Line Treatment Research Articles

Impact of cyclin dependent kinase 4/6 inhibitors on breast cancer brain metastasis outcomes

BackgroundCyclin dependent kinase 4/6 inhibitors (CDK4/6i) are recommended 1st line treatments in HR+HER2- metastatic breast cancer. However, the impact of prior CDK4/6i on the natural history of brain metastases (BM) is not well described. Materials and methodsWe reviewed retrospective data for 363 patients with HR+HER2- BM who received a CDK4/6i (CDK-Y) between 1 Jan 2015 to 31 July 2021 and 299 patients with HR+HER2- BM who did not receive a CDK4/6i (CDK-N) between 1 Jan 2010 to 31 Dec 2014.CNS PFS and OS were assessed in patients who received CDK4/6i after BM. OS from the time of BM development was assessed between patients who received CDK4/6i before BM and the CDK-N cohort ResultsIn the CDK-Y cohort of 363 patients, 203 (56 %) received a CDK4/6i before BM, 133 (37 %) received a CDK4/6i only after BM and 27 (7 %) received a CDK4/6i both before and after BM.Median CNS PFS was 21.4 months for patients receiving a CDK4/6i only after BM and 9.4 months for patients who received CDK4/6i both before and after BM (p = 0.006). Median OS was 24.9 months for patients receiving a CDK4/6i only after BM and 12.1 months for patients who received CDK4/6i both before and after BM (p = 0.0098). Median OS from time of BM development for patients receiving a CDK4/6i before BM versus the CDK-N cohort was 4.3 months and 7.7 months respectively (p = 0.0082). ConclusionsCDK4/6i exposure prior to BM may lead to development of resistance mechanisms which in turn reduces CNS PFS and OS upon rechallenging with a CDK4/6i after BM development. This motivates investigation of biomarkers for patient selection.

Acromegaly management in the Nordic countries:A Delphi consensus survey.

Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

Metformin Monotherapy With and Without Lifestyle Changes Affects Anthropometric Parameters, Blood Pressure, Blood Glucose, and Lipid Profile in Indian Patients With Newly Diagnosed Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a consequence of insulin resistance, insulin deficiency, or both. It is usually seen in adults and is a consequence of genetic (polygenic inheritance), endogenous (obesity and or hormonal factors), and environmental factors (e.g., obesogenic environment, endocrine disrupting chemicals, stress, and medicines). The prevalence of T2DM has increased over the past few decades. South Asians, including Indians, are more prone to central adiposity and develop lifestyle diseases like T2DM at body mass index values lower than those considered normal for the Western population. Generally, the first line of treatment is metformin monotherapy with lifestyle changes in patients with T2DM. Most of the research conducted on this drug is on Western subjects. Since the Indian population has genetic differences in the site of deposition of adipose and is more prone to develop lifestyle diseases, the effect of metformin may be different in Indians. Seventy-one (34 female, non-pregnant, non-lactating) adults with newly diagnosed T2DM were recruited in this short-duration pilot study after obtaining written informed consent. Patients regularly taking any drug were excluded, as were patients with chronic comorbidities. Treatment was initiated with metformin 500 mg OD. Lifestyle changes were recommended according to the age and physical condition of the patients. Anthropometric parameters (age, weight, height, BMI, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)), blood pressure, glycemic status (fasting and 2 h PP glucose and HbA1c), and lipid profile of the subjects were recorded before initiating and six months after initiating metformin monotherapy with lifestyle changes. Small but statistically significant improvements were observed in the WHR,WHtR, blood pressure, blood glucose, and glycated hemoglobin. Although improvement was also observed in weight and lipid profile, these changes were not statistically significant. This study shows that metformin monotherapy with lifestyle changes is suitable for patients of Indian origin and results in improvement in the WHR, WHtR, blood pressure, plasma glucose, and glycated hemoglobin.

