Standard Therapy Group Research Articles

Immediate and Prolonged Effects of Breathing Exercises on Pain, Quality of Life & Functional Disability in Patient of Upper Cross Syndrome: A Randomized controlled trial

Background: The advent of smartphone technology and its increased use, especially during the COVID-19 pandemic, has led to a rise in musculoskeletal disorders, including upper cross syndrome. This condition, characterized by muscle imbalances around the cervical spine and shoulder girdle, results in pain, functional disability, and decreased quality of life. Breathing exercises have been suggested as a therapeutic intervention to address these issues, yet empirical evidence on their effectiveness remains sparse. Objective: This study aimed to evaluate the immediate and prolonged effects of breathing exercises on pain, functional disability, and quality of life in patients with upper cross syndrome, filling a gap in the literature regarding non-pharmacological interventions for this condition. Methods: Conducted as a single-blinded randomized controlled trial at Jinnah Memorial Trust Hospital, Gujranwala, Pakistan, this study involved 76 participants with upper cross syndrome, randomized into control (standard physical therapy) and experimental (standard physical therapy plus breathing exercises) groups. Pain was assessed using the Numeric Pain Rating Scale (NPRS), functional disability with the Neck Disability Index (NDI), and quality of life through the SF-36 questionnaire. Assessments were made at baseline, after the first session, and after four weeks. Data analysis was performed using SPSS version 25, employing the Mann-Whitney U Test for between-group comparisons and the Paired Sample T-test for within-group analyses. Results: The experimental group demonstrated significantly superior improvement compared to the control group in NPRS scores after the first session (p<0.001) and after four weeks (p<0.001), NDI scores (p<0.001 at both intervals), and all eight domains of the SF-36 (p<0.05 for each domain after four weeks), indicating that breathing exercises significantly reduce pain and functional disability while enhancing quality of life. Conclusion: Breathing exercises are a safe and effective adjunct to standard physical therapy for patients with upper cross syndrome, significantly improving pain management, functional disability, and quality of life. This study underscores the potential of integrating breathing exercises into rehabilitation programs for musculoskeletal disorders related to excessive technology use.

DERAJAT APOPTOSIS SEL GANGLION RETINA PASCA PEMBERIAN TAMBAHAN EKSTRAK MORINGA OLEIFERA ORAL DIBANDINGKAN DENGAN TERAPI STANDAR Studi Eksperimental pada Tikus Wistar Model Methanol Toxic Optic Neuropathy

Abstract
 Introduction & Objectives : Methanol toxic optic neuropathy can lead to retinal ganglion cell apoptosis which causes visual disturbance. Moringa oleifera has been reported to have an anti-inflamatorry effect that can prevent inflammatory mediators from being relased in methanol toxic optic neuropathy
 Methods : Twenty-one Wistar methanol toxic optic neuropathy were divided into 3 groups, namely base line group, control group that given intravenous methylprednisolone 4.5mg/6 hours for 3 days, and given standard theraphy and additional administration of oral Moringa oleifera 300mg/kgbodyweight/day for 4 weeks. Assessment of the degree of apoptosis by Anatomical Pathology with histopatolocigal scaoring. The study used Mann Whitney comparative hypothesis test (Significant p<0.05)
 Results : The degree of retinal ganglion cell apoptosis was significantly lower in the treatment and standard therapy groups compared to the base line group. The treatment group compared to the standard therapy group was not significantly different (p = 1,000)
 Conclusion : The degree of retinal ganglion cell apoptosis in rat model methanol toxic optic neuropathy was not significantly different between the group that was given additional oral Moringa oleifera extract compared to the standard theraphy group

Early effectiveness and safety analysis of belimumab in addition to standard treatment in patients with systemic lupus erythematosus.

This study aimed to evaluate the early effectiveness and safety of belimumab in addition to standard therapy in patients with systemic lupus erythematosus (SLE) for 24 weeks. This retrospective study was conducted with 60 adult patients with active SLE between June 2020 and August 2022. The patients either received intravenous belimumab in addition to standard therapy (n=31; 24 females, 7 males; mean age: 33.7±14.1 years; range, 18 to 52 years) or only standard therapy (n=29; 22 females, 7 males; mean age: 34.1±13.4 years; range, 19 to 66 years) for 24 weeks. Outcome measures, including safety and effectiveness (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI]), changes in biomarkers (double-stranded DNA [deoxyribonucleic acid]), serum complement levels, and immunoglobin G (IgG) were recorded. Adverse events were recorded. Baseline demographic and clinical characteristics were similar between the two groups. More patients in the belimumab group achieved a reduction of ≥4 points in SELENA-SLEDAI at weeks 12 and 24 (week 12, 77.4% vs. 41.4%, p=0.008; week 24, 87.1% vs. 48.3%, p=0.002). The mean score of SELENA-SLEDAI was significantly lower in the belimumab group compared to the standard therapy group at week 12. However, a significant difference was not reached at week 24. Moreover, mean levels of serum C3 and C4 in the belimumab group were significantly higher than those in the standard therapy group at weeks 12 and 24. A higher proportion of patients in the belimumab group had a normal C3 level than in the standard therapy group. In addition, belimumab treatment resulted in a significant decrease in IgG levels at both weeks 12 and 24. At week 24, the belimumab group had a higher reduction in prednisone dose than the standard therapy group. Furthermore, the percentages of patients with more than 50% reduction in prednisone over baseline were significantly greater for belimumab versus standard therapy at week 12 (p=0.002). The occurrence of adverse events was similar between the two groups (standard therapy group, 44.8%; belimumab group, 51.6%). Intravenous belimumab was well tolerated and significantly improved disease activity in Chinese patients with SLE at the early stage of treatment. More importantly, belimumab treatment could result in a rapid reduction in prednisone dose as early as week 12.

