Months Of Continuous Treatment Research Articles

Efficacy of levetiracetam combined with oxcarbazepine in the treatment of adults with temporal lobe epilepsy and its impact on memory and cognitive function.

To explore the effect of levetiracetam combined with oxcarbazepine on the memory and cognitive function of adult patients with temporal lobe epilepsy. This retrospective analysis included 91 adult patients with temporal lobe epilepsy treated at Xianyang Hospital from June 2020 to December 2022. Based on their medication regimen, patients were categorized into an observation group (n=51) receiving levetiracetam plus oxcarbazepine and a control group (n=40) receiving only levetiracetam. Both groups underwent 3 months of continuous treatment. Therapeutic efficacy, pre- and post-treatment memory function (assessed using the Clinical Memory Scale, CMS), cognitive function (evaluated with the Wechsler Adult Intelligence Scale-Revised in China, WAISRC), anxiety and depression levels (measured by the Hamilton Anxiety Scale, HAMA, and Hamilton Depression Scale, HAMD), as well as adverse reactions, were compared between the two groups. Independent factors influencing treatment efficacy were also analyzed. CMS and WAISRC scores significantly increased in both groups after treatment (both P=0.001), with the observation group showing more significant improvements than the control group (P=0.001). The improvements in HAMA and HAMD scores in the observation group were significantly better than the control group (all P<0.001). Adverse reaction occurrence showed no significant difference between the two groups (P>0.05). Prognostic analysis identified seizure frequency and treatment regimen as independent factors influencing efficacy. Levetiracetam combined with oxcarbazepine effectively improves cognitive dysfunction in adults with temporal lobe epilepsy, with superior efficacy to levetiracetam alone, and good safety.

Multi-Omics Exploration of Adaptive Mechanism to BTK Inhibition By Ibrutinib in CLL Identified TMBIM6/BI-1 As a Poor Prognosis Variable and Potential Therapeutic Target

Introduction: Ibrutinib is currently part of the therapeutic armamentarium employed in patients with CLL. Despite being an active drug, its usage is not devoid of adverse effects and resistances leading to discontinuation. In addition, current evidence suggests that ibrutinib improves the T cell disfunction associated with CLL progression. The objective of our study was to longitudinally assess the T cell immune profile of ibrutinib-treated CLL patients, and to identify potential adaptive mechanisms to BTK inhibition in B cells in the first 12 months of continuous treatment. Methods: Blood samples from 28 patients from GELLC7 trial (NCT03280160, ibrutinib followed by ofatumumab consolidation) were collected before treatment (BT), and 1, 3, 6 and 12 months on treatment (at least two timepoints). Peripheral blood mononuclear cells and plasma were isolated and stored to perform multi-omics analyses including flow cytometry, RNA sequencing, cytokine determination, migration assays and targeted DNA sequencing. Results: T cell immunophenotyping revealed a decrease of CD4+ and CD8+ T cells expressing PD1 and CD244 and a reduction of regulatory T cells (Tregs) and T follicular helper (Tfh) cells after ibrutinib treatment. In addition, bulk-RNAseq of purified T cells revealed 170 differentially expressed genes (DEG) after 6 months of ibrutinib treatment. These genes participate in pathways related to cell stimulation and regulation of cell activation. Gene set enrichment analysis (GSEA) showed a downregulation of oxidative metabolism, proliferation, and activation pathways, indicating a reduction of the CLL inflammatory burden. Furthermore, there was a significant reduction of several inflammatory/migration chemokines in plasma at 6 months (CCL2/3/4, CXCL10, CXCL12, CXCL13, CCL19). In CLL cells, a decreased expression of adhesion (CD44/CD62L), immunosuppression- (CD200/BTLA), and migration-related markers (CXCR5/CCR7) at 6 months of ibrutinib treatment was observed. However, CXCR4 expression increased upon ibrutinib treatment, and the proliferative CXCR4dimCD5br population was reduced. We investigated CXCR4-mediated migration as a potential mechanism of CLL cell adaptation to ibrutinib in 14 patients at BT and 6 months of BTK inhibition. Reduced CXCR4-migratory capacity was observed, but some cells retained migration under BTK inhibition. Targeted-DNAseq and bulk-RNAseq were performed at BT and 6 months of ibrutinib to characterize CLL cells with retained migratory capacity. There was an alteration of the subclonal composition of CLL cells that retained migratory capacity under BTK inhibition in 7/12 patients with a recurrent enrichment of subclones with mutations in ATM and NFKBIE gene. BTK p.Cys481Ser mutation was acquired in one patient after 6 months of treatment with ibrutinib, while no PLCG2 mutations were detected. GSEA showed an upregulation of mTORC1 and Myc pathways in cells with retained migration. Among the DEG, TMBIM6 was the most significantly upregulated gene. TMBIM6 gene is associated with apoptosis, mTOR-Akt axis and poor prognosis in solid tumors. We evaluated the prognostic impact of TMBIM6 expression using public data from the CLL-map portal (Knisbacher et al. 2022 Nat Genet). TMBIM6 high expression was associated with poor overall survival in both univariate and multivariate analyses including age, gender, IGHV mutation status (Figure 1) and recurrent genetic alterations. When TMBIM6 was targeted with BIA, a TMBIM6 antagonist (Kim et al. 2020 Nat Commun), its effect on CXCR4-mediated migration was limited but it induced CLL cell apoptosis in suspension and co-cultured CLL cells (Figure 2). Moreover, BIA addition to ibrutinib treatment induced synergistic apoptosis. Collectively, these results indicate that TMBIM6 may be a potential novel target for CLL and that combination with ibrutinib could be a valid approach for time-limited therapy. Conclusions: Ibrutinib in T cells reduced the expression of exhaustion markers, Tregs and Tfh cells. In CLL cells, we observed a downregulation of markers related to adhesion, immunosuppression and migration, but an overexpression of TMBIM6 in CLL cells that retained migrative capacity towards CXCL12 under ibrutinib. Finally, we identified TMBIM6 expression as an independent poor prognostic factor and a potential novel target for CLL.

