Months Of Treatment Research Articles

Effectiveness and safety of finerenone in diabetic kidney disease patients: a real-world observational study from China

Aims Finerenone has been approved for treating diabetic kidney disease (DKD) with reducing cardiorenal risk. Real-world data on finerenone treatment for the management of DKD are presently lacking. This study aimed to investigate the effect of finerenone on the renal parameters of the Chinese DKD population in the real-world medical setting for the first time, especially in combination with renin–angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i). Methods Forty-two DKD patients were selected and completed a 6-month finerenone treatment. Renal parameters and adverse effects were collected at every visit. Results The median urine albumin-to-creatinine ratio (UACR) was 1426.11 (755.42, 3638.23) mg/g. Among them, the proportion of patients with a UACR of 300–5000 mg/g was 76.2%, and the proportion of patients with a UACR of >5000 mg/g was 14.3%. The median estimated glomerular filtration rate (eGFR) was 54.50 (34.16, 81.73) mL/min/1.73 m2. Finerenone decreased the UACR significantly throughout the study period (p < .05). The maximal decline of UACR at month 6 was 73%. Moreover, the proportion of patients with a 30% or greater reduction in UACR was 68.42% in month 6. There was a smaller decline (9–11%) in the eGFR after initiating finerenone (p > .05). One patient each discontinued finerenone due to hyperkalemia (2.4%) and acute kidney injury (2.4%). No patient reported hypotension, breast pain, and gynecomastia. Conclusions This study from China first demonstrated finerenone decreased UACR with manageable safety in real-world DKD treatment. A triple regimen of RASi, SGLT2i, and finerenone may be a promising treatment strategy for lowering albuminuria and reducing hyperkalemia risk in advanced DKD patients.

Red blood cell metabolomics identify ergothioneine as a key metabolite in DMARD-naïve rheumatoid arthritis and response to methotrexate

Using a new red blood cell (RBC) metabolite extraction protocol, we performed a metabolomic analysis on RBCs in rheumatoid arthritis (RA) patients treated or not with methotrexate (MTX), with the two following objectives: to compare the RBC metabolic profiles of MTX-naïve RA patients and healthy controls (HC), and to investigate whether RBC profiles before and after MTX treatment in RA differed between responders and non-responders. Plasma analysis was performed in parallel. Metabolites were extracted and identified in RBCs and plasma by liquid chromatography-mass spectrometry. We compared the metabolomic fingerprints of 31 DMARD-naïve RA patients and 39 HCs. We also compared the RBC and plasma metabolomes of 25 RA patients who responded or not to MTX therapy before (M0) and after a 3-month treatment period (M3). Significance was determined by Storey’s false discovery rate (FDR) q-values to correct for multiple testing. RA patients and HCs differed in the metabolomic signature of RBCs. The signature mainly contained amino acids (AA). Eleven metabolites, including 4 metabolites belonging to the carbohydrate subclass and 2 amino acids (creatine and valine) showed accumulation in RBCs from RA patients. Conversely, citrulline (fold change = 0.83; q = 0.025), histidine (fold change = 0.86; q = 0.014) and ergothioneine (EGT) (fold change = 0.66; q = 0.024), were lower in RBC of RA patients. Five plasma metabolites, including succinic acid and hydroxyproline, were higher in RA patients, and 7 metabolites, including DHEA sulfate, alanine, threonine and ornithine, were lower. Among RA patients undergoing MTX treatment pre-treatment (M0), EGT values were significantly lower in non-responders. In conclusion, low RBC levels of EGT, a food-derived AA barely detectable in plasma, characterize DMARD naïve RA patients and lack of response to MTX treatment.

Non-surgical treatment of residual periodontal pockets using sodium hypochlorite/amino acid gel and cross-linked hyaluronic acid—a 9-month pilot randomized controlled clinical trial

