Addition Of Agents Research Articles

Effects of SGLT-2i and GLP-1RA in vascular function parameters: the impact of the weight loss

Abstract Background Arterial stiffness and endothelial function markers flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients. Purpose To investigate the effects of novel antidiabetic agents on arterial stiffness and endothelial function as well as the metabolic parameters of HbA1c and Weight in T2DM patients. Patients and Methods: We enrolled 99 consecutive patients under stable antidiabetic therapy who did not reach therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Glycosylated hemoglobin (Hba1c) and weight expressed through Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) and flow-mediated dilatation (FMD), as biomarkers of arterial stiffness and endothelial function accordingly, were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups in traditional risk factors of age and sex or baseline HbA1c, BMI, PWV, and FMD levels (ps=NS for all). In both groups PWV values displayed a statistically significant improvement from 11.2±2.5 to 9.3±2.2 m/sec (p<0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group, as presented in Figure 1 through the differences in the values of PWV. FMD values were also significantly improve in both groups from baseline to follow-up; from 6.04±1.22 to 6.50±1.26% (p<0,001) for the GLP-1RA group and from 6.38±1.21 to 6.81±1.29% (p<0.001) for the SGLT-2i group. Moreover, both groups achieved better weight management goals in terms of BMI values between baseline and follow-up; from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group (p<0.001) and from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p<0.001), in addition to achieving better glycemic control in terms of HbA1c values, as seen in their paired differences: for GLP-1RA: 1.3±0.7% and for SGLT-2i: 0.8±0.5%. Interestingly, in the SGLT-2i group the magnitude of the PWV improvement was correlated with the weight loss (r=0.368, p=0.007). Conclusion These data provide evidence that the newer antidiabetic drugs, both GLP1-RA and SGLT-2i, have actions that benefit both vascular function, endothelium as well as metabolic parameters. Interestingly, in the patients receiving SGLT-2i the magnitude of the PWV improvement was correlated with the weight loss.delta PWV for SGLT-2i & GLP-1RA groupsCorrelation of deltaWeight & deltaPWV

Parallel improvement of arterial stiffness with weight loss following intensification of antidiabetic treatment

Abstract Background Arterial stiffness is a marker that can flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients. Purpose To investigate the effects of novel antidiabetic agents on arterial stiffness in T2DM patients as well as potential associations with their weight status before and after treatment. Patients and Methods We enrolled 118 consecutive patients under stable antidiabetic therapy. According to their physician they start treatment with an additional antidiabetic agent; either dipeptidyl peptidase-4 inhibitor (DPP-4i, n=19), or glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) as a biomarker of arterial stiffness were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups regarding their sex, age and other traditional risk factors or the values of PWV and BMI at baselined (p=NS for all). All groups achieved better glycemic control in terms of HbA1c values between baseline and follow-up; from 7.4±1.2% to 7.4±1.2% in the DPP4i group (p<0.001 for all), from 8.6±0.7% to 6.7±0.8% in the GLP-1RA group (p=0.07) and from 7.7±1.1% to 6.7±0.7% in the SGLT-2i group (p<0.001). PWV showed a decrease from 10.6±2.7 to 9.0±1.6 m/sec (p=0.001) in the DPP4-i group, from 11.2±2.5 to 9.3±2.2 m/sec (p<0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group as presented in Figure 1. Regarding BMI, a reduction in the values between groups from baseline to follow-up was also observed; from 27.4±5.3 to 26.1±5.0 kg/m2 for the DPP-4i group, from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group, from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p<0.001 for all). Moreover, in the entire study population there was significant correlation between PWV and BMI improvement following treatment initiation (rho=0.247, p=0.007) (Figure 2). Conclusion Diabetes mellitus treatment intensification with GLP1-RA or SGLT-2i or DPP4i, ameliorated arteriosclerosis, improved PWV and BMI while there is significant association between BMI and PWV improvement.Changes in PWV values among the groupsCorrelation between deltaBMI & deltaPWV

63 Utilization of vasopressin and norepinephrine in neonates with cardiorespiratory compromise: A multicenter retrospective cohort study in Canada

