Dual Regimen Research Articles

Ruthenium nanoparticles encrusted with nitrogen & sulphur magnetic quantum dots as an efficient electrochemical sensor for simultaneous determination of itraconazole and terbinafine; a dual regimen for black fungus: Magnetic solid phase micro-extraction for urine and plasma analysis

After COVID-19 pandemic, Mucormycosis (black fungus) spreads as one of its related complications, due to the decrease in immunity system after administration of COVID-19 treatment drugs. A combination therapy of Itraconazole (ITR) and Terbinafine (TEB) was proved to be effective for treatment of black fungus. A novel electrochemical sensor was designed for estimation of ITR & TEB simultaneously by square wave voltammetric (SWV) technique. The sensor was fabricated using N&S-codoped magnetic quantum dots (N,S-MQDs) and ruthenium nanoparticles (Ru NPs). The fabricated sensor was characterized by cyclic voltammetry (CV), scanning electron microscope (SEM), powder X ray diffraction (pXRD), Fourier transform-Infrared (FT-IR), Raman spectroscopy and electrochemical impedance spectroscopy (EIS). Full optimization study for various experimental and instrumental parameters, in addition to method validation following International conference on Harmonization (ICH) guidelines was achieved. A good linearity in the range of 0.5–30 μg mL−1 with limit of detection (LOD) 0.24 and 0.19 μg mL−1 for ITR and TEB, respectively were obtained. The sensor was applied for analysis of ITR and TEB simultaneously in human plasma and urine samples without any interferences by applying dispersive magnetic solid phase micro-extraction (dMSPE) technique, where excellent recovery results exceeding 95 % were achieved.

Dual Antiplatelet Therapy Regimens and Duration for Intracranial Stenting Procedures: Literature Review

Objectives of the study. Our aim was to analyse different antithrombotic drug regimens and duration in intracranial stenting procedures (stent assisted coiling, flow diverter) for unruptured aneurysms and based on the literature review from 2017–2023 to implement dual antiplatelet therapy algorithm for neuro-interventional procedures in Lithuania. Research methods and methodology. A comprehensive literature search of PubMed, BioMed Central, BMJ Journals, EBSCO Publishing, SAGE Journals Online, ScienceDirect, SpringerLink was conducted by two independent readers (MP, GŠ) for studies published from January 2017 to April 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. 23 studies: 6 retrospective cohort, 11 retrospective case-control, 1 prospective cohort, 1 prospective randomized-control, 1 systemic literature review, 3 metanalysis observational studies were identified. Results and conclusions. We found widespread variation in practices even among the same country centres, lending credence to the importance of a future prospective studies of dual antiplatelet drug therapy (DAPT) regimens and duration for the purpose of deriving optimal methods and streamlining tactics. Our suggested algorithm for DAPT in neuro-interventional procedures in Lithuania is provided in Graph 1.

Use of different anticholinergic scales and their correlation with anticholinergic symptom burden in a cohort of people living with HIV.

How to detect the clinical impact of anticholinergic (AC) burden in people with HIV (PWH) remains poorly investigated. We cross-sectionally described the prevalence and type of AC signs/symptoms and the screening accuracy of three AC scales in detecting their presence in a modern cohort of PWH. We calculated AC Burden Scale (ABS), AC Risk Score (ARS) and AC Drug Score (ADS) in 721 adult PWH and recorded the presence of AC signs/symptoms over the previous 3 months. High AC risk was defined by ABS score ≥2, and ARS or ADS score ≥3. Comparisons among the scale were based on Cohen's inter-rater agreement, and their screening accuracy was assessed by receiver operating characteristics (ROC) curves and performance measures. We enrolled 721 PWH, of whom 72.0% of participants were male; the median age was 53 years, and 164 participants (22.7%) were on at least one AC drug. Among these, 28.6% experienced at least one AC sign/symptom. Agreement in AC risk classification was substantial only between ARS and ADS (k = 0.6). Lower and higher risk of AC signs/symptoms was associated with dual regimens [adjusted OR (aOR) = 0.12 versus three-drug regimens, P = 0.002] and increasing number of AC drugs (aOR = 12.91, P < 0.001). Depression and COPD were also associated with higher risk of AC signs/symptoms in analysis unadjusted for number of AC drugs. ABS and ADS showed the best area under the ROC curve (AUROC) of 0.85 (0.78-0.92) and 0.84 (0.75-0.92; P < 0.001 for both). However, at the cut-off used for the general population, the sensitivity of all three scales was very low (34.0%, 46.8% and 46.8%). Up to one-fourth of participants in our cohort were exposed to at least one AC drug, and among them AC signs/symptoms affected more than one-fourth. Both polypharmacy (as number of antiretrovirals and of co-medications with AC properties) and to a lesser extent specific comorbidities shaped the risk of developing AC signs/symptoms. Sensitive screenings for AC risk in PWH should prefer ABS or ADS based on lower cut-offs than those suggested for the general population.

Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial

ObjectiveTo assess the efficacy and safety of pyrotinib (an irreversible pan-HER (human epidermal growth factor receptor) inhibitor), trastuzumab, and docetaxel compared with placebo, trastuzumab, and docetaxel for untreated HER2 positive...

A retrospective study: Can dual ART mitigate the risk of potential drug-drug interactions among PLWH under stable ART?

People living with human immunodeficiency virus (PLWH) are getting older. Age-related comorbidities in PLWH result in polypharmacy and increase the risk for potential drug-drug interactions (pDDIs). This study aimed to evaluate how the rate of pDDIs would change if the treatment of patients receiving different combined antiretroviral therapies (ARTs) were theoretically changed with dolutegravir/lamivudine (DTG+3TC) or cabotegravir/rilpivirine (CAB+RPV). This study was conducted at the infectious disease outpatient clinic of a university hospital as a follow-up of a previous study. The data of PLWH receiving at least 1 comedication other than antiretrovirals (ARVs) were retrospectively reviewed and analyzed. The Drugs.com/Drug Interactions Checker and University of Liverpool HIV Drug Interactions Checker databases were used to identify pDDIs and their severities. A total of 75 PLWH, of whom 83% were male, with a mean age (± standard deviation) of 46.5 (±12.98) years were included. Polypharmacy was observed in 59 (79%) of the participants; however, with dual ARV options, the probability of polypharmacy was 35 (47%) (p < 0.001). In the Drugs.com database, no significant difference was found in terms of pDDIs between the treatment of current ARTs (64%) and DTG/3TC (%44) (p = 0.06) or CAB/RPV (%64) (p = 0.521). However, in the University of Liverpool database, the current rate of pDDIs (55%) was significantly higher compared to the theoretical treatment of DTG/3TC (40%) (p = 0.029), oral CAB/RPV (48%) (p = 0.003), and injectable CAB/RPV (31%) use (p = 0.006). The results suggest that dual treatment regimens can reduce pDDIs, resulting in better tolerance and probably higher quality of life among PLWH.

Urgent Off-Label Use of Flow–Diverter Stents in the Endovascular Management of Tonsillar Loop-Associated Internal Carotid Artery Dissections Presenting with Carotid Occlusion or Near-Occlusion and Major Ischemic Stroke

We present our experience with the implantation of flow diverter stents (FDSs) for the management of internal carotid artery (ICA) dissections in tortuous tonsillar loop segments. A total of 16 patients (10 women, 62.5%; mean age 39 ± 8 years; median baseline NIHSS 13; median ASPECTS 8.5) with acute ischemic stroke due to ICA dissection in a tortuous tonsillar loop segment, with/without large intracranial vessel thrombotic occlusion diagnosed between June 2015–February 2022 were included in this retrospective study under a waiver of informed consent. An FDS device was deployed from the petrous ICA toward the upper cervical ICA, completely covering the tonsillar loop. Stentriever-assisted thrombectomy was performed when indicated. A dual antiplatelet regimen was used during and after the procedure. Thrombocyte inhibition levels were evaluated before, during, and after the intervention. The ICA occlusion/near occlusion was successfully recanalized in all 16 patients with mean postangioplasty residual stenosis of 34 ± 14% (range 0–50%). Stent-assisted thrombectomy was performed in 15/16 patients (93.7%), achieving revascularization (TICI 2b–3) in all. There were no procedural complications and no intraprocedural embolic events; one asymptomatic petechial hemorrhage was detected. At 3-month follow-up, mRS 0–2 was seen in all patients. This report provides pilot data for a subsequent study on the use of flow diverter stents for ischemic cerebrovascular conditions. Our encouraging preliminary results await confirmation from further experience and prospective randomized studies.