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study.

This is a summary of the article describing the EMPEROR-Reduced study of empagliflozin, which was published in the New England Journal of Medicine. Empagliflozin (brand name Jardiance®) is a new drug therapy for the treatment of chronic heart failure. Chronic heart failure is a long-term condition where the heart cannot pump enough blood around the body, leading to symptoms such as shortness of breath, fatigue and build-up of too much water in the body (fluid retention). It also increases the risk for premature death. The EMPEROR-Reduced study looked at the effects of empagliflozin, a medication taken once daily, in people with reduced ejection fraction. This is a type of heart failure where insufficient blood is pushed out of the heart muscle as it contracts. The study was conducted because more evidence is needed on the effects of empagliflozin and similar drugs in people with heart failure, including those with reduced ejection fraction. The main aim of the EMPEROR-Reduced study was to see if empagliflozin reduces the risk of being taken to hospital for complications of heart failure or dying from heart disease. Over 3700 people with heart failure and reduced ejection fraction were randomly given either empagliflozin or placebo (an identical pill lacking medication) daily for about 16months. This was a double-blind study, which means that neither the participants nor the researchers knew which treatment participants were receiving. After an average of 16months of continuous treatment, fewer patients taking empagliflozin (13.2%) needed to be hospitalized for complications of heart failure than those taking placebo (18.3%). Also, fewer patients taking empagliflozin (1.6%) developed serious kidney problems than those taking placebo (3.1%). Side effects were generally similar in participants who received empagliflozin and those who received placebo, except for genital tract infections, which affected more participants who received empagliflozin (1.7%) than placebo (0.6%). This study suggests that people with chronic heart failure with reduced ejection fraction may benefit from treatment with empagliflozin, mainly by needing to go to hospital less often because of complications of heart failure. Clinical Trial Registration: NCT03057977 (EMPEROR-Reduced study) (ClinicalTrials.gov).

Medical Cannabis Is Not Associated with a Decrease in Activities of Daily Living in Older Adults.

The proportion of older adults using medical cannabis is rising. Therefore, we aimed to assess the effects of herbal medical cannabis on the functional status of older adults. We conducted a prospective observational study of patients aged 65 years or older that initiated cannabis treatment for different indications, mostly chronic non-cancer pain, during 2018-2020 in a specialized geriatric clinic. The outcomes assessed were activities of daily living (ADL), instrumental activities of daily living (IADL), pain intensity, geriatric depression scale, chronic medication use, and adverse events at six months. A cohort of 119 patients began cannabis treatment: the mean age was 79.3 ± 8.5 and 74 (62.2%) were female. Of the cohort, 43 (36.1%) experienced adverse effects due to cannabis use and 2 (1.7%) required medical attention. The mean ADL scores before and after treatment were 4.4 ± 1.8 and 4.5 ± 1.8, respectively (p = 0.27), and the mean IADL scores before and after treatment were 4.1 ± 2.6 and 4.7 ± 3, respectively (p = 0.02). We concluded that medical cannabis in older adults has a number of serious adverse events, but was not associated with a decrease in functional status, as illustrated by ADL and IADL scores after six months of continuous treatment.

Med Check: No Accelerated Pathway for Donanemab and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: No Accelerated Pathway for Donanemab and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:24 Feb 2023https://doi.org/10.1176/appi.pn.2023.03.3.2FDA Declines Accelerated Approval for DonanemabThe U.S. Food and Drug Administration (FDA) has declined to accept Eli Lilly’s Alzheimer’s biologic donanemab into the accelerated approval pathway, the company announced in January. Donanemab is a monoclonal antibody that targets beta amyloid buildup in the brain, which is thought to contribute to Alzheimer’s disease.In its complete response letter to the accelerated approval application, the FDA specifically requested that Eli Lilly provide data from at least 100 patients who received a minimum of 12 months of continued treatment on donanemab.The FDA had previously granted Breakthrough Therapy designation for donanemab based on the results of a phase 2 clinical trial called TRAILBLAZER-ALZ that evaluated the safety and efficacy of donanemab in patients with Alzheimer’s disease. In the trial, 257 patients with early symptomatic Alzheimer’s disease received either donanemab or placebo intravenously every four weeks for up to 72 weeks. Compared with those who received placebo, those who received donanemab experienced less cognitive and functional decline over the course of the trial, as measured by the change from baseline on the Integrated Alzheimer’s Disease Rating Scale.Although the TRAILBLAZER-ALZ trial included more than 100 patients treated with donanemab, due to the speed of plaque reduction, many patients were able to stop dosing as early as six months of treatment, resulting in fewer than 100 patients receiving 12 months of donanemab. FDA Reviews Nasal Nalmefene for Treating Opioid OverdoseThe FDA has accepted for Priority Review a New Drug Application (NDA) for OPNT003 (nasal nalmefene) for the treatment of opioid overdose, Opiant Pharmaceuticals announced in January. Priority Review is granted to therapies that the FDA determines have the potential to provide a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition. OPNT003 was previously granted Breakthrough Therapy designation when a confirmatory pharmacokinetic study comparing a 3 mg spray of the drug with a 1 mg intramuscular nalmefene hydrochloride injection in 68 healthy patients revealed that OPNT003 achieved higher plasma concentrations compared with the intramuscular injection.The NDA also included data from a second study that found similar plasma concentrations of OPNT003 whether the treatment was administered as a single dose in each nostril or as two doses in a single nostril. A third study found the drug to be noninferior to intranasal naloxone and found that nasal nalmefene produced a greater reversal of remifentanil-induced respiratory depression that was nearly twice that produced by nasal naloxone at five minutes. Brexpiprazole Gets Priority Review for Treating Alzheimer’s Agitation In January Otsuka Pharmaceutical Co., Ltd. and H. Lundbeck A/S announced that the FDA has granted Priority Review for its supplemental NDA (sNDA) for brexpiprazole for the treatment of agitation associated with Alzheimer’s dementia.The sNDA submission includes data from two positive clinical phase 3 studies that investigated the treatment of brexpiprazole in patients with agitation related to Alzheimer’s dementia. In Study 331-12-283, 433 patients with agitation associated with Alzheimer’s took either 1 or 2 mg of brexpiprazole or placebo daily for 12 weeks. Those who took 2 mg of brexpiprazole had greater improvements in their Cohen-Mansfield Agitation Inventory (CMAI) Total Score from baseline to week 12 compared with placebo. In Study 331-14-213, which included 345 patients, patients were randomized to either 2 or 3 mg of brexpiprazole or placebo daily for 2 weeks. Those who took either dose of brexpiprazole had greater improvements in their CMAI Total Score from baseline to week 12 compared with placebo. ■ ISSUES NewArchived

