Severe MS Research Articles

Multiple sclerosis in Somali Americans: Nature or nurture?

BackgroundDifferences in the MS course between White and Black populations is well accepted. The existence of a large Somali immigrant population in Minnesota facilitates a study of MS characteristics in this immigrant native African population. The objective of this study was to compare Somali American (SA), African American (AA), and White American (WA) persons with MS (pwMS) regarding clinical features and disease modifying therapy (DMT) use. MethodsThis single center (Mayo Clinic) geographically-restricted retrospective cohort study (residing within 250 miles of Rochester, MN, USA) included participants seen before May 2023. Age at immigration to the USA; age at MS onset; DMT use/type; MS phase/phenotype; age at progressive MS (PMS) onset; and proportion with severe MS (expanded disability status scale-EDSS ≥6) were examined. Results18 SApwMS, 92 AApwMS, and 94 WApwMS were included. Of the 15 SApwMS not born in USA, 3/15 immigrated pre-puberty, 3/15 peri‑puberty, 8/15 post-puberty, and 1/15 at an unknown date. SApwMS were younger at MS onset (median years, interquartile range (IQR)=25, 22–33 vs. AApwMS: 31, 25–38; p = 0.049 vs. WApwMS: 35, 27–41; p = 0.022). DMT use frequencies were 13/19 SApwMS, 69/92 AApwMS, 80/94 WApwMS (p > 0.05). SApwMS were treated with DMT earlier than AApwMS (HR 2.16, p = 0.012) and WApwMS (HR 1.86, p = 0.041). SApwMS were less commonly treated with natalizumab (SApwMS 0 %, AApwMS 13 %, WApwMS 25 %; p = 0.035) and anti-CD20 therapies (SApwMS 23 %, AApwMS 23 %, WApwMS 48 %; p = 0.005). PMS occurred in 3/19 SApwMS, 28/92 AApwMS and 29/94 WApwMS (p > 0.05). Age of PMS onset in SApwMS (47 years, 34–57) was similar to WApwMS (47 years, 31–71; p > 0.05) but older than AApwMS (41 years, 18–7; p = 0.008). ConclusionsSApwMS that recently immigrated to the USA have similar disease course to WApwMS, and better than AApwMS from the same geographical region.

Humoral immune response and safety of Sars-Cov-2 vaccine in people with multiple sclerosis

BackgroundFor the past three years, the pandemic has had a major effect on global public health, mainly on those with underlying medical conditions, such as people living with Multiple Sclerosis. Vaccination among this group is of great importance, and the long-term impacts of vaccination and its safety on the health of these patients will continue to be revealed. Therefore, risks related to vaccination and immune response need to be assessed. The objective here was to characterize the immune response, short-term safety, and the effects of multiple variables on these factors after COVID-19 vaccination (mainly Sinopharm) among people with Multiple Sclerosis. We assessed the short-term safety and humoral SARS-COV-2 anti-RBD IgG response using a data collection form and Immunoassay, respectively.ResultsNo severe adverse events or MS relapse was observed. Myalgia/body pain (26.7%), low-grade fever (22.2%), and mild headache (15.6%) were the most common adverse events. The use and type of vaccine influenced the frequency of side effects with a p-value < 0.0001. Regarding immune response, patients on rituximab and fingolimod had a lower antibody titer compared to other medications. With a significant difference, hybrid immunity (p-value: 0.047) and type of DMTs (p-value: 0.017) affected the humoral response.ConclusionThere is a low incidence of serious adverse effects, MS worsening or relapse after COVID-19 vaccination, and mainly, side effects are similar to that of the general population. It appears that treatment with various disease-modifying therapies does not induce or worsen the post-vaccination side effects, although some, including Rituximab and fingolimod, may affect the immunity induced after vaccination.

Neuroimaging assessment of facility-bound severely-affected MS reveals the critical role of cortical gray matter pathology: results from the CASA-MS case-controlled study.