ObjectivesThis pilot randomized controlled clinical trial compares the clinical outcome obtained in persistent periodontal pockets during 9-month follow-up of supportive periodontal step 4 treatment performed by either combining subgingival instrumentation with adjunctively used sodium hypochlorite/amino acid gel and crosslinked hyaluronic acid (xHyA) or subgingival instrumentation alone.Materials and methodsStudy protocol is registered under NCT06438354 at Clinicaltrials.gov. Patients seeking further therapy after completed step 2 non-surgical periodontal treatment underwent either repeated subgingival instrumentation with adjunctive application of sodium hypochlorite/amino acid gel and crosslinked hyaluronic acid (group A) or repeated subgingival instrumentation alone (group B). One calibrated investigator performed the treatment sequence in both groups accordingly. Subgingival instrumentation of the residual pockets was carried out under local anaesthesia using hand- and ultrasonic instruments, as well as air polishing in both groups. Patients were instructed to continue oral hygiene without any restriction. At 3-month re-evaluation treatment was repeated accordingly at sites with persistent 5 mm probing depth and BoP + . Clinical attachment level (CAL), pocket probing depth (PPD), gingival recession (GR), and bleeding on probing (BoP) were recorded at baseline (T1), 3- (T2) and 9-month (T3) post-op, with CAL as a primary outcome measure.ResultsIn total 52 patients (20 females and 32 males, mean age 58.4 ± 2.4 years) presenting with 1448 sites which required further periodontal treatment were enrolled. Both groups exhibited homogeneity in terms of age, gender, smoking habit, initial number of sites, and BOP. At 9-month evaluation, PD reduction and CAL gain showed significant differences between the test and control group, favouring the adjunctive treatment. GR tended to exhibit more recovery in the test group compared to the control group. Although BOP frequency effectively reduced in both groups, there was no statistically significant difference between the two groups.ConclusionWithin the limits of the study, the present data indicates that, during subgingival instrumentation of persistent pockets, the adjunctive usage of sodium hypochlorite/amino acid gel and xHyA sufficiently improves the clinical outcomes. The continuous improvement of CAL in association with the GR scores observed in group A, indicates that sites subjected to adjunctive treatment may indicate a tendency for a regenerative response to treatment within the 9-month follow-up period.

Utility of the modified Ottawa score for identification of more preferable candidates of extended anticoagulation therapy in cancer-associated isolated distal deep vein thrombosis: insight from the ONCO DVT Study

BackgroundThe ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups. ObjectivesTo identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score. MethodsIn this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤−1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups. ResultsThe cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism–related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups. ConclusionA 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score.

A Comparison between Demyelinating and Omicron Variant Infection-Associated Optic Neuritis.

The connection between viral infection and the onset of demyelination has garnered considerable attention. Omicron, the most recent prevalent strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns. Optic neuritis (ON) associated with Omicron infection and spontaneous demyelinating ON may manifest distinct disease progressions. This study aims to contrast the features of these two distinct etiologies of ON. This case-control study comprised fifteen patients (21 eyes) diagnosed with Omicron infection-related ON and fifteen patients (24 eyes) with demyelinating ON serving as the control group. Clinical characteristics, cerebrospinal fluid (CSF) analysis, treatment protocols, and outcomes were compared between the two groups. The Omicron-infected group exhibited a higher incidence of pain upon ocular movement (p = 0.023) and peripapillary hemorrhages (p = 0.046). In CSF analysis, there was an elevation in white cell counts (WCCs) (p = 0.004), with lymphocytes being the predominant cell type in the Omicron-related ON group. However, oligoclonal bands (OCBs), indicative of intrathecal synthesis, were significantly lower and lagged behind those of the demyelinating ON group (p = 0.021). SARS-CoV-2 RNA was not directly detected in the CSF of the Omicron-related ON group, and the degree of WCC elevation was closely linked with peripapillary hemorrhages (odds ratio = 0.029, p = 0.02). Additionally, the Omicron-related ON group displayed more pronounced ganglion cell loss following 3-month treatment (p = 0.02). Omicron-related ON is distinguished by more pronounced clinical symptoms and distinct CSF characteristics compared to spontaneous demyelinating ON. The absence of viral RNA sequence in the CSF of Omicron-associated ON supports the use of steroid monotherapy; however, varying treatment options and prognoses should be considered for these two types of ON.

Germline AIP variants in sporadic young acromegaly and pituitary gigantism: clinical and genetic insights from a Han Chinese cohort.