The therapeutic features of EGFR L858R exon 21 mutation in non-small cell lung cancer

Introduction. Monotherapy with EGFR tyrosine kinase inhibitors (TKIs) results in a worse prognosis for patients with the exon 21 L858R mutation than for patients with exon 19 Del. Thus, the search for alternative drug strategies that improve treatment outcomes for patients with NSCLC with the L858R mutation is an urgent problem. This article presents preliminary results of a pilot study of the effectiveness of chemotherapy integrated into targeted anti-EGFR therapy for patients with non-small cell lung cancer (NSCLC) with a mutation in exon 21 of the EGFR gene.Aim. To improve progression-free survival results on first-line therapy in patients with NSCLC with the L858R mutation.Materials and methods. From 2015 to 2021 23 patients were included in the study with advanced L858R 21 exon mutation NSCLC for the first line of treatment. Patients received TKI therapy for the first 2 months, followed by discontinuation of targeted therapy and receiving 3 courses of paclitaxel and carboplatin. Target therapy was then resumed until disease progression. The follow up period was 36 months.Results. The objective response rate (ORR) was 59.1%. Median progression-free survival 23 months [95% CI: 16–36]. Four (18.1%) patients developed grade 3-4 toxicity during chemotherapy, and therefore the 3rd course of chemotherapy was canceled in one patient. Due to toxicity during targeted therapy, gefitinib dose was reduced in one patient and the drug was changed from gefitinib to afatinib in the other one patient.Conclusion. Preliminary results of our study showed that integrating chemotherapy into targeted treatment for this category of patients may become a new worthy option to increase median PFS.

Improving the technology of producing seamless hot‑rolled pipes from stainless steel l80 type 13Cr in the tube rolling workshop

The production of seamless hot‑deformed pipes from martensitic stainless steel with a high chromium content, used under the constant influence of aggressive environments, involves overcoming a series of technological challenges. These challenges are due to the metal’s structural features, such as relatively low plasticity, a narrow temperature range for hot deformation, a tendency to defect formation during rolling, and more intense wear on the rolling tools. The article discusses the main stages of research work on mastering the technology of producing seamless hot‑rolled pipes from stainless steel grade L80 type 13Cr at OJSC “BSW – Management Company of Holding “BMC”. It presents the results and complexities of mastering the technology for producing seamless stainless steel pipes, analyzes the results aimed at reducing the cost of finished products by increasing the durability of piercing mandrels, the resistance of disc saws for cutting blanks, eliminating metal adhesion to the piercing mill’s Dishar discs, increasing the productivity of the rolling line and heat treatment process.

Assessing the Effectiveness of Voice Therapy Techniques in Treating Dysphonia: An Otolaryngological Review.

Dysphonia is a prevalent condition that can impact individuals across all age groups. It occurs when normal voice quality is altered, caused by structural and/or functional issues. Evaluation and assessment from clinicians are warranted if dysphonia persists for more than four weeks and/or is coupled with risk factors or other concerning clinical manifestations. Additionally, voice disorders can increase the risk of depression and anxiety disorders, as well as raise stress levels and lower self-reported health indicators. Dysphonia can have a substantial influence on interpersonal interactions and lower overall quality of life since effective communication relies significantly on spoken language. Hence, managing dysphonia is essential for enhancing communication abilities, improving quality of life, maintaining vocational functioning, promoting psychological well-being, and addressing underlying health concerns. Speech and language therapy, medical management, surgery, or a combination of the aforementioned are all possible treatments for dysphonia. Speech and language therapy is often the first-line treatment option for dysphonia patients who do not meet the criteria for surgical intervention. Voice therapy is often beneficial and remains the first line of treatment, even when patients approach with benign vocal fold nodules. A well-designed voice therapy program improves both the quality of life and vocal performance. The majority of the studies in the existing literature advocate for and report beneficial outcomes associated with voice therapy; however, more research is needed to provide evidence-based findings to guide clinical practice and achieve optimal outcomes. This comprehensive review elaborately highlights the utilization and efficacy of various voice therapeutic modalities utilized for the management of dysphonia in light of current literature.

A rare case of retroperitoneal teratoma with evidence of papillary thyroid carcinoma: a case report

BackgroundTeratomas are germ cell tumors composed of somatic tissues from up to three germ layers. Primary retroperitoneal teratomas usually develop during childhood and are uncommon in adults and in the retroperitoneal space. While there are only a few cases of retroperitoneal thyroid tissue, we report a unique case of a retroperitoneal papillary thyroid carcinoma.Case presentationA 41-year-old woman presented in our institution due to intermitted unspecific abdominal pain. Magnetic resonance imaging detected a multi-cystic solid retroperitoneal mass ventral to the psoas muscle and the left iliac artery. After surgical removal of the retroperitoneal mass, histology sections of the specimen indicated evidence of papillary thyroid carcinoma cells. A staging computed tomography scan of the body showed no further manifestations. To reduce the risk of recurrence, total thyroidectomy was performed followed by radioiodine therapy with lifelong hormone substitution.ConclusionsPrimary retroperitoneal teratoma with evidence of papillary thyroid carcinoma is a rare condition. Preoperative diagnosis is difficult due to its non-specific clinical manifestation and lack of specific radiologic findings. Histopathology analysis is necessary for diagnosis. Although surgery is considered the first line treatment, there is still discussion about the extent of resection and the need for total thyroidectomy with adjuvant radioiodine therapy.