Antithrombotic Treatment in Coronary Artery Disease.

Coronary artery disease exhibits growing mortality and morbidity worldwide despite the advances in pharmacotherapy and coronary intervention. Coronary artery disease is classified in the acute coronary syndromes and chronic coronary syndromes according to the most recent guidelines of the European Society of Cardiology. Antithrombotic treatment is the cornerstone of therapy in coronary artery disease due to the involvement of atherothrombosis in the pathophysiology of the disease. Administration of antiplatelet agents, anticoagulants and fibrinolytics reduce ischemic risk, which is amplified early post-acute coronary syndromes or post percutaneous coronary intervention; though, antithrombotic treatment increases the risk for bleeding. The balance between ischemic and bleeding risk is difficult to achieve and is affected by patient characteristics, procedural parameters, concomitant medications and pharmacologic characteristics of the antithrombotic agents. Several pharmacological strategies have been evaluated in patients with coronary artery disease, such as the effectiveness and safety of antithrombotic agents, optimal dual antiplatelet treatment schemes and duration, aspirin de-escalation strategies of dual antiplatelet regimens, dual inhibition pathway strategies as well as triple antithrombotic therapy. Future studies are needed in order to investigate the gaps in our knowledge, including special populations.

Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention

PurposePatients with coronary artery disease have increased fracture risks. P2Y12 inhibitors may impact fracture risks. We compared the fracture risks associated with ticagrelor and clopidogrel in dual anti-platelet therapy (DAPT).MethodsWe identified all adults who underwent first-ever percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) between 2010 and 2017 from a territory-wide PCI registry in Hong Kong. Following 1:1 propensity-score matching for baseline characteristics, patients were followed up till event occurrence, death, or 30 June 2022. Outcomes of interest were major osteoporotic fractures (MOF) identified by validated ICD-9-CM codes. Cox proportional hazards regression was used to compute the hazard ratio (HR) for MOF associated with ticagrelor versus clopidogrel use.Results3018 ticagrelor users and 3018 clopidogrel users were identified after propensity-score matching (mean age: 61.4 years; 84.1% men). Upon median follow-up of 6.5 years, 59 ticagrelor users and 119 clopidogrel users sustained MOF (annualized fracture risks: 0.34% and 0.56%, respectively). Ticagrelor use was associated with lower risks of MOF (HR 0.60, 95%CI 0.44–0.83; p = 0.002). Consistent HRs were observed for fractures over vertebrae, hip and upper limbs. Subgroup analyses showed no interaction according to age, sex, presence of diabetes, presence of chronic kidney disease and prior fracture history.ConclusionAmong adults who underwent first-ever PCI for ACS, ticagrelor use in the DAPT was associated with a lower risk of MOF compared with clopidogrel. Our results support the use of ticagrelor in the DAPT from the perspective of bone health.

Empiric treatment with aspirin and ticagrelor is the most cost-effective strategy in patients with minor stroke or transient ischemic attack.