A subgroup of people with multiple sclerosis (pwMS) will develop severe disability. The pathophysiology underlying severe MS is unknown. The comprehensive assessment of severely affected MS (CASA-MS) was a case-controlled study that compared severely disabled in skilled nursing (SD/SN) (EDSS ≥ 7.0) to less-disabled (EDSS 3.0-6.5) community dwelling (CD) progressive pwMS, matched on age-, sex- and disease-duration (DDM). To identify neuroimaging and molecular biomarker characteristics that distinguish SD/SN from DDM-CD progressive pwMS. This study was carried at SN facility and at a tertiary MS center. The study collected clinical, molecular (serum neurofilament light chain, sNfL and glial acidic fibrillary protein, sGFAP) and MRI quantitative lesion-, brain volume-, and tissue integrity-derived measures. Statistical analyses were controlled for multiple comparisons. 42 SD/SN and 42 DDM-CD were enrolled. SD/SN pwMS showed significantly lower cortical volume (CV) (p < 0.001, d = 1.375) and thalamic volume (p < 0.001, d = 0.972) compared to DDM-CD pwMS. In a logistic stepwise regression model, the SD/SN pwMS were best differentiated from the DDM-CD pwMS by lower CV (p < 0.001) as the only significant predictor, with the accuracy of 82.3%. No significant differences between the two groups were observed for medulla oblongata volume, a proxy for spinal cord atrophy and white matter lesion burden, while there was a statistical trend for numerically higher sGFAP in SD/SN pwMS. The CASA-MS study showed significantly more gray matter atrophy in severe compared to less-severe progressive MS.

Essential trace element levels in multiple sclerosis: Bridging demographic and clinical gaps, assessing the need for supplementation

BackgroundMultiple sclerosis (MS) is a chronic demyelinating disorder intricately linked to perturbations in trace element levels. While previous studies have explored circulating trace elements in a limited sample, understanding the impact of demographic and clinical variables on the elemental profile within a larger cohort remains elusive. MethodsThis study aimed to evaluate essential trace elements (Cr, Mn, Co, Cu, Zn, and Se) in the sera of 215 MS patients compared to a meticulously matched control group of 100 individuals with similar gender and age. Our main objective was to identify potential variations in elemental profiles based on demographic and clinical parameters among MS patients, elucidating the prospective relevance of supplementing specific essential trace elements. ResultsData indicated a significant decrease in serum levels of Mn, Co, Zn, and Se, and an increase in Cr in MS patients compared to controls. These trace elements not only discriminated between MS patients and controls but also exhibited distinctive capabilities among demographic subgroups. Gender, smoking habits, and age strata (20–40 years and 41–60 years) revealed discernible variations in elemental profiles between MS patients and their control counterparts. Se demonstrated the singular ability to stratify cases of extreme MS severity, mild relapsing-remitting MS (RRMS) and highly severe secondary progressive MS (SPMS). In contrast, Co significantly differentiated RRMS from primary progressive MS (PPMS), while Cu significantly differentiated SPMS from PPMS. Additionally, Cu showed a negative correlation with MSSS, while Mn and Zn showed a positive correlation with EDSS. ConclusionThese findings underscore a substantive deficiency in Mn, Co, Zn, and Se in the MS cohort, supporting targeted supplementation with these trace elements. This study provides a comprehensive understanding of the intricate relationship between essential trace elements and MS, paving the way for further research into personalized nutritional interventions for this complex neurological disorder.

Impact of procedural success definitions on long-term outcomes in patients with rheumatic mitral stenosis treated with percutaneous mitral valvuloplasty