Abstract A002: Understanding mechanisms of resistance to WRN small molecule inhibitors

Abstract The Werner syndrome helicase (WRN) has emerged as a promising synthetic lethal target in cancers with microsatellite instability (MSI). This discovery has spurred numerous efforts developing therapeutics targeting WRN and the advancement of at least two WRN programs into Phase I clinical trials. The development of acquired resistance remains a significant obstacle for the durable efficacy of targeted therapies in oncology and this challenge may be particularly pronounced in the setting of mismatch repair deficient (dMMR) tumors, which inherently possess large reservoirs of mutational burden. Despite the potential of WRN-targeted treatments, there remains a notable gap in the literature concerning the mechanisms of resistance to these drugs. To explore potential acquired resistance mechanisms of WRN-directed therapies, we examined three helicase inhibitors—HRO761 and two proprietary compounds which all possess a similar mechanism of action (MOA). Continuous treatment of HCT116 and SW48 cell lines with these inhibitors rapidly lead to the emergence of phenotypically resistant cell populations. Subsequent sequencing of several independently derived resistant cultures identified 5 emergent point mutations within the helicase domain of WRN that are potentially responsible for the observed inhibitor resistance. Parallel in vivo studies with HRO761 in SW48 xenograft tumors also demonstrated the acquisition of resistance after an initial period of deep response. Whole exome sequencing of these tumors revealed 2 of the previously observed, as well as 4 novel WRN helicase mutations. Structural modeling of WRN with putative resistance mutations suggested their capacity to either directly impede inhibitor binding or disfavor the adoption of the compound binding confirmation. Surprisingly, despite the general similarity in MOA and ligand binding sites, cross-resistance analyses demonstrated that some mutations conferred preferential resistance to HRO761 and were only minimally detrimental to the activity of our proprietary compounds. We conclude that WRN inhibitor monotherapy leads to drug resistance by acquisition of on-target mutations that disrupt inhibitor binding through direct or indirect mechanisms. This process may be extremely rapid in the dMMR background that represents the intent to treat population for WRN-directed therapeutics and is potentially further exacerbated by the complex allosteric MOA of WRN inhibitors currently in the clinic. Notably, some WRN inhibitor-resistant cell lines were not resistant to all WRN inhibitors tested, suggesting the potential for employing different WRN inhibitors at different stages of treatment to overcome resistance. This study underscores the importance of understanding and addressing resistance mechanisms to enhance the effectiveness of WRN-targeted therapies in MSI cancers. Citation Format: Faith C. Fowler, Aileen Kelly, Cindy Jeffries, Jessica Gajda, Jonathan Hickson, Fei Han, Nate Elsen, Mariam George, Danli Towne, Xiangdong Xu, Nate Gesmundo, Wei Qiu, Henry Tang, Charlie Hutchins, Yunsong Tong, Mick Dart, Ari Firestone. Understanding mechanisms of resistance to WRN small molecule inhibitors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A002.

Phase II trial of BXCL701 and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (EXPEL-PANC): Preliminary findings.