Venetoclax Resistance in B-Cell Precursor Acute Lymphoblastic Leukemia Is Characterized By Increased Mitochondrial Metabolism and Can be Overcome By Co-Targeting Oxidative Phosphorylation

Deregulated cell death pathways are a hallmark of many cancers and contribute to leukemogenesis and treatment failure in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Apoptosis is controlled by different pro- and anti-apoptotic molecules either inducing or counteracting cell death induction. Inhibition of anti-apoptotic molecules like B-cell lymphoma 2 (BCL-2) has been developed as therapeutic strategy. Venetoclax (VEN) binds selectively to anti-apoptotic BCL-2 resulting in apoptosis induction and has shown clinical activity in lymphoid malignancies, but insensitivity and resistance have been described. In BCP-ALL, we and others have shown preclinical activity of VEN and VEN is evaluated in first clinical trials. In this study, we have addressed and modeled VEN resistance in BCP-ALL and investigated underlying mechanisms in cell lines and patient-derived xenograft (PDX) samples in order to identify potential strategies to overcome VEN insensitivity. Starting from the BCP-ALL cell line RS4;11, five VEN insensitive lines were generated in parallel by exposure to increasing concentrations of VEN over time (49 passages, 8 months of continuous treatment) and five control lines were exposed to corresponding concentrations of solvent (DMSO). Measuring half maximal effective concentrations (EC50) showed increasing EC50 values from 4 nM to 26.2 µM over time in all VEN treated lines, indicating acquired resistance in our model. VEN insensitive leukemia lines displayed unchanged proliferation and same sensitivities to the prototypic apoptosis inducer staurosporine, the induction therapy drugs vincristine/dexamethasone/asparaginase or the anthracycline daunorubicin as compared to controls, indicating acquisition of VEN specific resistance. In order to further characterize the mechanism of VEN insensitivity, we performed RNA-Seq analysis comparing five RS4;11 VEN insensitive to five control lines. Interestingly, gene set enrichment analysis on significantly regulated genes showed a significant upregulation of gene sets annotated to the citric/tricarboxylic acid cycle and the respiratory electron transport chain, pointing to increased mitochondrial metabolism in VEN resistant cells. We addressed mitochondrial activity and carried out metabolic profiling (Agilent Seahorse XF Cell Mito Stress Test) of VEN resistant and control lines (N=5+5). Most interestingly, in contrast to significant reduction of oxygen consumption rates (OCR) in VEN treated control lines, we found sustained high mitochondrial metabolism indicated by persistent high OCR in VEN resistant lines. To further validate our findings, we investigated a series of BCP-ALL PDX samples (N=30) and titrated VEN EC50 values identifying heterogenous VEN activities. Metabolic profiling (Mito Stress test) was performed on sensitive as compared to highly resistant leukemias (N=3+3). Most interestingly and in line with our findings in cells with acquired resistance, PDX samples with intrinsic VEN insensitivity showed higher oxygen consumption and ATP production rates, thus further highlighting that increased mitochondrial activity is a characteristic feature of VEN resistant ALL. Along this line, significant higher mitochondrial DNA content was found in highly insensitive PDX leukemias when compared to VEN sensitive samples. Moreover, we analyzed mitochondrial morphology by electron microscopy. Although numbers of mitochondria did not differ between VEN resistant and sensitive leukemias, the overall mitochondrial area and structure was found to be significantly larger and elongated, further corroborating our finding of augmented mitochondrial metabolism in VEN resistant ALL. Finally, we addressed whether VEN resistance in ALL can be overcome by directly targeting oxidative phosphorylation (OxPhos). Using oligomycin, an inhibitor of the complex V/ATPase subunit, we found synergistic induction of apoptosis together with VEN in BCP-ALL cell lines and PDX samples, showing that acquired and intrinsic VEN insensitivity can be overcome by co-targeting BCL-2 and the OxPhos pathway. Taken together, we show that VEN resistance in BCP-ALL is characterized by high mitochondrial metabolic activity. Co-targeting of BCL-2 and oxidative phosphorylation results in synergistic anti-leukemia activity setting the basis for further preclinical and potential clinical evaluation.