Abstract Background Three different definitions of PBMV success have been reported in the literature. It is uncertain which definitions should be used in practice or clinical studies since there have been no comparative studies on the impact of these definitions on long-term outcomes after PBMV. Purpose We assessed the impact of the three PBMV success definitions on long-term outcomes in rheumatic MS patients treated with PBMV. Methods This was a retrospective study on consecutive severe rheumatic MS patients treated with PBMV in tertiary-care university hospital center between January 2003 and October 2020. Patients with in-hospital complications (death, emergency surgery or stroke) were excluded. Definition A was post-PBMV mitral valve area (MVA) ≥ 1.5 cm2 or ≥ 50% increase in MVA and mitral regurgitation less than 3+. Definition B was MVA ≥ 1.5 cm2 and MR ≤ 2+, and definition C was ≥ 50% increase in MVA or area of ≥ 1.5 cm2, with no more than 1 grade increment in MR severity. The patients were grouped according to success or no success according to each success definition. Cox regression analyses were performed to assess the associations between PBMV success and the composite outcome of all-cause death, mitral surgery or re-PBMV at long-term. Net reclassification improvement (NRI) was used to compare the impact of the success definitions. Results Of 589 patients included in the study, 83.2% were women with a mean age of 41.6 years and median Wilkin score of 8. The mean follow-up time was 5.5 years. The PBMV success rates according to the A, B and C definitions were 81.15%, 60.27% and 74.87%, respectively. Patients with PBMV success according to the A or B definitions had significantly lower risk of the composite outcome than those without success (success vs no success, definition A – HR 0.64, [95% CI 0.46-0.87], p 0.005, definition B – HR 0.71, [95% CI 0.53-0.94], p 0.016). Patients with PBMV success according to definition C had a similar risk of the composite outcome as those without success (HR 0.78, [95% CI 0.57-1.05], p 0.10). Patients with PBMV success according to definition A had a significantly lower risk of all-cause death than their counterparts (adjusted HR 0.57, [95% CI 0.38 - 0.86], p 0.006). The risk of death in patients with PBMV success according to the B or C definitions were similar to those without success. The c-indexes and 95% CIs for the composite outcomes of definitions A, B and C were 0.56 [0.52-0.60], 0.57 [0.52-0.61], and 0.54 [0.50-0.58], respectively. The A definitions discriminated the composite outcome better than the C definition (NRI – A vs. C 38.07%, [95% CI 13.18%-84.86%). The discriminative ability of the B definition was similar to the C definition (NRI - B vs. C 24.38%,[95% CI 11.37%-78.87%]). Conclusions The PBMV success rate varied among the different success definitions. The impact of success definitions A and B on long-term outcomes seemed to be better than the C definition.Characteristics of study patientsKaplan-Meier cumulative event

Abstract 17125: Cardiovascular Mortality Defines Severe RV Enlargement in Pre-Capillary Pulmonary Hypertension by a RV to LV Volume Ratio &gt;2.0

Introduction: Cardiac magnetic resonance imaging (CMR) is emerging as a non-invasive, prognostic tool in pulmonary arterial hypertension (PAH). The right ventricular (RV) end diastolic volume (EDV) to left ventricular (LV) EDV ratio measured by CMR is a parameter to evaluate RV size in relationship to the patient’s own LV and determine severity of dilation in patients with pulmonary arterial hypertension (PAH). An RVEDV/LVEDV greater than 2.3 has been proposed as a cutoff for severe RV enlargement in PAH based on mortality risk 1 . This study aims to confirm this cutoff in pre-capillary (pc) pulmonary hypertension (PH) patients using CMR and mortality data from two additional cohorts. Materials and Methods: In this retrospective study, we analyzed primary outcome cardiovascular mortality and CMR parameters in a database of patients from 2014 to 2021 with pcPH (mean pulmonary artery pressure &gt; 20mmHg, PCWP&lt;15 mmHg, WU≥ 3) determined by right heart catheterization (RHC) from Ohio State University (OSU) (n=42) and West China Hospital (WCH) (n=58). Patients with congenital heart disease, ischemic heart disease, valvular heart disease (moderate to severe AS, AR, MS, or MR), ECV &lt;20 or &gt;28, and WHO group II PH were excluded from the analysis. The optimal cutoff values to classify severe RV enlargement by RVEDV/LVEDV was determined by a receiver operating characteristic (ROC) curve using cardiovascular mortality. Results: The event rates for cardiovascular mortality among the OSU and WCH cohorts were 14/42 and 14/58, respectively. Altmayer identified the optimal cut-off as 2.32 (sensitivity = 87.5%; specificity = 87.0%, AUC=82%) 1 . An RVEDV/LVEDV of 2.01 was the optimal cutoff to predict cardiovascular mortality using the ROC analysis from the OSU cohort (sensitivity= 71.4%, specificity = 82.1%, AUC 80.1%). It was 2.46 from the WCH cohort (sensitivity = 64.3%, specificity = 86.3%, AUC 77.7%). When data from the OSU and WCH cohort were combined, the optimal cutoff was 2.1 (sensitivity = 71%, specificity = 72%, AUC 77.1%). Conclusions: Using data from three different populations of pcPH patients, an RVEDV/LVEDV of at least &gt;2.0 can be used to partition severe RV dilation using cardiovascular mortality.