Patients with minor ischemic stroke or transient ischemic attacks (TIAs) are often treated with dual antiplatelet therapy regimens as part of secondary stroke prevention. Clopidogrel, an antiplatelet used in these regimens, is metabolized into its active form by the CYP2C19 enzyme. Patients with loss of function (LOF) mutations in CYP2C19 are at risk for poorer secondary outcomes when prescribed clopidogrel. We aimed to determine the cost-effectiveness of three different treatment antiplatelet regimens in ischemic stroke populations with minor strokes or TIAs and how these treatment regimens are influenced by the LOF prevalence in the population. Markov models were developed to look at the cost-effectiveness of empiric treatment with aspirin and clopidogrel versus empiric treatment with aspirin and ticagrelor, versus genotype-guided therapy for either 21 or 30 days. Effect ratios were obtained from the literature, and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). Empiric treatment with aspirin and ticagrelor was the most cost-effective treatment. Genotype-guided therapy was more cost-effective than empiric aspirin and clopidogrel if the LOF was above 48%. Empiric ticagrelor and aspirin was cost saving when compared to genotype-guided therapy. Results in models of dual antiplatelet therapy for 30 days were similar. This study suggests that in patients with minor stroke and TIA planned for dual antiplatelet regimens, empiric ticagrelor and aspirin is the most cost-effective treatment regimen. If ticagrelor is not available, genotype-guided therapy is the most cost-effective treatment regimen if the LOF prevalence in the population is more than 48%.

A Systematic Evaluation of the SARS-CoV-2 Vaccine-Induced Anti-S-RBD-Ig Response in a Population of Health Care Workers.

In the wake of the COVID-19 pandemic, the novel class of mRNA vaccines has been granted first-time approval for active immunization against SARS-CoV-2 alongside the already established viral vector-based vaccines. In this prospective single-center study, we set out to determine the vaccine-induced humoral immune response in a population of 1512 health care employees after the second and third vaccination, respectively. Anti-SARS-CoV-2 receptor-binding domain (RBD) and nucleocapsid antigen antibody concentrations were assessed using commercially available immunoassays. We could show that, in particular, young study subjects aged below 30 years, as well as those with a prior SARS-CoV-2 infection, developed significantly higher antibody concentrations. Our data further suggest that being in physically close contact with formerly SARS-CoV-2-positive people positively affects the post-vaccination response. Surprisingly, study subjects with a BMI > 30 produced the highest anti-S-RBD Ig antibody levels if they had recently received their third vaccination. Also, heterologous dual vaccine regimens consisting of a BNT162b2 and ChAdOx1 n-CoV-19, a homologous triple combination of BNT162b2, and an application of mRNA-1273 as the third vaccine, were most efficient at eliciting a humoral immune response. Our study substantiates existing evidence, but beyond that, scrutinizes the impact of vaccine agents and their respective combinations, as well as different time intervals on humoral immunogenicity.

Potential benefits of combining two long-acting injectable antipsychotic: a retrospective study.

The aim of this study was to evaluate the efficacy and tolerability of the combination of two long-acting injectable antipsychotics (LAIA) in psychiatric disorders, especially in schizophrenia. Eighty-three patients treated with dual LAIA were included in the study by retrospective screening from the hospital registration system. The present study was designed as an observational, retrospective, naturalistic mirror-image study. The number of hospitalizations before and after switching to dual LAIA was compared in patients who received oral antipsychotics and single LAIA during the study period. In addition, it was analyzed which was the preferred dual antipsychotic combination. Of the patients, 44.6% had schizophrenia, 41.0% had schizoaffective disorder, and 14.4% had other psychiatric disorders. The number of patients receiving oral treatment prior to dual LAIA use was 80 (96.4%). Data on dual LAIA regimens showed that 31.3% were receiving paliperidone and aripiprazole, 24.1% were receiving paliperidone and flupenthixol, 18.1% were receiving paliperidone and zuclopenthixol, and 26.5% were receiving the other combinations. After dual LAIA treatment, there was a significant decrease in the number of hospitalizations compared to before (from 5.95 to 0.99, p<0.001). In addition, while the number of patients who did not require hospitalization in the pre-treatment period was 10.8%, it reached 48.1% in the post-treatment period (p<0.001). No significant adverse effect related to the use of dual LAIA was observed in any patient during the treatment period. The use of dual LAIA instead of oral antipsychotics or single LAIA in chronic psychotic patients with poor social support and irregular medication use is thought to reduce hospitalization and related treatment costs and regularize medication use.

Two-Drug Regimen Containing Darunavir: Metabolic Evaluation of an Old Dual Therapy.