Variants in the Aryl hydrocarbon receptor-interacting protein (AIP) gene have been identified in sporadic acromegaly and pituitary gigantism, especially in young patients, with a predisposition to aggressive clinical phenotype and poor treatment efficacy. The clinical characteristics of patients with sporadic acromegaly and pituitary gigantism as well as AIP variants in Han Chinese have been rarely reported. We aimed to identify AIP gene variants and analyze the clinical characteristics of patients with sporadic acromegaly and pituitary gigantism in Han Chinese. The study included 181 sporadic acromegaly (N = 163) and pituitary gigantism (N = 18) patients with an onset age of no more than 45 years old, who were diagnosed, treated, and followed up in Huashan Hospital. All 6 exons and their flanking regions of the AIP gene were analyzed with Sanger sequencing or NGS. The clinical characteristics were compared between groups with and without AIP variants. Germline AIP variants were found in 15/181 (8.29%) cases. In patients with an onset age ≤30 years old, AIP variants were identified in 12/133 (9.02%). Overall, 13 variants were detected. The pathogenic (P) variants p.R304X and p.R81X were identified in four cases, with two instances of each variant. Six exon variants (p.C254R, p.K103fs, p.Q228fs, p.Y38X, p.Q213*, and p.1115 fs) have not been reported before, which were likely pathogenic (LP). Patients with P/LP variants had younger onset ages, a higher prevalence of pituitary gigantism, larger tumor volumes, and a higher percentage of Ki-67-positive cells in tumors. In addition, the group with P/LP variants showed a less significant reduction of GH levels in an acute octreotide suppression test (OST) [17.7% (0, 65.0%) vs. 80.5% (63.9%, 90.2%), P = 0.001], and a trend of less GH decrease after the 3-month treatment with long-acting somatostatin analogs (SSAs). Germline AIP variants existed in sporadic Chinese Han acromegaly and pituitary gigantism patients and were more likely to be detected in young patients. AIP variants were associated with more aggressive tumor phenotypes and less response to SSA treatment.

Emotions observed during sessions of dialectical behavior therapy predict outcome for borderline personality disorder.

We examined whether the emotions that clients experience within session are associated with treatment outcome in dialectical behavior therapy (DBT) for borderline personality disorder (BPD). Participants were 52 adults who met criteria for BPD and were enrolled in a 12-month DBT treatment. The Classification of Affective-Meaning States, an observer-rated measure of discrete emotions, was used to code videos of individual DBT sessions. Raters coded three psychotherapy sessions for each participant: one session from each of the early, working, and late phases of psychotherapy. Self-report measures of BPD symptoms were used to assess treatment outcome. More emotional experience overall during the early phase predicted fewer BPD symptoms at 12-month treatment outcome, explaining 19% of the variance in symptoms. However, increases across treatment in global distress predicted higher levels of BPD (24% of the variance explained) and depression symptoms (15% explained) at termination. Increases in emotional flexibility (i.e., variation between states) from the early to working phase predicted fewer depressive symptoms at termination (14% explained). Self-compassion coded during the working phase also predicted a better treatment outcome (explaining 19%-34%). Clients' in-session emotional experiences predict treatment outcome 8-10 months later. Clients with BPD may benefit from more overall exploration of their emotional experiences early in DBT, as well as expression of self-compassion. Increases in nonspecific, intense negative affect anticipates poor prognosis, whereas increases in emotional flexibility during early treatment anticipates better prognosis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Changes in the medial prefrontal cortex metabolites after 6 months of medication therapy for patients with bipolar disorder: A 1H-MRS study.

The study aimed to assess brain metabolite differences in the medial prefrontal cortex (mPFC) between acute and euthymic episodes of bipolar disorder (BD) with both mania and depression over a 6-month medication treatment period. We utilized 1H-MRS technology to assess the metabolite levels in 53 individuals with BD (32 in depressive phase, 21 in manic phase) and 34 healthy controls (HCs) at baseline. After 6 months of medication treatment, 40 subjects underwent a follow-up scan in euthymic state. Metabolite levels, including N-acetyl aspartate (NAA), glutamate (Glu), and Glutamine (Gln), were measured in the mPFC. Patients experiencing depressive and manic episodes exhibited a notable reduction in NAA/Cr + PCr ratios at baseline compared to healthy controls (p = 0.004; p = 0.006) in baseline, compared with HCs. Over the 6-month follow-up period, the manic group displayed a significant decrease in Gln/Cr + PCr compared to the initial acute phase (p = 0.03). No significant alterations were found in depressed group between baseline and follow-up. This study suggests that NAA/Cr + PCr ratios and Gln/Cr + PCr ratios in the mPFC may be associated with manic and depressive episodes, implicating that Gln and NAA might be useful biomarkers for distinguishing mood phases in BD and elucidating its mechanisms.