Efektivitas Citicoline dalam Terapi Demensia

Background: In the development of pharmacological therapy for dementia, especially Alzheimer's disease, several types of therapy are widely used: acethylcholine esterase inhibitors/AChEI, N-methyl-D-aspartate (NMDA) receptors inhibitors, and cholinergic precursor. Aim: To review the evidence on the effectiveness of citicoline supplementation to the standard therapy of dementia to prevent the progression or improve the manifestations of dementia. Methods: A literature search was performed in three following databases: Pubmed, EBSCOhost, Scopus, and Cochrane within the last ten years. Results: Of the 239 articles, five studies were eligible for critical appraisal. Four studies showed a significant mean MMSE score increase in the citicoline + standard therapy group (intervention) compared to the standard therapy group (control) during the follow up period between 3 – 12 months. One study showed a significant mean MMSE score increase of in the intervention group compared to the control group. Conclusion: Oral citicoline supplementation of 1,000 mg/day to the standard therapy showed a positive effect on cognitive function in dementia patients. Critical appraisal of validity and application of the included studies should be considered upon daily clinical application.

The intensity of neuropathic pain and the severity of insomnia in diabetic polyneuropathy

To determine the prevalence of insomnia and the effectiveness of its treatment in patients with a painful form of diabetic polyneuropathy (DPN). Fifty patients with the painful form of DPN were randomly divided into 2 groups: the standard therapy group (ST) and the extended therapy group (ET). In the ST group, a single lesson on sleep hygiene was conducted, in the ET group there were 3-4 face-to-face individual sessions for the treatment of insomnia for two weeks. Both groups were interviewed at the time of hospitalization, after 3 and 6 months. The severity of polyneuropathy and the nature of neuropathic pain were assessed using the Neuropathic Neuropathy Impairment Score in the Lower Limbs (NIS-LL) and the Neuropathy Total Symptom Score - 9 (NTSS-9); the intensity of pain was assessed using a Visual Analog Scale (VAS). Sleep disorders were analyzed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). Sleep disorders of varying severity were observed in 82% of patients in the initial survey. In both groups, improvement in sleep quality was noted during treatment, but significantly better results were in the ET group, the ISI score after 6 months was 7.15±2.08 for the ST group and 3.07±2.49 for the ET group (p<0.0001). In the ST group, there was no significant decrease in the intensity of pain and the severity of polyneuropathy in dynamics. In the ET group, a significant decrease in NTSS-9 and VAS scores was found during the initial survey and after 6 months (p<0.0001). The intensity of pain also significantly decreased in the ET group compared with the ST group (p<0.0001) at the end of follow-up, which indicates the importance of sleep normalization in the treatment of neuropathic pain. Most patients with the painful form of DPN have insomnia. Treatment of insomnia has shown its effectiveness as part of a multimodal approach to the managing of neuropathic pain in DPN and improving the quality of life of patients.