Abstract Background Data regarding neonatal clinical experience with Vasopressin (VA) and Norepinephrine (NE) are limited to small studies. The lack of large-scale studies with safety and efficacy data is preventing the widespread adoption of these agents. Objectives To describe epidemiological data on utilization of NE and VA in neonates including their indications, effectiveness and overall outcomes across 3 tertiary Neonatal Intensive Care Units (NICU) in Canada. Design/Methods This retrospective cohort study involved neonates who received NE or VA between January 1, 2015-December 31, 2020 at 3 tertiary NICUs. Data regarding demographic information, indications of use, dosing details, and clinical outcomes were described using mean, standard deviations (SD), frequencies and percentages. When appropriate, a comparative analysis was performed using Mann-Whitney U tests or the chi-square test as appropriate. Post-initiation changes in physiological variables and laboratory parameters over time were analyzed using repeated measure ANOVA. Results 133 neonates (VA:70, NE:63) were included in this study. Baseline demographic features, clinical characteristics at initiation, indication of use, dosing details and clinical response in neonates exposed to both agents are summarized in Table 1. VA was commonly used for oxygenation failure due to persistent pulmonary hypertension of the newborn (PPHN), while NE was commonly used for hypotension due to septic shock. NE was frequently used as a 1st line inotropic agent, whereas VA was used more as an additive agent [30 (47.6%) vs 12 (18.6%); p=<0.001]. During treatment, lower sodium levels were recorded in the VA group vs the NE group [126.5 (8.6) vs 132 (7); p=.035], but other safety parameters were similar. The time to reach predefined stability parameters were similar in both groups. Significant improvement in physiological parameters were seen over time with both agents (Figure 1). Mortality within 7 days of use was high in the cohort, but comparable between VA and NE groups [18 (25.7%) vs 22 (34.9%), p=0.206]. Other neonatal morbidities were comparable between groups (Table 1). Conclusion This multicenter study provides pragmatic insights into the current use of NE and VA in neonates. Our study reports the effective use of each agent in distinct patient subgroups. This cohort represented neonates with high illness severity; however, exposure to either agent did not independently increase the risk of mortality or adverse outcomes. Further prospective studies exploring its optimal use and cardiopulmonary effects would be interesting.

Maintenance Therapy Post-Stem Cell Transplantation for Patients with T-Cell Lymphomas.

Given the poor outcomes for peripheral T-cell lymphomas (PTCL), stem cell transplant (SCT) remains an important therapeutic approach. Post-SCT relapse is common and maintenance therapy post-SCT is increasingly being utilized. Here we review the use of post-SCT maintenance therapy for PTCL patients. Maintenance therapy is increasingly utilized to decrease post-SCT relapse and improve outcomes in PTCL. Ongoing and completed post-SCT maintenance trials utilizing agents such as romidepsin, brentuximab vedotin, duvelisib, and pembrolizumab have shown efficacy in decreasing relapse. Further, additional agents with efficacy in PTCL have emerged that may inform future maintenance approaches. Maintenance therapy is a promising approach to maintain response after SCT in PTCL. While several trials are ongoing to evaluate maintenance therapy in PTCL, current data suggests this may be an effective method to decrease post-SCT relapse.

Impacts of Waste Rubber Products on the Structure and Properties of Modified Asphalt Binder: Part II-Rubber Reclaim.

The issue of forming a reliable and stable structure of a crumb-rubber-modified binder is an important scientific and technical task. The authors supplemented existing concepts of the mechanism of effective interaction with rubber crumb by introducing a preliminary first stage: controlled partial physical destruction of rubber crumb-producing rubber reclaim. Proposed physical methods of rubber crumb destruction include high shear force (roll mills), high temperature, and a plasticizing medium. The controllability and degree of devulcanization of rubber were determined by acetone-chloroform extraction in different time intervals. The degree of devulcanization of rubber in the rubber reclaim was found to be 22 ± 0.24%, with stability over 14 days. It was found that the size of the particles of the rubber reclaim in the bitumen is less than 2 µm. The properties of the structure of the binder modified with rubber reclaim, characterizing the stability and sustainability, have been studied and established. The developed modified binders are stable in storage. Rheological parameters of the structure characterizing intermolecular interaction, such as shear stability for original and RTFOT-aged, modified bitumen, meet requirements of the state standard at test temperature 64 °C. The elastic structural component of the crumb-rubber-modified binder, as indicated by the relative irreversible deformation parameter J3,2, does not exceed 2.6 kPa (<4.5 kPa) at 64 °C. Additionally, it was determined that the rheological structural parameter for fatigue resistance, which characterizes the durability of road pavement under intensive operational conditions, does not exceed 4699 kPa (<5000 kPa) at 16 °C. The use of 10% rubber reclaim combined with waste frying oil provided the opportunity to obtain a modified binder with a stable and sustainable structure without the introduction of additional stabilizers and agents. Test results showed that the overall performance characteristics of the modified binder meet the 64(S)-40 grade standards.

