Adjunctive Therapy In Patients Research Articles

Safinamide as adjunctive therapy to levodopa monotherapy for patients with Parkinson's disease with wearing-off: The Japanese observational J-SILVER study

BackgroundSafinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. MethodsThis multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. ResultsIn total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change −7.0 [p = 0.012], −2.4 [p = 0.007] and − 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. ConclusionSafinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. Study registrationUniversity Hospital Medical Information Network in Japan; study ID: UMIN000044341.

Perampanel as monotherapy or first adjunctive therapy in pediatric and adult patients with epilepsy: the first United States-based phase IV open-label ELEVATE study.

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13weeks), Maintenance (39weeks), and Follow-up (4weeks) Periods. During Titration, perampanel was initiated at 2mg/day and up-titrated to 4mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8weeks and 32 (59.3%) patients completed the study. Retention rate at 12months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura

SummaryIn patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

Abstract PO1-05-11: Efficacy of metformin as adjunctive therapy in patients with de novo metastatic breast cancer: a retrospective cohort study

Abstract Background: Metformin, an oral biguanide used for the treatment of type-2 diabetes mellitus (DM), has been shown in a considerable number of studies to have an anti-tumorigenic impact against breast cancer cells through several mechanisms,thereby improving breast cancer outcomes. However, the impact of metformin treatment on survival outcomes in patients with non-diabetic breast cancer is still under debate, with very few data available regarding metformin administration in de novo metastatic breast cancer (dnMBC). This study was conducted to investigate and evaluate the impact on survival outcomes of patients with dnMBC treated with metformin as adjunctive therapy at our institutes. Methods: All dnMBC women who received chemotherapy-based systemic therapy or combined with metformin administered orally in our hospitals between March 2007 and November 2016 were enrolled in the study. Data were retrospectively extracted from the patients’case records. Data were analyzed according the clinicopathological features and treatment outcomes. All specimens were rechecked for the purpose of the research. Overall survival (OS), as the study endpoint, was defined as the time from pathologically confirmed diagnosis to all-cause death or end of the follow-up time.Kaplan-Meier estimate was used to calculate the survival rates.The difference between metformin and non-metformin groups was compared by the log-rank method.Cox regression analysis (uni-and multivariate analysis) was used to assess the effect of variables on survival outcomes.Analyses were performed by Stata 17 software for windows version. Results: A total of 252 women with dnMBC were included with an average age of 54.41±11.61 years. Among them, 97 patients (including 11 DM patients) received chemotherapy-based systemic therapy plus oral administration of metformin 850-1000mg twice daily (metformin group), and 155 patients received chemotherapy-based systemic therapy (non-metformin group). There was no significant difference in body mass index, age, N-stage, P53 index, ER/PR status, HER-2 expression and initial metastatic sites between metformin group and non-metformin group. But there were differences in T-stage and Ki67 index between the two groups (Table 1). The median follow-up was 70 months.The median OS was 24 months.The 3-year and 5-year OS rates for all patients were 29.8% (95% CI:24.2% to 35.4%) and 11.6% (95% CI:7.5% to 16.7%),respectively; Log-rank test showed that the metformin group had a significant advantage over the non-metformin group in OS rates(p=0.0002).The 3-year and 5-year OS rates in the metformin group were 42.3% (95% CI:32.4% to 51.8%) and 21.2% (95% CI:12.8% to 31.1%), respectively; the same rates for non-metformin group were 21.9% (95% CI: 15.8% to 28.7%) and 5.6% (95% CI: 2.4% to 11.1%), respectively. Results of proportional hazards model, after adjustment for T-stage and Ki67 index, depicted an independent prognostic value of metformin use with multivariate hazard ratio of 0.61 (95% CI: 0.45 to 0.81) for OS compared to non-metformin group (p=0.001).No survival advantage was found for DM patients (0.59;95% CI:0.29 to 1.22; p=0.159). Conclusions: Our data support a favorable outcome for survival associated with metformin use in dnMBC patients. However, the retrospective nature and small sample size of the current study are major limitations to reliable conclusions about metformin's potential to improve OS in patients. Therefore, prospective evidence from phase-3 randomized controlled trials on the feasibility of metformin use in dnMBC is required before its routine use can be recommended. Keywords: Metformin; De novo metastatic breast cancer; Adjunctive therapy; Survival outcomes Citation Format: Ren Chongxi, Sun Jianna, Kong Lingjun, Hongjun Yu. Efficacy of metformin as adjunctive therapy in patients with de novo metastatic breast cancer: a retrospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-11.

