Additional Treatment Research Articles

Antisense Oligonucleotides in Dyslipidemia Management: A Review of Clinical Trials.

Elevated serum total cholesterol levels, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, or a decreased serum high-density lipoprotein cholesterol concentration characterize dyslipidemia. Antisense Oligonucleotide therapy in dyslipidemia targets apolipoprotein B (ApoB), an essential component of low-density lipoprotein (LDL) associated with atherosclerosis development. This review aims to critically evaluate the efficacy and safety of this group of medications in mitigating dyslipidemia in at-risk individuals and its potential role in advancing personalized medicine in the management of dyslipidemias. A detailed search was conducted from multiple databases adhering to the PRISMA guidelines. Clinical trials and randomized controlled trials on antisense oligonucleotides for management of dyslipidemias were included, excluding non-English studies, case reports and all forms of reviews. Data was screened, with duplicates removed, and key findings were synthesized using a narrative approach. The potential of antisense oligonucleotides (ASOs) to treat dyslipidemia and other disorders has attracted much interest. Several studies and clinical trials have been conducted on the safety and tolerability of ASOs for dyslipidemia. Although statins are the mainstay management of hypercholesterolemia, there is evidence from clinical trials that ASOs can even be more effective with little to no side effects. Novel therapeutic approaches such as antisense oligonucleotides (ASOs) offer tailored therapeutic alternatives. ASOs such as Mipomersen and Volanesorsen provide additional treatment options for patients with inherited lipid abnormalities by lowering certain atherogenic lipoproteins such as apo B and ApoC-III, respectively.

Molecular tumor board in patients with metastatic breast cancer.

Comprehensive genomic profiling is becoming increasingly important in the management of patients with metastatic breast cancer (mBC). Real-world clinical outcomes from applying molecular tumor boards (MTBs) recommendations in this context remain limited. Accordingly, we conducted a retrospective, single-institution analysis to evaluate the clinical impact of discussing patients affected by mBC at the MTB. Clinicogenomic data of patients affected by mBCs referred to the European Institute of Oncology MTB between August 2019 and December 2023 were reviewed. Genomic alterations were classified by ESCAT framework. Clinical outcomes of patients showing actionable alterations and receiving molecular-matched therapy (MMT) were compared to those receiving standard therapy (ST). Ninety-six patients were included. Following MTB discussion, genetic counseling was recommended in 27% (n = 26) of patients, while additional molecular analyses were requested in 25% (n = 24) cases. Fifty-six patients (58%) displayed at least one actionable alteration. For patients with available follow-up (n = 50), 32 (64%) received MMTs and 18 (36%) ST. No differences in real-world progression-free survival (rwPFS) (4.07 months [95% CI 2.14-8.28] vs. 3.12 months [95% CI 1.51-NE], P = 0.8) and 12-month overall survival (OS) (58% [95%CI 43-78] vs. 57% [95%CI 34-97), P = 0.9) were observed between the MMT- and ST-group. Level I ESCAT alterations yielded longer rwPFS (5.82 months [95% CI 3.12-8.41]) compared to ESCAT II (2.14 months [95%CI 1.61-NE]) and ESCAT III (2.10 months [95% CI 2.04-NE]; P = 0.03). Twenty-four percent of patients showed a PFS2/PFS1 ratio > 1.3 from MMT. Molecular tumor boards can provide additional treatment options for patients affected by mBC. Besides treatment recommendations, MTBs also have the utility to assess the validity of discussed genomic reports and to identify alterations worthy of genetic counseling.

Real-world Referral Pattern of Unplanned Excision in Patients With Soft-tissue Sarcoma: A Multicenter Study Conducted by the Bone and Soft-tissue Tumor Study Group of the Japan Clinical Oncology Group.