Sleep Quality in patients with rheumatic mitral stenosis and the effect of percutaneous mitral balloon valvuloplasty on Sleep Quality

Background: Impaired sleep quality is common in patients with heart disease. However, data on the effects of mitral stenosis severity and percutaneous mitral balloon valvuloplasty on sleep quality are scarce.&#x0D; Materials and methods: 205 patients included in the study were divided into two groups as severe and non-severe (mild to moderate MS) rheumatic MS. 123 patients with mild to moderate MS and 82 patients with severe MS were analyzed. 82 patients with severe rheumatic MS who underwent percutaneous mitral balloon valvuloplasty were prospectively enrolled. Sleep quality was prospectively investigated immediately before and approximately six months after the percutaneous mitral balloon valvuloplasty procedure. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality.&#x0D; Results: The PSQI score was considerably higher in patients with severe MS compared to mild to moderate MS (3.7 ± 2.0 vs. 7.7 ± 2.9, p

A Comprehensive Review on Multiple Sclerosis

Multiple Sclerosis is an extremely frequent non-traumatic debilitating illness affecting youngsters. Multiple Sclerosis is becoming more common across the globe, as is the disease's economic effect. The fundamental etiology of Multiple Sclerosis plus the processes causing this rise remain unknown, yet complicated interactions between genes and the environment virtually definitely play an important part. The major source of injury in MS is swelling of the brain and spinal cord. The exact ingredients that cause this type of inflammation are unclear. According to research, environmental, genetic, and viral causes may all have a role in the onset of MS. MS statistics suggests that reduced blood vitamin D levels, cigarette smoking, obesity in kids, and Epstein-Barr virus infection all have a role in disease progression. Because of advancements in diagnostic procedures and standards, patients with MS can now be identified at a younger age. Along with this, the quantity, effectiveness, and danger of MS therapies have risen tremendously. The prospect of a 'pre-symptomatic MS' diagnosis, which might lead to the investigation of possible preventative therapies. MS epidemiological studies, probable aetiological variables, and pathogenesis are all reviewed throughout this detailed study prior proceeding on to therapeutic elements of MS diagnostic and therapy. Recent encouraging investigations of condition-modifying medications in progressive form of MS offer persons alongside severe MS the hope of slowing the progression of the disease while keeping residual functioning. It turns out that drugs appear to work at several stages of the illness's progression puts challenge on the traditional two-stage model of MS's inherent course.

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

Clinical and demographic profile of patients of rheumatic valvular heart disease

Background: Rheumatic heart disease (RHD) is a preventable structural heart disease involving cardiac valves affecting the young population of productive age-group having considerable morbidity and mortality due to associated complications. Aims and Objectives: To evaluate the clinic-demographical characteristics and complications of RHD patients and thus to build up a RHD valvular registry. Materials and Methods: In this study, we enrolled 570 consecutive patients diagnosed with rheumatic valvular affection as defined by echocardiographic criteria, and studied their demographic, valvular pathology, symptomatology, prophylaxis and complication profile. Results: Female patients dominated the population in number, mitral being the most affected valve, mitral stenosis the commonest lesion. Newly diagnosed patients constituting 20% of study population. One-fourth of the patients gave a proper history of acute rheumatic fever and oral prophylaxis was noted to be more compliant than parenteral. Case proportionality ratio for atrial fibrillation was highest with severe MS with AR and for pulmonary hypertension with severe MR with or without MS. Conclusion: RHD is a preventable disease and health professionals and policy making institutions at all levels should strive in unison to mitigate its incidence, disease severity and complications.