IMPACT OF PLATELET-RICH PLASMA ON INJURIED NASAL MUCOSA IN CHRONIC ATROPHIC RHINITIS

Relevance. The mucous membrane of the nasal cavity is a natural biological barrier that protects the upper respiratory tract from infection. Chronic atrophic rhinitis is characterized by a triad of symptoms and signs, which include progressive atrophy of the nasal mucosa, the formation of crusts and a characteristic unpleasant odor. A promising tool for the pathogenetic therapy of chronic atrophic rhinitis can include the use of platelet-rich plasma injections (PRP therapy).&#x0D; The purpose of this study is to investigate the effect of platelet-rich plasma on the content of markers of oxidative damage to biological polymers, the concentration of hydrogen sulfide, and the intensity of collagenolysis in the nasal mucosa under chronic atrophic rhinitis.&#x0D; Materials and methods. The study involved 68 patients, categorized into control (n=20) and experimental (n=48) groups. Within the experimental group, patients were randomly assigned to two subgroups: the standard therapy group (n=29) received conventional treatment as per protocols for 28 days, and the PRP therapy group (n=19) received PRP injections alongside standard therapy for chronic atrophic rhinitis over the same duration. The content of free L-oxyproline, the concentration of malondialdehyde, the concentration of hydrogen sulfide (H2S), and the content of oxidatively modified proteins were studied in the nasal mucosa.&#x0D; Results. PRP therapy included to the standard treatment for chronic atrophic rhinitis resulted in a significant 42.67% decrease in malondialdehyde content in the nasal mucosa compared to pre-treatment values. The presence of oxidatively modified proteins post-treatment, following the standard therapeutic regimen with the addition of PRP therapy, decreased by 39.25% compared to pre-treatment levels. The concentration of free L-oxyproline in the nasal mucosa, under standard treatment combined with PRP therapy, exhibited a reduction of 38.28% compared to pre-treatment values. Furthermore, the content of hydrogen sulfide (H2S) in the nasal mucosa decreased by 82.27% compared to pre-treatment levels.&#x0D; Conclusions. The integration of PRP therapy with standard treatment for chronic atrophic rhinitis enhances treatment efficacy by mitigating oxidative damage to lipids and proteins, reducing collagen breakdown, and limiting the accumulation of H2S in the nasal mucosa.

Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease

Hypertension adds to the pressure overload on the left ventricle (LV) in combination with aortic valve (AV) disease, but the optimal blood pressure (BP) targets for patients with AV disease remain unclear. We tried to investigate whether intensive BP control reduces LV hypertrophy in asymptomatic patients with aortic stenosis (AS) or aortic regurgitation (AR). A total of 128 hypertensive patients with mild to moderate AS (n=93) or AR (n=35) were randomly assigned to intensive therapy, targeting a systolic BP <130 mm Hg, or standard therapy, targeting a systolic BP <140 mm Hg. The primary end point was the change in LV mass from baseline to the 24-month follow-up. Secondary end points included changes in severity of AV disease, LV volumes, ejection fraction and global longitudinal strain (GLS). The treatment groups were generally well balanced regarding the baseline characteristics. The mean (±SD) age of the patients was 68 ± 8 years and 48% were men. The mean BP was 145 ± 12/81 ± 10 mm Hg at baseline. Medication at baseline was similar between the 2 groups. The 2 treatment strategies resulted in a rapid and sustained difference in systolic BP (P < .05). At 24-month, the mean systolic BP was 129 ± 12 mm Hg in the intensive therapy group and 135 ± 14 mm Hg in the standard therapy group. No patient died or underwent AV surgery during follow-up in either of the groups. LV mass was changed from 189.5 ± 41.3 to 185.6 ± 41.5 g in the intensive therapy group (P=.19) and from 183.8 ± 38.3 to 194.0 ± 46.4 g in the standard therapy group (P < .01). The primary end point of change in LV mass was significantly different between the intensive therapy and the standard therapy group (-3.9 ± 20.2 g vs 10.3 ± 20.4 g; P=.0007). The increase in LV mass index was also significantly greater in the standard therapy group (P=.01). No significant differences in secondary end points (changes in severity of AV disease, LV volumes, ejection fraction and GLS) were observed between the treatment groups. Among hypertensive patients with AV disease, intensive hypertensive therapy resulted in a significant reduction in LV hypertrophy, although progression of AV disease was similar between the treatment groups. http://ClinicalTrials.gov (Number NCT03666351).

CTNI-58. UPDATED RESULTS AND MOLECULAR SUBGROUP ANALYSES FROM THE RANDOMIZED PHASE 3 MIRAGE TRIAL ON MARIZOMIB IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND The standard of care for patients with newly diagnosed glioblastoma includes maximum safe resection followed by radiotherapy (RT) with concomitant and maintenance temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). Among potential new therapeutic strategies, targeting the proteasome has been considered promising because of its implication in numerous biological processes in tumors cells. Marizomib is a novel small molecule proteasome inhibitor that crosses the blood brain barrier and showed signs of activity in recurrent glioblastoma. METHODS EORTC 1709/CCTG CE.8 was a randomized, controlled, multicenter, open label phase 3 superiority trial. Major inclusion criteria were histologically confirmed newly diagnosed glioblastoma, age of 18 years or older and a Karnofsky performance status (KPS) &amp;gt; 70. Patients with tumors known to harbor an isocitrate dehydrogenase mutation were not eligible. RESULTS The trial was opened at 82 institutions in Europe, Canada and the US and 749 patients (of 750 planned) were randomized in a 1:1 ratio. Following a pre-planned interim analysis and a recommendation of the independent data monitoring committee, enrolment was discontinued. No significant difference in the median OS (mOS) was observed (standard arm: 17 months, marizomib arm: 16.5 months; p = 0.64; HR = 1.04). Median PFS was 6.0 vs. 6.3 months (p = 0.67; HR = 0.97). Patients with tumors harboring an unmethylated O6-methylguanine DNA methyltransferase (MGMT) promoter had a mOS of 14.5 months in the standard therapy group and 15.1 months in the marizomib arm (p = 0.27, HR = 1.13). Among patients with an MGMT promoter-methylated tumor, median OS was 29.4 months in the marizomib arm and 25.5 months in the standard arm (p = 0.41, HR = 0.86). More CTCAE grade 3/4 treatment-emergent adverse events were noticed in the marizomib arm than in the standard arm. CONCLUSIONS The addition of marizomib to standard temozolomide-based radiochemotherapy was associated with more toxicity but did not confer a survival benefit in glioblastoma patients, independent of the MGMT promoter methylation status.

