Predictive value of clinical risk factors for bladder dysfunction in Syrian patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) is a prevalent disorder that affects the endocrine and metabolic systems. Among the various complications associated with DM, diabetic bladder dysfunction (DBD) is the most frequently occurring genitourinary complication. The presence of DBD can lead to complications that affect the upper urinary tract, significantly impacting the quality of life for individuals with DM. Therefore, it is crucial to identify early risk factors for DBD and predict its onset. Given the absence of studies involving bladder dysfunction in patients with type 2 diabetes mellitus (T2DM) in Syria, this study aims to examine the risk factors associated with bladder dysfunction in T2DM patients and develop a predictive model to identify DBD early. Patients diagnosed with T2DM were enrolled in six endocrinology centers spread across four Syrian provinces between January 2018 and December 2023. Factors that showed an association with DBD in the bivariate analysis, with a significance level of p < 0.05, were included in a multiple logistic regression analysis. The logistic regression analysis was used to identify independent risk factors and develop a prediction model. The receiver operating characteristic (ROC) curve was used to assess the predictive performance of the identified risk factors and the prediction model for DBD. One hundred and eighty-four patients were included in this study, and they were divided into the DBD group (n = 88) and the non-DBD group (n = 96). Seven variables showed significance in the bivariate analysis. Furthermore, the multiple logistic regression analysis revealed that age (OR [95% CI]: 0.981 [0.614 - 1.337]), p < 0.007; diabetic peripheral neuropathy (DPN) (OR [95% CI]: 1.421 [1.027 - 3.308]), p = 0.03; glycated hemoglobin (HbA1c) (OR [95% CI]: 0.942 [0.821 - 1.141]), p = 0.042; and percentage of monocyte (Mono%) (OR [95% CI]: 1.109 [0.812 - 1.258]), p = 0.031 were independent risk factors for DBD. Analysis of the ROC curve revealed that the area under the curve (AUC) for age, DPN, HbA1c, and Mono were 0.703, 0.541, 0.613, and 0.836, respectively. Age, DPN, HbA1c, and Mono% were risk factors for DBD. The prediction model constructed based on the four risk factors had a good predictive value for predicting the occurrence of DBD.

Acceptance of peer physical examination in medical students in Wuhan, China: A cross-sectional study.

Background: Peer physical examination (PPE) is an essential part of the education of medical students. This study aimed to assess the acceptance level of PPE in Chinese society as well as other related factors. While there have been numerous studies on PPE acceptance in Western societies, there have been relatively few studies on this topic in China. Methods: A questionnaire was distributed via social media to clinical-year medical students in China. With 1890 students participating overall, the response rate was 86.9%. The questionnaire collected demographic information and previous experience with PPE, and utilized a 5-point Likert scale to assess acceptance of PPE and factors influencing it. Results: One thousand six hundred and forty-four percent of Chinese medical students accepted PPE, with 13% rejecting it and 19% neutral. Males were more accepting of PPE than females, and females were less accepting of being examined by someone of the opposite gender. The groin/thigh and breast areas were the most rejected for examination. There were no significant differences in acceptance rates between universities or academic performance groups. However, society had a significant impact on the acceptance of PPE. Conclusions: With a 67% acceptance rate of PPE among Chinese medical students, it could be considered a viable alternative to absent life models in Chinses universities. However, implementing PPE may come with its own set of difficulties, so it is recommended that a supervisor is present and that single-gender groups are formed, with friends paired together if possible.

Arabic version of the SF-Qualiveen: cross-cultural adaptation, translation, and validation of urinary disorder-specific instruments in patients with multiple sclerosis.

