Subsequent Treatment Research Articles

Impact of Slim Linear Echoendoscope on the Practice of EUS.

Standard linear echoendoscopes have a large distal tip and bending radius, which can preclude adequate examination in some patients. We examined the impact of having available slim linear echoendoscopes (SLE) on our endoscopic ultrasound (EUS) practice. As a quality improvement measure, data on the need for the use of SLE were documented in 2000 consecutive procedures performed over a 10-month period from February to November 2022. When examination using a standard size echoendoscope failed due to technical limitations, the procedure was reattempted in the same session using a SLE. The main outcome was the impact of SLE, which was defined as the establishment of a new diagnosis or if findings altered treatment plan. A complete EUS examination failed in 23 of 2000 procedures (1.15%, 95% CI, 0.73-1.72%) performed using standard size echoendoscope (14 male, median age 73y [IQR 66 to 79]). The examination was technically successful when using SLE in 22 of 23 (95.6%) patients. SLE impacted clinical management in all 22 patients (100%) by establishing tissue diagnosis in 19 and/or altering subsequent treatment plan in 5. Adverse event of transient hypoxia was observed in one patient (4.3%). A very experienced EUS team required SLE in 1.1% of consecutive examinations. Our findings suggest that when used, 95% of patients benefitted as it had a significant impact on their clinical management.

Untargeted Metabolomic Analyses of Body Fluids to Differentiate TBI DOC and NTBI DOC.

To investigate the metabolomic differences between Traumatic brain injury (TBI) disorder of consciousness (DOC) patients and non-traumatic brain injury (NTBI) DOC patients by using cerebrospinal fluid (CSF), serum and urine samples beneficial to understand the pathological mechanism differences between the two etiologies, provide potential clues for the subsequent treatment and prognosis, and investigate the metabolome differences and similarities between TBI and NTBI among three different body fluids. In total, 24 TBI DOC subjects and 29 NTBI DOC subjects were enrolled. CSF, serum and urine samples from TBI DOC and NTBI DOC patients were collected and analyzed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarkers and altered metabolic functions. When comparing TBI DOC and NTBI DOC, 36, 31 and 52 differential metabolites were obtained in CSF, serum and urine, respectively. The functional analysis of differential metabolites obtained in CSF, serum and urine were all related to amino acid metabolism. Except for amino acid metabolism, metabolic biomarkers in CSF, serum and urine mainly focus on central function, cognitive function, necrosis and apoptosis and neurological function, respectively. In CSF, the highest AUC was 0.864 (Isoproturon) and 0.816 (Proline betaine). Then, the AUC of NFurfurylformamide in serum was 0.941, while the AUC of Dihydronepetalactone and Doxepin N-oxide glucuronide were 1.0 in urine. CSF, serum and urine metabolomic analyses could differentiate TBI DOC from NTBI DOC and functional analyses showed a metabolic change difference between TBI DOC and NTBI DOC.

Comparative effectiveness of stereotactic, subdural, or hybrid intracranial EEG monitoring in epilepsy surgery.

Surgical intervention can be curative or palliative for drug-resistant focal epilepsy. However, if the seizure onset zone (SOZ) cannot be adequately localized via noninvasive tests, intracranial EEG (iEEG) recordings are often carried out to develop surgical plans in appropriate candidates. Stereotactic EEG (SEEG), subdural EEG (SDE), and SDE with depth electrodes (hybrid) are major tools used for investigation, but there is no class 1 or 2 evidence comparing the effectiveness of these modalities. The authors identified an institutional cohort of patients who underwent iEEG monitoring between 2001 and 2022. Demographic data, preoperative clinical features, iEEG intervention, and follow-up data were identified. Primary study endpoints included the following: 1) likelihood of SOZ localization; 2) likelihood of surgical treatment after iEEG; 3) seizure outcomes; and 4) complications. A total of 329 patients were identified (176 in the SEEG, 60 in the SDE, and 93 in the hybrid cohort) who were followed for a median of 5.4 (IQR 6.8) years. Baseline characteristics, including demographics, mean age at epilepsy diagnosis, mean age at iEEG investigation, number of preoperative antiseizure medications, and preoperative seizure frequency, were not statistically different across the 3 cohorts. Patients in the SEEG cohort were more likely to have their SOZ localized than were the patients in the SDE group (OR 2.3) and were less likely to undergo subsequent resection (OR 0.3) or to have complications (OR 0.4), although there was no statistical difference with respect to likelihood of undergoing any subsequent neurosurgical treatment, or with respect to favorable seizure outcomes. Patients in the hybrid cohort were more likely to have SOZ localized than were patients in the SDE group (OR 3.1), but were more likely to undergo resection (OR 4.9) or any neurosurgical treatment (OR 2.5) compared to patients in the SEEG group. Patients in the hybrid cohort had better seizure outcomes compared to the SDE (OR 2.3) but not to the SEEG group. Patients in the SEEG group were more likely to have their SOZ localized and patients in the SDE group were more likely to undergo resection, but they did not differ with respect to seizure outcomes.