AML in the Elderly - When less may be more.

We herein assess the distinct biological and clinical features of AML in older patients. We emphasize the importance of pre-treatment assessment to individualize care but note the changing treatment paradigm from intensive towards non-intensive therapy. Geriatric assessments and genetic data provide predictive information that guides treatment. During the past decade the FDA approved at least nine new targeted therapies, mostly small molecule inhibitors, in AML patients of all ages. These agents have created novel therapeutic options for this poorly chemo tolerant population whose AML tends to be intrinsically resistant to such therapy. Older AML patients may now be treated with less toxic therapy that provides similar, if not superior, efficacy compared with conventional chemotherapy. Although TP53 mutant AML remains a particular unmet need, additional novel agents on the horizon provide hope for improving outcomes for older adults with AML.

Expanding Treatment Opportunities: Reviewing the Current State of Injectable Antiretrovirals for Treatment of HIV.

Antiretroviral therapy has evolved significantly over the last 20-30years, from requiring multiple tablets multiple times per day to single-tablet regimens and most recently, in 2021, long-acting injectable antiretrovirals. These long-acting antiretrovirals have expanded the treatment options for individuals with HIV who may have difficulty adhering to daily oral medications, difficulty taking oral medications, and/or individuals with multidrug-resistant HIV. This article reviews the currently available long-acting injectable antiretrovirals, including cabotegravir/rilpivirine, lenacapavir, and ibalizumab. The available data supporting these agents and current place in therapy will be discussed. Data supporting the use of additional long-acting injectable agents, broadly neutralizing antibodies, currently in the pipeline will be reviewed as well.

Enhanced photocatalytic organic pollutant degradation, H2 production and N2 fixation via a versatile zinc oxide-based nanocomposite: Synthesis, characterization and mechanism Insight

Developing highly efficient photocatalysts for visible light utilization is crucial for water purification, N2 fixation, and H2 generation. This work presents a novel α-Fe2O3/CeO2-ZnO heterostructure photocatalyst synthesized through a facile impregnation technique. The synthesized catalysts were characterized via XPS, TEM, SEM, XRD, BET, PL, EIS, Mott-schottky, etc. analyses. The optimized 25 wt% of α-Fe2O3/CeO2 on ZnO (25-FeCeZ) catalyst achieved 100 % ofloxacin (OFX) photodegradation under light irradiation within 90 min. The charge transfer pathway was investigated via optical analyses within the 25-FeCeZ. Experimental investigations elucidated the potential intermediates, four proposed OFX photodegradation pathways and photocatalytic mechanism. Scavenger experiments and ESR spectroscopy identified •O2–, •OH, and h+ as the primary reactive species. Furthermore, the degraded OFX solution exhibited lower overall toxicity compared to the initial solution, based on QSAR predictions and E. coli viability assays. The 25-FeCeZ catalyst displayed a significantly enhanced hydrogen production rate (2.57mmol g−1h−1) compared to pristine ZnO (0.09 mmol/g·h). Notably, the catalyst achieved an NH3 evolution rate of 335.80μmol g−1h−1 without additional sacrificial agents, which is 4.5 times greater than pure ZnO. Additionally, the optimised photocatalyst depicted a superb stability across all three photocatalytic processes. This study illustrates a promising approach for designing potent ZnO-based photocatalysts for diverse applications, including N2 fixation, H2 generation, and organic pollutant degradation under visible light irradiation.