Effectiveness of patisiran after switching from tafamidis for the treatment of hereditary transthyretin-mediated amyloidosis with polyneuropathy.

Hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN [v for variant]) is a rare, progressive disease associated with multisystemic impairments. This study assessed the real-world outcomes of patients with ATTRv-PN who switched from tafamidis to patisiran, as well as the reasons for the treatment switch. This was a retrospective chart review study at a large expert referral center. Data were extracted from medical charts of patients with ATTRv-PN who switched from tafamidis to patisiran on or before 30 August 2019. Data elements included demographic and clinical characteristics, rationale for switch, and disease measures evaluated from tafamidis initiation through the 12-month patisiran treatment period. Among the 24 patients with ATTRv-PN included in the study, 50.0% had a V30M variant, and the mean (SD) age was 67.3 (8.0) years. During tafamidis treatment (mean [SD] = 30.1 [17.5] months) before switching to patisiran, patients worsened across multiple polyneuropathy measures, including walking ability, Neuropathy Impairment Score, and autonomic function. Neuropathic disease progression on tafamidis was the principal reason for switching to patisiran. After 12 months on patisiran (mean [SD] = 11.7 [1.4] months), patients experienced attenuated disease progression or improvement in the aforementioned measures of polyneuropathy. Switching from tafamidis to patisiran attenuated the rate of functional decline, and most patients experienced stabilization or improvement of at least one polyneuropathy measure within 12 months of patisiran treatment. Timely switch from tafamidis to patisiran can be beneficial to avoid rapid disease progression in patients with ATTRv-PN.

542P Long-term outcomes of neoadjuvant toripalimab with or without celecoxib in patients with dMMR/MSI-H locally advanced colorectal cancer: 3-month treatment cohort of the randomized phase II PICC trial

542P Long-term outcomes of neoadjuvant toripalimab with or without celecoxib in patients with dMMR/MSI-H locally advanced colorectal cancer: 3-month treatment cohort of the randomized phase II PICC trial

Impact of bedaquiline resistance probability on treatment decision for rifampicin-resistant TB

&lt;sec&gt;&lt;title&gt;BACKGROUND&lt;/title&gt;Accurate diagnosis of bedaquiline (BDQ) resistance remains challenging. A Bayesian approach expresses this uncertainty as a probability of BDQ resistance (prBDQR) with a 95% credible interval. We investigated how prBDQR information influences BDQ prescribing decisions.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;METHOD&lt;/title&gt;We performed a discrete choice experiment with 55 international rifampicin-resistant tuberculosis physicians. We employed mixed-effects multinomial logistic regression to quantify the effect of prBDQR, patient attributes, and contextual factors on the decision to continue BDQ or not when sequencing results become available.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;RESULTS&lt;/title&gt;PrBDQR was the most influential factor for BDQ decision-making, three times greater than treatment response. Each percentage point increase in prBDQR resulted in 8.2% lower odds (OR 0.92, 95% CI 0.90–0.93) of continuing BDQ as a fully effective drug and 5.0% lower odds (OR 0.95, 95% CI 0.94–0.96) of continuing it but not counting it as an effective drug. The most favourable patient profile for prescribing BDQ as a fully effective drug was a patient receiving the BPaLM regimen (BDQ, pretomanid, linezolid and moxifloxacin) with low prBDQR, good 1-month treatment response, fluoroquinolone-susceptible TB, and no prior BDQ treatment. Physicians with higher discomfort with uncertainty and more years of experience with BDQ were more inclined to stop BDQ.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;CONCLUSION&lt;/title&gt;Given the uncertainty of genotype-phenotype associations, physicians valued prBDQR for BDQ decision-making in rifampicin-resistant TB treatment.&lt;/sec&gt;

Confused Images Confused Eyes: A Case of Ultrasound Misdiagnosis of Pelvic Actinomycosis.