Progression pattern and post-progression survival following atezolizumab and bevacizumab treatment in advanced hepatocellular carcinoma.

Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival (PPS) remain unestablished. We conducted a multicentre retrospective study to evaluate PPS following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into three groups: BCLC stage B and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression. Of the 204 patients who started ATZ + BEV treatment between October 2020 and September 2022, 110 showed disease progression, with 33, 55 and 22 showing the BCLCp-B, BCLCp-C1 and BCLCp-C2 stages of the disease, respectively. Specifically, patients with the BCLCp-B stage of the disease showed better overall survival than those with the BCLCp-C1 and BCLCp-C2 stages (hazard ratios: 1.93 [95% confidence interval, CI, 1.06-3.51] and 2.64 [95% CI, 1.32-5.30] for HCC stages BCLCp-C1 and BCLCp-C2, respectively). Via multivariable analysis, we identified the BCLCp-C1 and BCLCp-C2 stages, as well as performance status, Child-Pugh class and alpha-fetoprotein as poor prognostic factors for PPS. BCLCp-B1 stage was identified as a better prognostic factor for PPS following ATZ + BEV treatment compared with BCLCp-C1 and BCLCp-C2 stages. This may help in making decisions regarding subsequent treatment after ATZ + BEV.

Retinal artery/arteriole occlusion risks after endovascular treatment for unruptured intracranial aneurysm

BackgroundTo evaluate the association between retinal artery/arteriole occlusion (RAO) and unruptured intracranial aneurysm (UIA).MethodsIncident UIA patients from a nationwide cohort (n=253 240) were categorised into three groups based on subsequent...

Determining the manner of death in victims in drug-induced psychosis: a case of an atypical head stab wound.

This case report presents a rare case of an atypical head stab wound suffered by a drug addict and inflicted with a screwdriver during drug-induced psychosis. It describes the diagnostic and treatment procedures in the hospital and the findings of the subsequent autopsy. It also analyzes the review of the interpretation of the CT scans made upon admission and the subsequent treatment by an independent medical review panel, which revealed signs of medical mismanagement. Therefore, it also discusses the legal consequences that the case may have involved for the attending physicians in addition to the consequences for the suspected perpetrator. The report raises many issues encountered in the case in terms of the clinical treatment and forensic determination of the manner of death in cases of injuries caused by sharp instruments and highlights the importance of comprehensive evaluation of the circumstantial evidence together with the clinical or autopsy findings, since such evidence may sometimes be overlooked in clinical practice.

Mechanical and electrical performances of ternary Cu-2.8%Ni-0.7%Si alloy modulated by ultrasonic solidification

One-dimensional (1D) and three-dimensional (3D) ultrasounds were introduced into the solidification process of ternary Cu-2.8wt%Ni-0.7wt%Si alloy together with the in-situ measurements of acoustic fields. In the case of 1D ultrasound, stable cavitation was the main form of acoustic energy transmission. The grain size of α-Cu dendrites was reduced because stable cavitation improved the wetting between impurities and alloy melt, which further promoted nucleation process. When 3D ultrasounds were applied, transient cavitation was the dominant mode of acoustic energy dissipation. This induced local high undercooling in alloy melt, causing a significant increase in bulk nucleation rates and the formation of numerous tiny α-Cu equiaxed grains. Meanwhile, as ultrasonic dimension increased, the strengthened acoustic streaming accelerated solute and thermal diffusion and weakened the preferred orientation of growing α-Cu grains. The proportion of low-angle grain boundaries (LAGBs) increased consequently, which suppressed the nucleation and growth of δ-Ni2Si discontinuous precipitates (DPs) during subsequent annealing treatment. The tensile strength and electrical conductivity of 3D ultrasonically solidified alloy after annealing reached 688.2 MPa and 2.7×107 S/m respectively, showing obvious advantages in synergetic mechanical and electrical performances.