Regimens containing darunavir are one of the first one with two drugs that demonstrated good efficacy as a simplification strategy. We wanted to describe the characteristics of patients followed in our center on a dual therapy regimen containing darunavir evaluating the metabolic aspects during follow-ups. We collected data from 208 patients switching to lamivudine plus darunavir with either ritonavir or cobicistat between 2010 and 2019. In all patients we found an increase in low-density lipoprotein (LDL), with no rising in creatinine, total cholesterol, or triglycerides. Twenty-five patients reached 120 weeks of follow-up. In these patients, no significant metabolic changes were described without concomitant treatment with drugs for dyslipidemia. These regimens seem to be more tolerable in metabolic profile compared with the data concerning three-drug therapies, leading only to a slight increase in LDL. The main reason for discontinuation was for a single-tablet therapy. None of the patients started treatment for dyslipidemia.

Efficacy and Safety of Switching to Dolutegravir/Lamivudine in Virologically Suppressed People Living with HIV-1 Aged Over 65 Years.

Clinical trials of dual regimen dolutegravir/lamivudine (DOL/3TC) demonstrated potent efficacy and favorable safety in both antiretroviral therapy-naïve and -experienced patients, but data on older people are lacking. We aimed to evaluate virological efficacy and safety of DOL/3TC in suppressed older patients over a 12-month period. We performed a retrospective cohort study evaluating people living with HIV (PLWHIV) aged ≥65 years at our HIV Clinic who were switched to DOL/3TC. Eligible patients had baseline HIV-1 RNA <20 copies/mL, and no previous virological failures or known resistance mutations for lamivudine or dolutegravir. Inclusion criteria were met by 72 patients: 59 were men, median age was 69.2 years, and one or more comorbidities were present in 89% of patients. The most common reason for switch was simplification, followed by drug-drug interactions (DDIs) and toxicities. After 12 months, 64 (88.9%, by the intention-to-treat analysis) patients maintained HIV-1 RNA <20 copies/mL, and reasons for treatment failure were virological failure in three cases, adverse events in three, and missing data in two. Genotype resistance testing showed no resistance mutations for lamivudine or dolutegravir in subjects with virological failure. The number of potential DDIs decreased from 92 to 12 after switching to DOL/3TC, and a significant reduction in median total and low-density lipoprotein cholesterol was reported, while median change in body weight was not significant. In this real-life cohort, switching to DOL/3TC was associated with maintenance of virological control and good tolerability among persons aged >65 years, supporting use of this dual regimen in older PLWHIV.

Immune Checkpoint Inhibitors in Solid Organ Transplant Recipients With Advanced Skin Cancers-Emerging Strategies for Clinical Management.

Use of immune checkpoint inhibitors (ICIs) in solid organ transplant recipients (SOTRs) with advanced skin cancers presents a significant clinical management dilemma. SOTRs and other immunosuppressed patients have been routinely excluded from ICI clinical trials with good reason: immune checkpoints play an important role in self- and allograft-tolerance and risk of acute allograft rejection reported in retrospective studies affects 10% to 65% of cases. These reports also confirm that cutaneous squamous cell carcinoma and melanoma respond to ICI therapy, although response rates are generally lower than those observed in immunocompetent populations. Prospective trials are now of critical importance in further establishing ICI efficacy and safety. However, based on current knowledge, we recommend that ICIs should be offered to kidney transplant recipients with advanced cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma if surgery and/or radiotherapy have failed. For kidney transplant recipients, this should be first line ahead of chemotherapy and targeted therapies. In SOTRs, the use of ICIs should be carefully considered with the benefits of ICIs versus risks of allograft rejection weighed up on a case-by-case basis as part of shared decision-making with patients. In all cases, parallel management of immunosuppression may be key to ICI responsiveness. We recommend maintaining immunosuppression before ICI initiation with a dual immunosuppressive regimen combining mammalian target of rapamycin inhibitors and either corticosteroids or calcineurin inhibitors. Such modification of immunosuppression must be considered in the context of allograft risk (both rejection and also its subsequent treatment) and risk of tumor progression. Ultimately, a multidisciplinary approach should underpin all clinical decision-making in this challenging scenario.

Dual Versus Mono Antiplatelet Therapy in Patients with Acute Mild-to-Moderate Stroke: A Multicentre Perspective Cohort Study.