This article introduces a case of pelvic actinomycosis, which is easily confused with an ovarian malignant tumor. These images are from a 52-year-old woman who was admitted to hospital with difficulty defecating. Colonoscopy and biopsy indicated inflammatory changes within the intestinal tract, but the anti-inflammatory treatment was not effective. Later, she was readmitted due to abdominal pain and emaciation, and laboratory findings revealed mild anemia and inflammation. Various tumor markers are normal. CT suggested inflammatory lesions in the sigmoid colon and upper rectum. PET-CT considered a high metabolic mass originating from the mesentery. Ultrasound scan revealed a mixed-echo mass adjacent to the right side of the uterus, poorly demarcated from the rectum and right ovary, suggesting a neoplastic lesion. A biopsy of the right ovarian mass indicated suppurative inflammation, with negative antacid staining and microscopic observation of yellowish sulfur granules, suggestive of Actinomyces infection. Following a 12-month treatment regimen involving the removal of an intrauterine device and administration of penicillin, the patient's condition markedly improved. Pelvic actinomycosis is usually characterized by abdominal pain accompanied by an abdominal mass, which is often related to an intrauterine device (IUD), and is very difficult to distinguish from pelvic tumors and tuberculosis, so it is necessary for doctors to understand its clinical and imaging features.

Effectiveness of Vortioxetine Treatment on Depression and Cognitive Functions in Patients with Alzheimer's Disease: A 12-Month, Retrospective, Observational Study.

This study aimed to assess the effectiveness of vortioxetine for improving depressive symptoms, cognitive performance, daily and global functioning in patients with Alzheimer's disease (AD) and major depressive disorder (MDD) in real-world clinical practice. We retrospectively identified 46 AD patients who had received treatment for 12 months with vortioxetine. Drug effects were evaluated at baseline, 4, 8, and 12 months. The primary endpoint was change from baseline in the Hamilton Depression Rating Scale (HDRS) and in the Cornell Scale for Depression in Dementia (CSDD) to month 12. Cognitive and daily and global functioning changes were also evaluated. Significant baseline-to-endpoint improvement in depressive symptom severity was observed (p < 0.0001). At month 12, the least-square mean (standard error) change score from baseline was -10.48 (±0.42) on the HDRS and -9.04 (±0.62) on the CSDD. Significant improvements in cognitive performance were observed for the Rey Auditory Verbal Learning Test, the Symbol Digit Modalities Test, the Letter Fluency Test, the Category Fluency Test, and the Trail Making Test-A. Patients also experienced significant improvements in daily and global functioning. Vortioxetine was safe and well tolerated. Patients with AD and MDD receiving vortioxetine showed meaningful improvements in depressive symptoms, cognitive performance, and daily and global functioning over the 12-month treatment period.

What impact did the COVID-19 pandemic have on psychosis and the delivery of early intervention psychosis services?

BackgroundIn Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients. MethodsThis prospective cohort study analysed routine data from 15 headspace Early Psychosis centres in Australia. Participants were 12 to 25 years, meeting criteria for First Episode Psychosis (FEP) or Ultra High Risk of psychosis (UHR) comparing those who commenced treatment ‘pre-COVID-19’ (between 16th August 2018 and 15th August 2019), and ‘during-COVID-19’ (between 1st March 2020 and 15th September 2020). Clinical symptoms at treatment commencement were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Kessler Psychological Distress Scale (K10). with outcomes after 6 months compared between cohorts using linear mixed-effects regression, controlling for confounders. ResultsOf 1246 young people analysed (653 FEP, 596 UHR), significant improvements were observed with treatment in both groups (5 to 13-point reduction in BPRS score per 6-months treatment). Treatment effectiveness reduced during-COVID-19 for psychosis symptoms, with the FEP BPRS treatment effect lower by 4.3 points (95%CI: 0.5, 8.1). UHR clients had lower BPRS negative symptoms during-COVID-19 (p = 0.020). Service contacts increased during-COVID-19, with increased telehealth services (p < 0.001). ConclusionsEarly intervention remained effective for FEP and UHR, despite the pandemic and transition of EIP services to virtual service delivery. Reduced treatment efficacy in FEP psychosis symptoms may indicate potential limitations of telehealth. Further research to examine longer term clinical and functional outcomes due to the pandemic is required.

Qiliqiangxin Alleviates Imbalance of Inflammatory Cytokines in Patients with Dilated Cardiomyopathy: A Randomized Controlled Trial.

Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM. The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment. At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant. QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.