MDS-502 Supportive Care in Low-Risk Myelodysplastic Syndromes: Role of Erythropoiesis Stimulating Agents (ESAs)

Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients, and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS. An analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non transfusion-dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed. 183 patients, treated with standard-dose ESAs, have been retrospectively analyzed. Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum erythropoietin (EPO) concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1-118). ORR was 83.6% (153/183); no difference among WHO and IPSS subgroups was found. 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease (non-responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic-responders group, 83.2% exhibited again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic-responders group, 89.8% exhibited again normocytosis, while 10.2% become macrocytic. In these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion-dependence, regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group 89% exhibited again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibited again macrocytosis, while 24% become normocytic. These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly due to stimulating erythroid production in MDS clones; in the minority of patients probably it happens due to recruiting residual polyclonal erythropoiesis. It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses.

Stage IV Non-small Cell Lung Adenocarcinoma in Complete Response for 5 Years Post-first-line Nivolumab Immunotherapy: Are We Talking about a Cure?

Background: Metastasis of the Central Nervous System (CNS) is one of the frequently occurring complications of advanced Non-Small Cell Lung Cancer (NSCLC) and has been observed in 24–44% of patients. Patients suffering from NSCLC along with CNS metastases have a generally poor prognosis.&#x0D; Case Report: A 57-year-old nonalcoholic, non-diabetic, heavy smoker male patient was diagnosed with stage IV NSCLC (non-small cell lung cancer) (Adenocarcinoma), PD-L1 expression 80% with liver, spleen, and brain metastases. In June 2016, the patient was diagnosed with Stage III-A EGFR wild right-sided lung adenocarcinoma (T4N0M0), for which he underwent Curative Concurrent chemo-radiotherapy in Jordan, followed by two cycles of Etoposide plus CDDP (Cisplatin). In February 2017, the patient came to the hospital with the chief complaint of massive hemoptysis. His CT scan showed an appearance in keeping with the right upper-lobe cavitating tumor with possible contralateral lung, splenic, and hepatic metastases. The patient was offered pneumonectomy but refused it. Interventional radiology (IR) tumor embolization of the apical and posterior (A1 and A2) branches of the right superior pulmonary artery with no procedural complication was performed to stop the bleeding.&#x0D; At the end of that same month, on February 28, 2017, he presented to emergency with seizures, for which a contrast CT scan showed two enhancing lesions, one of the left parietal lobe posteriorly 1.8 cm with marked white matter oedema causing a mass effect and the effacement of the posterior horn of the left lateral ventricle. The second is a small ring-enhancing deposit of the right occipital lobe 6 mm with surrounding oedema.&#x0D; The liver biopsy failed to show any malignancy. After the MDT discussion, the largest lesion in the brain was removed and a small lesion was kept. The left occipital metastasis was resected and was found to be a metastatic adenocarcinoma of lung origin. It was positive for TTF-1 and positive for Moc 31. P63 and CK5/6 were negative (no squamous component is seen). No brain radiotherapy was offered. First-line palliative Nivolumab was started on March 20, 2017. Nivolumab first proved to be highly successful against brain metastases. However, it was discontinued as the patient developed myelitis after seven months of continuous treatment. After the discontinuation and improvement of myelitis symptoms, Nivolumab was resumed. The amazing thing about this treatment approach was that his disease was completely cleared up and he had been in complete remission for five years. Additionally, all of his tumor indicators had decreased and normalized.&#x0D; Conclusion: Our case report demonstrated a full response to first-line Nivolumab in a patient with PD-L1-positive NSCLC having visceral and brain metastases. However, our patient suffered from myelitis, which may have been a Nivolumab-related adverse event.&#x0D; The important point is that he has been achieving a durable complete response for nearly 5 years, so are we talking about the certain biology of a tumor that can be cured by immunotherapy?

Short- and long-term effects of siponimod on autonomic nervous system in secondary progressive multiple sclerosis

ObjectivesThe aim of this study was to investigate the short- and long-term effects of siponimod on autonomic nervous system (ANS) function, in people with secondary progressive multiple sclerosis (pwSPMS) MethodsThe following ANS tests were performed in 26 pwSPMS: a 10 min supine resting position, Valsalva maneuver, deep breathing test and a 10 min tilt-up table test. Heart rate variability (HRV) was performed for the 10 min in supine resting position (M0) and for a 3 h period after siponimod treatment initiation (M0s1-6). All ANS tests were repeated after at least 6 months of treatment with siponimod (M6). ResultsIn all 6 intervals after siponimod ingestion (M0s1-6), standard deviation of NN intervals (SDNN) was higher compared to M0. After 6 months of continuous treatment with siponimod, SDNN was significantly lower compared to M0. At M6, Valsalva ratio and respiratory sinus arrhythmia were lower compared to M0 values (1.510±0.338 vs 1.864±0.456, p=0.003 and 7.969±2.865 vs 13.091±4.687, p<0.001, respectively). Cardiovagal index was significantly higher at M6 compared to M0 (1 (range 0-2) vs 0 (range 0-1), p=0.008, respectively). Active Magnetic Resonance Imaging (MRI) one year prior to starting siponimod was a positive predictor of M6 SDNN and Adrenergic Index (AI) at M0 was a negative predictor of M6 SDNN. ConclusionThis study has shown an inverse relationship in short- versus long-term effects of siponimod on ANS function. A shift towards parasympathetic predominance was observed during the first three hours after ingestion, while after 6 or more months of continuous treatment with siponimod, a shift towards sympathetic predominance was observed.