Despite the well-publicized clinical outcomes after unplanned excision (UE) and re-excision (re-excision) in patients with soft-tissue sarcoma (STS), there is little information about the real-life referral patterns for UE, such as patient profile, details of procedures, and subsequent management after UE. We aimed to investigate the characteristics of patients with UE who were referred to sarcoma-specific centers. Between May 2022 and June 2023, we registered 97 patients who underwent UE and were referred to sarcoma-specific centers in Japan. We excluded those with well-differentiated liposarcomas and dermatofibrosarcoma protuberances. We investigated the details of UE and additional treatment after UE. There were 49 men and 48 women, with a mean age of 62 years. A broad range of surgeons performed UE; 36 plastic surgeons, 22 orthopedic surgeons, 17 general surgeons, 17 dermatologists, and 5 others. The mean tumor size was 4.1 cm. Local anesthesia was administered to 58 patients. Forty-five patients underwent UE without prior magnetic resonance imaging. Inappropriate transverse skin incisions were performed in 42 patients. Of the 97 patients, 82 underwent re-excision after UE. The mean time between UE and date of initial presentation at the referral hospital was 46 days. The mean interval between UE and re-excision was 96 days. Of the 82 patients, 59 underwent soft-tissue reconstruction after re-excision. A broad range of surgeons performed UE. Continuous education about STS should be considered for all surgeons. UE should be avoided because residual tumors are common, and reconstructive surgery may be necessary.

Clinical Investigation of Short-Term Axial Elongation Control After Orthokeratology Lens Correction: Exploring Its Predictive Role in Long-Term Therapeutic Efficacy

Objective: This study was developed with the goal of exploring the efficacy of orthokeratology (OK) as an approach to controlling axial length (AL) growth and identifying factors predictive of the long-term efficacy of this approach. Methods: This was a retrospective study that enrolled 157 myopic children 7 to 15 years of age undergoing OK correction for over 3 years. The short- and long-term effectiveness of this approach at 1 and 3 years post-OK correction, respectively, was assessed. All participants were classified into two groups based on whether they exhibited good or poor long-term efficacy outcomes. Measurements of changes in AL were made at baseline and at 1 and 3 years post-OK. Univariate analyses and binary logistic regression approaches were used to evaluate baseline age, baseline spherical equivalent refraction, baseline keratometry (K) values of flat and steep meridians, and short-term effectiveness with the goal of identifying predictors of long-term efficacy. Results: Univariate analyses led to the identification of significant differences in baseline age, baseline spherical equivalent refraction, baseline AL, and short-term efficacy between these two groups (P<0.05), whereas gender, baseline flat K, and baseline steep K did not differ significantly (P>0.05). In binary logistic regression analyses, baseline AL (P=0.017) and short-term efficacy (P<0.001) were both found to significantly influence long-term efficacy. Receiver operating characteristic curves demonstrated that short-term efficacy offered an area under the curve value >0.8, consistent with its highly accurate performance as a predictor of long-term efficacy. Conclusion: These results suggest that short-term efficacy outcomes can feasibly be used to predict the long-term effectiveness of OK correction in children. In patients exhibiting poor short-term efficacy, timely replacement or the incorporation of additional treatment modalities may aid efforts to better control the progression of myopia.

Investigating the role of psychosocial stress factors in back pain patients

Abstract Background In 2022, 27.35 million people in Germany were diagnosed with back pain. This results in a 1-year prevalence of 32.64 percent of the population and 96,8 million days of incapacity to work. Moreover, patients with back pain often suffer from additional mental disorders (e.g. anxiety, depression). This study investigated the influence of other health-related factors such as psychosocial stress in these patients. Methods A randomized controlled study was conducted with 297 gainfully employed participants in a rural rehabilitation center in Germany Bad Zwischenahn who received a 4-week multimodal pain therapy. 150 participants were allocated to the intervention (IG) who received an additional 12-month relapse prevention treatment while 147 were allocated to the control group (CG) who received no such additional treatment. Data was obtained via questionnaire (three measurement points) and claims data. Among other health-related outcomes, the number of sick days was examined. A 10-item subscale of the Patient Health Questionnaire (PHQ) was included to measure common psychosocial stress factors. Results The evaluation of the PHQ (summary) scores revealed a mild stress level at all three dates. Of the ten psychosocial stress factors surveyed, the highest level was reported in the IG and CG on the scale “Worrying about health”. The IG improved significantly (p = .017) compared to the CG after one year reporting decreased health worries. Further analyses carried out by analysis of variance (ANOVA) showed that health worries are significantly associated to a higher number of sick days in the IG (p = .002) and CG (p = .010). Conclusions With regard to psychosocial stressors, the participants were primarily affected by health worries. The results indicate that health concerns are the primary psychosocial stress factor associated with back pain and should be taken into account in the treatment of back pain. Key messages • A 12-month relapse prevention treatment significantly reduced the psychosocial stress experienced by people with back pain after their rehabilitation treatment. • Concerning psychosocial stress factors, the participants of both groups were primarily affected by health worries.

