Standard Of Care For Patients Research Articles

Inhibitors of the transactivation domain of androgen receptor as a therapy for prostate cancer

The androgen receptor (AR) is a modular transcription factor which functions as a master regulator of gene expression. AR protein is composed of three functional domains; the ligand-binding domain (LBD); DNA-binding domain (DBD); and the intrinsically disordered N-terminal transactivation domain (TAD). AR is transactivated upon binding to the male sex hormone testosterone and other androgens. While the AR may tolerate loss of its LBD, the TAD contains activation function-1 (AF-1) that is essential for all AR transcriptional activity. AR is frequently over-expressed in most prostate cancer. Currently, androgen deprivation therapy (ADT) in the form of surgical or chemical castration remains the standard of care for patients with high risk localized disease, advanced and metastatic disease, and those patients that experience biochemical relapse following definitive primary treatment. Patients with recurrent disease that receive ADT will ultimately progress to lethal metastatic castration-resistant prostate cancer. In addition to ADT not providing a cure, it is associated with numerous adverse effects including cardiovascular disease, osteoporosis and sexual dysfunction. Recently there has been a renewed interest in investigating the possibility of using antiandrogens which competitively bind the AR-LBD without ADT for patients with hormone sensitive, non-metastatic prostate cancer. Here we describe a class of compounds termed AR transactivation domain inhibitors (ARTADI) and their mechanism of action. These compounds bind to the AR-TAD to inhibit AR transcriptional activity in the absence and presence of androgens. Thus these inhibitors may have utility in preventing prostate cancer growth in the non-castrate setting.

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p=0.04), more than three suspicious nodes on initial US (30% vs 13%; p≤0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p=0.0004), and more positive TAD nodes (median, 2 vs 1; p≤0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p≤0.0001), more positive TAD nodes (OR, 1.1; p≤0.0001), larger clipped node metastasis (OR, 1.1; p≤0.0001), and larger residual tumor on pathology (OR, 1.1; p=0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial

The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial. COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0-1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450-1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT03682536; active, not recruiting). Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69-80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4-27·7) for the luspatercept group and 16·9 months (10·1-26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] vs 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8-35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2-32·4) for the luspatercept group and 20·3 months (12·7-30·9) for the epoetin alfa group. Common grade 3-4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis. Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups. Celgene and Acceleron Pharma.

Post-Mastectomy Breast Reconstruction Disparities: A Systematic Review of Sociodemographic and Economic Barriers

Background: Breast reconstruction (BR) following mastectomy is a well-established beneficial medical intervention for patient physical and psychological well-being. Previous studies have emphasized BR as the gold standard of care for breast cancer patients requiring surgery. Multiple policies have improved BR access, but there remain social, economic, and geographical barriers to receiving reconstruction. Threats to equitable healthcare for all breast cancer patients in America persist despite growing awareness and efforts to negate these disparities. While race/ethnicity has been correlated with differences in BR rates and outcomes, ongoing research outlines a multitude of issues underlying this variance. Understanding the current and continuous barriers will help to address and overcome gaps in access. Methods: A systematic review assessing three reference databases (PubMed, Web of Science, and Ovid Medline) was carried out in accordance with PRISMA 2020 guidelines. A keyword search was conducted on 3 February 2024, specifying results between 2004 and 2024. Studies were included based on content, peer-reviewed status, and publication type. Two independent reviewers screened results based on title/abstract appropriateness and relevance. Data were extracted, cached in an online reference collection, and input into a cloud-based database for analysis. Results: In total, 1756 references were populated from all databases (PubMed = 829, Ovid Medline = 594, and Web of Science = 333), and 461 duplicate records were removed, along with 1147 results deemed ineligible by study criteria. Then, 45 international or non-English results were excluded. The screening sample consisted of 103 publications. After screening, the systematic review produced 70 studies with satisfactory relevance to our study focus. Conclusions: Federal mandates have improved access to women undergoing postmastectomy BR, particularly for younger, White, privately insured, urban-located patients. Recently published studies had a stronger focus on disparities, particularly among races, and show continued disadvantages for minorities, lower-income, rural-community, and public insurance payers. The research remains limited beyond commonly reported metrics of disparity and lacks examination of additional contributing factors. Future investigations should elucidate the effect of these factors and propose measures to eliminate barriers to access to BR for all patients.

PACIFIC-9: Phase III trial of durvalumab+oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer.