Effect of Folic Acid on Homocysteine Level in Ischemic Stroke Patients in a Tertiary Level Hospital in Rajshahi.

Background: A number of risk factors are responsible for ischemic stroke some are modifiable and some are not modifiable. Homocysteine is a modifiable, independent risk factor of ischemic stroke. Objective: To evaluate the effectiveness of folic acid on homocysteine levels in ischemic stroke patients. Materials and Methods: This study was an experimental study carried out in the Department of Pharmacology and Therapeutics, Rajshahi Medical College in collaboration with the Department of Neurology, Rajshahi Medical College Hospital from July 2016 to June 2017. A total number of 90 ischemic stroke patients diagnosed by CT scan findings who came for treatment in the Neurology department of Rajshahi Medical College Hospital were enrolled in this study. Simple random sampling is done. The patients were divided into two groups: experimental group (45 patients) who were treated with 5mg folic acid along with other traditional treatment, control group (45 patients) who were treated by only traditional therapy given by the neurology department. Before starting treatment, along with other investigations, serum homocysteine level of both experimental and control groups was estimated. After three months of continuous treatment with folic acid in the experimental group, the serum homocysteine level of both groups was measured again. Data were analyzed using SPSS version 16 for windows. Results: The results showed that there was a small numerical difference in homocysteine level before and after treatment in the experimental and control group, yet the change was statistically significant in the experimental group after three months of treatment with 5mg folic acid. Conclusion: It is revealed that use of folic acid may play an important role in reducing homocysteine level in ischemic stroke patients. KYAMC Journal Vol. 13, No. 01, April 2022: 13-17

Association of tumor necrosis factor-alpha promoter region gene polymorphism at positions -308G/A, -857C/T, and -863C/A with etanercept response in Iraqi rheumatoid arthritis patients.

This study aims to evaluate the association between polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-α) gene at locations -308G/A, -857C/T, and -863C/A with the tendency of being non-responder to etanercept. Between October 2020 and August 2021, a total of 80 patients (10 males, 70 females; mean age: 50 years; range, 30 to 72 years) with rheumatoid arthritis (RA) receiving etanercept for at least six months were included. The patients were divided into two groups responders and non-responders, based on their response after six months of continuous treatment. Following polymerase chain reaction amplification of the extracted deoxyribonucleic acid, sequencing by Sanger method was performed to identify the polymorphism at the TNF-α promoter region. In the responder group, the GG genotype of (-308G/A) and the AA genotype of (-863C/A) were both significantly present. The CC genotype of (-863C/A) was significantly present in the non-responders group. The CC of (-863C/A) SNP was the only genotype that appeared to increase the likelihood of being resistant to etanercept. The GG genotype of (-308G/A) was negatively correlated with the likelihood of being a non-responder. The (-857CC) and (-863CC) genotypes were significantly more prevalent in the non-responders group. The presence of the (-863CC) genotype, alone or in combination with (-857CC), is linked to an increased likelihood of becoming a non-responder to etanercept. The GG genotype of -308G/A and the AA genotype of -863C/A significantly increase the likelihood of becoming responder to etanercept.

The Effect of Combination Use of Hemodialysis and Hemoperfusion on Microinflammation in Elderly Patients with Maintenance Hemodialysis

Background: Patients with maintenance hemodialysis (MHD) generally have a microinflammatory state. The aim of this study was to investigate the effects of hemodialysis (HD) combined with hemoperfusion (HP) on microinflammatory state in elderly patients with MHD. Methods: One hundred and fifty elderly patients with MHD were randomly divided into the control group and the observation group. The control group received simple HD treatment, and the observation group received combined HD + HP treatment on the basis of the control group. After 6 months of continuous treatment, the patients were evaluated to compare the quality of life, inflammation, adverse reactions, and nutritional indicators in the 2 groups before and after treatment. Results: There was no significant difference in the quality of life between the 2 groups before treatment. After treatment, the scores of psychological aspects, physiological aspects, social aspects, environmental aspects, and independent ability in the observation group were higher than those in the control group, with statistical significance (p < 0.05). There was no statistical significance in the level of inflammation between 2 groups before treatment. After treatment, the levels of hs-CRP, Hcy, IL-6, and TNF-α in the observation group were significantly lower than those in the control group, with statistical significance (p < 0.05). The incidence of dry mouth, skin reaction, neuritis, and subcutaneous tissue fibrosis in the observation group was lower than that in the control group, with statistical significance (p < 0.05). There was no statistical significance in nutritional level indexes between 2 groups before treatment (p₁ > 0.05). After treatment, the levels of hemoglobin, total protein, albumin, and transferrin in the observation group were significantly higher than those in the control group, with statistical significance (p < 0.05). Conclusion: The clinical effect of HD combined with HP in elderly MHD patients is significant, which can effectively reduce the incidence of adverse reactions and inflammation in the patients and improve the quality of life and nutritional indicators of the patients.

Efficacy of Yangxin Recipe in Combination with Conventional Western Medicine in Treatment of Angina Pectoris of Coronary Heart Disease.

