered ACE2plus showed higher ACE2 and TMPRSS2 mRNA expression levels than currently used Calu3 and commercial A549ACE2/TMPRSS2 cells. ACE2 and TMPRSS2 proteins were also highly and ubiquitously expressed in ACE2plusC3 cells. Additionally, antiviral drugs like Camostat mesylate, EIDD-1931, and Remdesivir strongly inhibited SARS-CoV-2 replication. Notably, multinucleated syncytia, a clinical feature commonly observed in severe COVID-19 patients was induced in ACE2plusC3 cells either by virus infection or by overexpressing the Spike proteins of different variants of SARS-CoV-2. Syncytial process was effectively blocked by the furin protease inhibitor, Decanoyl-RVKR-CMK. Taken together, we have developed a robust human A549 lung epithelial cell-based model that can be applied to probe SARS-CoV-2 replication and to facilitate the discovery of SARS-CoV-2 inhibitors.

Neuroimaging Findings in Racemose Neurocysticercosis: Case Description and Literature Review

Neurocysticercosis (NCC), the most common central nervous system (CNS) parasitic infection among the immunocompetent population can imitate every clinical feature of brain-diseases accurately, drawing attention away from the real culprit and delaying the proper treatment. There are two types of NCC, the parenchymal and the extraparenchymal form. The extraparenchymal NCC include the ventricular cysticercosis, the subarachnoid cysts including giant cysts or racemose cysticercosis with chronic meningitis, the spinal (intra- or extramedullary) cysticercosis and the ophthalmic cysticercosis. It is estimated that about 30% of epilepsy cases in endemic countries are due to NCC and especially the racemose NCC is more aggressive and associated with higher mortality rates. There is a significant heterogeneity in clinical phenotypes, regarding the racemose NCC, which depends on the parasite load and evolutionary stage in association with its location in CNS and the host’s immune response. Crucial for the management of the racemose NCC is the early recognition of the symptoms and the swift initiation of antiparasitic therapy with anti-inflammatory agents in combination with the shunt-insertion in cases of obstructive hydrocephalus. In view of the former considerations we conducted a narrative literature review on racemose NCC and described the diagnostic challenges of a relevant case that we had evaluated in our Department of Neurology.

ДЕКОМПЕНСОВАНИЙ ВИПАДОК ГІПОТИРЕОЗА З УРАЖЕННЯМ СЕРЦЕВО-СУДИННОЇ СИСТЕМИ

We present a clinical case that demonstrates a lack of compliance in a patient with hypothyroidism, which led to severe complications of the cardiovascular system. The clinical feature of this case is the development of severe complications of hypothyroidism due to the patient’s low adherence to therapy and untimely treatment. The patient had all characteristic signs of severe hypothyroidism with heart and skin lesions (total alopecia, edema, dryness and peeling of the skin). Fully available diagnostic criteria were as follows: critical disorders of thyroid hormone levels in the blood, hyperenzymemia, hypothyroidism, fluid in the pleural cavity, increased heart shadow, fluid in the pericardial cavity, left ventricular dilatation, decreased ejection fraction, arrhythmia. The predominant lesion of the cardiovascular system is characteristic of such cases and prevailed in the clinical presentation of the disease and was the direct reason for seeking medical help. Under the influence of treatment, the patient's sinus rhythm was restored, myocardial contractility improved, there was no fluid in the pericardial cavity and pleural cavity, edema decreased, mental activity and emotional state improved. However, the patient flatly refused further observation and treatment. As a result, hypothyroidism is underdiagnosed. Initiation of treatment in the early stages of the disease and prevention of complications relies on early diagnosis through systematic screening according to the recommendations. Heart disease, associated with hypothyroidism is a condition that can be prevented if it is detected and treated by family doctors in a timely manner in an outpatient setting. Timely detection of the disease and hospitalization will allow avoiding serious complications of hypothyroidism, timely diagnosing this pathology and prescribing adequate therapy according to the stage of the disease.