Effects of pirfenidone on scar size and ventricular remodeling after myocardial infarction: a preclinical study

Abstract Background An intense fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Pirfenidone is a drug currently approved for the treatment of idiopathic pulmonary fibrosis, and reduces LV fibrosis in patients with heart failure and preserved ejection fraction. We aimed to characterize the different profiles or protein expression in the infarct zone in rats receiving or not receiving pirfenidone on top of standard therapy for MI. Methods Male Wistar rats were randomized to: sham procedure (group 1; n=13), reperfused MI induced by surgical ligation of the left anterior descending artery (LAD) for 45 minutes (group 2; n=17), reperfused MI plus standard therapy (aspirin, angiotensin-converting enzyme inhibitor, beta-blocker, and also mineralocorticoid receptor antagonist [MRA]) (group 3; n=17), reperfused MI plus pirfenidone alone (group 4; n=17), reperfused MI plus standard therapy and pirfenidone (group 5; n=17). Rats surviving LAD ligation and reperfusion underwent cardiac magnetic resonance (CMR) after 72 hours and 30 days from MI, and were sacrificed the day after the second CMR exam. The primary endpoint was the change in late gadolinium enhancement (LGE) mass as a percentage of LV mass. Results Forty-six rats survived until the second CMR. Percent changes in LV end-diastolic and end-systolic volume (p=0.370 and 0.423, respectively), ejection fraction (p=0.236) and mass (p=0.815) did not differ significantly between rats on pirfenidone plus standard therapy compared with those receiving standard therapy alone. The decrease in LGE mass was significantly greater in rats on pirfenidone plus standard therapy vs. those on standard therapy alone: -22.0% (interquartile range, -37.1 to -5.7, range -51.1 to +37.5) vs. +1.9% (-7.7 to +12.5, range -19.8 to +56.5), p=0.029. Conclusions Pirfenidone had additive effects to standard therapy for MI (including an MRA) in reducing LV fibrosis in a rat model of reperfused MI, while it did not further improve LV function, volumes or mass.

Abstract 19151: Late Gadolinium Enhancement (LGE) in Recurrent Pericarditis Patients on Il-1 Blockers and Standard Anti-Inflammatory Therapy

Introduction: Recurrent pericarditis is defined as the recurrence of pericarditis after a symptom-free interval of 4-6 weeks. Our study aimed to investigate the improvement in the late gadolinium enhancement on cardiac resonance imaging (CMR) in recurrent patients on IL-1 blockers and standard anti-inflammatory therapy. Hypothesis: We hypothesize that patients on IL-1 inhibitor show a better improvement of LGE on CMR in recurrent pericarditis. Methods: This is a retrospective comparative cohort study of 37 recurrent pericarditis patients on IL-1 inhibitor and 107 recurrent pericarditis patients on standard anti-inflammatory therapy. We included patients with LGE tracing and compared both groups. Patients were treated for at least 12 months and were followed for a duration minimum of 12 months. Results: The patients' mean age in the IL-1 inhibitor group was 51.16 ±16, and the standard therapy group was 54.26 ± 14.32. Patients had a median baseline ESR of 5 mm/hr and median hs-CRP of 2.2 mg/L in the IL-1 inhibitor group and a median baseline ESR of 7.5 mm/hr and median hs-CRP of 1.5 mg/L in the standard therapy group. At baseline, patients in the IL-1 inhibitor group had 5.4% none LGE, 43.24% mild LGE, 37.83% moderate LGE, and 13.5% severe LGE. Over the follow-up of 12-24 months, IL-1 inhibitor patients had improvement in LGE, with 35.13% of patients having none LGE and 64.86% having mild LGE. In the standard group, 27.1% had none LGE, 54.2% had mild LGE, 15.88% had moderate LGE, and 2.8% had severe LGE at baseline. Over 12-24 months follow-up, standard therapy group patients had some improvement as well as worsening of LGE in some patients, with 35.51% having none LGE, 59.81% having mild LGE, and 4.6% having moderate LGE. Conclusions: IL-1 inhibitors serve as a competitive antagonist of IL-1 cytokine and block its pro-inflammatory functions. Pericardial delayed enhancement is significant in determining disease course and improvement in patients with pericarditis.