Degradation and Migration in Olive Oil Packaged in Polyethylene Terephthalate under Thermal Treatment and Storage Conditions

The research addresses challenges in food safety related to the migration of contaminants from plastics to food. It focused on the physicochemical and sensory degradation of olive oils packaged in polyethylene terephthalate (PET) and subjected to thermal exposure at 40 °C and 60 °C for several weeks and a subsequent 12 months of storage, as well as the stability and migration of compounds from the PET packaging itself. Olive oils (OO) from Spanish supermarkets (a mixture of refined and virgin, with commercial identifications of mild and intense) were selected and subjected to thermal treatments at 40 °C and 60 °C for 1, 2, and 3 weeks, followed by 12 months of storage. The treatments were conducted through the following two independent experiments: Experiment A focused on immediate analysis post-thermal treatment, while Experiment B included a 12-month storage period post-thermal treatment. The presence of antimony (Sb) was analyzed using acid digestion with nitric acid (HNO3) and high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), while the metals cadmium (Cd), copper (Cu), lead (Pb), and iron (Fe) were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The PET characterization was assessed using Fourier transform infrared spectroscopy in the mid-infrared range (FT-IR/MIR), carbonyl index, and differential scanning calorimetry (DSC). The results showed increases in the acidity index by 0.29%, the peroxide value by 25.92%, and the K268 coefficient by 51.22% between the control sample and the most severe treatments, with more pronounced effects observed after 12 months. Sensory quality declined, with reduced intensity of the “fruity” attribute and increased presence of the “rancid” defect. PET degradation was reflected in an increase in the carbonyl index and greater structural amorphization. Fe was the predominant metal, and Sb concentration increased after thermal treatments. The lack of studies on the raw consumption of oils packaged in PET and the concerns about the migration of compounds from the packaging to the food highlight the relevance of this research. This study provides new insights into the effects of thermal exposure and storage on the migration of PET contaminants into oils, contributing to the development of strategies to ensure food safety and product quality.

Real-World Clinical Outcomes and Treatment Patterns Among Black and Non-Black Patients With Prostate Cancer Initiated on Apalutamide in a Urology Setting

Background: The use of androgen receptor signaling inhibitors, including apalutamide, in combination with androgen deprivation therapy is recommended for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC). Objective: To describe real-world treatment patterns and clinical outcomes among patients with mCSPC or nmCRPC who initiated apalutamide in the United States. Methods: A retrospective cohort study of patients with mCSPC or nmCRPC who initiated apalutamide was conducted using electronic medical record data from US community-based urology practices (Feb. 1, 2017–April 1, 2022). Persistence with apalutamide was reported at 6-, 12-, and 18-months post treatment initiation. Clinical outcomes described up to 24 months after apalutamide initiation using Kaplan-Meier analyses included progression to castration resistance, castration resistance-free survival (CRFS), and metastasis-free survival (MFS). Outcomes were reported separately based on mCSPC or nmCRPC status and race (ie, Black or non-Black). Results: This study included 589 patients with mCSPC (mean age, 75.9 years) and 406 patients with nmCRPC (mean age, 78.8 years). Using a treatment gap of &gt;90 days, persistence with apalutamide at 12 months remained high for both the mCSPC (94.9%) and nmCRPC (92.7%) cohorts, and results were descriptively similar among Black and non-Black patients, and when a treatment gap of &gt;60 days was considered. In patients with mCSPC, overall progression to castration resistance rates at 12 and 24 months were 20.9% and 33.5%, and overall CRFS rates were 76.2% and 62.0%, respectively. In patients with nmCRPC, overall MFS rates at 12 and 24 months were 89.7% and 75.4%, respectively. Rates of these clinical outcomes were descriptively similar between Black and non-Black patients. Discussion: While clinical trials have demonstrated the efficacy and safety of apalutamide, there is limited real-world data describing treatment persistence and clinical outcomes among patients with mCSPC and nmCRPC who initiated apalutamide. Conclusions: In this real-world study of patients with mCSPC or nmCRPC initiated on apalutamide, treatment persistence was high and apalutamide demonstrated robust real-world effectiveness with respect to progression to castration resistance, CRFS, and MFS, overall and among Black and non-Black patients.

Real-World Clinical Outcomes and Treatment Patterns Among Black and Non-Black Patients With Prostate Cancer Initiated on Apalutamide in a Urology Setting.