Central nervous system manifestations of mucormycosis

<p><strong>Background:</strong> There has been an unprecedented increase in the number of mucormycosis cases post the second wave of COVID-19 in India, with a variety of clinical manifestations. The central nervous system manifestations have proven to be especially fatal, hence these require special attention. Aims and objectives of current investigation was to study the epidemiology, clinical features, risk factors, diagnostic modalities, management and complications of CNS manifestations of mucormycosis.</p><p><strong>Methods:</strong> This is a retrospective study, conducted on the mucormycosis patients admitted in G.G. hospital Jamnagar. Patients with clinically and radiologically evident central nervous system involvement were included in the study. The records of the patients were followed for 3 months post the diagnosis. 47 patients were included in the study.</p><p><strong>Results:</strong> The mean age of the patients was 51 years. 72.34% of patients were males, and 27.65%, were females. The most common clinical feature was headache 100% followed by fever 55%. Most of the patients (97.87%) had history of COVID 19 or had active infection. 63.96% had diabetes Mellitus. The most common radiological finding was cavernous sinus thrombosis (32.60%), 72.34% underwent surgical debridement, and all the patients were administered Amphotericin B. The outcome improved significantly with surgical debridement, with recovery seen in 51.06% patients.</p><p><strong>Conclusions:</strong> There has been a steep rise in the cases of mucormycosis following the COVID-19 pandemic. It is an extremely virulent infection which spreads rapidly, often causing the involvement of the central nervous system. However, early diagnosis and intervention have been found to alter the prognosis significantly.</p>

There is More Than Meets the Eye: Identification of Dual Molecular Diagnosis in Patients Affected by Hearing Loss

Hearing loss (HL) is the most common sensory impairment, and it is characterized by a high clinical/genetic heterogeneity. Here we report the identification of dual molecular diagnoses (i.e., mutations at two loci that lead to the expression of two Mendelian conditions) in a series of families affected by non-syndromic and syndromic HL. Eighty-two patients who displayed HL as a major clinical feature have been recruited during the last year. After an accurate clinical evaluation, individuals have been analyzed through whole-exome sequencing (WES). This protocol led to the identification of seven families characterized by the presence of a dual diagnosis. In particular, based on the clinical and genetic findings, patients have been classified into two groups: a) patients with HL and distinct phenotypes not fitting in a known syndrome due to mutations at two loci (e.g., HL in association with Marfan syndrome) and b) patients with two genes involved in HL phenotype (e.g., TMPRSS3 and MYH14). These data highlight for the first time the high prevalence of dual molecular diagnoses in HL patients and suggest that they should be considered especially for those cases that depart from the expected clinical manifestation or those characterized by a significant intra-familiar variability.

Consultations for clinical features of possible cancer and associated urgent referrals before and during the COVID-19 pandemic: an observational cohort study from English primary care

Background It remains unclear to what extent reductions in urgent referrals for suspected cancer during the COVID-19 pandemic were the result of fewer patients attending primary care compared to GPs referring fewer patients. Methods Cohort study including electronic health records data from 8,192,069 patients from 663 English practices. Weekly consultation rates, cumulative consultations and referrals were calculated for 28 clinical features from the NICE suspected cancer guidelines. Clinical feature consultation rate ratios (CRR) and urgent referral rate ratios (RRR) compared time periods in 2020 with 2019. Findings Consultations for cancer clinical features decreased by 24.19% (95% CI: 24.04–24.34%) between 2019 and 2020, particularly in the 6–12 weeks following the first national lockdown. Urgent referrals for clinical features decreased by 10.47% (95% CI: 9.82–11.12%) between 2019 and 2020. Overall, once patients consulted with primary care, GPs urgently referred a similar or greater proportion of patients compared to previous years. Conclusion Due to the significant fall in patients consulting with clinical features of cancer there was a lower than expected number of urgent referrals in 2020. Sustained efforts should be made throughout the pandemic to encourage the public to consult their GP with cancer clinical features.

Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants

Neurofibromatosis type 1 (NF1) is the most frequent disorder associated with multiple café-au-lait macules (CALM) which may either be present at birth or appear during the first year of life. Other NF1-associated features such as skin-fold freckling and Lisch nodules occur later during childhood whereas dermal neurofibromas are rare in young children and usually only arise during early adulthood. The NIH clinical diagnostic criteria for NF1, established in 1988, include the most common NF1-associated features. Since many of these features are age-dependent, arriving at a definitive diagnosis of NF1 by employing these criteria may not be possible in infancy if CALM are the only clinical feature evident. Indeed, approximately 46% of patients who are diagnosed with NF1 later in life do not meet the NIH diagnostic criteria by the age of 1 year. Further, the 1988 diagnostic criteria for NF1 are not specific enough to distinguish NF1 from other related disorders such as Legius syndrome. In this review, we outline the challenges faced in diagnosing NF1 in young children, and evaluate the utility of the recently revised (2021) diagnostic criteria for NF1, which include the presence of pathogenic variants in the NF1 gene and choroidal anomalies, for achieving an early and accurate diagnosis.