Evaluation of the convalescent plasma therapy effectiveness and the factors that influence the therapeutic outcome in hospitalized COVID-19 patients: A retrospective cohort study.

Background: As an effective antiviral therapy is not available for the treatment of the current rapidly and continuously spreading coronavirus disease (COVID-19), it is very crucial to find an alternative treatment strategy. Convalescent plasma (CP) therapy has been used for prevention and treatment of many emerging infectious diseases, however, the results of current studies on CP in COVID-19 are not consistent. Therefore, this study aimed to evaluate the effectiveness of CP therapy in hospitalized patients with COVID-19, while evaluating patient and donor-related factors that might influence the therapeutic outcome. Methods: We conducted a retrospective cohort study on 312 patients with either severe or critical COVID-19, who were admitted to Al-Hakeem and Al-Amal hospitals in Al-Najaf city, Iraq from June to August 2020. The patients were allocated to either the plasma therapy group (152 patients) who received CP combined with standard therapy or the standard therapy group (160 patients). The outcome measures were the 21-day mortality rate and time to clinical improvement. Results: The overall cumulative survival rate was significantly higher in patients who received CP compared to standard therapy alone at 21 days (68.3% vs. 46.8%, p-value = 0.010), with mean survival at 17.6 vs. 15.3 days, (p-value = 0.010). In multivariate analysis, the plasma therapy effect was an independent predictor of survival (adjusted hazard ratio, 95% confidence interval: 0.368, 0.177 – 0.765). In terms of clinical improvement, the use of CP resulted in shorter clinical improvement (median duration of improvement: 8 vs. 11 days, p-value = 0.007), with 74.3% improvement rate after 21 days in CP compared to 65.0% in standard therapy. Conclusions: Therapy with CP in combination with standard therapy, independently improved survival in hospitalized patient with severe or critical COVID-19.

The Efficacy of Topical Formulation Containing Ciplukan (Physalis angulata Linn.) in Modulating Interleukin-17 and Interferon Gamma Expression in Mice (Mus musculus) Psoriasis Model.

Interleukin 17 (IL-17) and interferon gamma (IFN-γ) play a role in the pathogenesis of psoriasis vulgaris (PV). Topical corticosteroids are still utilised as first-line therapy for mild to moderate PV. However, long-term use of corticosteroid is associated with various side effects. Physalis angulata Linn. (Ciplukan) possesses anti-inflammatory properties that could serve as a potential alternative topical therapy for PV. To assess the efficacy of topical ciplukan as an anti-inflammatory agent targeting the expression of IL-17 and IFN-γ. Psoriasis was induced using imiquimod cream, therefore divided into five groups. Group I, the psoriasis control group, received only imiquimod cream. Groups C1 and C2 received imiquimod cream followed by a mixture of Ciplukan and vaseline in a 1:2 and 1:4 ratio, respectively. Group M, the standard therapy group, received imiquimod cream, followed by mometasone furoate cream. Lastly, group V, the vehicle group, received imiquimod cream followed by vaseline album. Expression of IL-17 and IFN-γ in mice's skin tissue was analysed using reverse transcription polymerase chain reaction (RT-PCR) after seven days of treatment. The mean expression of IL-17 in Group C1 (22.60) was significantly lower (p = 0.012) than in the psoriasis control group (23.60), and there was no significant difference (p = 0.613) in Group M (22.41). The mean expression of IFN-γ in Group C1 (26.97) and Group C2 (27.03) was also significantly lower (p = 0.026 and p = 0.026, respectively) than Group I (28.80), and there was no significant difference (p = 0.180 and p = 0.093, respectively) than Group M (26.03). Expression of IL-17 and IFN-γ in the ciplukan group is lower than in the psoriasis control group, and there is no significant difference compared to the standard therapy group.

Standard Therapy vs. Individualized Therapy in Elderly Locally Advanced Nasopharyngeal Carcinoma: A Real-World Study