A Systematic Review and Meta-Analysis of Efficacy and Safety of Cilostazol Prescription in Patients With Femoropopliteal Peripheral Artery Disease After Endovascular Therapy.

The purpose of this study is to assess the efficacy and safety of cilostazol prescription in patients with femoropopliteal peripheral artery disease (PAD) after endovascular therapy (EVT). We conducted a systematic review and meta-analysis of all studies reporting the outcomes of cilostazol after femoropopliteal EVT of PAD up to September 2022. Clinical outcomes of interest included primary patency, in-stent restenosis (ISR), vessel re-occlusion, freedom from target lesion revascularization (TLR), repeat revascularization, all-cause mortality, amputation, major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs), and bleeding complication. A total of 4 randomized controlled trials (RCTs) and 8 observational studies containing a total of 4898 patients met the inclusion criteria and were included in this systematic review and meta-analysis. We found that the use of cilostazol was associated with higher primary patency after femoropopliteal artery EVT (odds ratio [OR]=1.67, 95% confidence interval [CI]=1.50-1.87, p<0.001, I2=33.2%), a lower risk of ISR (OR=0.43, 95% CI=0.29-0.63, p<0.001, I2=37.6%), repeat revascularization (OR=0.43, 95% CI=0.24-0.76, p<0.005, I2=27.4%), and vessel re-occlusion (OR=0.59, 95% CI=0.38-0.93, p<0.05, I2=0%). There was an increase in freedom from TLR rate (OR=2.19, 95% CI=1.58-3.05, p<0.001, I2=0%), as well as a reduction in the occurrence of MALEs (OR=0.50, 95% CI=0.29-0.85, p<0.05, I2=0%). However, there was no significant difference in amputation, MACEs, all-cause mortality, and major bleeding complications. Subgroup analysis showed that cilostazol treatment in patients with femoropopliteal drug-eluting stents (DES) implantation remained associated with higher primary patency and a lower risk of ISR. After EVT of femoropopliteal artery lesions, additional oral cilostazol enhances primary patency, reduces the occurrences of ISR and vessel re-occlusion, diminishes the risks associated with MALEs, lowers the need for repeat revascularization, and increases freedom from TLR rates. However, it does not impact amputation, MACEs, all-cause mortality, or major bleeding complications. These findings suggest cilostazol as a potentially safe and effective adjunct therapy in patients with femoropopliteal PAD after EVT. After undergoing endovascular therapy (EVT) for femoropopliteal artery lesions, the addition of cilostazol to antiplatelet therapy can significantly improve primary patency, reducing the incidence of in-stent restenosis, repeat revascularization, vessel re-occlusion, and major adverse limb events while increasing freedom from target lesion revascularization rate. The simultaneous use of drug-eluting stents in the femoropopliteal artery lesions, combined with cilostazol, potentially results in a synergistic anti-stenotic effect. This therapeutic approach does not appear to be associated with an increased risk of major bleeding events or all-cause mortality. These findings provide additional evidence supporting the treatment of anti-stenosis in patients with femoropopliteal artery lesions after EVT.

WCN24-1723 Exercise as an Adjunctive Therapy for Patients on Maintenance Hemodiafiltration: A 6-Month Retrospective Analysis

WCN24-1723 Exercise as an Adjunctive Therapy for Patients on Maintenance Hemodiafiltration: A 6-Month Retrospective Analysis

Repurposing of dextromethorphan as an adjunct therapy in patients with major depressive disorder: a randomised, group sequential adaptive design, controlled clinical trial protocol

BackgroundTherapeutic latency, lack of efficacy and adverse drug reactions are the major concerns in current antidepressant therapies. To overcome these treatment hurdles, add-on therapy to conventional antidepressant medications may lead...