BACKGROUND: The Short Form Qualiveen (SF-Qualiveen) questionnaire assesses the effect of bladder and urinary symptoms on patients' quality of life (QoL) with urological impairment caused by neurological diseases. There is no validated SF-Qualiveen questionnaire in Arabic, so this study aims to provide a translated and validated version of the SF-Qualiveen questionnaire among Arabic-speaking patients with multiple sclerosis (MS). METHODS: The English version of the SF-Qualiveen was translated into Arabic using an algorithm for linguistic and cultural adaptation. MS patients completed the SF-Qualiveen, and the Neurogenic Bladder Symptom Score(NBSS) questionnaire. Psychometric features such as content and construct validity, test-retest reliability, and internal consistency were analyzed. Construct validity was evaluated by contrasting the SF-Qualiveen with the NBSS questionnaire. Internal consistency was measured using Cronbach's alpha, whereas the intraclass correlation coefficient (ICC) was employed to assess the test-retest reliability. RESULTS: One hundred and two patients with MS were included in this study. The internal consistency of the total SF-Qualiveen, and the domains "Bother with limitations," "Fear," "Feeling," and "Frequency of limitations" showed good internal consistency (Cronbach's alpha of > 0.7). ICC was 0.91 for the total score 0.85 for the Bother with limitations, 0.81 for Fears, 0.86 for Feeling, and 0.81 for Frequency of limitations. The correlation analysis revealed a positive association between the total scores on the NBSS and the domains of the SF-Qualiveen, comprising bother with limitations (r = 0.473, p = 0.027), fears (r = 0.611, p = 0.031), feelings (r = 0.572, p = 0.04), and frequency of limitations (r = 0.514, p = 0.013). CONCLUSIONS: The findings of this validation study revealed that the SF-Qualiveen is a reliable and valid instrument appropriate for Arabic-speaking patients with MS in both research and clinical practice.

Arabic version of the SF-Qualiveen: cross-cultural adaptation, translation, and validation of urinary disorder-specific instruments in patients with spinal cord injury.

BACKGROUND: The Short-Form Qualiveen (SF-Qualiveen) questionnaire assesses the effect of bladder and urinary symptoms on patients' quality of life (QoL) with urological impairment caused by neurological diseases. There is no validated SF-Qualiveen questionnaire in Arabic, so this study aims to provide a translated and validated version of the SF-Qualiveen questionnaire among Arabic patients experiencing spinal cord injury (SCI). METHODS: Psychometric features such as content and construct validity, test-retest reliability, and internal consistency were analyzed. Construct validity was evaluated by contrasting the SF-Qualiveen with the Neurogenic Bladder Symptom Score Short-Form (NBSS-SF) questionnaire. Internal consistency was measured using Cronbach's alpha, whereas the intraclass correlation coefficient (ICC) was employed to assess the test-retest reliability. Factorial validity was established by principal component analysis (PCA). RESULTS: The internal consistency of the total SF-Qualiveen and the domains "Bother with limitations," "Fear," "Feeling," and "Frequency of limitations" showed good internal consistency (Cronbach's alpha of > 0.7). ICC was 0.90 for the total score, 0.83 for the bother with limitations, 0.80 for fears, 0.84 for feeling, and 0.81 for frequency of limitations. The correlation analysis revealed a positive association between the total scores on the NBSS-SF and the domains of the SF-Qualiveen, comprising bother with limitations (r = 0.53, p = 0.02), fears (r = 0.44, p = 0.03), feelings (r = 0.49, p = 0.04), and frequency of limitations (r = 0.46, p = 0.02). The best-fit four-factor model for confirming overall item communalities ranged from 0.552 to 0.814, which indicates moderate to high communalities, and confirms the homogeneity of the SF-Qualiveen using PCA. CONCLUSIONS: The findings of this validation study revealed that the SF-Qualiveen is a reliable and valid instrument appropriate for Arabic-speaking patients with SCI in both research and clinical practices.

Epidemiology features of traumatic and non-traumatic spinal cord injury in China, Wuhan.

Spinal cord injuries are incredibly disabling and can have fatal consequences. At present, there is a lack of available information regarding the epidemiological characteristics of patients who have experienced spinal cord injury (SCI) in China. This retrospective hospital-based study was conducted in the Rehabilitation department of Wuhan's Tongji Hospital between 2016 and 2022. A total of 649 individuals diagnosed with SCI (both traumatic and non-traumatic) were admitted during this period. Data regarding various epidemiological features were gathered, including sex, age, etiology, occupation, neurological level of injury, the American Spinal Injury Association Impairment Scale at the time of admission, and information on any accompanying injuries. Out of the 649 cases of SCI, there were 539 cases of traumatic SCI and 110 cases of non-traumatic SCI. The mean age at the time of injury was 45.6 ± 14.8 years. The ratio of male to female patients was higher in traumatic SCI at 2.82:1compared to non-traumatic SCI at 1.68:1. Traffic accidents were the most common cause of TSCI, accounting for (n = 207/539; 38.40%) of cases. On the other hand, neoplasm was the most common cause of NTSCI, accounting for (n = 38/110; 34.54%) of cases. The findings indicated a higher proportion of males, with traffic accidents being the main cause of injury among TSCI patients. It is crucial to prioritize the risk of falling among older adults and allocate more attention to this issue. These results emphasize the need for tailored preventive strategies that consider the unique characteristics of different types of SCI patients.