Concurrent chemoradiotherapy (CRT) with/without induction chemotherapy has been the standard therapy (ST) for locally advanced nasopharyngeal carcinoma (LA-NPC). However, most patients supporting these clinical trials were younger than 65 years of age. For the toxicity of CRT and the poor tolerance of elderly patients, it is still controversial whether ST could bring the most promising survival benefits for elderly NPC compared with individualized therapy (IT). Thus, in this real-world study we compared the survival and safety of ST with IT in elderly LA-NPC to explore an effective and tolerable treatment strategy for elderly LA-NPC. A total of 109 newly diagnosed elderly LA-NPC (>65 years old) from Jan. 2013-Jul. 2020 were retrospectively enrolled and divided into the ST group and IT group according to the original treatment tendency. ST refers to CRT with/without induction chemotherapy. IT group included patients not suitable for CRT and were given individualized treatment fully discussed by at least two oncologists from our head and neck team. A 1:1 propensity score matching (PSM) generated a matched cohort of ST and IT. The survivals and treatment related toxicities were compared between the two groups. There were 46 cases in the ST group and 63 cases in the IT group. The 5-year overall survival (OS) rate, cancer-specific survival (CSS) rate, progression- free survival (PFS) rate, local recurrence-free survival (LRFS) rate and distant metastasis-free survival (DMFS) rate were 68.64%, 76.42%, 73.69%, 85.67% and 86.82%, respectively. By 1:1PSM, 35 cases in each group were matched. No significant differences of OS, CSS, PFS, LRFS and DMFS were found between ST and IT groups in the PSM-matched cohorts (P = 0.87, P = 0.79, P = 0.51, P = 0.81 and P = 0.24, respectively). Compared with patients in the ST group, cases received IT were associated with less severe acute toxicities including anemia, leucopenia, neutropenia, and thrombocytopenia. For elderly LA-NPC, IT had similar survivals while less severe toxicities compared with ST, which revolutionarily challenged the role of ST for elderly LA-NPC. In the future, more studies are need to explore a less toxic treatment modality with noninferior efficacy for elderly LA-NPC.

Prospective Efficacy of Two Cycles Toripalimab Plus Induction Chemotherapy in T4 or N3 Locoregionally Advanced Nasopharyngeal Carcinoma: A Retrospective and Mechanistic Study

Gemcitabine-cisplatin (GP) as the most commonly used induction chemotherapy is the standard first-line systemic treatment for advanced nasopharyngeal carcinoma. However, the toxicity of three cycles induction chemotherapy following on chemoradiotherapy remains a pertinent issue. Additional monoclonal antibody against human programmed death-1 (PD-1) has shown promising efficacy in recurrent or metastatic nasopharyngeal carcinoma. In this study, we compared three cycles of gemcitabine and cisplatin as classical induction chemotherapy with two cycles of induction chemotherapy plus toripalimab, and then both groups treated with the similar concurrent chemoradiotherapy. Patients with locoregionally advanced nasopharyngeal carcinoma staging T4 or N3 were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1-3), administered every 3 weeks for three cycles, or GP combined with toripalimab (at a dose of 240mg) for two cycles. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. A total of 60 patients were included in the trial (30 patients in the toripalimab combined induction chemotherapy group and another 30 in the standard-therapy group). Among 60 patients evaluable for response assessment after induction therapy, all patients had overall response in combined group, including 10 patients (30%) with complete response (CR) in the primary tumor site. 21 patients (70%) were evaluated as partial response (PR) in the standard induction chemotherapy, and another 9 patients were assessed as SDa. At a median follow-up of 27.6 months, the 6-months, 1-, 2-year recurrence-free survival was 100% vs 86.7%, 100% vs 80%, 93% vs 70% in the toripalimab combined induction chemotherapy group and standard-therapy group (stratified hazard ratio for recurrence or death, 0.62; 95% confidence interval [CI], 0.38 to 0.87; P = 0.001). Overall survival at 2 years was 93.3% and 100%, respectively (stratified hazard ratio for death, 0.53; 95% CI, 0.29 to 0.79). The incidence of acute adverse events of grade 3 or 4 was 76.8% in the standard-induction chemotherapy group and 56% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 10.2% in the induction chemotherapy group and 10.4% in the combined-therapy group. Two cycles of toripalimab combined with induction chemotherapy of and CCRT shows excellent distant metastatic control with acceptable safety, which is a new promising and effective systemic therapy regimen for high-risk of metastatic NPC patients.

ETIOTROPIC THERAPY OF MILD COVID-19 IN OUTPATIENT PATIENTS: MOLNUPIRAVIR IS IN FOCUS

The aim of the study was to evaluate the efficacy and tolerability of the drug Molnupiravir in adult outpatients with mild Covid–19. Materials and methods. A randomized comparative open clinical trial of Molnupiravir (800 mg twice daily for 5 days in addition to symptomatic/pathogenetic therapy) was conducted in confirmed COVID-19 in comparison with a standard therapy. 240 patients (average age – 43.5 years; 70% had risk factors) were randomized in a 1:1 ratio to the Molnupiravir group and the standard therapy group. Clinical efficacy was assessed based on the analysis of the patient's daily diary, physical examination data and SARS-CoV-2 RNA in the smear from the oropharynx and nasopharynx. The primary endpoint was the proportion of patients with the transition of COVID-19 course to a more severe degree relative to the initial state 2 weeks after the onset of the disease. Significance was assessed using a two-sided version of the Fisher Exact test. Results. Molnupiravir: a) reduced the risk of disease progression by 4 times by the 14th –15th day of follow-up, compared with the risk in the control group (2.5% and 10% of patients, respectively, p = 0.0149); b) accelerated virus elimination by the 6th – 7th day of follow-up (71.67% vs. 58.33%, respectively); c) accelerated clinical recovery (which by day 6-7 had 19% of patients in the Molnupiravir group, and 6% of patients on standard therapy); d) reduced the frequency and severity of COVID-19 symptoms: cough, ageusia. The incidence of adverse events in the study participants was comparable. Conclusions. Molnupiravir administration reduces the risk of COVID-19 progression to a severe course, reduces the severity of COVID-19 clinical manifestations, probably by accelerating the virus elimination. The data obtained indicate feasibility of using Molnupiravir for COVID-19 treatment on an outpatient basis.