Adjuvant surgical resection for nontuberculous mycobacterial pulmonary disease: Effectiveness and complications.

Standard antibiotic treatment for nontuberculous mycobacteria pulmonary disease (NTMPD) has unsatisfactory success rates. Pulmonary resection is considered adjunctive therapy for patients with refractory disease or severe complications, but surgical indications and extent of resection remain unclear. We present surgical treatment outcomes for NTMPD and analyzes risk factors for unfavorable outcomes. We conducted a retrospective investigation of medical records for patients diagnosed with NTMPD who underwent surgical treatment at Asan Medical Center between 2007 and 2021. We analyzed clinical data including microbiological and surgical outcomes. A total of 71 NTMPD patients underwent thoracic surgery. Negative conversion of acid-fast bacillus (AFB) culture following pulmonary resection was observed in 51 (73.9%) patients. In terms of long-term outcomes, negative conversion was sustained in 38 cases (55.1%). Mortality occurred in 7 patients who underwent pulmonary resections for NTMPD. Statistically significant associations with factors for recurrence or non-negative conversion of AFB culture were found in older age (odds ratio [OR] =1.093, 95% confidence interval [CI]: 1.029-1.161, P = 0.004), male sex (OR = 0.251, 95% CI: 0.071-0.892, P = 0.033), and extensive NTMPD lesions involving three lobes or more (OR = 5.362, 95% CI: 1.315-21.857, P = 0.019). Interstitial lung disease (OR = 13.111, 95% CI: 1.554-110.585, P = 0.018) and pneumonectomy (OR = 19.667, 95% CI: 2.017-191.797, P = 0.018) were statistically significant risk factors for postoperative mortality. Pulmonary resection can be an effective adjuvant treatment option for NTMPD patients, with post-operative antibiotic treatment as the primary treatment. Careful patient selection is crucial, considering the associated risk factors and resectability due to complications and recurrence.

SARS-CoV-2 and the Angiotensin-Converting Enzyme 2 Receptor: Angiotensin-Converting Enzyme Inhibitor/Angiotensin 2 Receptor Blocker Utilization and a Shift Towards the Renin-Angiotensin-Aldosterone System Classical Pathway.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, uses the surface angiotensin-converting enzyme 2 (ACE2) receptor as the site of entry into host cardiac, respiratory, intestinal, renal, and nervous system cells. Predisposing risk factors such as cardiovascular disease increase the risk of developing severe disease. Hypertension is characterized by the stimulation of the renin-angiotensin-aldosterone system (RAAS). Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin 2 receptor blockers (ARBs), medications used to treat hypertension, inhibit RAAS and its downstream effects; however, they have also been shown to upregulate ACE2 receptors. In this review, we aim to evaluate the effectiveness of ACEi/ARBs as an adjunct therapy in patients with SARS-CoV-2 as well as examine the possible protective effects and impact on infection rate and disease severity. A PubMed literature search excluding sources outside the United States and duplicates was performed using the following search criteria: "COVID-19 AND cardiovascular disease AND ACEi AND ARB", "SARS-COVID-19 OR COVID-19, AND ACEi AND ARB AND Infection rate", "COVID-19 AND ACEi and ARB", "Omicron BA.1 and BA.2 AND ACE2 OR ARBs", "Omicron AND ACEi AND ARBs". This resulted in 33 final sources. The review concluded that ACEi/ARB therapy may continue to improve COVID-19 survival as previous treatment is associated with positive clinical outcomes. Patients taking ACEis or ARBs were found to have a decreased risk of hospitalization, reduced severity of COVID-19 pneumonia, a lesser need for mechanical ventilation, and an overall reduction in mortality rate. No statistically significant association between ACEi/ARB use and enhanced COVID-19 infectivity was found. The Omicron variant is theoretically more infectious and was associated with increased negative clinical outcomes in those undertreated with ACEis/ARBs. The majority of the literature supports the current guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), and Heart Failure Society of America (HFSA), which state that ACEi and ARB medications should not be withdrawn from or initiated on patients with cardiovascular disease who are infected with SARS-CoV-2. More research needs to be conducted on the association between the emerging COVID-19 variants and ACEis/ARBs to give clinicians confidence when treating patients within this subgroup of the population.