Evidence from the Phase III PACIFIC trial established durvalumab, a monoclonal antibody (mAb) targeting PD-L1, following concurrent chemoradiotherapy (cCRT) as a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). There remains an unmet need to improve upon the outcomes achieved with the PACIFIC regimen. Combining durvalumab with other immunotherapies may improve outcomes further. Two such immunotherapies include oleclumab, an mAb targeting CD73, and monalizumab, an mAb targeting NKG2A. Both agents demonstrated antitumor activity in early-phase trials. PACIFIC-9 (NCT05221840) is an international, double-blind, randomized, placebo-controlled, Phase III trial comparing durvalumab plus either oleclumab or monalizumab with durvalumab plus placebo in patients with unresectable, stage III NSCLC and no disease progression following cCRT.Clinical Trial Registration: NCT05221840 (ClinicalTrials.gov).

Low dose lenalidomide versus placebo in non-transfusion dependent patients with low risk, del(5q) myelodysplastic syndromes (SintraREV): a randomised, double-blind, phase 3 trial

Lenalidomide is the standard of care for patients who are transfusion dependent with chromosome 5q deletion (del[5q]) myelodysplastic syndromes. In the SintraREV trial, we aimed to investigate whether an early intervention of low lenalidomide doses for 2 years could delay transfusion dependency in patients with anaemia who were not transfusion dependent. This randomised, double-blind, phase 3 trial, was conducted at 22 sites (University Hospitals) in Spain, France, and Germany. Eligible patients were aged 18 years or older diagnosed with low-risk or intermediate-1-risk del(5q) myelodysplastic syndromes with non-transfusion-dependent anaemia (according to the IPSS), were erythropoietin-stimulating agents naive, and had an ECOG performance status of 2 or less. Patients were randomly assigned (2:1) by means of a telephone system to receive lenalidomide 5 mg daily in 28-day cycles versus placebo for 2 years. The primary endpoint was time to transfusion dependency based on blinded independent central review. Analysis were by intent-to-treat (ITT) and evaluable population. Safety analyses included all participants who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT01243476) and EudraCT (2009-013619-36) and is complete. Between Feb 15, 2010, and Feb 21, 2018, 61 patients were randomly assigned to receive lenalidomide (n=40; two did not receive treatment) or placebo (n=21). The median age was 72·2 (IQR 65·4-81·9) years, 50 (82%) patients were female, and 11 (18%) were male. The median follow-up time was 60·6 (IQR 32·1-73·9) months. Regarding primary endpoint, median time to transfusion dependency was not reached (95% CI not applicable) in the lenalidomide group versus 11·6 months (95% CI 0·00-30·11) in the placebo group (p=0·0027). Lenalidomide significantly reduced the risk of transfusion dependency by 69·8% (hazard ratio 0·302, 95% CI 0·132-0·692; p=0·0046). The most frequent treatment-related adverse event was neutropenia, occurring in 24 (63%) of 38 patients in the lenalidomide group (grade 3 and 4 in 17 [45%] patients and one [3%], respectively) and in four (19%) of 21 patients in the placebo group (grade 3 in one [5%] patient). Thrombocytopenia was detected in seven (18%) of 38 patients receiving lenalidomide (grade 3 in two [5%] patients). Regarding the non-haematological toxicity, skin disorders (rash nine [23%] of 38 patients) were the most frequently described toxicities among patients receiving lenalidomide, being grade 3 in one (3%) of 38 patients. 19 serious adverse events were reported in 13 patients, 18 in the lenalidomide group and one in the placebo group, five of which were potentially related to the study drug. No treatment-related deaths were identified. An early approach with low doses of lenalidomide across two years delays the time to transfusion dependency and improves the rate and quality of the responses, with a manageable safety profile in patients who are non-transfusion dependent with del(5q) low-risk myelodysplastic syndromes. Bristol Myers Squibb.

Augmented Reality Assisted Intraoperative Navigation Increases Precision of Glenoid Inclination in Reverse Shoulder Arthroplasty