Intravenous versus Partial Oral Antibiotic Therapy in the Treatment of Uncomplicated Bloodstream Infection Due to Streptococcus Species.

This retrospective cohort study examines effectiveness of partial oral antibiotic regimens in uncomplicated bloodstream infections (BSIs) due to Streptococcus species compared to standard intravenous therapy. Adult patients with uncomplicated streptococcal BSIs from April 2016 to June 2020 in seven hospitals in South Carolina, USA, were evaluated. Multivariate Cox proportional hazards regression was used to examine the time to treatment failure within 90 days of a BSI after adjustment for the propensity to receive partial oral therapy. Multivariate linear regression was used to examine the hospital length of stay (HLOS). Among the 222 patients included, 99 received standard intravenous antibiotics and 123 received partial oral therapy. Of the standard intravenous therapy group, 46/99 (46.5%) required outpatient parenteral antibiotic therapy (OPAT). There was no difference in the risk of treatment failure between partial oral and standard intravenous therapy (hazards ratio 0.53, 95% CI 0.18, 1.60; p = 0.25). Partial oral therapy was independently associated with a shorter HLOS after adjustments for the propensity to receive partial oral therapy and other potential confounders (-2.23 days, 95% CI -3.53, -0.94; p < 0.001). Transitioning patients to oral antibiotics may be a reasonable strategy in the management of uncomplicated streptococcal BSIs. Partial oral therapy does not seem to have a higher risk of treatment failure and may spare patients from prolonged hospitalizations and OPAT complications.

Efficacy and safety of acetazolamide in patients with NYHA class II-IV decompensated heart failure: protocol of an open-label prospective randomized multicenter study (ORION-A)

Aim. To study the efficacy and safety of acetazolamide administered orally to patients with decompensated heart failure (HF) at the hospital stage within 72 hours from admission, compared with standard therapy.Material and methods. This open-label, prospective, randomized, multicenter study is planned to include 400 patients urgently admitted to hospital with NYHA class II-IV decompensated HF: 200 patients each in the standard therapy group and additional acetazolamide (tablets) group. The primary endpoint includes the number of patients who achieved compensation in accordance with the criteria for diuretic therapy discontinuation. There are secondary endpoints: increase in urine output in the first 72 hours of hospitalization (since randomization), weight loss, 24-hour natriuresis, length of stay in hospital, length of stay in the intensive care unit, 90-day any-cause death, 90-day cardiovascular death, 90-day death due to chronic HF decompensation or acute decompensated HF, the number of pleuro- and pericardiocentesis episodes during the hospitalization, scale for clinical condition assessment of HF patient (SHOKS) at discharge from the hospital, 6-minute walk test at discharge from the hospital. The planned follow-up duration is a hospital period with an assessment of the clinical picture and laboratory parameters. Telemedicine contact with patients is carried out after 14, 30 and 90 days using a structured questionnaire.Conclusion. Analysis of clinical, laboratory and echocardiographic parameters of patients using acetazolamide tablets will make it possible to determine the criteria for the effectiveness of diuretic therapy in patients with decompensated HF in the short and long term.

Changes of natriuresis and prediction of cardiovascular events in patients with type 2 diabetes and decompensated heart failure over therapy with sodium-glucose cotransporter 2 inhibitors and standard diuretic therapy