The purpose of this study was to evaluate the association between different antiplatelet therapy regimens and the functional outcomes and bleeding complications among mild-to-moderate ischaemic stroke patients based on real-world data. We used data from the SEACOAST trial (Safety and efficacy of aspirin-clopidogrel in acute noncardiogenic minor ischaemic stroke) to analyse the data of patients with mild-to-moderate stroke within 72 h after onset who were treated with aspirin or clopidogrel alone or a combination of clopidogrel and aspirin from September 2019 to November 2021. Propensity score matching (PSM) was used to balance the differences between groups. We performed an analysis to evaluate the association of different antiplatelet regimens and 90-day disability, which was defined as a modified Rankin Scale score ≥2, as well as disability ascribed to index or recurrent stroke by the local investigator. In terms of safety, we then compared the bleeding events between the two groups. A total of 2822 mild-to-moderate ischaemic stroke patients were treated with either clopidogrel plus aspirin (n = 1726, 61.2%) or aspirin/clopidogrel (n = 1096, 38.8%). Of 1726 patients in the dual antiplatelet group, 1350 (78.5%) received less than or equal to 30 days of combined therapy. At 90 days, 433 (15.3%) patients were disabled. Patients who received combined therapy had a lower overall disability rate (13.7% versus 17.9%; OR 0.78 (0.6-1.01); P = 0.064). However, investigators found that index stroke was the reason for significantly fewer patients in the dual antiplatelet group having disability (8.4% versus 12%; OR, 0.72 (0.52-0.98); P = 0.038). There was no statistically significant difference in the incidence of moderate to severe bleeding complications between the dual and mono antiplatelet drug regimens (0.4% versus 0.2%; HR 1.5 (0.25, 8.98); P = 0.657). Aspirin plus clopidogrel was associated with a reduction in the incidence of disability attributed to index stroke. There was no statistically significant difference in the incidence of moderate to severe bleeding complications between the two antiplatelet drug regimens. ChiCTR1900025214.

Polypharmacy and Aging in People Living with HIV: 6 Years of Experience in a Multidisciplinary Outpatient Clinic.

Despite the availability of potent antiretroviral drugs, the management of human immunodeficiency virus (HIV) infection still presents some important challenges, especially in older patients who often experience age-related comorbidities and complex polypharmacy. To describe the results of our 6 year experience with the outpatient clinic [Gestione Ambulatoriale Politerapie (GAP)] for the management of polypharmacy in people living with HIV (PLWH). Demographic characteristics, antiretroviral regimens, and number and type of comedications were collected in all PLWH included in the database of GAP from September 2016 to September 2022. Therapies were stratified based on the number of anti-HIV drugs (dual versus triple regimens) and on the presence of pharmacokinetic boosters (ritonavir or cobicistat). A total of 556 PLWH were included in the GAP database. Overall, the enrolled patients were administered 4.2 ± 2.7 drugs (range 1-17) in addition to antiretroviral therapies. The number of comedications greatly increased with age (3.0 ± 2.2 versus 4.1 ± 2.5 versus 6.3 ± 3.2 in PLWH aged < 50 versus 50-64 versus > 65 years; p < 0.001 for all comparisons). PLWH on dual antiretroviral therapies were significantly older (58 ± 9 versus 54 ± 11 years; p < 0.001) and were concomitantly treated with more drugs (5.1 ± 3.2 versus 3.8 ± 2.5; p < 0.001) compared with those on triple therapies. A significant reduction of boosted antiretroviral regimens (53% versus 23%; p < 0.001) and in the number of comedications (4.0 ± 2.9 versus 3.1 ± 2.2 drugs; p < 0.001) was observed in the subgroup of patients (n = 198) with two GAP visits. The high prevalence of polypharmacy in PLWH, especially among older adults, place these patients at high risk for clinically relevant drug-drug interactions (DDIs). A multidisciplinary approach involving physicians and clinical pharmacologists could help to optimize medication regimens associated with reduced risk.