RESOLUTION OF LEFT ATRIAL THROMBUS IN SEVERE MITRAL STENOSIS PATIENTS AFTER THREE MONTHS OF ANTICOAGULATION

Objectives: To determine frequency of LA clot resolution in patients with severe MS after three months of anticoagulation. Methodology: A descriptive study was conducted over 6 months from Jul 2018 to Jan 2019 including 49 patients who fulfilled the inclusion criteria and visited Cardiology department, NICVD Hospital-Karachi. After clinical evaluation, warfarin therapy was given for 3 months followed by Transesophageal echocardiography (TEE) to access the resolution of LA thrombus. Chi-square test and Fisher Exact test were used to assess the effect of patient characteristics and echocardiographic findings on the resolution of thrombus. Results: The mean age of the study patients was 47.51±9.93 years. The average mitral valve area (cm2) was observed to be 0.68±0.16, while the average size of left atrial (mm) was 54.38±7.19. At the end of 2 months, TEE showed successful resolution of clot in 11 (22.4%). While by the end of 3 months, only 6 (12.2%) patients showed successful resolution of clot. Conclusion: After 3 months of oral anticoagulation, the LA thrombus resolved in almost 1/4th of the study patients. Successful clot resolution showed positive correlation with history of stroke, hemoptysis and clot mobility and negative correlation with severity of tricuspid regurgitation.

Patients With Severe Multiple Sclerosis Exhibit Functionally Altered CD8+ Regulatory T Cells.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. Studies of immune dysfunction in MS have mostly focused on CD4+ Tregs, but the role of CD8+ Tregs remains largely unexplored. We previously evidenced the suppressive properties of rat and human CD8+CD45RClow/neg Tregs from healthy individuals, expressing Forkhead box P3 (FOXP3) and acting through interferon-gamma (IFN-γ), transforming growth factor beta (TGFβ), and interleukin-34 (IL-34). secretions to regulate immune responses and control diseases such as transplant rejection. To better understand CD8+CD45RClow/neg Tregs contribution to MS pathology, we further investigated their phenotype, function, and transcriptome in patients with MS. We enrolled adults with relapsing-remitting MS and age-matched and sex-matched healthy volunteers (HVs). CD8+ T cells were segregated based on low or lack of expression of CD45RC. First, the frequency in CSF and blood, phenotype, transcriptome, and function of CD8+CD45RClow and neg were investigated according to exacerbation status and secondarily, according to clinical severity based on the MS severity score (MSSS) in patients with nonexacerbating MS. We then induced active MOG35-55 EAE in C57Bl/6 mice and performed adoptive transfer of fresh and expanded CD8+CD45RCneg Tregs to assess their ability to mitigate neuroinflammation in vivo. Thirty-one untreated patients with relapsing-remitting MS were compared with 40 age-matched and sex-matched HVs. We demonstrated no difference of CSF CD8+CD45RClow and CD8+CD45RCneg proportions, but blood CD8+CD45RClow frequency was lower in patients with MS exacerbation when compared with that in HVs. CD8+CD45RCneg Tregs but not CD8+CD45RClow showed higher suppressive capacities in vitro in MS patients with exacerbation than in patients without acute inflammatory attack. In vitro functional assays showed a compromised suppression capacity of CD8+CD45RClow Tregs in patients with nonexacerbating severe MS, defined by the MSSS. We then characterized murine CD8+CD45RCneg Tregs and demonstrated the potential of CD45RCneg cells to migrate to the CNS and mitigate experimental autoimmune encephalomyelitis in vivo. Altogether, these results suggest a defect in the number and function of CD8+CD45RClow Tregs during MS relapse and an association of CD8+CD45RClow Tregs dysfunction with MS severity. Thus, CD8+CD45RClow/neg T cells might bring new insights into the pathophysiology and new therapeutic approaches of MS.

A Retrospective Study to Evaluate the Maternal and Fetal Outcome in Patients of Heart Disease in Pregnancy at a Tertiary Rural Hospital