Effects of cholinesterase inhibition on attention and working memory in Lewy body dementias.

Cholinesterase inhibitors are frequently used to treat cognitive symptoms in Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies). However, the selectivity of their effects remains unclear. In a novel rivastigmine withdrawal design, Parkinson's disease dementia and dementia with Lewy bodies patients were tested twice: once when taking rivastigmine as usual and once when they had missed one dose. In each session, they performed a suite of tasks (sustained attention, simple short-term recall, distractor resistance and manipulating the focus of attention) that allowed us to investigate the cognitive mechanisms through which rivastigmine affects attentional control. Consistent with previous literature, rivastigmine withdrawal significantly impaired attentional efficacy (quicker response latencies without a change in accuracy). However, it had no effects on cognitive control as assessed by the ability to withhold a response (inhibitory control). Worse short-term memory performance was also observed when patients were OFF rivastigmine, but these effects were delay and load independent, likely due to impaired visual attention. In contrast to previous studies that have examined the effects of dopamine withdrawal, cognitively complex tasks requiring control over the contents of working memory (ignoring, updating or shifting the focus of attention) were not significantly impaired by rivastigmine withdrawal. Cumulatively, these data support that the conclusion that cholinesterase inhibition has relatively specific and circumscribed-rather than global-effects on attention that may also affect performance on simple short-term memory tasks, but not when cognitive control over working memory is required. The results also indicate that the withdrawal of a single dose of rivastigmine is sufficient to reveal these impairments, demonstrating that cholinergic withdrawal can be an informative clinical as well as an investigative tool.

Clinical assessment of parietal lobe function.

The notion of specific assessments of the function of a particular lobe of the brain is in many ways archaic. Advances in our understanding of brain network function have revealed that brain functions are underpinned by large-scale networks with long range connections between cortical distant regions. It would, therefore, be more correct to discuss the contributions of parietal areas to specific functions. Nevertheless, in clinical practice, as we show here, simple bedside assessment can still often point towards parietal dysfunction, or at least reveal an impairment in a function to which parietal regions normally contribute.

Effect of neurogenic bowel dysfunction symptoms on quality of life after a spinal cord injury.

BACKGROUND: Neurogenic bowel dysfunction (NBD) is a common problem among people with spinal injury; management of bowel dysfunction and related problems are considered significant factors in daily life after injury. But despite the critical relevance of bowel dysfunction in the daily life of SCI survivors, there have been few published studies on the management of NBD. So, this study aimed to describe the bowel programmers utilized by people with SCI in China and the impact of bowel dysfunction on the quality of life (QoL). DESIGN: A cross-sectional online survey. SETTING: Rehabilitation Medicine Department of Wuhan's Tongji Hospital. PARTICIPANTS: SCI patients who had been diagnosed with neurogenic bowel dysfunction and who were receiving regular medical monitoring at the rehabilitation medicine department were invited to participate in our study. OUTCOME MEASURES: A neurogenic bowel dysfunction (NBD) score is a questionnaire developed to evaluate the severity of neurogenic bowel dysfunction. A Short Form-12 (SF-12) was designed to measure the quality of life in people with SCI. Demographic and medical status information was extracted from their medical records. RESULTS: The two questionnaires were sent to 413 SCI patients. Two hundred ninety-four subjects (43.1 ± 14.5 years of age; men, 71.8%) responded. Most of the respondents performed their bowel movement daily 153 (52.0%), a defecation time was 31-60 min among 70 (23.8%) of them, 149 (50.7%) used medication (drops or liquid) to treat constipation, and 169 (57.5%) used digital stimulation more than once per week to boost the bowel evacuation. This study found a significant association between the QoL score and the time used for each defecation, autonomic dysreflexia (AD) symptoms, taking medication to treat fecal incontinence, using digital stimulation, having uncontrollable flatus and perianal skin problems. CONCLUSION: Management of bowel dysfunction is complex and associated with QoL in people with SCI. Items of the NBD questionnaire that greatly deteriorated the QoL were time in one defecation > 60 min, symptoms of AD during or before defecation, taking medication (drops or liquid), and using digital stimulation. Dealing with those problems can improve the life quality of spinal cord injury survivors.

The validity and reliability of the Arabic version of the short form of neurogenic bladder symptoms score in patients with spinal cord injury.