Adjunct Intraarterial or Intravenous Tirofiban Versus No Tirofiban After Successful Recanalization of Basilar Artery Occlusion Stroke: The BASILAR Registry.

Approximately half of patients who achieve successful reperfusion do not achieve functional independence. The present study sought to investigate the clinical outcomes and safety of intraarterial or intravenous tirofiban as adjunct therapy in patients with acute basilar artery occlusion who had achieved successful recanalization with endovascular treatment. In the national, prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study) registry, 458 patients who met inclusion criteria were divided into 3 groups based on tirofiban administration (no tirofiban, n=262; intravenous tirofiban, n=101; intraarterial+intravenous tirofiban, n=95). Their clinical outcomes were compared with 90-day modified Rankin Scale scores. Adjusted odds ratios (aORs) and 95% CIs were obtained by logistic regression models and propensity score matching. Safety outcomes included any intracranial hemorrhage (ICH), symptomatic ICH, and mortality. Among 458 included patients, 184 (40.2%) achieved a favorable outcome (modified Rankin Scale score 0-3). There were no differences between the intravenous tirofiban group and the no tirofiban group in terms of safety and clinical outcomes (all P>0.05). Compared with the no tirofiban group, the intraarterial+intravenous tirofiban group had higher odds of 90-day modified Rankin Scale score 0 to 3 (aOR, 2.44 [95% CI, 1.30-4.64], P=0.006) and lower 3-month mortality (aOR, 0.38 [95% CI, 0.19-0.71], P=0.002) without an increase in any ICH (aOR, 0.34 [95% CI, 0.09-1.01], P=0.07) or symptomatic ICH (aOR, 0.23 [95% CI, 0.03-0.90], P=0.05). Similar results of intraarterial+intravenous tirofiban on improving clinical outcomes were detected in novel cohorts constructed by propensity score matching. Intraarterial+intravenous rather than intravenous tirofiban improved clinical outcomes without increasing the frequency of symptomatic ICH among patients with basilar artery occlusion after successful endovascular treatment. Further studies are needed to delineate the roles of intraarterial+intravenous tirofiban in patients with basilar artery occlusion receiving endovascular treatment.

The effects of Salvia miltiorrhiza and ligustrazine injection combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis.

In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different studies have reported conflicting results. Therefore, a systematic review and meta-analysis are necessary to assess the efficacy and safety of SML injection for the treatment of DKD. We searched 6 electronic literature databases comparing randomized controlled trials (RCTs) of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), SML injection in combination with ACEIs/ARBs that were conducted from inception until September 5, 2023. Two reviewers extracted data and independently assessed the risk of bias. Using the Cochrane Risk of Bias Tool for Risk Assessment. Mean differences (MD) were combined with random-effects models and the corresponding 95% confidence intervals (CI) were reported. Review Manager 5.4 software was used for meta-analysis. Stata 17.0 software was used for sensitivity analysis and Egger test. The combined results show that the use of SML injection along with ACEI/ARB led to better outcomes than the use of controls in terms of enhancing recovery: renal function: Serum creatinine (MD = -14.69, 95% CI (-19.38, -10.00)), Blood urea nitrogen (MD = -1.23, 95% CI (-1.72, -0.74)), Urinary β2-microglobulin (MD = -4.58, 95% CI (-7.72, -1.44)); urinary protein: Urinary albumin excretion rate (MD = -45.74, 95% CI (-58.92, -32.56)), Urine albumin-creatinine ratio (MD = -11.93, 95% CI (-13.89, -9.96)), 24-h urine proteinuria (MD = -0.59, 95% CI (-0.86, -0.32)), Urine microalbumin (MD = -13.50, 95% CI (-20.18, -6.83)). Additionally, adjuvant therapy with SML injection enhanced results in blood glucose, blood pressure, lipids, and inflammatory responses, and no significant variations in adverse events were discovered between the 2 groups. In patients with DKD, combining SML injection with ACEI/ARB improves renal function, renal proteinuria, hyperglycemia, blood pressure, dyslipidemia, and inflammatory response.