LBA4132 Background: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options and is thought to be a “cold” tumor that does not respond to immunotherapy, due to a tumor microenvironment (TME) consisting of a desmoplastic stroma and poor T cell infiltrate. BXCL701 is an oral synthetic dipeptide that competitively inhibits dipeptidyl peptidases DPP4, DPP8, DPP9 and fibroblast activation protein (FAP). BXCL701 exerts antitumor activity via inhibition of DPP8/9, which is associated with induction of proinflammatory cytokines, as well as inhibition of FAP, which disrupts tumor-stromal interactions. Preclinical xenograft models demonstrate synergy between BXCL701 and PD-1 blockade, reducing tumor growth and promoting an increase in intratumoral CD4+ and CD8+ T cells, macrophages and NK cells, with induction of host-protective immunity. Methods: This is a phase II trial of BXCL701 in patients with metastatic PDAC (mPDAC) following progression on 1 line of treatment for advanced disease and amenable to serial biopsies. BXCL701 is administered at 0.2 mg PO BID days 1-7 and 0.3 mg BID days 8-14 during cycle 1 (21 days) followed by 0.3 mg BID days 1-14 every 21 days in all other cycles, given with pembrolizumab 200 mg IV every 21 days (all cycles). The primary objective is to determine the 18-week progression-free survival rate (PFS18weeks). We estimate that historical 2nd-line PFS18weeks is 30% or less; using a Simon’s two-stage (minimax) design, a type I error rate of 0.05 and power of 80% if the true rate is 50%, we will need 19 patients in stage 1 and 20 in stage 2 (39 total). There is a safety lead-in phase of 6 patients. We plan to enroll 43 patients to account for a predicted 10% drop out of unevaluable patients. Correlative pharmacodynamic studies include imaging mass cytometry to examine 36 markers of the PDAC TME in tissue biopsies, as well as blood-based analyses of KRAS circulating tumor DNA, circulating markers of fibrosis, and IL-6. Enrollment began in Q3 2023 (NCT05558982). Results: Six patients have enrolled, 3 women and 3 men, median age 57.5 (range 37-80). One patient was progression-free at 18 weeks and 1 patient had stable disease (SD) at 9 weeks, not yet evaluable for the 18-week landmark. Objective response rate is 16% and disease control rate is 50% (RECIST: 1 partial response, -41%, and 2 patients with SD, -18% and 0%). Three patients had significant reductions in CA19-9 from baseline (-100%, -73%, and -97%). Median PFS and overall survival have not been reached (NR, 95% CI 1.45 months-NR and 0.92 months-NR, respectively). There have been no serious treatment-related safety events. The safety lead-in will complete after the next patient completes the 6-week safety window (1 patient was unevaluable). Conclusions: BXCL701 plus pembrolizumab is well-tolerated and shows early signs of potential clinical activity in patients with mPDAC refractory to chemotherapy. Clinical trial information: NCT05558982 .

Lived experiences of Iranian prehospital emergency technicians in facing women’s emergencies: a phenomenological study

Introduction: This study aimed to investigate the work problems and challenges of male prehospital emergency technicians when faced with female medical emergencies. Given that qualitative research has not been done in this field, planning to find the weak points and improve the quality of prehospital emergency as the first line of treatment for female emergency patients, which is considered an important part of the health care system, is considered important and valuable. Therefore, this phenomenological study was conducted in 2023.MethodsThis study was conducted using a qualitative method of phenomenology in 2023. The environment of the research was urban and road prehospital emergency centers in Iran and the data were collected through interviews with EMS technicians. The collected data were analyzed using Smith’s approach to explain the lived experiences of EMS technicians facing female emergencies or women’s emergencies in Iran.ResultsAll the 15 participants were men. Their mean age was 35 years, with a range of 25 to 45 years, and with a mean work experience of 10.54 years with a range of 4 to 20 years. The lived experiences of 115 emergency technicians in facing women’s emergencies in Iran were placed in four main themes cultural-social factors, organizational factors, human resources-related factors, and administrative-legal factors.ConclusionEMS personnel face various obstacles in carrying out missions related to women’s emergencies, Considering the critical nature of women’s emergencies, it is recommended that policymakers and clinical educators improve the level of community culture, communication skills, theoretical and practical training, respecting privacy, hiring female personnel, adding specialized equipment, amending and changing laws, removing road-traffic obstacles and to support personnel, patients and their families psychologically to optimize performance in women’s emergencies.

Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial.