BACKGROUND: The Neurogenic Bladder Symptom Score-Short Form (NBSS-SF) evaluates the impact of disease-specific symptoms on the quality of life in individuals with neurogenic bladder (NB). There is no data on the validity and reliability of the NBSS-SF questionnaire in the Arabic language, so this study aimed to examine the psychometric characteristics of the Arabic NBSS-SF in patients with spinal cord injury (SCI). METHODS: International standards were followed when culturally adapting the questionnaire. The Arabic version was conducted in patients with neurogenic bladder caused by SCI twice within a 14 day period. Psychometric properties such as content validity, construct validity, internal consistency, and test-retest reliability were tested. Internal consistency and test-retest reliability was evaluated using Cronbach's alpha, and the Intraclass Correlation Coefficient (ICC), respectively. Construct validity was assessed by comparing the NBSS-SF with the Short Form (SF-12) and the Qualiveen questionnaire. RESULTS: One hundred and one patients with SCI participated in the study. The internal consistency for the overall NBSS-SF score (Cronbach's α of 0.82) and for each subdomain was variable (urinary incontinence 0.84; storage/voiding 0.72; consequences 0.57). ICC was 0.91 for the overall score and 0.94 for the urinary incontinence subdomain, 0.72 for storage/voiding, and 0.90 for consequences. The correlation analysis showed that the Arabic version of NBSS-SF has good construct validity. CONCLUSION: Our results showed that the Arabic version of NBSS-SF is a valid and reliable instrument for evaluating NB symptoms in the Arabic population suffering from SCI.

Impact of the COVID-19 pandemic on the quality of life and accessing rehabilitation services among patients with spinal cord injury and their fear of COVID-19.

BACKGROUND: The unanticipated coronavirus disease (COVID-19) had a negative effect on the quality of life (QoL) of patients with spinal cord injury (SCI) and made significant changes in their daily routine. Patients with SCI face additional health risks, especially mental, behavioral, and physical. Without regular physiotherapy sessions, patients' psychological and functional abilities can deteriorate, and complications can occur. There is little information available about the impact of COVID-19 on the quality of life of patients with SCI, and their access to rehabilitation services during the pandemic. OBJECTIVE: This study was designed to examine the effects of the COVID-19 pandemic on the quality of life of patients with SCI and also their fear of COVID-19. The pandemic's impact on the accessibility of rehabilitation services and attendance at physiotherapy sessions in one Chinese hospital were also documented. DESIGN: An observational study based on an online survey. SETTING: Outpatients clinic at the rehabilitation department of Wuhan's Tongji Hospital. PARTICIPANTS: People who had been diagnosed with a spinal cord injury (SCI) and who were receiving regular medical monitoring as outpatients at the rehabilitation department were invited to participate in our study (n = 127). INTERVENTION: Not applicable. OUTCOME MEASURES: A 12-Item Short-Form Health Survey (SF-12) designed to measure participants' quality of life before and during the pandemic. Their fear of COVID-19 was quantified using the Fear of COVID-19 Scale (FCV-19S). Demographic and medical status information was extracted from their medical records. Their use of rehabilitation services and attendance at physical therapy sessions was also documented. RESULTS: Seventy-nine patients with SCI completed the SF-12 and FCV-19 scale. The mental and physical aspects of the participants' quality of life declined significantly, during the epidemic compared to the pre-epidemic period. More than half of the participants have experienced fear of COVID-19 based on FCV-19S. Most received only irregular physical therapy during routine checkups. Worry about virus transmission was the most common cause cited for not attending regular physical therapy sessions. CONCLUSIONS: The quality of life of these Chinese patients with SCI declined during the pandemic. Most of the participants were shown a high level of fear of COVID-19 and were classified as having an intense fear of COVID-19, in addition to the impact of the pandemic on their access to rehabilitation services and attendance at physical therapy sessions.

Cross-cultural adaptation, translation, and validation of the Arabic version of the short form of Neurogenic Bladder Symptoms Score.