Efficacy of cranial electrotherapy stimulation in patients with burning mouth syndrome: a randomized, controlled, double-blind pilot study.

The Burning mouth syndrome (BMS) is a chronic pain syndrome characterized by a burning sensation in the oral mucous membranes. The etiology and pathophysiology of BMS is largely unexplained. To date, there is no evidence-based treatment strategy for BMS. Cranial electrical stimulation (CES) represents a non-invasive treatment option with a low side effect profile that is approved for the treatment of pain, depression, anxiety disorder and insomnia. It has shown efficacy in studies for chronic pain such as fibromyalgia and neuropathic pain after spinal cord injury. This study aimed to investigate the therapeutic effectiveness of CES in combination with local transcutaneous electrical nerve stimulation (TENS) as an adjunct therapy in patients with BMS compared to sham stimulation. This randomized, double-blind, sham-controlled pilot study enrolled 22 patients, aged 18 years and over, with the diagnosis of BMS meeting the ICHD-3 criteria from August 2020 to June 2021. The study duration was 4 weeks (28 days) per participant. After randomization, the active group participants (n = 11) received a 100 μA CES treatment for 60 min a day whereas the devices in the Sham group did not emit electricity. Simple linear regression was used to determine whether the interventions promoted significant differences in pain intensity. The linear regression showed that the period of stimulation significantly predicted decrease in the intensity of pain in the active group [β = -0.036; t(26) = -7.219; p < 0.001] as in the sham group [β = -0.026; t(26) = -2.56; p < 0.017]. With the applied cutoff of 30% pain reduction within the stimulation period, both the active and sham groups had 36% responders (n = 4) (Fisher's exact test, p = 1.00). In both groups (active stimulation and sham group), a significant decrease in the intensity of pain, somatic symptoms and an improvement in sleep quality over the study period was observed. Subjects reported no adverse events during the study. Although CES is an easily applicable and safe therapeutic option for chronic facial pain, active stimulation was not superior to sham stimulation. Among other reasons, this could be due to the short double-blinded treatment period, duration of the daily stimulation session or the small sample size.

Acute effect of transcranial direct current stimulation on photoparoxysmal response

IntroductionTranscranial direct current stimulation (tDCS) is a non-invasive technique, used to modify the excitability of the central nervous system. The main mechanism of tDCS is to change the excitability by subthreshold modulation by affecting neuronal membrane potentials in the direction of depolarization or repolarization. tDCS was previously investigated as an alternative adjunctive therapy in patients with epilepsy. We aimed here to investigate the acute effect of tDCS on the photoparoxysmal response (PPR) in EEG. MethodsWe enrolled 11 consecutive patients diagnosed with idiopathic generalized epilepsy who had PPR on at least 2 EEGs. Three different procedures, including sham, anodal, and cathodal tDCS were applied to the patients at intervals of one week by placing the active electrode over Oz, for 2 mA, 20 minutes. Spike-wave indices (SWI) were counted by two researchers independently and were compared during intermittent photic stimulation (IPS) on EEGs both before and after the application. ResultsAfter cathodal tDCS, SWI increased compared to baseline EEG and sham EEG in 3 patients, and after anodal tDCS, SWI increased in 2 patients. Although the SWI values did not change significantly, 8 patients reported subjectively that the applications were beneficial for them and that they experienced less discomfort during photic stimulation after the sessions. There were no side effects except transient skin rash in one patient, only. ConclusionsIn our sham controlled tDCS study with both cathodal and anodal stimulation, our data showed that there was no significant change in SWI during IPS, despite subjective well-being. tDCS’ modulatory effect does not seem to act in the acute phase on EEG parameters after photic stimulation.

Atomoxetine and bupropion interaction

In addition to its approved use for the treatment of patients with attention‐deficit hyperactivity disorder (ADHD), the selective norepinephrine reuptake inhibitor atomoxetine is sometimes used off‐label as an adjunctive therapy for patients with major depressive disorder. Bupropion, a norepinephrine/dopamine reuptake inhibitor approved for the treatment of depression, is also used off‐label for ADHD. Bupropion is a potent inhibitor of CYP2D6, the cytochrome P‐450 isoenzyme responsible for mediating the primary hydroxylation pathway of atomoxetine to its active metabolite 4‐hydroxy‐atomoxetine.