Maribavir use in pediatric immunocompromised hosts: A case series to talk about real-world experience

Abstract Background Cytomegalovirus (CMV) is a common infection affecting pediatric immunocompromised hosts. The treatment of CMV in solid organ (SOT) or hematopoietic stem cell transplant (HSCT) patients is challenged by the toxicities associated with antiviral therapies (myelosuppression with valganciclovir, ganciclovir and cidofovir; nephrotoxicity with foscarnet and cidofovir) and the prevalence of resistant/refractory CMV. Maribavir, a novel benzimidazole, competitively inhibits CMV UL97 protein kinase to inhibit DNA synthesis and block nuclear exit of viral particles from CMV-infected cells. It is FDA approved for use in patients at least 12 years of age and weighing at least 35 kg. The use of maribavir in pediatric patients is of interest due to its availability as an oral dosage formulation and improved side effect profile. To date, there are no pediatric case series or studies describing the use of maribavir for CMV treatment. Methods This study is a retrospective case series compiling the findings the first pediatric patients at Children’s National Hospital, DC that received maribavir. We included children who received maribavir from 01/2017 – 10/2023. Patients were included if they were on maribavir monotherapy, or combination therapy with additional anti-CMV agent(s). The medical records were reviewed for indication of medication use, viral response to therapy and side effects. Side-effects review specifically evaluated for increased LFTs, increased serum creatinine, and decreased absolute neutrophil count or factors that may contribute to early discontinuation of maribavir. Results (table) Maribavir was used in three male patients with varied conditions – including solid organ transplant (SOT), hematopoietic stem cell transplant (HSCT) and Severe Combined Immunodeficiency (SCID) s/p HSCT. Two cases had signs of CMV disease, and one had CMV viremia. All cases included documented CMV resistance (n=2) or refractory CMV (n=1) and had previously been receiving at least one antiviral with CMV activity for at least 14 days and had increasing CMV DNA-emia in the blood. None of the patients had side effects such as nephrotoxicity, liver toxicity or myelosuppression that aggravated after starting maribavir. Dosing of 400mg BID (range 12mg/kg/day to 55mg/kg/day) was used. Once started, maribavir was continued until CMV quantitative levels were undetectable for two weeks. Clearance of CMV and was achieved in all the patients on maribavir or combination of maribavir with other drugs (n=1). Duration of maribavir treatment ranged from 4.2 to 6.2 weeks. Conclusion This is the first case series describing use of maribavir in a pediatric population. In this small cohort maribavir is effective and well tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.

Application of non-acid stripping solution in hydrophobic membrane process for high-purity ammonia recovery from high-strength ammonium wastewater

Recently, resource recovery from wastewater has been in the spotlight due to climate change and the energy crisis. Ammonia has significant value as a resource that serves as fertilizer or eco-friendly fuel, with a market value ranging from $0.4 to $1.0 per kg-N. In the membrane contactor (MC) process, an acid stripping solution such as H2SO4 is generally used for high ammonia recovery efficiency. However, the ammonia-recovered stripping solution often has limited applications as fertilizer due to the presence of anions, necessitating costly downstream processes like electrochemical treatments to separate ammonia from these contaminants. This study introduces a novel approach that dynamically compares various stripping solutions to reduce chemical consumption while achieving high-purity ammonia recovery. Notably, the recovered ammonia from the membrane contactor showed no detectable levels of nitrate, other ions, or organic carbon, all without the use of acidic solutions. Furthermore, the benefit-cost ratio of 1.42, derived from the dynamic comparison, highlights the cost-effectiveness and demonstrates the practicality of this method compared to traditional acidic stripping approaches.This innovative comparison underscores the membrane contactor system’s ability to recover high-purity ammonia, presenting a sustainable and economically viable solution for ammonia recovery in wastewater treatment. It achieves this without the need for additional chemical agents or expensive downstream processes, offering a more efficient alternative to conventional methods.

Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape and Future Developments.