BackgroundReverse Total Shoulder Arthroplasty (RTSA) is the standard of care for patients with glenohumeral osteoarthritis and rotator cuff deficiency. Preoperative RTSA planning based on medical images and patient-specific instruments has been established over the last decade. This study aims to determine the effects of using augmented reality assisted intraoperative navigation (ARIN) for baseplate positioning in RTSA compared to preoperative planning. It is hypothesized that ARIN will decrease deviation between preoperative planning and postoperative baseplate positioning. Moreover, ARIN will decrease deviation between the (senior) more (> 50 RTSA/year) and less experienced (junior) surgeon (5-10 RTSA/year). MethodsPreoperative CT scans of sixteen fresh-frozen cadaveric shoulders were obtained. Baseplate placements were planned using a validated software. The data was then converted and uploaded to the augmented reality system (NextAR; Medacta International, Castel San Pietro, Switzerland). Each of the eight RTSAs were implanted by a senior and a junior surgeon, with four RTSAs utilizing ARIN and four without. A postoperative CT scan was performed in all cases. The scanned scapulae were segmented, and the preoperative scan was laid over the postoperative scapula by nearest iterative point cloud analysis. The deviation from the planned entry point and trajectory was calculated regarding the inclination, retroversion, medialization (reaming depth)/lateralization, antero-posterior position and superior/inferior position of the baseplate. Data are reported as mean ± standard deviation (SD) or mean and 95% confidence interval (CI). P values <0.05 were considered statistically significant. ResultsThe use of ARIN yielded a reduction in the absolute difference between planned and obtained inclination from 9° (SD: 4°) to 3° (SD°:2) (p=0.011). Mean difference in planned-obtained inclination between surgeons was 3° in free-hand surgeries (95%CI: -4,10, p=0.578), while this difference reduced to 1° (95%CI: -6, 7, p=0.996) using ARIN. Retroversion, medialization (reaming depth)/lateralization, antero-posterior position and superior/inferior position of the baseplate were not affected by using ARIN. Surgical duration was increased using ARIN for both the senior (10 mins) and junior (18 mins) surgeon. ConclusionsThe implementation of augmented reality assisted intraoperative navigation (ARIN) leads to greater accuracy of glenoid component placement, specifically with respect to inclination. Further studies have to verify if this increased accuracy is clinical important. Furthermore, ARIN allows less experienced surgeons to achieve a similar level of accuracy in component placement comparable to more experienced surgeons. However, the potential advantages of ARIN in RTSA are counterbalanced by an increase in operative time.

Telemedicine and Teamwork Among Health Care Professionals: State of the Science.

Background: As telemedicine becomes further rooted in standard patient care delivery, it is critical to understand how it may affect teamwork among health care providers. Understanding the state of the science between telemedicine and teamwork is an important first step. Obejctive: The purpose of this state-of-the-science review was to synthesize the published research on teamwork within the context of telemedicine. Methods: Data abstraction and analysis were structured following the Virtual Team Performance and the "Big Five" of Teamwork theoretical frameworks. The concepts within these models were used to organize data extraction. This state of the science used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Results: A total of 14 studies met the inclusion criteria after final review. The most common variables were communication, tasks, leadership, team orientation, and team cohesion. Despite variable commonalities across the included articles, there was a discrepancy between improved and reduced teamwork outcomes with telemedicine. Conclusions: Multiple teamwork variables are influential across health care teams using telemedicine technologies-those that include communication, task facilitation, leadership, team orientation, and cohesion appear to have the greatest impact. However, it is not an individual teamwork variable, type of technology, or care environment alone that influences positive or negative outcomes among health care teams using telemedicine. Instead, it is a combination of factors and mechanisms that facilitate or hinder teamwork outcomes. A comprehensive model that describes the interaction of these common variables in teamwork among blended virtual and in-person health care teams is needed.

Cultivating and Sharing Tacit Knowledge in the Medical Field

This study explores tacit knowledge transfer in healthcare, aiming to identify barriers and opportunities in sharing this nuanced expertise among practitioners and its impact on patient care standards. Employing a mixed-methods approach, it gathers data from healthcare professionals, analyzing it via reliability, statistical tests, and multinomial logistic regression. Results show moderate scale reliability, significant relationships between responses, and various factors influencing patient care quality, such as patient confidentiality, effectiveness of mentoring programs, and engagement in online forums. Challenges in tacit knowledge transfer were found insignificant, yet specific factors like mentoring and online participation are crucial for care quality. The study concludes that mentorship and organizational strategies play vital roles in enhancing care delivery by facilitating tacit knowledge sharing, underlining the importance of addressing confidentiality issues, and promoting innovation through active online engagement and effective knowledge use.

Perceived social support mediates cancer and living meaningfully intervention effects on quality of life after breast cancer surgery.

Aim: To explore the role of perceived social support in enhancing psychological resilience and quality of life in postoperative breast cancer patients. Materials & methods: The Managing Cancer and Living Meaningfully (CALM) intervention was used to improve indicators such as psychological resilience in breast cancer patients, while the role of perceived social support in this was assessed. Results: The intervention group exhibited significant improvements compared with the control group in psychological resilience (F=9.059, p<0.01). The analysis showed that increased social support in the control group partly mediated the link between psychological resilience and quality of life. Conclusion: CALM improves overall well-being, indicating that incorporating it into standard care for post-mastectomy patients can positively impact their mental health.