BACKGROUND: The Neurogenic Bladder Symptom Score-Short Form (NBSS-SF) evaluates the impact of disease-specific symptoms on the quality of life (QoL) in individuals with neurogenic bladder (NB). There is no data on the validity and reliability of the NBSS-SF questionnaire in the Arabic language, so this study aimed at providing the translation, cultural adaptation, and validation of the Arabic NBSS-SF in patients with multiple sclerosis (MS) and spinal cord injury (SCI). METHODS: The original English language version of the NBSS-SF was translated into Arabic according to the cultural and linguistic adaptation algorithm. People with SCI and MS completed the NBSS-SF, demographic and clinical information, and Qualiveen QoL questionnaire. Responses were recorded twice within a 14-day period. Psychometric properties such as content validity, construct validity, internal consistency, and test-retest reliability were tested. Internal consistency and test-retest reliability was evaluated using Cronbach's alpha, and the intraclass correlation coefficient (ICC), respectively. Construct validity was assessed by comparing the NBSS-SF with the Qualiveen questionnaire. RESULTS: Thirty-nine patients with MS and 97 with SCI participated in the study. The internal consistency for the overall NBSS-SF score (Cronbach's α of 0.82) and for each subdomain was variable (urinary incontinence 0.82; storage/voiding 0.73; consequences 0.53). ICC was 0.93 for the overall score and 0.96 for the urinary incontinence subdomain, 0.74 for storage/voiding, and 0.91 for consequences. The correlation analysis showed a significantly strong correlation between the QoL item of NBSS-SF and the Qualiveen total score (r = 0.72, p < 0.000). There was a significant moderate positive correlation between the total scores on the Arabic version of the NBSS-SF and the subdomains of the Qualiveen, including limitations (r = 0.51, p = 0.04), fears (r = 0.57, p = 0.04), feelings (r = 0.46, p = 0.01), and constraints (r = 0.59, p = 0.03). CONCLUSIONS: Our results showed that the Arabic version of NBSS-SF is a valid and reliable instrument for evaluating neurogenic lower urinary tract dysfunction symptoms in the Arabic population suffering from SCI and MS.

Epidemiological features of traumatic spinal cord injury in Wuhan, China.

BACKGROUND: Spinal cord injuries are extremely debilitating and fatal injuries. There is currently little research focusing on traumatic spinal cord injuries, and there is little information available about the epidemiological characteristics of patients with traumatic spinal cord injury (TSCI). OBJECTIVE: To describe the epidemiological features of traumatic spinal cord injury in Wuhan, China. DESIGN: A retrospective hospital-based study. SETTING: Rehabilitation department of Wuhan's Tongji Hospital. PARTICIPANTS: People who had been diagnosed with a traumatic spinal cord injury (TSCI) were admitted to Tongji Hospital from 2016 to 2021 (n = 463). INTERVENTIONS: Not applicable. OUTCOME MEASURES: Epidemiological features such as sex, age, marital status, etiology, occupation, neurological level of injury, and the American Spinal Injury Association Impairment Scale on admission, hospitalization, and concomitant injuries were collected. RESULTS: The mean age of patients with TSCI was 39.4 ± 14.3 years, and the male/female ratio was 3:1. The leading causes of TSCIs were traffic accidents (38.4%), followed by falls (low falls 24.0%, high falls 13.2%). The most common injury site was the cervical spinal cord, followed by the thoracolumbar level. Of all patients, 463 patients (67.2%) had complications and other injuries. During the hospitalization period, a total of 217 patients experienced complications, with a percentage of 46.9%. Urinary tract infection was the most common (15.6%), followed by pulmonary infection (14.0%). CONCLUSION: The results found that the proportion of males was greater, and the first two main reasons were falls and traffic accidents. Farmers and workers are the occupations most vulnerable to SCI. We need to pay more attention to the elderly's risk of falling. These findings suggested that preventive strategies should be based on the features of different types of TSCI patients. Finally, the importance of SCI rehabilitation must be highlighted.

Long-term histopathological changes of the nasal mucosa after total laryngectomy: a prospective cohort study.

BACKGROUND: Changes in the nasal function following total laryngectomy resulted in histopathological alterations of the nasal mucosa. We aimed to evaluate the long-term histopathological changes and the mucociliary clearance (MCC) of the nasal mucosa after total laryngectomy. METHODS: We performed a histological examination of inferior turbinate biopsy, and saccharine test to assess the MCC time for patients who were candidates for total laryngectomy before the procedure, 6-12 months after surgery, and at least two years postoperatively. RESULTS: Seventy-five patients scheduled for total laryngectomy were initially enrolled in our study. We excluded patients who received postoperative radiotherapy or were lost during the follow-up period. Eventually, 63 and 54 patients were available for assessment 6-12 months after surgery and at least two years postoperatively, respectively. Except for ciliary and goblet cell destruction, which were significantly reduced 6-12 months postoperatively, there were no statistically significant differences in the histopathological findings of the nasal mucosa before surgery and 6-12 months postoperatively. After two years, the histopathological alterations of the nasal mucosa were statistically more evident than those before surgery and 6-12 months postoperatively; the most common histopathological findings were mononuclear cell infiltration and stromal fibrosis. The mean MCC time preoperatively was 12.56 minutes that statistically significantly decreased to 11.81 minutes 6-12 months after surgery; then, it significantly increased to 20.98 minutes at least two years postoperatively. CONCLUSIONS: After total laryngectomy, the nasal mucosa showed histopathological alterations and early enhancement of the MCC, which was later impaired due to nasal mucosal atrophy and the saprophytic infection.