Primary sclerosing cholangitis (PSC) is a rare, chronic liver disease with no approved therapies. The ursodeoxycholic acid (UDCA) has been widely used, although there is no evidence that the use of UDCA delays the time to liver transplant or increases survival. Several candidate drugs are currently being developed. The largest group of these new agents is represented by FXR agonists, including obeticholic acid, cilofexor, and tropifexor. Other agents that target bile acid metabolism are ASTB/IBAP inhibitors and fibroblasts growth factor (FGF)19 analogues. Cholangiocytes, the epithelial bile duct cells, play a role in PSC development. Recent studies have revealed that these cells undergo a downregulation of GPBAR1 (TGR5), a bile acid receptor involved in bicarbonate secretion and immune regulation. Additional agents under evaluation are PPARs (elafibranor and seladelpar), anti-itching agents such as MAS-related G-protein-coupled receptors antagonists, and anti-fibrotic and immunosuppressive agents. Drugs targeting gut bacteria and bile acid pathways are also under investigation, given the strong link between PSC and gut microbiota.

Effect of colistin combined with sulbactam: 9 g versus 12 g per day on mortality in the treatment of carbapenems resistant Acinetobacter baumannii pneumonia: a randomized controlled trial.

The current treatment recommendation involves administering a high dose of sulbactam alongside at least one additional agent. However, there remains a lack of data regarding the optimal dosage of sulbactam. We investigated whether administering sulbactam at a dosage of 12 g/day decreases the mortality rate among patients with CRAB pneumonia compared to 9 g/day. The study was an open-label, superiority, randomized controlled trial conducted at Phramongkutklao Hospital between September 2019 and September 2023 in patients diagnosed with CRAB. Participants were randomly assigned to receive a combination of colistin with either 9 or 12 g/day of sulbactam. The primary endpoint was the all-cause mortality rate at 28 days post-randomization. Among the 138 participants, there was a trend toward a lower mortality rate in the 12 g/day group (59.4% vs. 47.8%; p = 0.158). After adjusting for factors associated with mortality, a lower mortality was observed in the 12 g/day group (adjusted HR 0.54 [95% CI 0.33-0.87]; p = 0.0110). The microbiological cure rate at day 7 was higher in the 12 g/day group (73.2% vs. 89.4%; p = 0.02). Colistin in combination with sulbactam at a dosage of 12 g/day may improve mortality compared to 9 g/day.

Metolazone Versus Chlorothiazide in Acute Heart Failure Patients With Diuretic Resistance and Renal Dysfunction: A Retrospective Cohort Study.

Guidelines recommend intravenous loop diuretics as first-line therapy for patients hospitalized with acute heart failure (AHF) and volume overload. Additional agents can be used for augmentation, but there is limited guidance on agent selection. The study objective was to determine if chlorothiazide or metolazone is associated with differences in diuretic efficacy or safety in loop diuretic-resistant patients with AHF and renal dysfunction (eGFR <45 mL/min/1.73 m²). We conducted a multicenter, retrospective cohort study of patients hospitalized with AHF and renal dysfunction who received metolazone or chlorothiazide in addition to intravenous loop diuretics. The primary end point was a comparison of 24-hour urine output (UOP) between the 24 hours before and after thiazide administration. Secondary and safety end points included weight change, requirement for vasopressors or inotropes, electrolyte abnormalities, and changes in renal function. A total of 221 patients were included. The mean daily diuretic doses were chlorothiazide 632 mg and metolazone 7 mg. The mean 24-hour UOP increased more among chlorothiazide-treated (from 1668 mL to 3826 mL) versus metolazone-treated patients (from 1672 mL to 2834 mL) ( P < 0.001) after the addition of the second diuretic. Statistically significant reductions in serum creatinine were observed in the chlorothiazide group following 72 hours of treatment ( P = 0.016). More hypomagnesemia was observed in the chlorothiazide group; no differences in other electrolytes or changes in weight were observed. Overall, chlorothiazide was associated with a greater increase in 24-hour UOP than metolazone without an excess of potassium or serum creatinine derangements. However, weight changes did not differ significantly between groups. Future prospective studies are needed to confirm potential differences in diuretic response and safety.