Background: Heart disease(HD) in pregnancy remains an important cause of maternal, fetal morbidity and mortality especially in a developing country like India, where incidence of cardiac disease that complicates pregnancy is between 1% to 4% &amp; Rheumatic heart disease (RHD) still remains the most common type of heart disease complicating pregnancy due to Poor socioeconomic condition. Methods: This is a retrospective observational study carried out in Department of Obstetrics and Gynaecology at S.M.B.T. Institute of medical sciences, Dhamangaon during the period of 24 months to assess the maternal and fetal outcome on patients of heart disease with pregnancy. Result: Among the 3182 patients delivered in the study 35 had cardiac disease with prevalence of 1.1%, all patients were booked and diagnosed with heart disease during ANC checkup. Rheumatic Heart disease (70%) was the commonest form of heart disease with MS with MR predominating (22%). NYHA grade 2 patients (41%) were maximum with Anemia as the associated complicating factor.4 patients with severe MS required balloon mitral valvotomy (BMV) of them 1 patient went into pulmonary edema. There was no maternal mortality. 2 patients underwent medical termination of pregnancy (MTP) for cardiac reason and there was 1 neonatal mortality. Conclusion: RHD is still the commonest heart disease in pregnancy; BMV can be performed in third trimester on patients with severe MS reducing intra and postpartum complications. Giving good and timely antenatal, Intranatal and postnatal care at a tertiary care hospital with good cardiac, obstetric &amp; Neonatal care setup reduces maternal and fetal morbidity in patients of heart disease with pregnancy. Keywords: Rheumatic heart disease in pregnancy, Congenital heart disease in pregnancy, Balloon Mitral Valvotomy in pregnancy

The Effectiveness of Physiotherapy Interventions for Mobility in Severe Multiple Sclerosis: A Systematic Review and Meta-Analysis

Background People with Multiple Sclerosis (pwMS) prioritise gait as the most valuable function to be affected by MS. Physiotherapy plays a key role in managing gait impairment in MS. There is little evidence on the effectiveness of physiotherapy for severe MS. Objective To undertake a systematic review and meta-analysis of the literature to identify evidence for the effectiveness of physiotherapy for gait impairment in severe MS. Methods. The available literature was systematically searched, using a predetermined protocol, to identify research studies investigating a physiotherapy intervention for mobility in people with severe MS (EDSS ≥ 6.0). Data on mobility related endpoints was extracted. Meta-analysis was performed where a given mobility end point was reported in at least 3 studies. Results 37 relevant papers were identified, which included 788 pwMS. Seven mobility-related endpoints were meta-analysed. Robot-Assisted Gait Training (RAGT) was found to improve performance on the 6-minute walk test, 10-metre walk test, fatigue severity scale, and Berg Balance Scale. Neither body weight supported training nor conventional walking training significantly improved any mobility-related outcomes. Conclusion Physiotherapy interventions are feasible for mobility in severe MS. There is some evidence for the effectiveness of RAGT.

EFFICACY OF SGLT2I IN ACUTE DECOMPENSATED HEART FAILURE WITH TYPE 2 DIABETES MELLITUS

Objective: We hypothesized that Sodium Glucose cotransporter 2 inhibitors (SGLT2i) exerts positive effects in patients admitted with ADHF and type 2 diabetes mellitus (T2DM). Design and method: Prospective case control study with 1-month follow up. All the patients who admitted to Cardiology center, Hue Central Hospital between 01/12/2020 and 01/06/2021. Inclusion criteria: Adults diagnosed with T2DM with hypervolemic ADHF reduce LVEF and planned treatment with IV loop diuretic therapy. Exclusion criterias: fasting blood glucose (FBG) &lt; 4.4 mmol/L, Systolic blood pressure &lt; 90mmHg, requires inotrope therapy, eGFR &lt; 30 ml/min/1.73m2, severe anemia, breastfeeding or pregnant, severe AS or MS without repair, severe hepatic impairment, acute coronary syndrome or history of coronary artery stenting. The study primary end-point: Length of hospitalization, in-hospital death, death within 30 days after discharge and re-hospitalized within 30 days. The study safety end-point: Urinary tract infection, worsening renal function, ketonacidosis or hypovolemic shock. Results: The proportion of in-hospital mortality, 30-days mortality and the length of hospitalization by day tended to be higher in the group of patients not using SGLT2i but not significant. The proportion of re-hospitalized for 30 days was higher in group not using SGLT2i (p = 0.014). The patient group of non-SGLT2i using re-hospitalized sooner than the patient using SGLT2i (p = 0.029). The eGFR of the patient use the SGLT2i show significantly improvement after 30 days (p = 0.024) but in day 4, it’s shown no improvement. In patient who don’t use the agent, the eGFR get worst in day 4 with p = 0.01 then it improve in day 30 but not significant. The group of using SGLT2i seems much more effective in reduce NT-proBNP and FBG (p values: NT-proBNP:0.026 to 0.044; FBG: 0.021 to 0.038, respectively). Complications that should be considered in patients using SGLT2i were UTIs and discontinuation of treatment due to feeling lose weight too fast. Conclusions: The using of SGLT2i reduce the numbers of re-hospitalization in first 30-day after discharged, prolong the duration between re-hospitalization period and only the patient groups using SGLT2i could improve the eGFR after 30-days with no significant adverse effects.