Coronary stent edge segments as determinant of clinical outcomes: An OCTOBER Trial Substudy

Abstract Background Small lumen dimensions and high plaque burden in stent edge segments are known risk factors for subsequent clinical events after percutaneous coronary intervention (PCI). The evidence using intravascular optical coherence tomography is scarce. Purpose This study aimed to characterize edge segments after PCI and the relation to clinical outcomes in the randomized OCTOBER trial on bifurcation PCI optimized using optical coherence tomography. Methods This is a predefined substudy of the OCTOBER Trial. Edge segments were analysed in detail for degree of stenosis and plaque composition using a dedicated software. Data was planned to be analysed using multi-level cox regression analysis, but descriptive statistics was applied due to very low event rates after OCT-guided PCI. Main endpoints were OCT-detected edge residual stenosis, lipid plaque, calcification, and dissections. Post PCI coronary angiography was analysed for diameter stenosis, edge segment length and minimal lumen diameter. Patients with cardiac events were diagnosed with angiography duringt the two-year follow-up period. Results A total of 597 patients were treated with OCT-guided PCI. Analysable final OCT scans with no additional treatment was available for 505 patients in the main vessel and for the side branch in 289 cases. At deadline for abstract submission 242 scans with 474 edges were analysed and included in preliminary results.Lesions with ≥30% diameter stenosis was found in 20% of proximal edges, 24% of distal edges and 37% of side branch (SB) edges. A plaque burdenOCT ≥180° was found in 74% of proximal edges, 48% of distal edges, and 52% of SB edges. A lipid plaque wafound in 35%, 11% and 14%, dissections in 15%, 6% and 12%, and ≥180° calcium was found in 7%, 4% and 4% of edges respectively. Six patients (1%) of the total OCT-guided population had an edge-related event during the median two-year follow-up. Only two of these 6 patients had post-procedural OCT-scans of the event-related edge, thus 4 of the cases were effectively angiographic guided. Conclusion Only a small fraction of edge segments in the OCTOBER Trial were left with residual edge disease exceeding protocol thresholds. This resulted in historically very low rate of edge related events. No evaluation of a stent edge by OCT in otherwise OCT guided patients appeared to be the main predictor of edge related events. Final results are presented at ESC 2024.

Evaluation of clinical need, effectiveness, and safety of the first myosin inhibitor mavacamten in real world patients

Abstract Background Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow tract (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but clinical real world data are lacking. Methods In this ongoing study, consecutive patients with current or previous diagnosis of HOCM presenting at a single referral centre for hypertrophic cardiomyopathy from March 2023 to February 2024 were included and analysed by treatment modality. In patients initiating mavacamten therapy, clinical data of 4 weekly follow ups were assessed, including efficacy (NYHA class, LVOT gradient and biomarkers) and adverse events. Results A total of 72 patients were included (59.1 ± 13.0 years, 68% male). Mavacamten treatment was started in 30/72 (41.7%) patients, 3/72 (4.1%) were referred for transcatheter septal reduction therapy (SRT), and 39/72 (54.2%) did not require any escalation in their treatment due to low gradient with current treatment or few symptoms. Of the latter, 3/39 (7.7%) had previous SRT, 36/39 (92.3%) were stable on negative inotropic medication. The average age of patients selected for mavacamten therapy was 58.0 ± 13.0 years, 80% were male, and the average thickness of the interventricular septum was 18.8 ± 2.8 mm. 22/30 (73.3%) were on baseline therapy with beta-blockers, 3/30 (10.0%) with calcium channel blockers, 2/30 (6.7%) with both, and 4/30 (13.3%) had additional treatment with disopyramide. As shown in table 1, there was a significant decrease in the LVOT gradient under Valsalva maneuver observed 4 weeks after initiation of mavacamten treatment (p=0.006), while the reduction in peak exercise LVOT gradient was statistically significant after 8 weeks (p=0.02). Simultaneously, a significant decrease in Nt-pro-BNP levels was observed after 4 weeks of therapy (p<0.001). A significant drop in troponin T levels compared to baseline was only noted after 20 weeks of treatment (p=0.02). At baseline, 66.7% patients were classified as NYHA class III/IV, and 12.5% after 20 weeks of treatment. 75% of the patients improved ≥1 NYHA class after 20 weeks. Regarding adverse events, there was one case of ejection fraction dropping to <50%, which resolved after halting treatment. Additionally, there were two reports of dizziness and one reported syncope, all of which resolved without taking any actions. Conclusion In this real-world single centre HOCM cohort, 41.7% of patients had an indication for myosin inhibitor therapy. The safety and effectiveness in lowering the LVOT gradient and improving NYHA class were consistent with findings from the approval studies.