Association between psychopharmacotherapy and postpartum hemorrhage

BackgroundPrior studies evaluating the relationship between psychopharmacotherapy (PPT), and postpartum hemorrhage (PPH) have yielded inconsistent findings. Clarifying this potential relationship is important for effective counseling and risk stratification. ObjectivesOur primary objective was to evaluate the association between prenatal exposure to PPT (any drug class) and the occurrence of PPH requiring transfusion of packed red blood cells (PPH+pRBC) after systematically adjusting for known hemorrhage risk factors at the time of admission for delivery. Secondary objectives were to evaluate the association between individual PPT drug classes and PPH+pRBC, and the association between treatment intensity of mental health condition and PPH+pRBC. Finally, we evaluated the association between PPT and a broader definition of PPH that included deliveries requiring multiple uterotonic drugs. Study designThis is a retrospective cross-sectional study of all pregnancies delivered at 23 weeks of gestational age or greater at seven hospitals within a large academic health system in New York between January 2019 and December 2022. There were no exclusion criteria, as postpartum hemorrhage risk assessment is necessary for all patients admitted for delivery. We assessed exposure to prenatal PPT, including selective serotonin reuptake inhibitors (SSRIs: escitalopram, fluoxetine, sertraline), serotonin-norepinephrine reuptake inhibitors (SNRIs: duloxetine, venlafaxine), dopamine-norepinephrine reuptake inhibitors (DNRIs: buproprion), benzodiazepines (alprazolam, diazepam, lorazepam), and others (buspirone, trazodone, zolpidem). Multivariable logistic regression was performed to evaluate the relationship between PPT and PPH+pRBC, while systematically adjusting for known hemorrhage risk factors at the time of hospital admission. Similar regression analyses were performed to address the secondary objectives. ResultsA total of 107,425 deliveries were included. Non-Hispanic White patients constituted the largest race and ethnicity group (43.4%), followed by Hispanic patients (18.7%), Asian or Pacific Islander patients (13.2%), and non-Hispanic Black patients (12.3%). Prenatal exposure to PPT occurred in 3.6% of pregnancies (n=3,834). The overall rate of PPH+pRBC was 2.9% (n=3,162). PPH+pRBC occurred more frequently in pregnancies exposed to PPT than in pregnancies which were not exposed (5.5% vs. 2.8%, respectively; aOR 2.10, 95% CI: 1.79–2.44). SSRIs and benzodiazepine monotherapy were each associated with higher odds of PPH+pRBC than nonexposure. Compared to patients without a mental health condition, monotherapy was associated with nearly 2-fold increased odds and combination PPT was associated with nearly 4-fold greater odds of PPH+pRBC after adjustment for confounding variables (monotherapy: aOR 1.94, 95% CI: 1.64–2.28; combination PPT: aOR 3.96, 95% CI: 2.61–5.79). Patients with untreated mental health conditions (no PTT) had no increased odds of PPH+pRBC compared to those without mental health conditions. Finally, after adjusting for covariates, a positive association was found between PPT and PPH requiring pRBC transfusion and/or the use of two additional uterotonic agents beyond routine postpartum oxytocin (aOR 1.53, 95% CI: 1.35–1.73). ConclusionsPrenatal PPT exposure is associated with increased odds of clinically significant PPH+pRBC after adjusting for other hemorrhage risk factors. Combination PPT was associated with greater odds of PPH+pRBC than monotherapy.

Insights from Clinical Trials: Evidence-Based Recommendations for Induction Treatment of Newly Diagnosed Transplant-Eligible Multiple Myeloma.

Multiple myeloma (MM) is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens. This analysis includes a comprehensive literature review of research from major databases and conferences conducted between 2010 and 2023, culminating in the detailed evaluation of 47 studies. The findings underscore the superiority of quadruple regimens in TE NDMM, notably those incorporating daratumumab, in achieving superior responses including progression-free survival (PFS), minimal residual disease (MRD) negativity, objective response rate (ORR), and overall survival (OS) when compared to triple-drug regimens. As treatment regimens evolve with additional agents, the improved outcomes with treatment-related adverse events should be carefully balanced. This review advocates for a paradigm shift towards quadruple induction therapies for TE NDMM, offers a detailed insight into the current landscape of MM treatment, and reinforces a new standard of care.