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Pseudomyxoma Peritonei.

The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) constitutes the established standard of care for pseudomyxoma peritonei patients. However, the role of HIPEC lacks validation through randomized trials, leading to diverse proposed treatment protocols. This consensus seeks to standardize HIPEC regimens and identify research priorities for enhanced clarity. The steering committee applied the patient, intervention, comparator, and outcome method to formulate crucial clinical questions. Evaluation of evidence followed the Grading of Recommendations, Assessment, Development, and Evaluation system. Consensus on HIPEC regimens and research priorities was sought through a two-round Delphi process involving international experts. Out of 90 eligible panelists, 71 (79%) participated in both Delphi rounds, resulting in a consensus on six out of seven questions related to HIPEC regimens. An overwhelming 84% positive consensus favored combining HIPEC with CRS, while a 70% weak positive consensus supported HIPEC after incomplete CRS. Specific HIPEC regimens also gained consensus, with 53% supporting Oxaliplatin 200mg/m2 and 51% favoring the combination of cisplatin (CDDP) associated with mitomycin-C (MMC). High-dose MMC regimens received an 89% positive recommendation. In terms of research priorities, 61% of panelists highlighted the importance of studies comparing HIPEC regimens post CRS. The preferred regimens for such studies were the combination of CDDP/MMC and high-dose MMC. The consensus recommends the application of HIPEC following CRS based on the available evidence. The combination of CDDP/MMC and high-dose MMC regimens are endorsed for both current clinical practice and future research efforts.

The role of ERAS in pancreaticoduodenectomy: A systematic review and meta-analysis.

Introduction This study aimed to compare the safety and short-term outcomes of ERAS with standard care for patients undergoing pancreatoduodenectomy (PD) based on literature published following the first publication of ERAS guidelines for PD. Methods Five medical databases were searched for studies that compared ERAS to standard care in adults undergoing PD. Data on postoperative complications, length of hospitalization, readmissions, and time to chemotherapy were analyzed using either a fixed- or random-effects model meta-analysis. Meta-regressions were conducted to investigate the role of operative technique, study origin, and study design. Results Our analysis included 22 studies involving 4043 patients. ERAS was associated with fewer complications (RR: 0.83; 0.75 to 0.91), particularly Clavien-Dindo (CD) grade 1 and 2 complications (RR: 0.82; 0.72 to 0.92), delayed gastric emptying (RR: 0.69; 0.52 to 0.93), and postoperative fistula (POPF) (RR: 0.76; 0.66 to 0.89), and a shorter time to chemotherapy (SMD: -0.68; 95% CI: -0.88 to -0.48). ERAS did not affect the risk for CD grade 3 and 4 complications (RR: 1.00; 0.72 to 1.38), post-pancreatectomy hemorrhage (RR: 0.88; 0.67 to 1.14), length of stay (SMD: -0.56; 95% CI: -1.12 to 0.01), readmission (RR: 1.01; 0.84 to 1.21), and mortality (RR: 0.81; 0.54 to 1.22). The continent of origin was an effect moderator in the role of ERAS in CD grade 1 and 2 complications (p= 0.047) and POPF (p=0.02). Conclusion Implementing ERAS principles in PD improves surgical outcomes without compromising safety. ERAS may also accelerate time to chemotherapy, an essential issue for future research.

An Insight Into Risk Assessment and Reformulation of Drug Products Manufactured Using Benzene Grade Carbomer: A Regulatory Perspective.

Cancer has been an enormous pain point for patients and regulatory bodies across the globe. In Dec. 2023, the US FDA released guidance on benzene-grade carbomer formulations, which triggered pharmaceutical manufacturers to assess risk, test finished products, and reformulate drug products with benzene-grade carbomer. The immediate implementation of the stoppage of finished products with benzene-grade carbomers has threatened pharmaceutical excipients and finished product manufacturers. The gravity of this situation prompted the US Pharmacopeia to extend the deadline for discontinuation from August 1, 2025, to August 1, 2026, allowing manufacturers ample time for reformulation and regulatory compliance.There is an immediate need to understand the guidance and to learn how manufacturers should do the risk assessment and approach reformulation. This review provides an in-depth analysis of the risk assessment and reformulation processes involved in various dosage forms utilizing benzene-grade carbomer, supported by specific case studies.This review offers insights into navigating the USFDA guidelines to ensure formulation safety and compliance, thus enabling pharmaceutical practitioners to uphold the highest standards of patient care and tackle life cycle management challenges.The decision of the USFDA to restrict the usage of high benzene content of carbomer in the formulation is a welcome move. This article has shown a way for researchers to see opportunities in the path and provide best-in-class medicines to patients with a better formulation safety profile.