LBA1001 Background: The combination of CDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) is the standard first line treatment for HR+, HER2- advanced breast cancer (ABC). While disease progression occurs in nearly all patients (pts) with ABC, the optimal treatment for pts who experience progression on a CDK4/6i + ET remains uncertain. Real-world evidence suggests that use of abemaciclib after disease progression on a prior CDK4/6i prolongs progression-free survival (PFS) in ABC; however, Phase 2 trials with other CDK4/6i have generated mixed results. Here we present the primary outcome analysis for the Phase 3 postMONARCH trial (NCT05169567) of fulvestrant + abemaciclib or placebo in pts with HR+, HER2- ABC following disease progression on prior CDK4/6i + ET. Methods: postMONARCH was a global, double-blind, placebo-controlled study with pts randomized 1:1 to abemaciclib + fulvestrant or placebo + fulvestrant. Eligible pts had disease progression on a CDK4/6i + AI as initial therapy for ABC or relapse on/after a CDK4/6i + ET as adjuvant therapy for early breast cancer. No other prior treatment for ABC was permitted. Primary endpoint was investigator-assessed PFS; secondary endpoints included PFS by blinded independent central review (BICR), overall survival (OS), objective response rate (ORR), and safety. Assuming a hazard ratio (HR) of 0.7, the study had ~80% power to detect superiority for abemaciclib, with a cumulative 2-sided type I error of 0.05. Kaplan-Meier method was used to estimate PFS curves and treatment effect was estimated using a stratified Cox proportional hazard model. Results: A total of 368 pts were randomized to abemaciclib + fulvestrant (n = 182) or placebo + fulvestrant (n= 186). Most pts (99%) enrolled directly after CDK4/6i + ET as initial therapy for ABC. Prior CDK4/6i was 59% palbociclib, 33% ribociclib, and 8% abemaciclib. At interim analysis, the study reached the pre-specified criteria for significantly improved investigator-assessed PFS with abemaciclib + fulvestrant compared to placebo + fulvestrant (169 events, HR = 0.66; 95% CI 0.48 – 0.91; p = 0.01). At primary analysis (258 events), the HR was 0.73 (95% CI 0.57 – 0.95), with PFS rates at 6 months of 50% vs 37% for the abemaciclib and placebo arms, respectively. Consistent effect was seen across major clinical and genomic subgroups, including pts with baseline ESR1 or PIK3CA mutations. ORR was improved with abemaciclib compared to placebo (17% vs 7%, respectively, in pts with measurable disease). PFS according to BICR was also improved with HR = 0.55 (95% CI 0.39 - 0.77). OS remains immature (20.9% event rate). Safety was consistent with the known profile of abemaciclib. Conclusions: Abemaciclib + fulvestrant demonstrated statistically significant PFS improvement in pts with ABC progression on prior CDK4/6i-containing therapy. Clinical trial information: NCT05169567 .

Dose optimization of second window indocyanine green in meningioma patients

ObjectiveSurgery remains the first line treatment for meningiomas and can benefit from fluorescence-guided surgical techniques such as second-window indocyanine green (SWIG). In the current study, we compared the use of the standard SWIG dose of 5.0 mg/kg relative to 2.5 mg/kg indocyanine green (ICG) in meningioma patients. MethodsPatients were prospectively enrolled in an IRB-approved study of SWIG and received either the standard dose of 5.0 mg/kg or a reduced dose of 2.5 mg/kg of ICG around 24 h prior to their surgery. Intraoperative near-infrared fluorescence imaging was performed with exo- and endoscopic systems. Signal-to-background ratio (SBR) was calculated to quantify fluorescence and was compared between 5.0 mg/kg and 2.5 mg/kg ICG. All patients received pre-operative MRI and, in select cases, the pre-operative MRI was correlated to intraoperative fluorescence imaging. Results/DiscussionIn the current study, we found no significant difference in the SBR of meningiomas in patients that were administered with either 5.0 mg/kg or 2.5 mg/kg ICG. However, in five patients that received the standard-dose SWIG regimen of 5.0 mg/kg ICG we observed dose-related fluorescence quenching − referred to as “inversion” − that interfered with tumor visualization during fluorescence-guided surgery (FGS). When correlated to pre-operative MRI, a similar rim pattern was observed around the primary tumor on T2 FLAIR, which, in retrospect, could be used as a predictor for inversion during FGS in meningioma patients receiving standard-dose ICG. ConclusionThis study demonstrated that a reduced ICG dose was as effective as standard-dose SWIG in meningioma patients. We therefore recommend to adjust the standard ICG dose for meningioma patients to 2.5 mg/kg particularly when rim enhancement is observed on pre-operative T2 FLAIR.

Promoting sleep health during pregnancy for enhancing women’s health: a longitudinal randomized controlled trial combining biological, physiological and psychological measures, Maternal Outcome after THERapy for Sleep (MOTHERS)