Mini review of diagnostic and therapeutic approaches in myositis-associated interstitial lung disease

Myositis-associated interstitial lung disease (ILD) presents a significant challenge in terms of diagnosis and management due to its heterogeneity and potential for rapid progression. This review outlines the current strategies for diagnosing and managing myositis-associated ILD, focusing on mild to moderate and severe or rapidly progressive cases. Initial diagnosis involves comprehensive clinical evaluation, high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and serological testing for myositis-specific antibodies and myositis-associated antibodies. Management of mild to moderate ILD includes using corticosteroids and steroid-sparing agents, supported by oxygen therapy, pulmonary rehabilitation, and preventive vaccinations. Regular monitoring through PFTs, HRCT, and clinical assessments is essential to ensure effective management and detect disease progression. In cases of severe or rapidly progressive ILD, aggressive treatment with high-dose corticosteroids, additional immunosuppressive agents such as cyclophosphamide, rituximab, and calcineurin inhibitors, and the use of anti-fibrotic agents like Nintedanib and Pirfenidone are crucial. Supportive care measures, including oxygen therapy and mechanical ventilation, may be necessary for patients with severe respiratory failure. Implementing structured algorithms for diagnosis and management helps streamline the process and improve patient outcomes. Continuous research and advancements in immunology and pharmacology are essential for developing more effective treatments for this challenging condition.

Precise Regulation of Interlayer Stacking Modes in Trinuclear Copper Organic Frameworks for Efficient Photocatalytic Reduction of Uranium(VI).

The interlayer stacking modes of 2D covalent-organic frameworks (COFs) directly influence their structural features, ultimately determining their functional output. However, controllably modulating the interlayer stacking structure in traditional 2D metal-free COFs, based on the same building blocks, remains challenging. Here, two trinuclear copper organic frameworks are synthesized successfully with different interlayer stacking structures: eclipsed AA stacking in Cu3-PA-COF-AA and staggered ABC stacking in Cu3-PA-COF-ABC, using the same monomers. Remarkably, various functionalities, including porosity and electronic and optical properties, can be effectively regulated by interlayer stacking. As a result, Cu3-PA-COF-AA and Cu3-PA-COF-ABC exhibit significantly different activities toward the photoreduction of U(VI), presenting a promising strategy for removing radioactive uranium pollution. Due to its broader visible-light absorption range and superior photogenerated carrier migration and separation efficiency, Cu3-PA-COF-AA achieves a U(VI) removal ratio of 93.6% without additional sacrificial agents in an air atmosphere-≈2.2 times higher than that of Cu3-PA-COF-ABC (42.0%). To the best of the knowledge, this is the first study to elucidate the effect of interlayer stacking in COFs on the photocatalytic activity of U(VI) reduction. This finding may inspire further exploration of the structure-function relationship in COFs as photocatalysts and their potential for photoinduced removal of radionuclides.

Second-Line Uterotonics for Uterine Atony: A Randomized Controlled Trial.

To evaluate the comparative efficacy of two of the most commonly used second-line uterotonics-methylergonovine maleate and carboprost tromethamine. We conducted a double-blind randomized trial at two large academic perinatal centers in patients undergoing nonemergency cesarean delivery with uterine atony refractory to oxytocin, as diagnosed by the operating obstetrician. The intervention included administration of a single dose of intramuscular methylergonovine or carboprost intraoperatively at diagnosis. The primary outcome, uterine tone on a 0-10 numeric rating scale 10 minutes after study drug administration, was rated by operating obstetricians blinded to the drug administered. Secondary outcomes included uterine tone score at 5 minutes, administration of additional uterotonic agents, other interventions for uterine atony or hemorrhage, quantitative blood loss, urine output, postpartum change in serum hematocrit, transfusion, length of hospital stay, adverse drug or transfusion reactions, and postpartum hemorrhage complications. A sample size of 50 participants per group was planned to detect a 1-point difference (with estimated within-group SD of 1.5) in the mean primary outcome with 80% power at a two-sided α level of 0.05 while accounting for potential protocol violations. A total of 1,040 participants were enrolled, with 100 randomized to receive one of the study interventions. Mean±SD 10-minute uterine tone scores were 7.3±1.7 after methylergonovine and 7.6±2.1 after carboprost, with an adjusted difference in means of -0.1 (95% CI, -0.8 to 0.6, P=.76). Additional second-line uterotonics were required in 30.0% of the methylergonovine arm and 34.0% in the carboprost arm (adjusted odds ratio 0.72, 95% CI, 0.27-1.89, P=.505), and geometric mean quantitative blood loss was 756 mL (95% CI, 636-898) and 708 mL (95% CI, 619-810) (adjusted ratio of geometric means 1.06, 95% CI, 0.86-1.31, P=.588), respectively. No differences were detected in the occurrence of other interventions for uterine atony or postpartum hemorrhage. No difference was detected in uterine tone scores 10 minutes after administration of either methylergonovine or carboprost for refractory uterine atony, indicating that either agent is acceptable. ClinicalTrials.gov, NCT03584854.