Cardiopulmonary exercise testing in long-term calcium channel blockers responders, does it normalize in the same way as pulmonary vascular resistance?

Abstract Background and aims Long-term calcium channel blockers (CCB) responders represent <10% of pulmonary arterial hypertension (PAH) patients and are known to have an excellent prognosis on high dose CCB. The few reports of lung histology of these patients suggest a predominant muscular thickening of the precapillary arterioles. Nevertheless, the classic intimal proliferation characteristic of PAH has also been reported, although to a lesser extent. Hence, we hypothesized that long-term CCB responders are likely to exhibit some degree of ventilatory inefficiency as a result of their impaired alveolo-capillary membrane. In this study, we aimed to evaluate the exercise performance of a contemporary cohort of long-term responders to CCB in terms of both exercise capacity and ventilatory efficiency, and whether there are differences depending on the haemodynamic severity. Methods We evaluated all long-term CCB responders with regular follow-up at our institution between 1996 to 2024 with at least one cardiopulmonary exercise test (CPET) and a right heart catheterization (RHC) within a three-year period, provided they had remained clinically stable without changes in pulmonary vasodilator treatment. Patients with additional PAH specific treatment were excluded. For data analysis purposes, the population was divided into 2 groups according to pulmonary vascular resistance (PVR). The cut-off point for PVR was set at ≥3. Results Twenty-four patients (91,6% female) with complete data were retrospectively enrolled. Baseline characteristics were as follows: median age 45.5 years (59-33) median mean pulmonary artery pressure of 26 mmHg (29-24) and median PVR of 3 WU (3-2.6). Regarding the whole cohort, peak oxygen consumption (pVO2) revealed mild impairment of functional capacity (mean pVO2: 1281 ± 245 ml/kg – 75 ± 15% of predicted). Ventilatory efficiency parameters were also mildy affected with low end-tidal carbon dioxide pressure at the anaerobic threshold (PETCO2@AT) (33.7±3.6mmHg), and increased minute ventilation (VE)/carbon dioxide output (VCO2) slope (33.5±4.5). The subgroup analysis depending on PVR showed no significant differences between groups in terms of pVO2 (1291.9 ±240 Vs. 1150 ±350 ml/kg, p:0.29 / 79%±16 vs 67%±12, p:0.8), VE/VCO2 slope (33 Vs. 34, p:0.21), or PETC02@AT (35 Vs. 33 mmHg, p:0.25). All CPET parameters by subgroups are displayed in Table 1. Conclusions Long-term CCB responders exhibit mildly reduced functional capacity. Moreover, they often fail to normalize the ventilatory efficiency parameters in most of the cases, even when PVR reaches close to normal values, suggesting persistent endothelial impairment.Results according to PVR

High discontinuation rate of statins among PCSK9i users: a nationwide study from 2015-2023