Oral medications administration through enteral feeding tube: Clinical pharmacist-led educational intervention to improve knowledge of Intensive care units' nurses at Jordan University Hospital.

INTRODUCTION: Medication administration through enteral feeding tubes is a practice that is commonly encountered in hospital settings, particularly in critically ill patients. This study aims to evaluate the knowledge of intensive care unit nurses regarding enteral medication administration and evaluate the effect of an educational intervention led by a clinical pharmacist that would improve nurses' knowledge regarding the subject. METHODS: A pre/post interventional study was conducted. Improvement in nurses' knowledge regarding medication administration through an enteral feeding tube was assessed using a validated questionnaire. RESULTS: Data were coded, entered, and analyzed using the Statistical Package for Social Sciences (IBM SPSS statistics 22). Independent samples t-test and paired t-test were used to detect any statistically significant differences in the mean total knowledge scores both between and within each group respectively. A P-value of <0.05 was considered statistically significant. The mean total knowledge score for nurses in the intervention and control group at the pre-interventional phase of the study was inadequate. There was a statistically significant improvement in the mean total knowledge score for the interventional group at the post-interventional phase of the study, while that of the control group remained inadequate (Intervention group total mean knowledge score at baseline 12.11 ± 3.75, post-intervention 21.50 ± 2.36, p-value <0.001; Control group total mean knowledge score at baseline 12.05 ± 3.12, post-intervention 12.60 ± 3.76, p-value 0.96). CONCLUSION: Incorrect drug preparation and administration for patients with feeding tubes can affect patients. The knowledge of nurses regarding the subject can be improved significantly via an educational intervention. The activation of clinical pharmacists' role and collaboration between pharmacists, physicians, and nurses is highly recommended in this clinical setting.

Noninvasive Monitoring of Mantle Cell Lymphoma by Immunoglobulin Gene Next-Generation Sequencing in a Phase 2 Study of Sequential Chemoradioimmunotherapy Followed by Autologous Stem-Cell Rescue.

BACKGROUND: Minimal residual disease (MRD) monitoring has been used to identify early molecular relapse and predict clinical relapse in mantle cell lymphoma (MCL). Few published data exist in MCL on the performance of next-generation sequencing-based assay of immunoglobulin gene rearrangements for MRD assessment. PATIENTS AND METHODS: In a prospective clinical trial (NCT01484093) with intensive induction chemotherapy and autologous stem-cell transplantation, posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with an earlier version of the Adaptive Biotechnologies MRD assay. RESULTS: Of the 7 patients whose disease remained in remission, the MRD test remained negative in 5 (71%). Of the 9 patients who experienced relapse, the MRD test was positive at least 3 months before relapse in 6 patients (67%) and positive at the time of relapse in 1 patient (11%). All patients with at least 2 positive MRD tests experienced relapse. CONCLUSION: The next-generation sequencing-based MRD assay identified early molecular relapse, and we observed more sensitivity in the cellular (circulating leukocytes) versus acellular (plasma cell-free DNA) compartment. This observation may be due to availability of tumor target or a limitation of the assay.