Evaluating the effect of multivalvular disease on mortality after transcatheter aortic valve replacement for aortic stenosis: a meta-analysis and systematic review.

Aims: To determine the prognosis of multivalvular disease in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis. Methods: Patients undergoing TAVR for aortic stenosis with covariate-adjusted risk of mortality associated with concomitant valve disease (mitral regurgitation [MR], mitral stenosis [MS] or tricuspid regurgitation [TR]) were included. Results: Moderate-to-severe MR was associated with increased mortality at 30 days (hazard ratio [HR]: 1.60; 95% CI: 1.11-2.30; p=0.01) and 1 year (HR: 1.87; 95% CI: 1.22-2.87; p=0.004). The presence of all-grade MS did not impact 30-day or 1-year mortality (HR, 30 days: 1.60; 95% CI: 0.71-3.63; p=0.26; and HR, 1 year: 1.90; 95% CI: 0.98-3.69; p=0.06); however, an increased risk of 1-year mortality (HR: 1.67; 95% CI: 1.03-2.70; p=0.04) was observed with severe MS compared with no MS. Moderate-to-severe TR had a higher risk of all-cause mortality at 1 year (HR: 1.49; 95% CI: 1.24-1.78; p<0.001) compared with no or mild TR. Conclusion: Moderate-to-severe MR or TR, and severe MS, significantly increase mid-term mortality after TAVR.

The Exacerbation of Lutembatcher Syndrome in The Setting of COVID-19 infection: A Rare Case Report

Lutembatcher syndrome is a rare cardiac condition characterized by a combination of the atrial septal defect (ASD; congenital or iatrogenic) and mitral stenosis (MS; congenital or acquired). Patients with Lutembatcher syndrome and adults with congenital heart disease (ACHD) in general may be at high risk when accompanied by coronavirus disease 2019 (COVID-19). Since there is no published study on the impact of COVID-19 on ACHD, little is known about management strategies in this subset of patients. Herein, we report a young adult female presented with abdominal discomfort, swollen legs, fever, cough, and dyspnea. The patient had developed palpitation and exercise intolerance five years ago but paid it no attention. Echocardiography revealed large secundum type ASD with severe MS (Wilkins score of eight) and a nasopharyngeal swab confirmed SARS-COV-2 infection. The patient was diagnosed with Lutembacher syndrome and COVID-19. Intensive treatment was given to relieve symptoms due to heart failure and to treat COVID-19 pneumonia. Patients with Lutembatcher syndrome are at a higher risk of being infected with COVID-19 and manifest into severe infections. Therefore, determining the risk of infection and the severity of COVID-19 in ACHD patients are required during the pandemic.

Wet Mount Microscopy of the Vaginal Milieu Does Not Predict the Outcome of Fertility Treatments: A Cross-sectional Study.

The aim of the study was to evaluate whether vaginal dysbiosis (bacterial vaginosis [BV] or moderate/severe aerobic vaginitis [AV]/desquamative inflammatory vaginitis) in women subjected to intrauterine insemination (IUI) or in vitro fertilization/intracytoplasmic sperm injection influences the rates of pregnancy. This is a cross-sectional study involving 392 women who underwent IUI or in vitro fertilization/intracytoplasmic sperm injection at a fertility clinic. All had a slide collected for phase contrast wet mount microscopy (WMM), which was classified according to the International Society for the Study of Vulvovaginal Disease recommendations. Correlation between flora patterns and the rate of pregnancy were evaluated. There were no differences in any of the groups in terms of pregnancy rate (biochemical, clinical, at first trimester ultrasound, or live birth) after stratifying for the presence of BV, moderate or severe (ms) AV, BV and/or moderate or severe AV, cytolysis, or abnormal vaginal flora (lactobacillary grade ≥ IIb). The presence of Candida species, cocci, or bacilli morphotypes other than lactobacilli also showed no differences. The vaginal flora assessment by WMM at the time of IUI or oocyte retrieval was not predictive of the success of fertility treatments.The absence of differences may be due to intrinsic limitations of WMM (i.e., identifying only bacterial morphotypes), a positive impact of the treatments in the vaginal flora or because the sperm and embryo transfer is made directly into the uterine cavity, thus overcoming any cervical or vaginal dysbiosis disadvantage. Future studies should focus on the endometrial milieu, rather than in the vaginal and/or cervical one.