Clostridium difficile infection and immune mediated diarrhea and colitis in patients with cancer on immune checkpoint inhibitors.

e14683 Background: Immune checkpoint inhibitors (ICIs) have altered the landscape of cancer treatment. ICIs are associated with immune mediated diarrhea and colitis (IMDC) which can be challenging to diagnose and differentiate from other etiologies of diarrhea. Clostridium difficile infection (CDI) is a common cause of diarrhea in patients with cancer and can have similar symptoms. In a similar study, CDI was found to be relatively common in ICI-treated cancer patients and especially those with IMDC requiring immunosuppressants. Our study evaluates the incidence of CDI and IMDC in patients with ICI exposure and compares clinical characteristics between the two to determine risk factors that may predispose patients to CDI or IMDC. Methods: This is a retrospective, single-center study of cancer patients on an ICI from 1/1/2011 to 4/7/2022 who were tested for Clostridium difficile with stool nucleic acid amplification tests during or after treatment with an ICI. Patients were determined to have CDI if clinically suspected and had to have a positive stool GDH Ag along with positive C. difficile toxins A &amp; B or a positive stool C. difficile toxin B gene. Patients with positive GDH Ag in the stool but with negative toxins A&amp;B were determined to be colonized. The diagnosis of IMDC was based on the clinical presentation and had to be made by the treating oncologist. Results: 375 patients met our study criteria and got CDI testing at any point during or after ICI exposure. 27 patients tested positive for CDI, whereas 24 were colonized. 105 patients were determined to have IMDC and 97/105 received treatment with steroids or immunosuppressants. Among patients determined to have IMDC, 6 were colonized for clostridium difficile. There were no patients with IMDC who were also positive for clostridium difficile. 71 patients were on a dual ICI regimen whereas 304 patients were on a single ICI. In patients on the dual ICI regimen, 67.6% were diagnosed with IMDC when compared to patients on a single ICI regimen where 18.8% of patients were diagnosed with IMDC (p&lt;0.0001). The absolute lymphocyte count on the day of CDI testing was 1.185 ± 0.066 in the IMDC group when compared to 0.948 ± 0.044 in the non-IMDC group (p=0.003). The mean duration of diarrhea was longer in the IMDC group at 16.905 ± 1.211 days when compared to the CDI group at 9.852 ± 2.387 days (p= 0.0094). Smoking status, sex, history of autoimmunity, and history of prior immune related adverse events did not impact incidence of IMDC or CDI. Conclusions: IMDC was a common cause of diarrhea in patients with ICI exposure who were tested for CDI. We did not find IMDC to be a risk factor for CDI. IMDC has a longer duration of diarrhea and colitis symptoms when compared to CDI. The absolute lymphocyte count on symptom onset is higher in patients with IMDC when compared to patients with CDI and may be useful in identifying patients with IMDC earlier.

Efficacy and safety of encorafenib-based regimens in colorectal cancer: A systematic review of clinical trials.