The British variant of the new coronavirus-19 (Sars-Cov-2) should not create a vaccine problem.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus that infects humans and a number of animal species causing coronavirus disease-19 (COVID-19), a respiratory distress syndrome which has provoked a global pandemic and a serious health crisis in most countries across our planet. COVID-19 inflammation is mediated by IL-1, a disease that can cause symptoms such as fever, cough, lung inflammation, thrombosis, stroke, renal failure and headache, to name a few. Strategies that inhibit IL-1 are certainly helpful in COVID-19 and can represent one of the therapeutic options. However, until now, COVID-19 therapy has been scarce and, in many cases, ineffective, since there are no specific drugs other than the vaccine that can solve this serious health problem. Messenger RNA (mRNA) vaccines which are the newest approach, are already available and will certainly meet the many expectations that the population is waiting for. mRNA vaccines, coated with protected soft fatty lipids, use genetic mRNA (plus various inactive excipients) to make a piece of the coronavirus spike protein, which will instruct the immune system to produce specific antibodies. The soft fatty lipids allow the entry of mRNA into cells where it is absorbed into the cytoplasm and initiates the synthesis of the spike protein. In addition, vaccination also activates T cells that help the immune system respond to further exposure to the coronavirus. mRNA induces the synthesis of antigens of SARS-CoV-2 virus which stimulate the antibody response of the vaccinated person with the production of neutralizing antibodies. The new variant of the coronavirus-19 has been detected in the UK where, at the moment, the London government has imposed a lockdown with restrictions on international movements. The virus variant had already infected 1/4 of the total cases and in December 2020, it reached 2/3 of those infected in the UK. It has been noted that the spreading rate of the British variant could be greater than 70% of cases compared to the normal SARS-CoV-2 virus, with an R index growth of 0.4. Recent studies suggest that coronavirus-19 variation occurs at the level N501Y of the spike protein and involves 23 separate mutations on the spike, 17 of which are linked to the virus proteins, thus giving specific characteristics to the virus. In general, coronaviruses undergo many mutations that are often not decisive for their biological behavior and does not significantly alter the structure and the components of the virus. This phenomenon also occurs in SARS-CoV-2. It is highly probable that the variants recently described in the UK will not hinder vaccine-induced immunity. In fact, the variant will not break the vaccine although it may have some chance of making it a little less effective. Therefore, it is pertinent to think that the vaccine will work against the SARS-CoV-2 variant as well. In today's pandemic, the D614G mutation of the amino acid of corronavirus-19, which emerged in Europe in February 2020 is the most frequent form and causes high viral growth. The previously infrequent D614G mutation is now globally dominant. This variant, which is being tested by many international laboratories, is rapidly spreading across the countries and a series of vaccinated subjects are testing to see if their antibodies can neutralize the new variant of SARS-CoV-2. This variant has a very high viral growth and is less detectable with the RT-PCR technique in the laboratory. It has been reported that the British variant that increases viral load does not cause more severe effects in the respiratory tract and lung disease, therefore, it is certain that the variant is growing rapidly and must be kept under control; for this reason, laboratory data is expected impatiently. The study on the many variants that coronavirus-19 presents is very interesting and complete and clearer data on this topic will be ready in the near future. In addition, it is still unclear whether the different variants discovered in many countries, including Africa, share the same spike protein mutation and therefore, this is another study to elaborate on. In order to be certain and to not have unexpected surprises, we need to reduce the spread and the transmission speed of viral variants that could appear around the world, creating new pandemics. For this reason, the scientific community is on the alert since laboratory tests on serum antibodies from COVID-19 survivors have been reported to be less effective in attacking the variant. In light of the above, the scientific community must be on the alert as larger variants of the spike protein could escape vaccine-induced antibodies, which for now are of great help to the community and can save millions of lives. Deepening the study of spike protein mutations will help to better understand how to combat coronavirus-19 and its variants.

Coronavirus-19 (SARS-CoV-2) induces acute severe lung inflammation via IL-1 causing cytokine storm in COVID-19: a promising inhibitory strategy.