ObjectiveTo study the efficacy of Yangxin Recipe (YXR) in patients with stable angina pectoris of coronary heart disease and its impacts on coronary CT angiography.MethodsA total of 78 patients with coronary heart disease and angina pectoris were randomly divided into a control group (n = 39) and a YXR group (n = 39). The control group adopted conventional Western medicine while the YXR group received conventional western medicine + oral administration of YXR. After six months of continuous treatment, the clinical efficacy, traditional Chinese medicine (TCM) syndrome scores, Pittsburgh Sleep Quality Index (PSQI), and the level of coronary CT vascular stenosis were observed.ResultsAfter treatment, the total effective rate of YXR was 92.31%, which was higher than (P < 0.01) that of the western medicine control group. The total score of TCM syndromes in the YXR group was (14.44 ± 9.87), which was significantly lower than (P < 0.001) that in the simple western medicine control group (22.44 ± 13.87). The degree of coronary stenosis in the YXR group decreased to (49.87 ± 7.82) %, which was significantly lower than (P < 0.001) that in the western medicine control group (57.05 ± 9.92) %.ConclusionThe efficacy of YXR + conventional western medicine in treating coronary heart disease and angina pectoris is significantly improved compared with the simple conventional western medicine.

Динаміка гормональних та імунологічних показників у процесі консервативного лікування хворих на дифузний токсичний зоб

У дослідженні вивчено динаміку структурного та функціонального стану щитоподібної залози, а також рівні антитиреоїдних антитіл у хворих на дифузний токсичний зоб (ДТЗ) у процесі довготривалої терапії тиреостатичними препаратами. Мета дослідження — провести аналіз змін рівнів антитіл до рецептора тиреотропного гормона (АТ рТТГ), антитіл до тиреоїдної пероксидази (АТ ТПО) при маніфестації ДТЗ та на фоні довготривалої медикаментозної терапії, а також визначити рівні АТ рТТГ при рецидивуючому перебігу захворювання. Матеріали і методи. Обстежено 112 пацієнтів із ДТЗ. Тривалість захворювання на момент початку обстеження була від одного місяця до 15 років. Усі хворі були розподілені на дві групи залежно від тривалості ДТЗ: першу групу становили 46 осіб із тривалістю захворювання до року (у середньому 3,96 міс.), другу групу — 66 осіб, які хворіли понад 1 рік (у середньому 3,32 року). Такий розподіл обумовлений бажанням вивчити динаміку рівнів антитиреоїдних антитіл при маніфестації захворювання та при довготривалому перебігу автоімунного процесу. Результати. На тлі прийому тиреостатиків збільшувалась кількість пацієнтів з вогнищевими утвореннями щитоподібної залози. При аналізі рівнів антитиреоїдних антитіл на початку дослідження виявлено, що рівень АТ ТПО в обох групах хворих на ДТЗ вірогідно перевищував показники контрольної групи (група 1 — 283,33 ± 86,61 Од/мл проти 35,65 ± 4,9 Од/мл; група 2 — 207,34 ± 42,52 Од/мл проти 35,65 ± 4,90 Од/мл) і не залежав від тривалості захворювання та строків попереднього лікування. Через 6 місяців лікування рівень АТ ТПО в обох групах не зменшувався. При вивченні динаміки АТ рТТГ у процесі тиреостатичної терапії виявлено, що у хворих першої та другої групи зниження рівня АТ рТТГ зафіксовано лише через 6–12 місяців після початку тиреостатичної терапії (група 1 — з 17,19 ± 2,17 мОд/л до 6,95 ± 2,39 мОд/л, р &lt; 0,05; група 2 — з 14,20 ± 2,04 мОд/л до 5,81 ± 2,26 мОд/л, р &lt; 0,05). Через 24 місяці лікування рецидиви тиреотоксикозу спостерігались у 24 хворих (21,4 %). При дослідженні рівнів АТ рТТГ у хворих з рецидивуючим перебігом захворювання спостерігалось їх суттєве збільшення (24,27 ± 2,86 мОд/л проти 12,28 ± 3,57 мОд/л). Через 6 місяців тиреостатичної терапії рівні АТ рТТГ у хворих з рецидивами суттєво не зменшувались і значно перевищували аналогічні показники хворих на ДТЗ у стадії ремісії (17,22 ± 3,37 мОд/л проти 4,64 ± 1,99 мОд/л). Висновки. У хворих на ДТЗ рівень АТ рТТГ зменшується лише через 6–12 місяців після початку тиреостатичної терапії. У хворих із рецидивуючим перебігом захворювання спостерігаються вірогідно більші розміри зоба, а також рівні АТ рТТГ, що через 6 місяців безперервного лікування значно перевищують нормальні значення й показники хворих з ремісією захворювання.

Erythropoiesis Stimulating Agents (ESAS) in Supportive Care of Low-Risk Myelodysplastic Syndromes: Recamds Registry FINAL Results

Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It's matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs.Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion-dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed.183 patients, treated with standard-dose ESAs, have been retrospectively analyzed. Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1-118).ORR was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease(non-responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic-responders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic-responders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion-dependence, regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group 89% exhibit again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibits again macrocytosis, while 24% become normocytic.These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly stimulating erythroid production in MDS clones; in the minority of patients probably it happens recruiting residual polyclonal erythropoiesis.It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses. [Display omitted] DisclosuresMartinelli: Roche: Consultancy; Stemline Therapeutics: Consultancy; Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy; Daichii Sankyo: Consultancy; Astellas: Consultancy, Speakers Bureau.

Study on the Effect of Combination of Prednisone and Vitamin D in the Treatment of Primary Nephrotic Syndrome in Children.