Aim. To evaluate the influence and changes of clinical and water-electrolyte parameters on the risk of cardiovascular events in the early period after decompensated heart failure (HF) in patients with type 2 diabetes (T2D), taking into account the influence of standard diuretic therapy and diuretic therapy in combination with sodium-glucose cotransporter 2 (SGLT-2) inhibitors.Material and methods. The study included 119 patients with type 2 diabetes and class III-IV HF. The duration of diagnosed HF at the time of enrollment was 6,9±1,1 years.Patients who met the inclusion criteria at the time of hospital admission were randomized into a group of standard therapy for decompensated HF (control group) and a group of combined diuretic therapy — loop diuretics + SGLT-2 inhibitors (main group).Results. Against the background of combined diuretic therapy with SGLT-2 inhibitors, a significant increase in diuresis was achieved, starting from the 2nd day: on day 2 — in the main group 1,342,83±159,74 ml/day and 1,250,17±134,53 ml/day in the control group (p=0,001, 95% confidence interval (CI)), on day 3, in the main — 1,895,17±249,95 ml/day, and in the control — 1,723,78±252,49 ml/day (p=0,004, 95% CI), on day 4, in the main — 2,382,50±246,29 ml/day and in the control — 2,124,83±2,86,44 ml/day (p=0,000002, 95% CI), on day 5, in the main — 2,785,50±282,38 ml/day and in the control group 2,458,39±273,36 ml/day (p&lt;0,001, 95% CI).A comparison of the two groups showed a significant increase in natriuresis in the main group on day 5 (+111,1±10,54 ml) compared to the control (+75,53±15,01 ml, p&lt;0,001, 95% CI). Extracellular fluid volume, determined by bioelectrical impedance analysis on day 5, decreased significantly higher when taking SGLT-2 inhibitors: in the main group the decrease was by 5,48±2,19 kg, in the control group — by 2,92±0,73 kg (p=0,02, 95% CI), On day 5, we revealed a significant inverse relationship between natriuresis level and extracellular fluid volume (r=0,217, p=0,018). Dapagliflozin (D), like empagliflozin (E), significantly and equally increases the level of natriuresis (D +108,25±13,56 mmol/day, p&lt;0,001, E +112,52±8,50, p=0,00009) and reduces the extracellular fluid volume (D -5,05±1,46 kg, p&lt;0,001, E -5,69±2,47, p&lt;0,001) on day 5.Conclusion. In patients with type 2 diabetes hospitalized for decompensated HF, therapy with SGLT-2 inhibitors + loop diuretics lead to a significantly greater diuresis, natriuresis and a greater decrease in extracellular fluid volume. A significant inverse relationship was found between the extracellular fluid volume and natriuresis level on day 5. Dapagliflozin effectiveness in edema, assessed by natriuresis level on day of treatment, is identical to the empagliflozin.

Colchicine is an effective therapeutic agent in erosive hand osteoarthritis

Background/Aim: The efficacy of colchicine has been assessed in hand osteoarthritis; however, no studies have investigated its use in the more severe subtype of hand osteoarthritis, known as erosive hand osteoarthritis (EHOA). This retrospective cohort study investigated whether colchicine therapy could provide symptomatic relief and improve inflammation markers in patients with EHOA. Methods: The study included a total of 43 EHOA patients using colchicine (2×0.5 mg) + paracetamol (3×500 mg) daily (colchicine group) and 43 EHOA patients using only paracetamol (3×500 mg) (standard therapy group). Both groups were evaluated for various parameters. Results: The groups were similar in terms of age, sex distribution, and other sociodemographic variables. The decreases in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels from baseline were significantly greater in the colchicine group (P&lt;0.001). Additionally, the visual analog scale (VAS) and Australian Canadian Osteoarthritis Hand Index (AUSCAN) scores, which include pain, stiffness, function, and total score, were significantly better in the colchicine group at 3 months compared to the standard therapy group (P&lt;0.001). Furthermore, although both groups showed significant improvements in these parameters, the amount of improvement was significantly greater in the colchicine group (P&lt;0.001). Conclusion: The combined use of colchicine and paracetamol improved CRP and ESR levels, VAS score, and all AUSCAN scores in patients with EHOA. Moreover, these benefits were significantly greater than standard therapy with paracetamol alone. Colchicine appears to be an effective therapeutic agent in the treatment of EHOA.

Spatial Neglect Therapy With the Augmented Reality App “Negami” for Active Exploration Training: A Randomized Controlled Trial on 20 Stroke Patients With Spatial Neglect

ObjectiveTo investigate the efficacy of the augmented reality (AR) app “Negami” as an active exploration training for the treatment of spatial neglect. Improvements of the ipsilesional attention and orientation bias (and resulting contralesional neglect) will be examined in stroke patients with spatial neglect and compared with a control group. DesignRandomized controlled trial with an experimental Negami group, consisting of patients with spatial neglect, and a group of neglect patients receiving standard neglect therapy. SettingThree rehabilitation hospitals. ParticipantsTwenty right hemispheric stroke patients with spatial neglect (N=20). InterventionOver a period of 2 weeks, both groups received 5 training sessions per week (à 25 minutes). Neglect behavior was assessed weekly over a 5-week period, with the Negami therapy group receiving a second follow-up assessment at 1-to-2-month intervals after completion of training. Main Outcome MeasuresLetter Cancellation, Bells Test, Copying Task, Line Bisection Task, and a self-developed “Exploration Test”. ResultsBoth groups improved significantly. While the Negami therapy group improved in 4 of 5 neglect tests used, the standard therapy group improved in only 1 of these tests. We observed significantly better improvement in the Negami group already after the first week of training. This difference was also significant after the end of the training as well as 1 week after the end of training and remained stable 1-2 months after the end of treatment. ConclusionNegami can be used as an effective alternative or addition to current standard neglect therapy, and may even be superior to it.