Assessment of the Antibiofilm Performance of Silver-Containing Wound Dressings: A Dual-Species Biofilm Model.

Background It is commonly accepted that microorganisms found within hard-to-heal wounds are present in biofilm form. Biofilms are often polymicrobial in nature, which increases their virulence and tolerance to antimicrobial agents. The aim of this study was to compare the antibiofilm activity of silver-containing antimicrobial wound dressings in a dual-species simulated wound biofilm model. Materials and methods Four silver-containing wound dressings were evaluated in vitro: Aquacel® Ag+ Extra™ dressing, KerraContact® Ag dressing, Durafiber* Ag dressing, and UrgoClean Ag dressing. Each dressing was applied to a simulated wound assembly containing biofilm-gauze inoculated with Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). Each biofilm-inoculated gauze was incubated at 35±3ºC for 6, 24, 48 and 72 hours. Enumeration of surviving biofilm bacteria at each time point was performed in triplicate for each test dressing and its equivalent control. Results Aquacel® Ag+ Extra™ dressing was observed to reduce the biofilm population within 24 hours with a >4 log10 kill observed for K. pneumoniae and >6 log10 for MRSA from an initial biofilm challenge of 4.16×109 CFU/mL. This kill rate was sustained for the duration of the challenge period, with Aquacel®Ag+ Extra™ dressing reducing the biofilm population to non-detectable levels (<30 Colony Forming Units (CFU) per test) by 72 hours for K. pneumoniae and by 48 hours for MRSA. KerraContact® Ag dressing demonstrated an initial reduction at 6 hours of ~2 log10 in both K. pneumoniae and MRSA. Durafiber* Ag dressing exhibited a slight, gradual reduction in biofilm population over the course of the test period, reducing each challenge organism by ~2.5 log10 by 72 hours. UrgoClean Ag was shown to have little to no impact on the dual-species biofilm with levels remaining similar or greater than that recovered prior to dressing application. The no-dressing biofilm-colonised gauze control demonstrated that the biofilm bacteria remained viable throughout the test period and species population proportionality was maintained. Conclusion Using a dual-species simulated wound biofilm model comprising the pathogens K. pneumoniae and MRSA, Aquacel® Ag+ Extra™ dressing demonstrated significantly greater antibiofilm activity than the other silver-containing dressings. The enhanced antibiofilm activity of Aquacel® Ag+ Extra™ dressing in this study may be attributed to the additional antibiofilm agents, ethylenediaminetetraacetic acid and benzethonium chloride, contained within the dressing.

Chemotherapy-Induced Alopecia by Docetaxel: Prevalence, Treatment and Prevention.

Docetaxel is a commonly used taxane chemotherapeutic agent in the treatment of a variety of cancers, including breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, gastric cancer, and head and neck cancer. Docetaxel exerts its anti-cancer effects through inhibition of the cell cycle and induction of proapoptotic activity. However, docetaxel also impacts rapidly proliferating normal cells in the scalp hair follicles (HFs), rendering the HFs vulnerable to docetaxel-induced cell death and leading to chemotherapy-induced alopecia (CIA). In severe cases, docetaxel causes persistent or permanent CIA (pCIA) when hair does not grow back completely six months after chemotherapy cessation. Hair loss has severe negative impacts on patients' quality of life and may even compromise their compliance with treatment. This review discusses the notable prevalence of docetaxel-induced CIA and pCIA, as well as their prevention and management. At this moment, scalp cooling is the standard of care to prevent CIA. Treatment options to promote hair regrowth include but are not limited to minoxidil, photobiomodulation (PBMT), and platelet-rich plasma (PRP). In addition, a handful of current clinical trials are exploring additional agents to treat or prevent CIA. Research models of CIA, particularly ex vivo human scalp HF organ culture and in vivo mouse models with human scalp xenografts, will help expedite the translation of bench findings of CIA prevention and/or amelioration to the clinic.