BackgroundSleep is vital for maintaining individuals’ physical and mental health and is particularly challenged during pregnancy. More than 70% of women during the gestational period report insomnia symptoms. Sleep dysfunction in the peripartum increases the risk for a cascade of negative health outcomes during late pregnancy, birth, and postpartum. While psychological interventions are considered the first line treatment for sleep difficulties, they are still scarcely offered during pregnancy and there is a lack of longitudinal research combining psychological and physiological indices.MethodsThe present protocol outlines a randomized controlled trial aimed at testing the long-term effectiveness of an automatized digitalized psychoeducational intervention for insomnia for expectant mothers complaining insomnia symptoms without comorbidity. Outcomes include physiological, hormonal, and subjective indices of maternal psychopathology, stress, and emotional processes, and sleep and wellbeing of the family system.The trial is part of a longitudinal study evaluating expectant mothers from early pregnancy (within the 15th gestational week) to 6-months postpartum through 6 observational phases: baseline (BSL), 6- and 12-weeks from BSL (FU1-FU2), 2-to-4 weeks after delivery (FU3), and 3- and 6-months after delivery (FU4-5). We plan to recruit 38 women without sleep difficulties (Group A) and 76 women with sleep difficulties (Group B). Group B will be randomly assigned to digital psychological control intervention (B1) or experimental psychoeducational intervention targeting insomnia (B2). At 3 time points, an ecological-momentary-assessment (EMA) design will be used to collect data on sleep and emotions (diaries), sleep-wake parameters (actigraphy) and stress reactivity (salivary cortisol). We will also test the DNA methylation of genes involved in the stress response as biomarkers of prenatal poor sleep. Information on partner’s insomnia symptoms and new-borns’ sleep will be collected at each stage.DiscussionThe proposed protocol aims at testing an easily accessible evidence-based psychoeducational intervention for expectant mothers to help them improving sleep, health, and wellbeing in the peripartum. The results could improve the understanding and management of sleep difficulties and peripartum depression.Trial registrationThe study protocol has been registered on 22 April 2024 with ClinicalTrials.gov Protocol Registration and Results System (PRS), ID: NCT06379074. Protocol version: April 23, 2024.

Combined low-dose isotretinoin and long-pulsed nd: YAG laser in the treatment of post-acne erythema

Post-acne erythema (PAE) is a bothering skin condition that emerges from inflammatory acne and persists after its resolution. It is characterized by telangiectasia and erythematous macules. the role of 1064-nm Nd: YAG when combined with low-dose isotretinoin in the acne erythema treatment. forty-eight PAE patients were involved in the study. They were divided into two groups; group (A) patients administering a low dose of oral isotretinoin (10 mg/day) and underwent a total of six two-week interval sessions of 1064 ND-YAG laser treatment, group (B) patients administering a low dose of oral isotretinoin (10 mg/day) only. All adverse effects experienced during the course of therapy were documented, and photos were taken before the start of the treatment and following the end of the treatment duration. Following the completion of the therapeutic intervention, a significant improvement in clinical condition was observed in both groups, with more improvement in group (A) compared to group (B) as evidenced by a notable improvement in the score on the Clinician Erythema Assessment Scale (CEAS) and also a significant decrease in the mean value of optical density of the erythema. combined 1064-nm Nd: YAG with low-dose isotretinoin may be an efficient and secure line in the PAE treatment. Also, the combined therapy had superior results when compared to low-dose isotretinoin alone.

FUNCTIONAL OUTCOME OF GIANT CELL TUMOR OF DISTAL RADIUS AFTER EN-BLOC RESECTION AND NON-VASCULARIZED FIBULAR BONE GRAFTING