Objective To study the effect of prednisone combined with vitamin D in the treatment of primary nephrotic syndrome in children. Method 73 cases of primary nephrotic syndrome admitted to the nephrology department of our hospital were randomly selected and retrospectively analyzed. 36 cases were treated with prednisone as the control group, and 37 cases were treated with prednisone combined with vitamin D as the observation group. The efficacy was compared after 3 months of continuous treatment. Result After 3 months of treatment, the blood calcium of the observation group was higher than that of the control group, PTH was lower than that of the control group, and 25-(OH)2D3 and 1,25-(OH)2D3 were higher than those of the control group (P < 0.05). After 1, 2, and 3 months of treatment in the observation group, Scr and 24-h urine protein quantification were lower than those in the control group and eGFR was higher than that in the control group (P < 0.05). CD4+ and CD4+/CD8+ were lower in the observation group than in the control group after 3 months of treatment (P < 0.05). The serum sTfR and TGF-β1 levels were lower in the observation group than in the control group after 3 months of treatment (P < 0.05). The total effective rate of the observation group was 83.78% after 3 months of combined treatment with prednisone and vitamin D, which was significantly higher than the total effective rate of the control group of 61.11% (P < 0.05). The incidence of nausea and vomiting, heartburn, headache, dry cough, hypercalcemia, and constipation during treatment in the observation group was not statistically different from that in the control group (P > 0.05). Conclusion Combined treatment of primary nephrotic syndrome in children with prednisone and vitamin D can more significantly improve the level of clinical indicators, improve renal function and immune function, and obtain more satisfactory efficacy, without significantly affecting the safety of treatment.

Obstructive Sleep Apnea Syndrome Treated Using a Positive Pressure Ventilator Based on Artificial Intelligence Processor.

With the acceleration of people's life rhythm, obstructive sleep apnea syndrome appears more and more frequently. This research mainly discusses the treatment of obstructive sleep apnea syndrome with a positive pressure ventilator based on artificial intelligence processor. The information storage function of the smart positive pressure ventilator is included in the local medical terminal, presented after logging in with the user authority. It is mainly composed of data collection, data processing, and medical interface design, which embeds data request, data transmission, data analysis, and detailed tasks such as data compression and storage, and functions such as data display, image drawing, and alarm notification are realized by the medical interface. When the CPAP ventilator transmits respiratory data to the local medical terminal, it sends real-time respiratory information data packets. The data packet is collected and sent in real time in a fixed period and then received and analyzed by the local medical terminal. In the CPAP ventilator telemedicine system, the function of alarm message processing is mainly used to detect the patient's breathing status in real time, extract the alarm-related information, and generate an alarm. This function specifically includes several tasks such as alarm detection, alarm prompt, alarm storage, and remote transmission of alarm messages. The confirmed OSAS patients were pressure-titrated with a smart CPAP ventilator and then treated for 5 hours a day, followed by echocardiography after 5 months of continuous treatment. During the study, the average BMI was (28.9 ± 7.2) kg/m2 and the average AHI index was (53.1 ± 37.8) times/h. This study may help improve the quality of life of patients with obstructive sleep apnea syndrome.

Immunoregulatory Effects of Adjuvant therapy with Statins in Rheumatoid Arthritis Population

Background: Rheumatoid arthritis (RA) is considered by symmetrical peripheral arthritis, synovitis &amp; joint destruction. Statins, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme ductase, significantly reduce coronary artery disease by helping to lower plasma low-density lipoprotein cholesterol levels. Experimental studies, more recently, several clinical trials have convincingly shown that statins play a vital role in Rheumatoid arthritis, primarily due to their anti-inflammatory and immunomodulatory properties. Aim: To assess the effectiveness of statin adjunctive therapy versus standard treatment with disease-modifying antirheumatic drugs (DMARDs) in patients with RA. Methods: In this research, patients with a diagnosis of RA among the ages of 30 and 65 years were recruited according to the "Open Rheumatoid Pathologist" inclusion criteria. Among the selected patients, two distinct patient strata were identified. Strata 1 included 40 RA patients who are currently taking DMARDs with statins; Strata 2 included 40 patients with RA who are currently receiving DMARDs; observed for 6 months; To compare the outcomes of RA in both strata, standard parameters DAS28, ESR, and CRP were estimated. Results: There were eighty subjects included in the research; this study demonstrated a significant beneficial role of additional statin drugs when administered alongside conventional DMARDs in patients with active RA. The clinical significance index of disease activity in RA was significantly (P &lt;0.05) lower in the statin adjuvant strata (strata 1) than in the conventional DMARD treatment strata (P &lt;0.05). Strata 2) after 6 months of Continuous treatment. Two other important biochemical markers of RA disease activity, ESR and CRP, were also significantly lower in RA patients taking statins (strata 1) (P &lt;0.05). Compared to strata 2, which includes only RA. the patient was treated with a conventional DMARD without statins. Conclusion: The results suggest a supportive and possibly beneficial role for statin therapy in cases of active RA, leading to clinically and biochemically significant improvements. Keywords: inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme is reductase, disease activity indicator 28,

The Effect of Bortezomib on Renal Dysfunction in African American Patients with Multiple Myeloma

