Berkshire Medical Center

Breaking the Boundary of the Concept of Inventor in Patent Law in the Age of Artificial Intelligence——The Limitations of Anthropocentric Legislation: A Look at the DABUS Case-Future Trends in AI Research-Hill Publishing Group

ABSTRACTRadiation therapy is a fundamental component of cancer treatment, benefiting 50%–70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial–mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N‐cadherin, and downregulating epithelial markers, such as E‐cadherin. EMT under radiation involves principal signaling pathways, including TGF‐β, Wnt/β‐catenin, Notch, and ERK, which regulate EMT through transcription factors such as Snail, Slug, Twist, and Zeb1/2. These alterations drive cytoskeletal reorganization, decrease cell–cell adhesion, and enhance extracellular matrix degradation via integrins, MMP‐2, and MMP‐9. We also explored how growth hormones, inflammatory cytokines, and hypoxia in the tumor microenvironment affect radiation‐induced EMT. Targeting EMT pathways with monoclonal antibodies and small‐molecule inhibitors of signaling pathways may help overcome radioresistance. However, due to the dual role of EMT in cancer progression and tissue regeneration, precise treatment strategies are essential. There is a lack of comprehensive multi‐omics studies that provide insights into postradiation EMT progression. This review examines how radiation induces EMT and its impact on metastasis and immune responses while also proposing therapeutic approaches. Integrating EMT‐targeting strategies with existing cancer treatments could enhance the effectiveness of radiotherapy and improve patient outcomes.

The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS. We systematically searched electronic databases for studies on patients with PSS on ASMs. Our outcomes were seizure recurrence, adverse events, drug discontinuation rate, and mortality. We assessed the risk of bias using Cochrane Risk of Bias tool for randomized controlled trials and Risk Of Bias In Non-randomized Studies of Interventions tools. Using levetiracetam as the reference treatment, we conducted a frequentist network meta-analysis and determined the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Our search yielded 15 studies (3 randomized, 12 nonrandomized, N = 18,676 patients (121 early and 18,547 late seizures), 60% male, mean age 69 years) comparing 13 ASMs. Three studies had moderate and 12 had high risk of bias. Seizure recurrence was 24.8%. Compared with levetiracetam, very low-certainty evidence suggested that phenytoin was associated with higher seizure recurrences (odds ratio [OR] 7.3, 95% CI 3.7-14.5) and more adverse events (OR 5.2, 95% CI 1.2-22.9). Low-certainty evidence suggested that carbamazepine (OR 1.8, 95% CI 1.5-2.2) and phenytoin (OR 1.9, 95% CI 1.4-2.8) were associated with high drug discontinuation rates. Moderate to high-certainty evidence suggested that valproic acid (OR 4.7, 95% CI 3.6-6.3) and phenytoin (OR 8.3, 95% CI 5.7-11.9) were associated with higher mortality rates. Considering all treatments and using the GRADE approach for treatment ranking, very low-certainty evidence suggested that eslicarbazepine, lacosamide, and levetiracetam had the fewest seizure recurrences. Low to very low-certainty evidence suggested that lamotrigine had the fewest adverse events and drug discontinuations, whereas lamotrigine and levetiracetam exhibited low mortality rates with moderate-certainty evidence. We found that levetiracetam and lamotrigine may be safe and tolerable ASMs for PSS. Despite ASM use, the seizure recurrence rate remains high in the PSS population. Owing to bias and confounding risks, these findings should be interpreted cautiously. PROSPERO: CRD42022363844.