Abstract Background Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are recommended as additional lipid-lowering drug treatment for high-risk patients if the low-density lipoprotein cholesterol (LDL-C) targets are not achieved with statins and ezetimibe alone. Nationwide data from clinical practice on the use of PCSK9i are lacking. In 2015, PCSK9i became available in Norway with reimbursement restricted to patients with familial hypercholesterolemia (FH) and/or atherosclerotic cardiovascular disease (ASCVD) with LDL-C above certain levels. Purpose To investigate the use and adherence of lipid lowering drugs among a nationwide cohort of PCSK9i users, utlizing complete pharmacy dispensation data. Methods Information on all PCSK9i users ≤80 years with at least one year of follow-up after the first dispensation were extracted from the Norwegian Prescribed Drug Registry. We evaluated adherence to PCSK9i by calculating the proportion of days covered (PDC) during the initial year of PCSK9i therapy. Poor adherence was defined as PDC <80%, and discontinuation was defined as a gap in treatment ≥180 days during the follow-up period. We analyzed treatment patterns of statins and ezetimibe during the 1-year period before and after PCSK9i initiation by determining the proportion of patients with at least one dispensation of statin and/or ezetimibe treatment. Results A total of 2,997 PCSK9i users were identified. Median age at treatment initiation was 62 (IQR: 13) years and 43% were female. Non-adherence to PCSK9i was observed in 16% of the patients, and 18% discontinued treatment (Table). Non-adherence to PCSK9i was more prevalent in females, and in the lowest and highest age quartiles. No significant difference in non-adherence was found among patients with ASCVD compared to patients with FH. In the year preceding PCSK9i initiation, 74% of patients used statins (including combinations with ezetimibe), 11% used ezetimibe monotherapy, and 15% did not use any statin or ezetimibe treatment (Figure). During the year following PCSK9i initiation, 35% used statins (including combinations), 17% used ezetimibe monotherapy, and 48% did not use any statin or ezetimibe treatment. Among patients with ASCVD, 72% used statins prior to PCSK9i initiation, and 22% used statins after. Among patients with FH, 77% used statins prior to PCSK9i initiation, while 51% used statins after. Conclusion In this nationwide study of incident PCSK9i users, we observed a substantial decrease in usage of statins and ezetimibe following PCSK9i initiation. Further, almost 1 in 5 patients discontinued treatment with PCSK9i. There is a large potential for optimizing treatment and adherence to PCSK9i and conventional lipid-lowering drugs among Norwegian patients with ASCVD and familial hypercholesterolemia.Adherence and discontinuation to PCSK9iUse of statin and ezetimibe

Assesing health needs of women with breast cancer in a Regula Hospital Dispensary in Crete, Greece

Abstract Background Understanding the health needs of women with breast cancer is essential for tailor-made care. Socio-economic factors impact care access and outcomes. Previous research has indicated variations in healthcare experiences based on factors such as education level, employment status, and income. However, specific insights into the health needs of women with breast cancer in Crete, Greece, remain limited. Purpose The current study aimed at assessing the health needs of women with breast cancer. Methods A total of 161 women were surveyed between June 2023 and December 2023 in a regular Hospital Dispensary at a General Hospital in Heraklion, Greece. Results The majority were married (46%) and had an average of 2 children. 16% were graduates of secondary education and 42 % graduates of higher education, 33% retired and 19% full-time employees. Most participants (45%) reported a family income between 10,001 to 20,000 €, 29% under 10000 € and 26 % between 20001 to 30000 €. The majority had received additional medical treatment (75%), with surgery being the most common (30.6%). Other treatment included radiation therapy (28%), chemotherapy (23%), and hormone therapy (18%). Prevalence of comorbidities was high, with hypertension (97%), coronary heart disease (92%), cholesterol issues (43.5%), arrhythmias (82%), thyroid disease (81%), diabetes mellitus (79.5%), and bleeding disorders (43.5%) being reported. Smoking was also prevalent among participants (79.5%). Conclusions This study highlights the complex health needs of women with breast cancer in Crete region, Greece and emphasizes the prevalence of comorbidities and the importance of tailored support services and comprehensive care approaches for this population. Key messages • Considering socio-economic factors is critical in healthcare planning and intervention strategies. • Emphasizing the importance of tailored support services and comprehensive care approaches for this population.

Adherence to First-Line Intravesical Bacillus Calmette-Guérin Therapy in the Context of Guideline Recommendations for US Patients With High-Risk Non-muscle Invasive Bladder Cancer.