MARVEL: A Randomized Double‐Blind, Placebo‐Controlled Trial in Patients Undergoing Endovascular Therapy: Study Rationale and Design

Background Steroids have pleiotropic neuroprotective actions including the regulation of inflammation and apoptosis which may influence the effects of ischemia on neurons, glial cells, and blood vessels. The effect of low‐dose methylprednisolone in patients with acute ischemic stroke in the endovascular therapy era remains unknown. This trial investigates the efficacy and safety of low‐dose methylprednisolone (2 mg/kg IV for 3 days) as adjunctive therapy for patients with acute ischemic stroke undergoing endovascular therapy within 24 hours from symptom onset. Methods The MARVEL (Methylprednisolone as Adjunctive Therapy for Acute Large Vessel Occlusion: A Randomized Double‐Blind, Placebo‐Controlled Trial in Patients Undergoing Endovascular Therapy) trial is an investigator‐initiated, prospective, randomized, double‐blind, placebo‐controlled multicenter clinical trial. Up to 1672 eligible patients with anterior circulation large‐vessel occlusion stroke presenting within 24 hours from symptom onset are planned to be consecutively randomized to receive methylprednisolone or placebo in a 1:1 ratio across 82 stroke centers in China. Results The primary outcome is the ordinal shift in the modified Rankin scale score at 90 days. Secondary outcomes include 90‐day functional independence (modified Rankin scale score, 0–2). The primary safety end points include mortality rate at 90 days and symptomatic intracerebral hemorrhage within 48 hours of endovascular therapy. Conclusion The MARVEL trial will provide evidence of the efficacy and safety of low‐dose methylprednisolone as adjunctive therapy for patients with anterior circulation large‐vessel occlusion stroke undergoing endovascular therapy.

The effectiveness of probiotics as an adjunct therapy in patients under mechanical ventilation: an umbrella systematic review and meta-analysis.

The literature regarding the role of probiotics in critically ill patients who have undergone mechanical ventilation (MV) is unclear; therefore, this umbrella systematic review and meta-analysis was carried out to clarify the effects of probiotics on the clinical outcomes of mechanically ventilated patients. The Scopus, PubMed/Medline, ISI Web of Science, and Google Scholar online databases were searched up to February 2023. All meta-analyses evaluating the impact of probiotics in patients under MV were considered eligible. The assessment of multiple systematic reviews (AMSTAR) questionnaire was used to evaluate the quality of the studies. Data were pooled using the random-effects approach. Thirty meta-analyses and nine clinical outcomes were re-analyzed. Probiotics significantly decreased ventilator-associated pneumonia (VAP) incidence, nosocomial infections, intensive care unit (ICU) length of stay, hospital length of stay, ICU mortality, hospital mortality, MV duration, duration of antibiotic use, and diarrhea. The obtained results of the current umbrella meta-analysis indicate that probiotic administration could be considered an adjunct therapy for critically ill patients; however, no specific probiotic treatment regimen can be recommended due to the diverse probiotics used in the included meta-analyses. The following microorganisms were used at various doses and combinations throughout the studies: Lacticaseibacillus casei, Lactiplantibacillus plantarum, L. acidophilus, L. delbrueckii, L. bulgaricus, Bifidobacterium longum, B. breve, B. salivarius, Pediococcus pentosaceus, Lactococcus raffinolactis, B. infantis, B. bifidum, Streptococcus thermophilus, Ligilactobacillus salivarius, L. lactis, B. lactis, Saccharomyces boulardii, L. rhamnosus GG, L. johnsonii, L. casei, S. faecalis, Clostridium butyricum, Bacillus mesentericus, L. sporogenes, S. boulardii, L. paracasei, B. subtilis, and Enterococcus faecium.

Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial

Background and AimsCoconut water is anti-inflammatory, can manipulate the gut microbiome and is a rich source of potassium. Gut microbiome modulation improves outcomes in UC, and potassium possesses in vitro anti-inflammatory property. We evaluated the effect of coconut water as an adjunct therapy for patients with mild-moderate UC. MethodsThis single-center double-blind placebo-controlled trial randomized patients with mild-moderate(simple clinical colitis activity index-SCCAI:3–9) endoscopically active UC(ulcerative colitis endoscopic index of severity-UCEIS>1) in 1:1 ratio to coconut water + standard medical therapy-SMT(CW) vs placebo + SMT. 400ml of coconut water was administered for 8weeks. Primary outcome measure was clinical remission(SCCAI ≤2) and secondary outcome measures were clinical response(SCCAI decline ≥3) and adverse events at 8weeks. Microbiome was analyzed at baseline and 8weeks. ResultsOf 121 patients screened, 95 were included for modified intention to treat analysis(49-CW, 46-placebo)[mean age-37.2±11.2years; males-54.1%; disease duration-48(IQR:24–90)months; pancolitis-26.1%; SCCAI-5(IQR:4 – 6); UCEIS-4(IQR:3 – 5)]. Clinical response[57.1% vs 28.3%, p=0.01, OR-3.4(95%CI:1.4 – 7.9)], remission[53.1% vs 28.3%, p=0.02, OR-2.9(95%CI:1.2 – 6.7)] and proportion of patients with fecal calprotectin(FCP)<150μg/g[30.6% vs 6.5%, p=0.003, OR-6.3(95%CI:1.7 – 23.6)] were significantly higher in CW. The relative abundance of bacterial taxa which had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP, increased at 8weeks in CW, and this effect was independent of disease activity and dietary fiber. Adverse events were comparable and no patient developed hyperkalemia. ConclusionCoconut water was more effective than placebo for induction of clinical remission in patients with mild to moderate UC.The trial was prospectively registered on clinical trials registry India (No: CTRI/2019/03/01827)

Impact of Dapagliflozin Adjunctive Therapy on Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes and CKD Stage 2–5

This meta-analysis was conducted by searching PubMed, Scopus, Cochrane, Ovid till November 2022 for randomized controlled trials (RCTs) that utilized dapagliflozin 10 mg as adjunctive therapy in patients with T2DM and CKD stage 2-5 and reported its renal efficacy in terms of mean change in estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) from baseline. From 1682 identified records, nine studies representing 13,057 patients were selected for this study. Pooled estimate of five studies showed that dapagliflozin did not affect eGFR but caused significantly less chronic eGFR decline than placebo in two studies [Mean difference (MD) +2.74 (95% CI: 1.55, 3.92; p &lt; 0.00001)]. Pooled estimate of four studies showed that dapagliflozin significantly reduced UACR[-23.99 % MD (95% CI - 34.82, -13.15, p-value &lt; 0.0001; = 0%)]. This confirms that long-term dapagliflozin use significantly attenuates eGFR decline and reduces albuminuria in T2DM and CKD stages 2-5 patients.&#x0D; Keywords: Chronic kidney disease, Dapagliflozin, Estimated GFR, eGFR, SGLT2 inhibitors, Type 2 diabetes mellitus, Urine albumin to creatinine ratio, UACR.

Systemic lupus erythematosus with diffuse alveolar hemorrhage.

Systemic lupus erythematosus with diffuse alveolar hemorrhage.

Case of Hemolytic Disease of the Fetus and Newborn Treated Without Blood Products.

Hemolytic disease of the fetus and newborn (HDFN) affects 3/100,000 to 80/100,000 patients yearly and can cause severe anemia and hyperbilirubinemia. Recombinant human erythropoietin has been used as an adjunct therapy in patients with HDFN and hypo-regenerative anemia in the setting of receiving intrauterine blood transfusions. This case describes a patient with HDFN, in which the family were Jehovah Witnesses, and blood transfusions were declined. The patient had symptomatic anemia with a hematocrit nadir of 18.6%. The patient was successfully treated with recombinant human erythropoietin, ferrous sulfate, and folic acid, avoiding the need for transfusion.