Introduction -Renal dysfunction (RD) is a major negative prognostic factor in multiple myeloma (MM). Approximately 50% of patients have RD throughout the course of their disease, which is associated with a more aggressive clinical course, poorer quality of life, and shortened overall survival. Bortezomib, a potent proteasome inhibitor, has shown significant anti-myeloma activity and is known to have a protective renal effect. In addition, it is well known that African Americans (AA) are twice as likely to be diagnosed with MM compared to Caucasians and tend to have worse outcomes. At our cancer center, which is in a large urban hospital, nearly 85% of MM patients are AA. To date, there has been no study specifically looking at the reversibility of RD in this population. We evaluated the effectiveness of bortezomib on RD in AA patients with MM in a large urban hospital.Methods -We conducted a retrospective analysis to investigate the outcome of bortezomib based therapy in 51 AA patients diagnosed with MM and RD from 2004-2015, including 4 cases requiring hemodialysis. Renal dysfunction was defined as Cr ³ 2.0 mg/dL or GFR < 60 mL/min/1.73m2. Patients required at least 3-6 months of continuous treatment with a bortezomib based regimen to be eligible for analysis. Laboratory data was collected prior to initiation of treatment, and again at 3 months and 6 months. Both newly diagnosed and relapsed or refractory patients were included.Results -Approximately 75% of patients treated with bortezomib were > 65 years old, with an equal distribution of males and females. At presentation, 80% had anemia (Hb<10 g/dL), 14% hypercalcemia (Ca>11 mg/dL), 37% elevated LDH, 61% elevated B2 microglobulin. The majority of patients had normal risk cytogenetics and 33% were ISS stage III. Myeloma subtype was IgM 65%, IgA 16%, IgM 2%, light chain only 16%. Sixty percent were kappa light chain subtype. The median M spike was 2.54 (range 0.5-16), creatinine 2.41 mg/dL (range 1.1-10.48), GFR 38 mL/min/1.732 (range 6-60). Treatment was bortezomib based in 100% patients: 6% had bortezomib, 45% bortezomib/dexamethasone (VD), 22% VD/cyclophosphamide (VCD), 12% VD/lenalidomide (VRD), 12% VD/melphalan (VMP), 2% VD/thalidomide (VTD), 2% VD/doxorubicin (PAD). A partial response or better was seen in 55% of patients by month 3 and 63% of patients by month 6.Improvement of RD was observed in 85% of patients by month 3. The average creatinine improved by approximately 24.5% (p<0.001), GFR improved by 52.6% (p<0.001). A plateau effect was noticed by month 6, as creatinine and GFR improved by 19.5% and 44.7%, respectively. Newly diagnosed patients had a greater reversal of RD compared to relapsed/refractory disease (p=0.032). None of the 4 patients who began hemodialysis were able to discontinue this therapy.Conclusion -A statistically significant improvement in RD was observed in AA patients with MM based on Cr and GFR treated with a bortezomib based regimen. The greatest response was seen in the first 3 months of therapy which plateaued by month 6. These differences were magnified in de novo compared to relapsed/refractory disease. No patients were able to discontinue hemodialysis if already initiated prior to starting treatment. Bortezomib is a safe and effective drug in the subset of AA patients with impaired renal function. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Inheritance of Mildly Activating ABCC8 Mutation From a Mother With MODY Causes Permanent Neonatal Diabetes Mellitus (NDM) in Two Siblings Who Also Carry a Second Inactivating Mutation: Genetic Testing Allows for Improved Treatment With Sulfonylureas (SU)

Background: Heterozygous activating mutations in KCNJ11 or ABCC8 are the most common cause of neonatal diabetes (NDM). ABCC8 (SUR1) mutations more often cause transient NDM. Inactivating ABCC8 mutations can cause congenital hyperinsulinism (HI), but very rarely will such mutations be inherited together. Mildly activating KATP mutations can also be a cause of MODY, but even if genetic testing is considered, many commercial testing panels do not include these genes, despite the significant difference in treatment that can result due to sulfonylurea (SU) responsiveness.Clinical Case: The proband was diagnosed with DM at 11 months old and fortuitously treated with SU for 3 years. He was switched to insulin and had poor DM control thereafter. Sister was diagnosed at 3.5 months old and had poor DM control on insulin. Mother was diagnosed with DM at 27 years old and treated with various medications including insulin. Genetic testing revealed that mother carried ABCC8 mutation R1380C previously described to cause transient NDM and/or later-onset DM consistent with her phenotype. Both children inherited this mutation from her and inherited a variant (L1148R) from their father without diabetes that has been reported in association with HI. The L1148R allele may reduce cell surface expression thereby increasing the relative expression and pathogenic effect of the R1380C allele that has not previously been described to cause permanent NDM.We assessed SU responsiveness by measuring maximal beta-cell function through combined mixed meal and arginine testing. Mother exhibited easily detectable C-peptide levels at baseline that improved by SU treatment. In contrast, the children displayed almost undetectable baseline beta-cell function with variable response to SU: the sister who had been chronically poorly controlled on insulin therapy displayed barely improved C-peptide production, while her brother who had previously been treated with SU as an infant had markedly improved beta-cell function on SU. Within two months of continued treatment with high doses of SU only, he was able to start lowering his SU dose with improved glycemia. His sister was started on high-dose SU in addition to insulin, but continued to have difficulty adhering to her treatment regimen. Her blood sugar improved after the addition of long-acting GLP-1 agonist (liraglutide) but she later became pregnant and returned to insulin only. Her glycemic control improved when re-started on SU after pregnancy. The mother exhibited excellent DM on a lower dose of exclusive SU therapy.Clinical Lesson: Genetic testing can dramatically alter management and must be pursued in both NDM and family members with diabetes later in life. Careful assessment of clinical characteristics along with genetic testing for segregation patterns in family members can greatly improve understanding of the causality of previous uncharacterized variants.