CSF1R Inhibition in Patients With Advanced Solid Tumors or Tenosynovial Giant Cell Tumor: A Phase 1 Study of Vimseltinib.

Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control tyrosine kinase inhibitor designed to selectively and potently inhibit the CSF1 receptor. This first-in-human, multicenter, open-label, phase 1/2 study of vimseltinib in patients with malignant solid tumors (N = 37) or TGCT not amenable to surgery (N = 32) followed a pharmacologically guided 3 + 3 study design (NCT03069469). The primary objectives were to assess safety and tolerability, determine the recommended phase 2 dose (RP2D), and characterize the pharmacokinetics (PK); exploratory objectives included pharmacodynamics and efficacy. Vimseltinib was well tolerated; the majority of non-laboratory treatment-emergent adverse events were grade 1/2. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The RP2D was determined to be 30 mg twice weekly (no loading dose), and vimseltinib plasma exposure increased with the dose. In patients with TGCT, the median treatment duration was 25.1 months (range, 0.7 to 46.9), and the objective response rate as assessed by independent radiological review using Response Evaluation Criteria in Solid Tumors version 1.1 was 72%. Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT whose disease is not amenable to surgery.

Stereotactic body radiation therapy for multiple lung cancers in a patient with six primary cancers: a case report

BackgroundSurgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer.Case presentationWe report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings.ConclusionA total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.

Limited access to transcranial Doppler screening and stroke prevention for children with sickle cell disease in Europe: Results of a multinational EuroBloodNet survey.

Ensuring equitable access to adequate standard of care for patients with rare hematological disease is one of the aims of the European Reference Network (ERN) EuroBloodNet. Stroke is one of the most devastating complications for children with sickle cell disease (SCD). For effective prevention of stroke risk, annual transcranial Doppler (TCD) according to a defined protocol is recommended for patients aged 2-16years, with red blood cell transfusion therapy for those at risk. There is no information regarding screening for stroke risk and stroke prevention programs in Europe. Seven SCD experts of five healthcare providers (HCPs) of ERN EuroBloodNet developed an online survey to assess the access to TCD screening and stroke prevention programs for children with SCD in Europe. Eighty-one experts in 77 HCPs from 16 European countries responded to 16 online questions. Thirty-two of 77 (51%) HCPs were EuroBloodNet reference centers, and 36% physicians reported not having a dedicated TCD/TCD imaging service for children with SCD. Only 30% of physicians provided estimates that all their patients received annual TCD according to the standard protocol due to lack of trained staff (43%), lack of TCD instruments (11%), refusal of patients due to logistical difficulties (22%), and lack of funds for dedicated staff or equipment (11%). This multinational European survey provides the first comprehensive picture of access to TCD screening and stroke prevention in European countries. Identifying the potential underlying causes of the lack of effective standardized screening, this survey also addresses possible dedicated actions to cover these needs.

Limited access to transcranial Doppler screening and stroke prevention for children with sickle cell disease in Europe: Results of a multinational EuroBloodNet survey.

Ensuring equitable access to adequate standard of care for patients with rare hematological disease is one of the aims of the European Reference Network (ERN) EuroBloodNet. Stroke is one of the most devastating complications for children with sickle cell disease (SCD). For effective prevention of stroke risk, annual transcranial Doppler (TCD) according to a defined protocol is recommended for patients aged 2-16years, with red blood cell transfusion therapy for those at risk. There is no information regarding screening for stroke risk and stroke prevention programs in Europe. Seven SCD experts of five healthcare providers (HCPs) of ERN EuroBloodNet developed an online survey to assess the access to TCD screening and stroke prevention programs for children with SCD in Europe. Eighty-one experts in 77 HCPs from 16 European countries responded to 16 online questions. Thirty-two of 77 (51%) HCPs were EuroBloodNet reference centers, and 36% physicians reported not having a dedicated TCD/TCD imaging service for children with SCD. Only 30% of physicians provided estimates that all their patients received annual TCD according to the standard protocol due to lack of trained staff (43%), lack of TCD instruments (11%), refusal of patients due to logistical difficulties (22%), and lack of funds for dedicated staff or equipment (11%). This multinational European survey provides the first comprehensive picture of access to TCD screening and stroke prevention in European countries. Identifying the potential underlying causes of the lack of effective standardized screening, this survey also addresses possible dedicated actions to cover these needs.