SARS-Cov-2 infection causes local and systemic inflammation mediated by pro-inflammatory cytokines and COX-2 eicosanoid products with metabolic dysfunction and tissue damage that can lead to patient death. These effects are primarily induced by IL-1 cytokines, which are involved in the elevation of hepatic acute phase proteins and fever. IL-1 has a broad spectrum of biological activities and participates in both innate and acquired immunity. In infections, IL-1 induces gene expression and synthesis of several cytokines/chemokines in both macrophages and mast cells (MCs). The activation of MCs triggers the secretion of mediators stored in the granules, and the de novo synthesis of pro-inflammatory cytokines. In microorganism infections, the release of IL-1 macrophage acts on adhesion molecules and endothelial cells leading to hypotension and septic shock syndrome. IL-1 activated by SARS-CoV-2 stimulates the secretion of TNF, IL-6 and other cytokines, a pro-inflammatory complex that can lead to cytokine storm and be deleterious in both lung and systemically. In SARS-CoV-2 septic shock, severe metabolic cellular abnormalities occur which can lead to death. Here, we report that SARS-CoV-2 induces IL-1 in macrophages and MCs causing the induction of gene expression and activation of other pro-inflammatory cytokines. Since IL-1 is toxic, its production from ubiquitous MCs and macrophages activated by SARS-CoV-2 can also provokes both gastrointestinal and brain disorders. Furthermore, in these immune cells, IL-1 also elevates nitric oxide, and the release of inflammatory arachidonic acid products such as prostaglndins and thromboxane A2. All together these effects can generate cytokine storm and be the primary cause of severe inflammation with respiratory distress and death. Although, IL-1 administered in low doses may be protective; when it is produced in high doses in infectious diseases can be detrimental, therefore, IL-1 blockade has been studied in many human diseases including sepsis, resulting that blocking it is absolutely necessary. This definitely nurtures hope for a new effective therapeutic treatment. Recently, two interesting anti-IL-1 cytokines have been widely described: IL-37 and IL-1Ra. IL-37, by blocking IL-1, has been observed to have anti-inflammatory action in rodents in vivo and in transfected cells. It has been reported that IL-37 is a very powerful protein which inhibits inflammation and its inhibition can be a valid therapeutic strategy. IL-37 is a natural suppressor of inflammation that is generated through a caspase-1 that cleaves pro-IL-37 into mature IL-37 which translocates to the nucleus and inhibits the transcription of pro-inflammatory genes; while IL-1Ra inhibits inflammation by binding IL-1 to its IL-1R (receptor). We firmly believe that blocking IL-1 with an anti-inflammatory cytokine such as IL-37 and/or IL-1Ra is an effective valid therapy in a wide spectrum of inflammatory disorders including SARS-CoV-2-induced COVID-19. Here, we propose for the first time that IL-37, by blocking IL-1, may have an important role in the therapy of COVID-19.

Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19.

SARS-CoV-2 virus is an infectious agent commonly found in certain mammalian animal species and today also in humans. SARS-CoV-2, can cause a pandemic infection with severe acute lung injury respiratory distress syndrome in patients with COVID-19, that can lead to patient death across all ages. The pathology associated with pandemic infection is linked to an over-response of immune cells, including virus-activated macrophages and mast cells (MCs). The local inflammatory response in the lung that occurs after exposure to SARS-CoV-2 is due to a complex network of activated inflammatory innate immune cells and structural lung cells such as bronchial epithelial cells, endothelial cells and fibroblasts. Bronchial epithelial cells and fibroblasts activated by SARS-CoV-2 can result in the up-regulation of pro-inflammatory cytokines and induction of MC differentiation. In addition, endothelial cells which control leukocyte traffic through the expression of adhesion molecules are also able to amplify leukocyte activation by generating interleukin (IL)-1, IL-6 and CXC chemokines. In this pathologic environment, the activation of mast cells (MCs) causes the release of histamine, proteases, cytokines, chemokines and arachidonic acid compounds, such as prostaglandin D2 and leukotrienes, all of which are involved in the inflammatory network. Histamine is stored endogenously within the secretory granules of MCs and is released into the vessels after cell stimulation. Histamine is involved in the expression of chemokine IL-8 and cytokine IL-6, an effect that can be inhibited by histamine receptor antagonists. IL-1 is a pleiotropic cytokine that is mainly active in inflammation and immunity. Alveolar macrophages activated by SARS-CoV-2 through the TLR produce IL-1 which stimulates MCs to produce IL-6. IL-1 in combination with IL-6 leads to excessive inflammation which can be lethal. In an interesting study published several years ago (by E. Vannier et al., 1993), it was found that histamine as well as IL-1 are implicated in the pathogenesis of pulmonary inflammatory reaction, after micorganism immune cell activation. IL-1 in combination with histamine can cause a strong increase of IL-1 levels and, consequently, a higher degree of inflammation. However, it has been reported that histamine alone has no effect on IL-1 production. Furthermore, histamine enhances IL-1-induced IL-6 gene expression and protein synthesis via H2 receptors in peripheral monocytes. Therefore, since MCs are large producers of histamine in inflammatory reactions, this vasoactive amine, by increasing the production of IL-1, can amplify the inflammatory process in the lung infected with SARS-CoV-2. Here, we have proposed for the first time an emerging role for histamine released by MCs which in combination with IL-1 can cause an increase in lung inflammation induced by the viral infection SARS-CoV-2.