Background: Bacillus Calmette-Guérin (BCG) can reduce recurrence and delay progression among patients with high-risk non-muscle invasive bladder cancer (NMIBC), but is associated with a substantial emotional, physical, and social burden. Objectives: This study evaluated the adequacy of first-line intravesical BCG treatment among high-risk NMIBC patients in the United States, including the subgroup with carcinoma in situ (CIS) of the bladder. Methods: Adults with high-risk NMIBC treated with BCG were selected from de-identified MarketScan® Commercial, Medicare, and Medicaid Databases (1/1/2010-2/28/2021). Adequacy of BCG induction and maintenance was evaluated from the first BCG claim until the end of the patient's observation, using a previously published claims-based algorithm (induction: ≥5 instillations within 70 days; induction and maintenance: ≥7 instillations within 274 days of first instillation) and a definition based on the landmark Southwest Oncology Group (SWOG) trial (induction: ≥5 instillations without gaps >7 days; followed by ≥2 instillations at month 3, 6, and every 6 months thereafter). Proportions of patients with adequate BCG induction and maintenance were reported overall and compared between those with and without CIS. Results: Of 5803 high-risk NMIBC patients treated with first-line BCG (mean age, 67.3 years; 20.6% female), 930 (16.0%) had CIS. After first-line BCG, 56.6% received another treatment. Although 86.9% had adequate BCG induction based on the claims-based algorithm (SWOG, 73.6%), only 41.5% had adequate BCG induction and maintenance (SWOG, 1.6%). Similar trends were observed for patients with and without CIS, with higher adherence to guidelines for patients with CIS (adequate induction using claims-based algorithm: 90.3% vs 86.2%; adequate induction and maintenance: 50.8% vs 39.7%, all P < .001). A greater proportion of CIS patients than non-CIS patients had cystectomy (CIS, 14.4%, non-CIS, 8.5%; P < .001) after first-line BCG. Discussion: Among patients with NMIBC treated with first-line intravesical BCG, most received adequate BCG induction but less than half had adequate BCG maintenance. BCG treatment was also inadequate for patients with CIS, with only half of patients receiving adequate BCG maintenance and a higher proportion undergoing cystectomy following first-line BCG. Conclusions: Results emphasize the need for additional treatment options for patients with NMIBC.

Adherence to First-Line Intravesical Bacillus Calmette-Guérin Therapy in the Context of Guideline Recommendations for US Patients With High-Risk Non-muscle Invasive Bladder Cancer

Background: Bacillus Calmette-Guérin (BCG) can reduce recurrence and delay progression among patients with high-risk non–muscle invasive bladder cancer (NMIBC), but is associated with a substantial emotional, physical, and social burden. Objectives: This study evaluated the adequacy of first-line intravesical BCG treatment among high-risk NMIBC patients in the United States, including the subgroup with carcinoma in situ (CIS) of the bladder. Methods: Adults with high-risk NMIBC treated with BCG were selected from de-identified MarketScan® Commercial, Medicare, and Medicaid Databases (1/1/2010-2/28/2021). Adequacy of BCG induction and maintenance was evaluated from the first BCG claim until the end of the patient’s observation, using a previously published claims-based algorithm (induction: ≥5 instillations within 70 days; induction and maintenance: ≥7 instillations within 274 days of first instillation) and a definition based on the landmark Southwest Oncology Group (SWOG) trial (induction: ≥5 instillations without gaps &gt;7 days; followed by ≥2 instillations at month 3, 6, and every 6 months thereafter). Proportions of patients with adequate BCG induction and maintenance were reported overall and compared between those with and without CIS. Results: Of 5803 high-risk NMIBC patients treated with first-line BCG (mean age, 67.3 years; 20.6% female), 930 (16.0%) had CIS. After first-line BCG, 56.6% received another treatment. Although 86.9% had adequate BCG induction based on the claims-based algorithm (SWOG, 73.6%), only 41.5% had adequate BCG induction and maintenance (SWOG, 1.6%). Similar trends were observed for patients with and without CIS, with higher adherence to guidelines for patients with CIS (adequate induction using claims-based algorithm: 90.3% vs 86.2%; adequate induction and maintenance: 50.8% vs 39.7%, all P &lt; .001). A greater proportion of CIS patients than non-CIS patients had cystectomy (CIS, 14.4%, non-CIS, 8.5%; P &lt; .001) after first-line BCG. Discussion: Among patients with NMIBC treated with first-line intravesical BCG, most received adequate BCG induction but less than half had adequate BCG maintenance. BCG treatment was also inadequate for patients with CIS, with only half of patients receiving adequate BCG maintenance and a higher proportion undergoing cystectomy following first-line BCG. Conclusions: Results emphasize the need for additional treatment options for patients with NMIBC.