Updates on the diagnosis and management of subdural hematoma.

Intracranial hemorrhage is a potentially life-threatening condition categorized into four main groups by the location of bleeding: epidural, subdural, subarachnoid, and intraparenchymal. Subdural hematoma (SDH) is increasingly common as the population of older adults increases. Clinicians must recognize the typical presentations and order diagnostic imaging studies to make a timely diagnosis and referral to neurosurgery for definitive treatment. Understanding the pathophysiology and risk factors for chronic or expanding SDH informs decision-making in managing anticoagulants. Emerging treatments offer potential alternatives to the traditional evacuation of SDH by craniotomy, which remains the standard of care for most symptomatic patients.

Analysis of Circulating Tumor DNA Predicts Outcomes of Short-Course Consolidation Immunotherapy in Unresectable Stage III NSCLC

IntroductionThe current standard of care for patients with inoperable stage III NSCLC includes chemoradiotherapy (CRT) followed by 1 year of checkpoint inhibitor (CPI) therapy. Nevertheless, the optimal duration of consolidation CPI remains unknown. Here, we characterized the relationship between circulating tumor DNA (ctDNA) minimal residual disease (MRD) and clinical outcomes of patients with unresectable locally advanced NSCLC treated on a phase 2 trial of short-course consolidation immunotherapy after CRT, with the goal of testing whether ctDNA may be able to identify patients who do not require a full year of treatment. MethodsPlasma samples for ctDNA analysis were collected from patients on the BTCRC LUN 16-081 trial after completion of CRT, before C2D1 of CPI (i.e., 1 mo after treatment start), and at the end of up to 6 months of treatment. Tumor-informed ctDNA MRD analysis was performed using CAPP-Seq. Levels of ctDNA at each time point were correlated with clinical outcomes. ResultsDetection of ctDNA predicted significantly inferior progression-free survival after completion of CRT (24-mo 29% versus 65%, p = 0.0048), before C2D1 of CPI (24-mo 0% versus 72%, p < 0.0001) and at the end of CPI (24-mo 15% versus 67%, p = 0.0011). In addition, patients with decreasing or undetectable ctDNA levels after 1 cycle of CPI had improved outcomes compared with patients with increasing ctDNA levels (24-mo progression-free survival 72% versus 0%, p < 0.0001). Progression of disease occurred within less than 12 months of starting CPI in all patients with increasing ctDNA levels at C2D1. ConclusionsDetection of ctDNA before, during, or after 6 months of consolidation CPI is strongly associated with inferior outcomes. Our findings suggest that analysis of ctDNA MRD may enable personalizing the duration of consolidation immunotherapy treatment.

Therapeutic challenges and unmet needs in the management of myasthenia gravis: an Italian expert opinion.

Myasthenia gravis (MG) is a rare, autoimmune, neurological disorder. Most MG patients have autoantibodies against acetylcholine receptors (AChRs). Some have autoantibodies against muscle-specific tyrosine kinase (MuSK) or lipoprotein-receptor-related protein 4 (LRP4), and some are seronegative. Standard of care, which includes anti-cholinesterase drugs, thymectomy, corticosteroids (CS), and off-label use of non-steroidal immunosuppressive drugs (NSISTs), is bounded by potential side effects and limited efficacy in refractory generalized MG (gMG) patients. This highlights the need for new therapeutic approaches for MG. Eculizumab, a monoclonal antibody that inhibits the complement system, has been recently approved in Italy for refractory gMG. A panel of 11 experts met to discuss unmet therapeutic needs in the acute and chronic phases of the disease, as well as the standard of care for refractory patients. Survival was emphasized as an acute phase outcome. In the chronic phase, persistent remission and early recognition of exacerbations to prevent myasthenic crisis and respiratory failure were considered crucial. Refractory patients require treatments with fast onset of action, improved tolerability, and the ability to slow disease progression and increase life expectancy. The Panel agreed that eculizumab would presumably meet the therapeutic needs of many refractory gMG patients. The panel concluded that the unmet needs of current standard of care treatments for gMG are significant. Evaluating new therapeutic options accurately is essential to find the best balance between efficacy and tolerability for each patient. Collecting real-world data on novel molecules in routine clinical practice is necessary to address unmet needs.