Among persons with HIV (PWH), unhealthy alcohol use and polypharmacy contribute to bothersome symptoms (e.g., fatigue, dizziness, memory loss). However, effective risk communication targeting these associations is challenging. The HIV and Alcohol Research center focused on Polypharmacy (HARP) is conducting a pilot study that will generate feasibility and acceptability data on a clinical pharmacist-delivered counseling intervention targeting the modification of unhealthy alcohol use and polypharmacy in PWH. Counseling is guided by the Information-Motivation-Behavioral Skills-Motivational Interviewing (IMB-MI) model. Herein, we describe the study protocol. This pilot uses a one-group pre-test/post-test design. We will recruit 50 participants from those who participated in the consented cohort of the Veterans Aging Cohort Study. Participants must be prescribed ≥ 5 long-term medications, have a self-reported Alcohol Use Disorders Identification Test score > 0, and be living with HIV. We will exclude those with moderate-severe alcohol use disorder as identified by an Alcohol Symptom Checklist score ≥ 4. Data are collected using three self-administered surveys (baseline, immediately after booster intervention, and 30-days post-intervention), two PEth blood tests (baseline, 30 days post-intervention), and medication data from the electronic health record (baseline). The intervention includes a 60-minute IMB-MI-based counseling session followed by a booster session 2 weeks later. Some participants will also be asked to participate in a qualitative interview to provide feedback on the intervention. The pilot investigates the impact of an intervention on alcohol consumption and the use of multiple medications among PWH, exploring how best to reduce bothersome symptoms, communicate risk, and support behavior change in this population.

Background: Baclofen is a gamma-aminobutyric acid derivative that inhibits presynaptic motor neurons, resulting in central anti spasticity. It is commonly used to treat muscle spasticity caused by central nervous system disorders. Baclofen neurotoxicity cases are usually iatrogenic but are poorly recognized resulting in significant health problems, mortality, and hospital resource utilization. Therefore, we present here a review of cases published in literature in regard to baclofen induced toxicity in patients with impaired renal function. Methods: We searched pubmed database for key words: baclofen (adverse effects, poisoning, toxicity), chronic kidney failure, chronic renal insufficiency, end stage renal disease (Figure 1). Results: We reviewed 12 published articles, with 16 patients of avg. CKD stage IV or V who received variable baclofen dose and developed neurotoxicity (Figure 2). Conclusion: Our review emphasizes the association of baclofen use with adverse side effects in patients with chronic kidney disease including encephalopathy, dyskinesia, lethargy and tremors. The review highlights that as providers we need to recognize contraindications of baclofen use in patients with impaired renal function and consider other treatment options. Another important aspect is that there are currently no clear guidelines for dosing of baclofen in patients with decreased kidney function. Finally, the management of baclofen toxicity remains variable with no standard recommendations especially for patients with chronic kidney disease.