Microstructure evolution and mechanical properties of new Co-free maraging steel produced by wire arc additive manufacturing

In this work, P-MIG is used as additive process, a new low-cost Co-free maraging steel wire is used as raw material to additive manufacturing block component, and the microstructure and mechanical properties of the component is investigated. The microstructure of the component is composed of martensite and austenite, and the closer to the bottom, the more serious the elemental segregation and the more austenite content. From the top to the bottom the high-angle grain boundaries increase and the grain size decrease, the difference of the heat dissipation condition and the thermal cycle are the reasons for this phenomenon. The texture of austenite is mainly Cube texture, and the texture of martensite is Rotated Cube texture and Goss texture. The tensile strength of XD, YD, ZD three directions is 1172 ± 15 MPa, 1021 ± 7 MPa, 1139 ± 16 MPa, respectively, impact toughness is 64.7 ± 1.6 J/cm2, 51.1 ± 5.6 J/cm2, 51.4 ± 3.1 J/cm2, respectively, TRIP effect occurs in the process of tensile, the main mode of fracture in tensile and impact is toughness fracture. The microhardness decreases gradually from bottom to top, which is due to the short-lived aging strengthening by thermal cycle, the change of grain size and GND density. The results of the work reveal the successful application of the new low-cost Co-free maraging steel wire in WAAM and provide an important reference for the adjustment of additive process, subsequent heat treatment and the adjustment of wire composition.

Biodesalination of saline aquaculture wastewater with simultaneous nutrient removal and biomass production using the microalgae Arthrospira and Dunaliella in a circular economy approach

Freshwater scarcity is escalating due to factors such as climate change, droughts, increased demand, population growth, and poor water management practices. A promising sustainable solution to this challenge is biodesalination using microalgae. We demonstrate that Arthrospira platensis and Dunaliella salina can thrive in saline aquaculture wastewater, reducing both its salinity and the concentration of nutrients. The salinity removal ability was quantified through measurements of electrical conductivity (EC) and ICP-OES, revealing reductions in EC by up to 45 % (from 31.5 to 17.2 ms/cm) for A. platensis and 35 % (from 31.5 to 20.5 ms/cm) for D. salina. FESEM indicated the formation of a salt layer on the surface of both microalgae, suggesting biosorption and bioaccumulation as likely mechanisms. FTIR spectroscopy analysis demonstrated the binding of functional groups within the cell wall of A. platensis and the cell membrane of D. salina with the ions present in the medium. Scaling up the cultivation of A. platensis in a photobioreactor under non-sterile conditions validated the processes' potential for industrial-scale biodesalination. Although the treated water did not reach the standards for irrigation or potable use, this approach provides a preliminary desalination step, reducing burden on subsequent treatments and simultaneously providing nutrient removal and biomass production.

Role of the molecular structure of humified organic matter in rice plant response to environmental lead pollution.

Humified organic matter has been shown to decrease Pb toxicity in plants. However, there are still gaps in our understanding of the mechanism by which this phenomenon occurs. In this study, we aimed to assess the ability of humic substances (HSs), humic acids (HAs), and fulvic acids (FAs) to enhance defense mechanisms in rice plants under lead (Pb)-stressed conditions. HS fractions were isolated from vermicompost using the chemical fractionation methodology established by the International Humic Substances Society. These fractions were characterized by solid-state NMR and FTIR. Chemometric analysis was used to compare humic structures and correlate them with bioactivity. Three treatments were tested to evaluate the protective effect of humic fractions on rice plants. The first experiment involved the application of humic fractions along with Pb. The second comprised pretreatment with humic fractions followed by subsequent exposure to Pb stress. The third experiment involved Pb stress and subsequent treatment with humic fractions. The root morphology and components of the antioxidative defense system were evaluated and quantified. The results showed that HS + Pb, HA + Pb, and FA + Pb treatment preserved root growth and reduced the levels of O2- and malondialdehyde (MDA) in the roots by up to 5% and 2%, respectively. Pretreatment of the plants with humic fractions promoted the maintenance of root growth and reduced the contents of O2-, H2O2, and MDA by up to 48%, 22%, and 20%, respectively. Combined application of humic fractions and Pb reduced the Pb content in plant tissues by up to 60%, while pretreatment reduced it by up to 80%. The protective capacity of humic fractions is related to the presence of peptides, lignin, and carbohydrate fragments in their molecular structures. These results suggest that products could be developed that can mitigate the adverse effects of heavy metals on agricultural crops.