Background: The use of androgen receptor signaling inhibitors, including apalutamide, in combination with androgen deprivation therapy is recommended for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC). Objective: To describe real-world treatment patterns and clinical outcomes among patients with mCSPC or nmCRPC who initiated apalutamide in the United States. Methods: A retrospective cohort study of patients with mCSPC or nmCRPC who initiated apalutamide was conducted using electronic medical record data from US community-based urology practices (Feb.1, 2017-April 1, 2022). Persistence with apalutamide was reported at 6-, 12-, and 18-months post treatment initiation. Clinical outcomes described up to 24 months after apalutamide initiation using Kaplan-Meier analyses included progression to castration resistance, castration resistance-free survival (CRFS), and metastasis-free survival (MFS). Outcomes were reported separately based on mCSPC or nmCRPC status and race (ie, Black or non-Black). Results: This study included 589 patients with mCSPC (mean age, 75.9 years) and 406 patients with nmCRPC (mean age, 78.8 years). Using a treatment gap of >90 days, persistence with apalutamide at 12 months remained high for both the mCSPC (94.9%) and nmCRPC (92.7%) cohorts, and results were descriptively similar among Black and non-Black patients, and when a treatment gap of >60 days was considered. In patients with mCSPC, overall progression to castration resistance rates at 12 and 24 months were 20.9% and 33.5%, and overall CRFS rates were 76.2% and 62.0%, respectively. In patients with nmCRPC, overall MFS rates at 12 and 24 months were 89.7% and 75.4%, respectively. Rates of these clinical outcomes were descriptively similar between Black and non-Black patients. Discussion: While clinical trials have demonstrated the efficacy and safety of apalutamide, there is limited real-world data describing treatment persistence and clinical outcomes among patients with mCSPC and nmCRPC who initiated apalutamide. Conclusions: In this real-world study of patients with mCSPC or nmCRPC initiated on apalutamide, treatment persistence was high and apalutamide demonstrated robust real-world effectiveness with respect to progression to castration resistance, CRFS, and MFS, overall and among Black and non-Black patients.

Pro Re Nata brolucizumab for early onset and treatment-naïve diabetic macular edema: A prospective study.

To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up. Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year. A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events. Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

Beneficial Consequences of One-Month Oral Treatment with Cannabis Oil on Cardiac Hypertrophy and the Mitochondrial Pool in Spontaneously Hypertensive Rats.

Introduction: It has been demonstrated the dysregulation of the cardiac endocannabinoid system in cardiovascular diseases. Thus, the modulation of this system through the administration of phytocannabinoids present in medicinal cannabis oil (CO) emerges as a promising therapeutic approach. Furthermore, phytocannabinoids exhibit potent antioxidant properties, making them highly desirable in the treatment of cardiac pathologies, such as hypertension-induced cardiac hypertrophy (CH). Objective: To evaluate the effect of CO treatment on hypertrophy and mitochondrial status in spontaneously hypertensive rat (SHR) hearts. Methods: Three-month-old male SHR were randomly assigned to CO or olive oil (vehicle) oral treatment for 1 month. We evaluated cardiac mass and histology, mitochondrial dynamics, membrane potential, area and density, myocardial reactive oxygen species (ROS) production, superoxide dismutase (SOD), and citrate synthase (CS) activity and expression. Data are presented as mean ± SEM (n) and compared by t-test, or two-way ANOVA and Bonferroni post hoc test were used as appropriate. p < 0.05 was considered statistically significant. Results: CH was reduced by CO treatment, as indicated by the left ventricular weight/tibia length ratio, left ventricular mass index, myocyte cross-sectional area, and left ventricle collagen volume fraction. The ejection fraction was preserved in the CO-treated group despite the persistence of elevated systolic blood pressure and the reduction in CH. Mitochondrial membrane potential was improved and mitochondrial biogenesis, dynamics, area, and density were all increased by treatment. Moreover, the activity and expression of the CS were enhanced by treatment, whereas ROS production was decreased and the antioxidant activity of SOD increased by CO administration. Conclusion: Based on the mentioned results, we propose that 1-month oral treatment with CO is effective to reduce hypertrophy, improve the mitochondrial pool and increase the antioxidant capacity in SHR hearts.