Abstract Background: Patients with TNBC are highly encouraged to participate in clinical trials given the lack of targeted treatment options for this breast cancer subtype. Yet little is known regarding barriers to trial participation in this population, including the impact of patients’ understanding about TNBC biology. We examined whether disease knowledge and other patient-level factors were associated with TNBC patients’ participation in trials. Methods: From a multicenter, prospective cohort study of patients enrolled from 2019-present with newly diagnosed TNBC (ER/PR ≤10% also eligible), we identified those with stage I-III tumors who completed at least one survey. Surveys assessed demographics, TNBC knowledge, risk perceptions, and participation in clinical trials. Patients were assigned to Cohort A if surgery was the first intervention and Cohort B if neoadjuvant therapy was given. Medical records were reviewed to verify the accuracy of tumor characteristics reported by patients. Data was summarized with descriptive statistics and logistic regression was used to identify factors associated with trial participation. Results: Of the 137 patients included, median age was 56 years (IQR 46-63), 104 (82%) were non-Hispanic White, 10 (8%) Black, 5 (4%) Hispanic. and 110 (86%) had at least some college education. Overall, 55 (41%) had stage I tumors, 65 (48%) stage II, and 14 (10%) stage III. Among 116 patients with available clinical trial participation data, 55 (47%) reported trial participation, 59 (51%) reported no trial participation, and 2 (2%) were unsure. The majority (36/55, 65%) of trial participants were in Cohort B. Among 129 patients with TNBC knowledge data, 82 (64%) and 73 (57%) correctly reported their tumor stage and grade, respectively. Most (104/129, 81%) knew TNBC was defined as ER/PR/HER2-negative, but only 16% (21/128) knew the ER/PR-negative cut off was ≤1%. Of 98 patients with risk perception data, 30 (31%) estimated their likelihood of recurrence within the next 5 years as 0%, 60 (61%) between 10-50%, and 8 (8%) between 60-100%. When asked if TNBC patients who remain cancer-free after 3 years will most likely not experience recurrence, 44 (45%) said “True,” 13 (13%) said “False,” and 40 (41%) were unsure. On univariate analysis, trial participation was less likely in Cohort A patients (OR 0.42, 95% CI 0.20 – 0.89, P=0.02) and more likely in stage II patients (vs. stage I, OR 2.43, 95% CI 1.09 – 5.39, P=0.03). On multivariable analysis, patients with at least some college education had higher odds of trial participation compared to patients with a college degree or higher (OR 3.21, 95% CI 1.11 – 9.28, P=0.03). No associations were found for other factors, including TNBC knowledge. Conclusions: About half of TNBC patients surveyed reported participating in clinical trials. Most of these patients were undergoing neoadjuvant therapy, likely reflective of greater study availability in this setting. While TNBC knowledge was not significantly associated with trial participation in this small sample, a considerable number of patients reported their tumor characteristics incorrectly and/or appeared to underestimate their recurrence risks. This highlights the need for enhanced informational support for TNBC patients during treatment decision-making. More research is needed to understand barriers to trial participation in this population to leverage patient engagement and accelerate progress towards more effective treatments for TNBC. Citation Format: Megan Tesch, Noah Graham, Sean Ryan, Melissa Hughes, Eileen Wrabel, Nadine Tung, Steve Lo, Thomas Fynan, Meredith Faggen, Natalie Sinclair, Maria Constantinou, Sarah Sinclair, Nabihah Tayob, Nancy Lin, Ann Partridge, Eric Winer, Sara Tolaney, Ana Garrido-Castro. Association of patient-reported triple-negative breast cancer (TNBC) knowledge with clinical trial participation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-08.

Kalantar-Zadeh, Kamyar; Edwards, Dawn P.; Henner, David; Landry, Daniel L.; Molony, Donald A.; Yerram, Preethi; on behalf of the Medical Advisory Council of the National Forum of ESRD Networks Collaborators Landry, Daniel L. DO; Coritsidis, George MD; Norris, Keith MD, PhD; Palevsky, Paul MD; Brazie, Marc MD; Doran, John J. MD; Hain, Debra PhD, APRN; Tankersley, Martha MSN, RN; Huml, Anne MD, MS; Roseman, Daniel MD; Raymond, Louis MD; Yerram, Preethi MD; Rankin, Laura MD; Molony, Donald MD; Singh, Harmeet MD; Logar, Christine MD; Sam, Ramin MD; Kalantar-Zadeh, Kamyar MD, MPH, PhD Author Information

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Vaccinating dialysis patients may prevent morbidity and mortality in this vulnerable population. The National Forum of End-Stage Renal Disease (ESRD) Networks (the Forum) published a revised vaccination toolkit in 2021 to update evidence and recommendations on vaccination for patients receiving dialysis. Significant changes in the last 10 years include more data supporting use of a high-dose influenza vaccine, the introduction of the Heplisav-B® vaccine for Hepatitis B, and changes in pneumococcal vaccines, including the approval of the PCV15 and PCV20 to replace the PCV13 and PPSV23 vaccines. Additional key items include the introduction of vaccines against SARS-CoV-2, the virus that causes COVID-19, and a new vaccine to prevent respiratory syncytial virus (RSV) disease. Historically, influenza and pneumococcal vaccinations were routinely administered by dialysis facilities, and, due to possible risks of hematogenous spread of Hepatitis B, dialysis providers often have detailed hepatitis B vaccine protocols. In March 2021, COVID-19 vaccines were made available for dialysis facilities to administer, although with the end of the public health emergency, vaccine policies by dialysis facilities against COVID-19 remains uncertain. The RSV vaccine was authorized in 2023, and how dialysis facilities will approach this vaccine also remains uncertain. This review summarizes the Forum’s vaccination toolkit and discusses the role of the dialysis facility in vaccinating patients to reduce the risk of severe infections.