Heat-acid treatment of georgian and kazakhstani natural heulandite-chabazites

The article considers the processes leading to a change in the structure and properties as a result of thermal treatment followed by acid treatment of natural zeolites from the Rkoni plot of the Tedzami deposit, Georgia, containing up to 80% of heulandite and 10% of chabazite, and from the Chankanay deposit, Kazakhstan, containing up to 70% of heulandite-chabazite mixture, selected for the creation of new bactericidal zeolite filter materials for purification and desinfection of water from various sources. The influence of preliminary heat treatment of the studied natural zeolites on weight loss, the processes of dealumination and decationization during subsequent acid treatment, and the adsorption properties of the final products is described. It has been shown that mass loss is minimal for amorphized samples, dealumination and the participation of sodium ions in the decationization process slow down significantly, and the adsorption capacity for water and benzene sharply decreases with increasing calcination temperature; all these effects are clearly pronounced for heulandite-containing Rkoni tuff, and for the more acid-resistant Chankanay zeolite they are manifested to a lesser extent.

Feasibility of hepatitis C elimination by screening and treatment alone in high-income countries.

Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)'s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification. We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment. Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.

Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy for treating previously treated advanced endometrial cancer in Sweden

Objective Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective. Materials and methods A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted. Results Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76). Limitations Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment’s cost effectiveness in different countries. Conclusions This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

Pre-operative vs. post-operative stereotactic radiosurgery for operative metastatic brain tumors: study protocol for a phase III clinical trial

Background and ObjectivesAlmost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS.MethodsThis randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS.Expected outcomesIf pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline.DiscussionEmerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease.Trial registration numberNCT03750227 (Registration date: 21/11/2018).

Thermal pre-treatment of reactive aluminium alloy waste powders

AbstractThis study focussed on assessing the efficiency of thermal pre-treatment of Al alloy waste powders to facilitate their subsequent treatment and disposal. Five samples originating from aluminium surface finishing industries underwent thermogravimetric analyses and were subjected to a laboratory tub furnace. Four set temperatures (450, 475, 500, 525 °C) for the tubular furnace were selected based on the TG results. Using sequential images of the sample inside the tubular furnace, the ignition delay time was calculated. In addition, the efficiencies of medium-temperature thermal pre-treatment were determined using the gas volume method. The shot blasting samples (S1 and S2) exhibited shorter ignition delay times compared to the sandblasting (S3) and one of the polishing samples (S4). The influence of ZnO alloy content on the ignition delay time was investigated, revealing that the ignition delay time decreased with an increase in ZnO alloy content. The raw and pre-treated materials were analysed for morphology, composition and reactivity. The pre-treatment efficiency of the samples improved, especially with a retention time longer than the ignition delay of the samples. Recommendations for the storage and handling of pre-treated products were provided.

Predicting Ki-67 expression in hepatocellular carcinoma: nomogram based on clinical factors and contrast-enhanced ultrasound radiomics signatures.

To develop a contrast-enhanced ultrasound (CEUS) clinic-radiomics nomogram for individualized assessment of Ki-67 expression in hepatocellular carcinoma (HCC). A retrospective cohort comprising 310 HCC individuals who underwent preoperative CEUS (using SonoVue) at three different centers was partitioned into a training set, a validation set, and an external test set. Radiomics signatures indicating the phenotypes of the Ki-67 were extracted from multiphase CEUS images. The radiomics score (Rad-score) was calculated accordingly after feature selection and the radiomics model was constructed. A clinic-radiomics nomogram was established utilizing multiphase CEUS Rad-score and clinical risk factors. A clinical model only incorporated clinical factors was also developed for comparison. Regarding clinical utility, calibration, and discrimination, the predictive efficiency of the clinic-radiomics nomogram was evaluated. Seven radiomics signatures from multiphase CEUS images were selected to calculate the Rad-score. The clinic-radiomics nomogram, comprising the Rad-score and clinical risk factors, indicated a good calibration and demonstrated a better discriminatory capacity compared to the clinical model (AUCs: 0.870 vs 0.797, 0.872 vs 0.755, 0.856 vs 0.749 in the training, validation, and external test set, respectively) and the radiomics model (AUCs: 0.870 vs 0.752, 0.872 vs 0.733, 0.856 vs 0.729 in the training, validation, and external test set, respectively). Furthermore, both the clinical impact curve and the decision curve analysis displayed good clinical application of the nomogram. The clinic-radiomics nomogram constructed from multiphase CEUS images and clinical risk parameters can distinguish Ki-67 expression in HCC patients and offer useful insights to guide subsequent personalized treatment.