Response of nitrifier and denitrifier community to Epichloë endophytes mediated host litter decomposition under phosphorus addition treatments

Response of nitrifier and denitrifier community to Epichloë endophytes mediated host litter decomposition under phosphorus addition treatments

Biometric Parameters and Yield Components of Wheat (Triticum aestivum) as a Function of Lime and Phosphogypsum Reapplication

ABSTRACT The effects of lime and phosphogypsum (GY) on wheat (Triticum aestivum) nutrition are well documented. However, little is known about the influence of these soil amendments on biometric parameters or yield components. This study investigated the effects of lime and GY on wheat crops grown at cation base saturation (BS) levels of 44%, 70%, and 90%, achieved by surface application or soil incorporation of lime. Two additional treatments were included: surface liming to 70% combined with a standard rate of GY (3.71 Mg ha−1) or twice the recommended GY rate (7.42 Mg ha−1). The experiment was conducted during two crop seasons in Southern Brazil. The treatments did not influence dry biomass partitioning between spikes, stems, and leaves and total. In one season, liming increased flag leaf area, which was strongly associated with grain yield. Regardless of the rate, application method, and combined use of GY, liming increased the number of grains per spike in both seasons, which was the variable that most influenced wheat yield. Liming also increased spike length and the number of spikelets per spike in the 2018 season. No benefits were seen when lime was applied by soil incorporation, BS was raised to 90%, or liming was combined with GY application. The results showed a positive effect of liming on wheat yield components that are associated with grain yield.

EFFECT OF BIO-ORGANIC AND MINERAL FERTILIZATION, ON THE GROWTH AND YIELD OF CAULIFLOWER (Brassica oleraceae Var.botrytis)

A field experiment was carried out to study the effect of three factors, the first was biofertilization with four types (without addition, combination of A.brasilense + A. chroococcum combination of G.mosseae + T. harzianum, and combination of the two previous combinations), The second factor four types of organic fertilizer(without adding,vermicompost ,Orgevit, a combination of the two previous organic fertilizers),and the third factor mineral fertilizer with two levels (0% and 50%) of the fertilizer recommendation in addition to the full fertilizer recommendation treatment (second comparison).RCBD was used with three replications. The results showed that the triple interaction of the biofertilization treatments added with the organic fertilizer combination of organic fertilizer with 50% of the mineral fertilizer recommendation showed the highest averages for the characteristics of growth and the total yield, which gave79.740 Mg ha-1, and the content of leaves and the curd from N, P and K after harvest and the content of the soil of N, P and K after harvesting, which amounted to 70.81, 38.19, 370.44 mg kg soil-1,in comparison with the no addition treatment which gave the lowest averages .

EFFECT OF ADDING NATURAL AND NANO ZINC OXIDE TO THE DITE ON SOME GROWTH PARAMETERS OF CYPRINUS CARPIO L .

The research aimed to study the effect of natural and nano zinc oxide on some growth parameters of common carp Cyprinus carpio. Seven treatments were used, including the control without any addition, the second, third and fourth treatments by adding nano-zinc oxide at concentrations of 25, 50 and 75 mg/kg feed, respectively, and the fifth, sixth and seventh treatments by adding natural zinc oxide in the same concentrations above. The results showed that the fourth treatment was superior to the traits of the total weight gain, daily growth rate, relative and specific growth rate over the other treatments, which is an indication that the fish benefit from feed enhanced with nanoparticles by 75%, and it differed significantly )p (0.01&gt;from the rest of the treatments. T4 treatment was recorded the best daily growth was 0.29 g/day The best feed conversion ratio was recorded in the same treatment. It can be concluded from the study that the addition of zinc nanoparticles to the diet of fish improves the level of performance and growth without causing any harm to the fish.