Transcutaneous Electrical Acustimulation Ameliorates Motion Sickness Induced by Rotary Chair in Healthy Subjects: A Prospective Randomized Crossover Study

ObjectivesMotion sickness (MS) is a common physiological response to real or virtual motion. The purpose of this study was to investigate the effects of transcutaneous electrical acustimulation (TEA) on MS and the underlying mechanisms in healthy subjects. Materials and MethodsA total of 50 healthy participants were recruited and randomly assigned into two groups to complete two separate sessions in a crossover study. A Coriolis rotary chair was used as a model to provoke severe MS. The total tolerable rotation time and Graybiel scoring scale were recorded. Gastric slow waves were detected by electrogastrogram. The autonomic nervous function, including the vagal activity, was evaluated by the analysis of heart rate variability derived from the electrocardiogram recording. The serum levels of arginine vasopressin (AVP) and norepinephrine (NE) were examined. ResultsOf note, 22 participants in TEA and only 11 participants in the sham-TEA session completed the entire five-rotation MS stimuli (p = 0.019). TEA significantly prolonged the total tolerable rotation time of MS stimuli (220.4 ± 11.59 vs 173.6 ± 12.3 seconds, p < 0.001) and lowered MS symptom scores (12.56 ± 2.03 vs 22.06 ± 3.0, p < 0.001). TEA improved the percentage of normal gastric slow waves, compared with sham-TEA (56.0 ± 2.1% vs 51.6 ± 2.0%, p = 0.033). TEA also significantly enhanced vagal activity compared with sham-TEA (0.41 ± 0.02 vs 0.31 ± 0.02, p < 0.001). In addition, the increased serum levels of AVP and NE on MS stimulation were markedly suppressed by TEA treatment, compared with sham-TEA (AVP, 56.791 ± 4.057 vs 79.312 ± 10.036 ng/mL, p = 0.033; NE, 0.388 ± 0.037 vs 0.501 ± 0.055 ng/mL, p = 0.021). ConclusionsNeedleless TEA is a potent therapeutic approach for severe MS, as it increases participants' tolerance and ameliorates MS symptoms, which may be attributed to the integrative effects of TEA on autonomic functions and neuroendocrine balance.

Determination of Oxaliplatin by a UHPLC-MS/MS Method: Application to Pharmacokinetics and Tongue Tissue Distribution Studies in Rats

Oxaliplatin (OXP), a third-generation platinum-based chemotherapy drug, was often indirectly analyzed via total platinum by an ICP-MS because it was difficult to directly quantify using an LC-MS/MS method, due to its instability, bad column separability and severe MS signal inhibition. Here, we developed and validated a specific, sensitive and reproducible LC-MS/MS method for the quantification of OXP itself in rat plasma and tongue tissue on a SCIEX 4000 QTRAP® MS/MS system equipped with a Phenomenex Lux 5u Cellulose-1 column (250 × 4.6 mm, 5 μm). This method was validated at the lower limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 5 ng/mL and 10 ng/mL, with linearity of 10–5000 ng/mL (r2 > 0.99) and 10–2500 ng/mL (r2 > 0.99), in rat plasma and tongue homogenates, respectively. The intra- and inter-day precision (CV%) and accuracy (RE%) were within 15% for LLOQ, low-, medium- and high-quality control samples. The mean extraction recoveries were around 50% and 80% for plasma and tongue homogenates, respectively. This assay was successfully applied to pharmacokinetics study following intravenous administration of OXP, as well as tongue tissue distribution after 1 h and 4 h of a novel oral mucosal patch application.