e15600 Background: BRAF gene mutation is present in 10% of the world’s 3rd common cancer, i.e., colorectal cancer (CRC). Constitutive activation of the mitogen-activated protein kinase pathway (MAPKP) results from this mutation, abnormal activation of MAPKP, inhibiting apoptosis and enhancing proliferative activity. In this systematic review, we will assess the efficacy of encorafenib (a BRAF inhibitor) based regimens in CRC. Methods: We followed PRISMA guidelines to conduct this systematic review. A literature search was performed on PubMed, Embase, and Clinicaltrials.gov with mesh terms, ‘’Colorectal Neoplasms’’ and “Proto-Oncogene Proteins B-raf” from the inception of data till 01/05/2023. We screened 4572 articles and included 1 randomized clinical trial (RCT, N = 665), and 4 non-randomized trials (nRCTs, N = 175), measuring the efficacy of encorafenib (E) based regimens in BRAF V600-mutated CRC. Results: In 4 clinical trials (N = 840), 246 patients treated with a double regimen and 373 treated with a triple regimen of E. In 2 clinical trials (N = 319), triple therapy of E + C + Binimetinib showed an overall response rate (ORR) of 47.8% and 26% in the untreated metastatic CRC (mCRC) and phase III randomized trial triple regimen arm, respectively. A recent trial on triple therapy of E + C + nivolumab (N) showed an ORR of 45% with overall survival (OS) and progression-free survival (PFS) of 11.4 and 7.3 months, respectively. In 1 randomized trial (N = 665), ORR improved from 2% in the control arm to 26% and 20% in triple and double regimens, respectively, which was mainly partial response (PR) with complete response (CR) of 4-5% in both groups. The OS was 9 and 8.4 months with a hazard ratio (HR) for death vs. control of 0.52; (95% confidence interval [CI], 0.39 to 0.70; P &lt; 0.001) and 0.60; (95% CI, 0.45 to 0.79; P &lt; 0.001) in the triple and dual regimen, respectively. In 1 trial of dose escalation study, alpelisib (A) was added to E + C and the addition of this third drug showed minimal changes in the ORR from 18 to 19%, and PFS improved from 3.7 to 4.2 months. (Table 1). Conclusions: A combination of BRAF inhibitors with anti-EGFR monoclonal antibodies showed a clinically significant increase in antitumor activity in BRAF-mutated mCRC compared to standard therapy. The addition of MEK/PI3K inhibitor as a third drug to E + C also showed some improvement in ORR and PFS. Triple therapy with E + C + N was also effective and tolerated well by the microsatellite stable (MSS) BRAF mutated mCRC population. Randomized trials are needed. [Table: see text]

Single versus dual antibiotic regimen in women with term prolonged rupture of membranes and intrapartum fever: a retrospective study.

The impact ofE. coli in causing peripartum infections has been increasing due to rising ampicillin resistance. In this study, we compared maternal and neonatal outcomes of women with prolonged rupture of membranes (ROM >18h) and intrapartum fever, according to two antibiotic regimens they received, and describe the bacterial distribution focusing on risk factors for Enterobacteriaceae-related infectious morbidity. This 10-year retrospective study of women with ROM >18h and intrapartum fever included 62 women who were treated with ampicillin and gentamicin due to suspected intraamniotic infection and 79 without these signs who were treated with ampicillin alone. The primary outcomes were endometritis and neonatal early-onset sepsis (EOS) rates. Outcomes were compared using univariate and multivariate analyses. Among women who received ampicillin alone compared with dual therapy, rates were higher of endometritis (17% vs. 3%, p<0.001), neonatal early onset sepsis (7.5% vs. 0%, p=0.03), Enterobacteriaceae positive placental swab culture (67.9% vs. 15.7%, p<0.001), and histopathological subchorionitis (25.3% vs. 8.0%, p=0.008). Over 83% of Enterobacteriaceae isolates were ampicillin-resistant. Gestational age at delivery >41 weeks, meconium at delivery, ROM >24h and treatment with a single antibiotic agent were associated with the presence of a positive Enterobacteriaceae placental swab culture. Ampicillin compared to dual treatment in women with prolonged ROM and fever might promote the growth of ampicillin-resistant Enterobacteriaceae (including E.coli) and increase risks of maternal and neonatal infectious morbidity.

Middle Cerebral Artery Dissection: A Report of Two Cases With Treatments and Outcomes

In the present report, we describe two cases of right-sided M1 segment middle cerebral artery dissection in a 51-year-old Asian female and in a 28-year-old Caucasian male patient with no previous history of ischemic stroke or known intracranial atherosclerosis presenting with acute unilateral headache progressing to severe multifocal hemispheric infarction with nearly complete one-sided motor paralysis. In both patients, a middle cerebral artery dissection was detected on angiography; they were given exclusively medical therapy: patient 1 was not eligible to reperfusive therapies and was treated with a three-month course of acetylsalicylic acid and clopidogrel combined with low-dose enoxaparin, while patient 2 was initially treated with intravenous alteplase with no hemorrhagic complications and was later shifted to single antiplatelet therapy. Despite an initial worsening of clinical severity and an extensive ischemic lesion in both patients, neurologic function improved over time, eventually allowing recovery of unaided gait. Therefore, in the absence of signs of hemorrhage, intravenous thrombolysis or dual antiplatelet regimens could be considered in strokes related to middle cerebral artery dissection.