Do apologies promote the reintegration of former combatants? Lessons from a video experiment in Colombia

Transitional justice practices frequently involve public apologies where former combatants confess their wrongdoings and ask for forgiveness, with the underlying assumption that such displays facilitate the reintegration of ex-combatants into society. However, little is known about the public response to ex-combatant apologies. In this article, we investigate the causal effect of an armed group apology on attitudes toward ex-combatant reintegration in Colombia. Our study builds on a novel experiment implemented in Meta, a conflict-ridden department of Colombia. The experiment entailed exposing a subset of participants to a video in which a former rebel group leader apologizes for violent acts committed by their armed group during the civil war. To examine the extent to which external actors influence the effectiveness of apologies, we incorporated third-party ‘encouragements to forgive’ (endorsements) in two additional treatment conditions. Our analysis demonstrates that, on average, participants do not exhibit higher reintegration attitudes when exposed to the apology, regardless of third-party endorsements. However, the absence of a treatment effect is not due to an indifference to the apology. In an exploratory heterogeneity analysis, we show that the apology induces negative effects on some indicators of reintegration attitudes among participants that did not support the peace agreement. This finding aligns with qualitative data gathered in a follow-up survey, which indicates that opponents of the peace agreement generally describe negative emotional responses to the FARC-EP apology. The results call for a reconsideration of unchallenged prescriptions of public apologies after conflict.

Results of the complex treatment of temporomandibular joint disorders in patients with malocclusion

Temporomandibular joint disorders is an actual problem of modern dentistry. This study is aimed to improve the effectiveness of TMJ disorders treatment in patients with malocclusion using splint, kinesio- and botulinum therapy. The outcome evaluation of the treatment was after a month, a year and 2 years. After a month of the treatment masticatory muscles tone has already declined. It is recommended to use splint, kinesio- and botulinum therapy as additional treatment method to relieve the symptoms of disorders.

Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study.

Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open-label, multicenter, Phase 1b, dose-finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825). Patients with relapsing or primary progressive multiple sclerosis (aged 18-65 years; Expanded Disability Status Scale score 0.0-6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 mg. Following dose escalation, new patients in Group A were randomized (1:1) to receive a single 600 mg intravenous ocrelizumab dose or the candidate subcutaneous dose, which was predicted to result in similar exposure as the 600 mg intravenous dose while being safe and well tolerated. The area under the concentration-time curve for both formulations was used to select the subcutaneous ocrelizumab dose. Patients in all cohorts could enter a dose-continuation phase. Eighty-eight and 47 patients were enrolled into Group A and B, respectively; most patients were female (72.7%/63.0%), and mean age at baseline was 45.7 and 39.7 years, respectively. Subcutaneous ocrelizumab was well tolerated across all doses tested. The 920 mg subcutaneous ocrelizumab dose was selected for the OCARINA II study based on pharmacokinetic and safety data. Subcutaneous ocrelizumab may provide patients with multiple sclerosis with an additional treatment option.

Current Progress on Antibiotic Resistance Genes Removal by Composting in Sewage Sludge: Influencing Factors and Possible Mechanisms

Antibiotic resistance genes (ARGs) present in sewage sludge pose significant environmental and public health challenges. Composting has emerged as a promising method to mitigate these risks by reducing ARGs. This review paper evaluated the current progress in the removal of ARGs through composting, incorporating a bibliometric analysis of 228 publications from January 2010 to January 2024. This review highlights the increasing scholarly interest in this field, with a notable rise in publications since 2010. Key mechanisms identified include the denaturation of proteins and DNA at high temperatures, the adsorption of antibiotics and heavy metals by additives like biochar, and shifts in microbial communities, all contributing to the reduction of ARGs during composting. Despite these findings, challenges remain in achieving consistent ARG removal rates, addressing the potential for ARG regrowth, and understanding horizontal gene transfer post-composting. This review suggests further research into optimizing composting conditions and integrating additional treatment methods to enhance ARG removal and minimize associated risks.