Evaluation of Rubber Dam Use in Endodontic Treatments in Terms of Patients' Awareness Level, Acceptability, and Usage Experience

Objective: This study aimed to measure patients' awareness levels about rubber dam used in endodontic treatments and their opinions about the necessity of its use, to evaluate their endodontic treatment experiences with rubber dam, and to compare the relationship between these opinions and treatment experience. Methods: A survey including 16-questions was designed to access the participants' demographic information and previous rubber dam experiences, their current experience, and their preferences for the use of rubber dams in subsequent treatments. 9 questions aimed to measure the attitude via five-point Likert scale indicating measurements ranging from strongly agree to strongly disagree. The survey was completed when the number of participants reached 150 patients. Fisher-Freeman-Halton test, Fisher's Exact test and Pearson Chi Square test were used to compare categorical data, and multiple comparisons were examined with the Bonferroni Corrected Z test. p<0.05 was considered sufficient for statistical significance. Results: 27.3% of the participants had previously received dental treatment with rubber dam. It was determined that there were significantly more patients with primary education levels among those who did not know the benefits of rubber dam use before coming to treatment (p=0.013). There was a statistically significant connection between the question "I was informed by my dentist about the reasons for using rubber dam before the treatment" and the question "I think the use of rubber dam is necessary for the dentist/patient" (p<0.001). In this study, only 4 people were observed who did not prefer rubber dam for the next treatment. Conclusion: Before endodontic procedures, the advantages and necessity of rubber dam use should be explained to patients in detail and the questions in the patients' minds should be eliminated. The clinician should improve himself in the use of rubber dam and provide the patient with a more comfortable treatment.

Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial

Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. AbbVie.

Allelopathic Responses of Crop Species to Chromolaena odorata Root Exudate Extracts: A Comprehensive Study

This study investigates the allelopathic effects of root exudate extracts from Chromolaena odorata on the germination and growth of six crop species. The results reveal variable sensitivity among the species, with the control treatment consistently exhibiting superior germination percentages. Initially, some species, including Abelmoschus esculentus (okra), Solanum lycopersicum (tomato), and Cicer arietinum (chickpea), experienced a substantial decline in germination, indicating a potential inhibitory effect of the exudates, although partial recovery was observed in subsequent treatments. Phaseolus vulgaris (common bean) displayed a moderate decrease, while Zea mays (corn) exhibited the most significant drop in germination rates, albeit with slight recovery at higher concentrations of exudates. Conversely, Cucumis sativus (cucumber) appeared least affected by the exudates. Moreover, all species demonstrated reductions in shoot and root lengths with increasing concentrations of exudates. Chlorophyll content analysis revealed a significant reduction across most treatments, highlighting concerns regarding photosynthetic efficiency and overall plant health. The species-specific response to root exudates suggests varying metabolic or adaptive mechanisms among crops. Additionally, malondialdehyde (MDA) levels, indicative of oxidative stress, varied among species, with A. esculentus and P. vulgaris showing a dose-dependent increase, while S. lycopersicum displayed a peak at intermediate treatment levels. Z. mays exhibited marginal elevation in MDA content, potentially indicating the presence of protective compounds within the exudates. Conversely, C. arietinum and C. sativus showed a steady increase in MDA, suggesting limited mitigation of allelopathic effects. These findings feature the complexity of allelopathic interactions and highlight the need for further research into active compounds and their modes of action to develop sustainable weed management strategies while safeguarding crop health. Understanding these dynamics is crucial for maximizing the potential benefits of allelopathy in agriculture.

A Case of Cervical Malignant Lymphoma with Carotid Sinus Syndrome Resoluted by Lymph Node Dissection and Subsequent Treatment

A Case of Cervical Malignant Lymphoma with Carotid Sinus Syndrome Resoluted by Lymph Node Dissection and Subsequent Treatment