Introduction: Giant cell Tumors (GCT) are relatively common lesions that are most often encountered in middle aged women [Salunke AA, Shah J, Warikoo V, Chakraborty A, Pokharkar H, Chen Y, Pruthi M, Pandit J. Giant cell tumor of distal radius treated with ulnar translocation and wrist arthrodesis. J Orthop Surg 2017 25(1): 2309499016684972, 2017, https://doi.org/10.1177/2309499016684972 ]. As 25% of these are usually locally aggressive, early diagnosis, and treatment are of paramount importance [Dorfman HD, Czerniak B. Bone Tumors. St. Louis, Mosby (1998)]. Due to the high incidence of local recurrence following simple curettage, it is no longer a preferred line of treatment. In recent times, extended curettage, wide resection or en-bloc resection with bone grafting have supplanted simple curettage [Şirin E, Akgülle AH, Topkar OM, Sofulu Ö, Baykan SE, Erol B. Mid-term results of intralesional extended curettage, cauterization, and polymethylmethacrylate cementation in the treatment of giant cell tumor of bone: A retrospective case series. Acta Orthop Traumatol Turc 54(5): 524–529, 2020, https://doi.org/10.5152/j.aott.2020.19082 ]. Case Scenario: A 22-year-old female patient presented to the OPD with a swelling in her right wrist which she noticed two years back. The swelling gradually increased to the size of a lemon at presentation and was initially painless but eventually became painful. The patient was evaluated based on clinical history, examination, and radiography. A clinical and radiological diagnosis of GCT of the distal radius was made. FNAC was done to confirm the same. Further, the lungs were screened for metastasis. She underwent en-bloc resection of the lesion followed by reconstruction with non-vascularized proximal fibular autograft secured with a DCP and [Formula: see text] -wires. The excised specimen was dispatched for Fig. 1. The swelling at presentation histopathological examination and confirmed to be a Giant Cell Tumor. Regular follow-up schedule was initiated at 2 weeks, 6 weeks, 3 months, 1 year, 36 weeks, and 2 years postoperatively. Her functional outcome was monitored by assessing the wrist range of movements and the Mayo wrist scores. Results: The patient’s Mayo wrist scores showed an increasing trend during follow-up, indicating improved functional outcomes. Recurrence was not noted during the follow-up period. Discussion: Tumor in the distal radius metaphyseoepiphyseal region is commonly associated with extracompartmental involvement, cortical invasion, and pathologic fracture [Yang YF, Wang JW, Huang P, Xu ZH. Distal radius reconstruction with vascularized proximal fibular autograft after en-bloc resection of recurrent giant cell tumor. BMC Musculoskelet Disord 17(1): 346, 2016. https://doi.org/10.1186/s12891-016-1211-8 ]. Hence, curettage is not an optimal method in the distal radius. Thus, wide excision is the optimal choice of treatment. However, this creates a defect at the distal end of the radius. The preferred options for the management of the defect comprise of osteoarticular allografts, vascularized grafts, non-vascularized bone grafts, and custom-made prostheses [Saini R, Bali K, Bachhal V, Mootha AK, Dhillon MS, Gill SS. En bloc excision and autogenous fibular reconstruction for aggressive giant cell tumor of distal radius: a report of 12 cases and review of literature. J Orthop Surg Res 6 : 14, 2011, https://doi.org/10.1186/1749-799X-6-14 ]. Vascularized bone grafts have been proposed to have a better union rate and lesser complication rate as compared to non-vascularized options. Thus, with our case report, we would like to highlight the effectiveness of the non-vascularized proximal fibular autograft in the reconstruction following en bloc excision of the distal radius. Conclusion: Hence, en-bloc resection and non-vascularized fibular bone grafting is a valuable method of treatment of GCTs of the distal radius. It is also associated with low recurrence rates and improved wrist function in the course of follow-up.

Fertility preservation in lymphoma patients treated with immunochemotherapy regimens with or without radiotherapy: results of a retrospective multicenter Italian study (Ferty care)

This is a retrospective, multicentric study, aimed to describe the real-life application of fertility preservation methods during treatment in female lymphoma patients, aged 18–40 years old, diagnosed between Oct 1st/2010 and May 31st/2018. Among 414 women included, median age was 28 years old, histologies were: HL 74%, PMBCL 13%, DLBCL 10%, others 3%. First line treatments were: ABVD in 295 (71%), R-CHOP like in 102 (25%), higher intensity regimens in 17 (4%) cases. Fertility preservation strategies were: GnRHa in 315 (78%), Oral Contraceptive in 41 (10%), oocytes and ovarian tissue cryopreservation in 55 and 42 patients, respectively. After therapy, we observed a restored regular period in 293 (70%) and premature ovarian failure (POF) in 33 (8%), Furthermore we recorded 43 pregnancies, all spontaneous with 5 years median follow-up. Median age at diagnosis and number of lines of treatment correlate with higher rate of amenorrhea, risk of POF and menopause (p < 0.001).

Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer

Ferroptosis, an iron-dependent regulated cell death mechanism, holds significant promise as a therapeutic strategy in oncology. In the current study, we explored the regulatory effects of epigallocatechin gallate (EGCG), a prominent polyphenol in green tea, on ferroptosis and its potential therapeutic implications for non-small cell lung cancer (NSCLC). Treatment of NSCLC cell lines with varying concentrations of EGCG resulted in a notable suppression of cell proliferation, as evidenced by a reduction in Ki67 immunofluorescence staining. Western blot analyses demonstrated that EGCG treatment led to a decrease in the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while increasing the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4). These molecular changes were accompanied by an increase in intracellular iron, malondialdehyde (MDA), and reactive oxygen species (ROS), alongside ultrastructural alterations characteristic of ferroptosis. Through small RNA sequencing and RT-qPCR, transfer RNA-derived small RNA 13502 (tsRNA-13502) was identified as a significant target of EGCG action, with its expression being upregulated in NSCLC tissues compared to adjacent non-tumorous tissues. EGCG was found to modulate the ferroptosis pathway by downregulating tsRNA-13502 and altering the expression of key ferroptosis regulators (GPX4/SLC7A11 and ACSL4), thereby promoting the accumulation of iron, MDA, and ROS, and ultimately inducing ferroptosis in NSCLC cells. This study elucidates EGCG’s multifaceted mechanisms of action, underscoring the modulation of ferroptosis as a viable therapeutic approach for enhancing NSCLC treatment outcomes.

Timely care for age-related macular degeneration: a qualitative study among retina specialists in Israel

BackgroundAge-related macular degeneration (AMD) affects quality of life and independence, and its incidence and prevalence are increasing due to ageing of the population. Access to effective timely treatment can improve vision and reduce incidence of blindness. This study aimed to explore the perspectives of ophthalmologists in the Israeli public healthcare system regarding timely treatment of AMD patients.MethodsQualitative semi-structured interviews were conducted in 2020-2021 with 22 senior ophthalmologists, from 10 general hospitals and from two HMOs, representing different geographic regions. All interviewees specialize in retinal diseases and work with AMD patients. Interviews discussed patient pathways involved in the diagnosis and treatment of AMD, access to care, and obstacles to timely care. Thematic analysis was conducted.ResultsBased on the interviews, we describe the usual referral and treatment pathways. Themes included regional disparities, long wait times in some areas, a lack of retina specialists, differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second-line treatment not fully covered by insurance, most affecting the weakest segments of the population.ConclusionsLoss of vision incurs high health and societal costs. In the context of insufficient medical manpower in Israel, the healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population. Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. Awareness of AMD symptoms and the importance of early intervention could be highlighted by campaigns, particularly among high-risk groups.Highlights• Interviews with hospital-based and community ophthalmologists showed regional disparities in AMD treatment, with long wait times and a lack of retina specialists in some areas.• Differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second line treatment not fully covered by insurance were highlighted.• The healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population• Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment.• Awareness of AMD symptoms and the importance of early intervention should be emphasized in high-risk groups.

Switching to an Intravitreal Dexamethasone Implant after Intravitreal Anti-VEGF Therapy for Diabetic Macular Edema: A Review.

Among working-age people, diabetic retinopathy and diabetic macular edema are currently considered the main causes of blindness. Nowadays, intravitreal injections are widely acknowledged as a significant milestone in ophthalmology, especially for the treatment of several retinal diseases, including diabetic macular edema. In particular, anti-vascular endothelial growth factor (VEGF) agents are typically the first line of treatment; however, monthly injections are required, at least, during the loading dosage. Notably, an intravitreal 0.7 mg dexamethasone (DEX) implant (Ozurdex®, AbbVie Inc., North Chicago, IL, USA) is considered a legitimate substitute treatment for diabetic eyes that have not responded to anti-VEGF treatment. In fact, clinical trials and real-life studies have demonstrated the effectiveness and safety of an intravitreal DEX implant in treating such conditions over a period of three to six months. For this reason, wisely selecting diabetic patients might be crucial to decreasing the load of injections in clinics and hospitals. The purpose of this review is to analyze the available scientific literature to highlight the benefits, efficacy, and clinical criteria for choosing whether to switch from intravitreal anti-VEGF therapy to an intravitreal DEX implant in diabetic macular edema.

Gut-directed hypnosis and hypnotherapy for irritable bowel syndrome: a mini-review.

Irritable bowel syndrome (IBS) is a frequent health condition which can be associated with functional disability and reduced health-related quality of life. IBS is classified as a disorder of the brain-gut axis. IBS is a very heterogenous condition with regards to the underlying pathophysiological mechanisms, the clinical picture and the amount of functional impairment. Within a biopsychosocial model of IBS psychosocial factors can play a role in the in the predisposition, triggering and development of chronicity. Somatic or psychosocial or a mixture of both factors might predominate in an individual patient. Gut-directed hypnosis is a special type of medical hypnosis combining standardised gut-directed suggestions (hypnosis) with suggestions tailored to the psychological characteristics of the patient (hypnotherapy). Of brain-gut behavioral therapies, cognitive bahvioral-based interventions and gut-directed hypnosis have the largest evidence for both short-term and long-term efficacy in controlled trials for IBS and are recommended by current European and North American gastroenterology guidelines as second line treatment options. Standardised gut-directed hypnosis is available by audiotapes and can be part of a multicomponent self-management approach by digital health applications. It can be used - based on the patient's preferences-as first line therapy for mild forms of IBS. Severe forms of IBS require face-to-face interdisciplinary management. Standardised gut-directed hypnosis and hypnotherapy tailored to the individual patient can be part of this approach.