Side Effects Of Long-term Treatment Research Articles

The Price of Success-The Long-Term Outcomes of Children with Craniopharyngioma-Two Institutions' Experience.

An analysis of patients below 21 years old treated due to craniopharyngioma in the years 1979-2022 was performed with the aim of evaluating the long-term outcome and treatment side-effects. The standard statistical tests were used, and 56 patients with a median age of 11 years were evaluated. Surgery was the primary treatment in 55 patients; however, in only 29 it was the only neurosurgical intervention. Eighteen children were treated with radiotherapy (RTH) in primary treatment. The most common neurosurgical side effects observed were visual and endocrine deficits and obesity, which were diagnosed in 27 (49%), 50 (91%), and 25 (52%) patients, respectively. Complications after RTH were diagnosed in 14 cases (32%). During the median follow-up of 8.4 years (range: 0.4-39.8 years), six patients died and the 5- and 10-year overall survival was 97% and 93%, respectively. Five-year progression-free survival for gross total resection, resection with adjuvant RTH, and non-radical resection alone was 83%, 68%, and 23%, respectively (p = 0.0006). Surgery combined with RTH provides comparable results to gross tumor resection in terms of oncologic outcome in craniopharyngioma patients. Adjuvant irradiation applied in primary or salvage treatment improves disease control. The rate of complications is high irrespective of improved surgical and radiotherapeutic management.

Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes.

Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study. Gene expression and DNA methylation were investigated at a genome-wide level at screening, after 100 days of treatment, and at one-year follow-up. We identified intra-individual longitudinal changes in gene expression and DNA methylation in patients receiving amoxicillin, while few changes were observed in patients receiving placebo. After 100 days of amoxicillin treatment, 28 genes were significantly differentially expressed, including the downregulation of 19 immunoglobulin genes. At one-year follow-up, the expression levels were still not completely restored. The significant changes in DNA methylation (n = 4548 CpGs) were mainly increased methylation levels between 100 days and one-year follow-up. Hence, the effects on gene expression occurred predominantly during treatment, while the effects on DNA methylation occurred after treatment. In conclusion, unrecognized side effects of long-term amoxicillin treatment were revealed, as alterations were observed in both gene expression and DNA methylation that lasted long after the end of treatment.

Kinetic and structural studies of Mycobacterium tuberculosis dihydroorotate dehydrogenase reveal new insights into class 2 DHODH inhibition

Tuberculosis (TB) is a leading cause of death worldwide. TB represents a serious public health threat, and it is characterized by high transmission rates, prevalence in impoverished regions, and high co-infection rates with HIV. Moreover, the serious side effects of long-term treatment that decrease patient adherence, and the emergence of multi-resistant strains of Mycobacterium tuberculosis, the causing agent of TBs, pose several challenges for its eradication. The search for a new TB treatment is necessary and urgent. Dihydroorotate dehydrogenase (DHODH) is responsible for the stereospecific oxidation of (S)-dihydroorotate (DHO) to orotate during the fourth and only redox step of the de novo pyrimidine nucleotide biosynthetic pathway. DHODH has been considered an attractive target against infectious diseases. As a first step towards exploiting DHODH as a drug target against TB, we performed a full kinetic characterization of both bacterial MtDHODH and its human ortholog (HsDHDOH) using both substrates coenzyme Q0 (Q0) and vitamin K3 (K3). MtDHODH follows a ping-pong mechanism of catalysis and shares similar catalytic parameters with the human enzyme. Serendipitously, Q0 was found to inhibit MtDHODH (KI (Q0) = 138 ± 31 μM). To the best of our knowledge, Q0 is the first non-orotate like dihydroorotate-competitive inhibitor for class 2 DHODHs ever described. Molecular dynamics simulations along with in silico solvent mapping allowed us to successfully probe protein flexibility and correlate it with the druggability of binding sites. Together, our results provide the starting point for the design of a new generation of potent and selective inhibitors against MtDHODH.

Overview of radiotherapy-induced chronic pain in childhood cancer survivors: A narrative review.

Radiotherapy is an important aspect of oncological treatment in several childhood cancers. However, radiotherapy is known to have numerous side effects, including detrimental effects on growth, neurocognitive impairment, and the development of secondary malignancies. One less studied long-term side effect of pediatric radiotherapy treatment is chronic pain. While the short-term toxicities of radiotherapy resolve over a few weeks to months, the chronic pain caused by radiotherapy-induced tissue damage can significantly affect children's quality of life. As long-term childhood cancer survivors age into adulthood, they are typically followed up by a wide variety of doctors, not all of whom may be familiar with radiotherapy-induced chronic pain and its management. The aim of this review is to discuss the various common manifestations of radiotherapy-related pain in children, as well as ways to identify and manage these. Common radiotherapy-related side effects leading to chronic pain symptoms include radiation fibrosis, enteritis, dermatitis, lymphedema, neuropathic pain, and effects on bone development. The pathophysiology, evaluation and management of these are briefly summarized in this review. This is followed by an overview of radiotherapy techniques that allow greater sparing of normal tissue, minimizing future painful side effects. Finally, the assessment of pain in children is described, as well as strategies for management, and red flag symptoms that should prompt urgent specialist referral. In conclusion, a good understanding of the long-term side effects of radiotherapy treatment in children is essential for the various medical professionals that follow-up the child in the years after treatment. For young children, the evaluation of pain is in itself a challenge, and effects on growth, development, and learning are crucial. For older children, social and psychological factors become increasingly important. As radiation therapy techniques continue to advance, the spectrum and incidence of chronic pain syndromes may change over time.

Obacunone targets macrophage migration inhibitory factor (MIF) to impede osteoclastogenesis and alleviate ovariectomy-induced bone loss

IntroductionOsteoporosis is the most common bone disorder where the hyperactive osteoclasts represent the leading role during the pathogenesis. Targeting hyperactive osteoclasts is currently the primary therapeutic strategy. However, concerns about the long-term efficacy and side effects of current frontline treatments persist. Alternative therapeutic agents are still needed. ObjectivesObacunone (OB) is a small molecule with a broad spectrum of biological activities, particularly antioxidant and anti-inflammatory effects. This study aims to examine OB’s therapeutic potential on osteoporosis and explore the rudimentary mechanisms. MethodsOsteoclast formation and osteoclastic resorption assays were carried out to examine OB’s inhibitory effects in vitro, followed by the in-vivo studies of OB’s therapeutic effects on ovariectomy-induced osteoporotic preclinical model. To further study the underlying mechanisms, mRNA sequencing and analysis were used to investigate the changes of downstream pathways. The molecular targets of OB were predicted, and in-silico docking analysis was performed. Ligand-target binding was verified by surface plasmon resonance (SPR) assay and Western Blotting assay. ResultsThe results indicated that OB suppressed the formation of osteoclast and its resorptive function in vitro. Mechanistically, OB interacts with macrophage migration inhibitory factor (MIF) which attenuates receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced signaling pathways, including reactive oxygen species (ROS), NF-κB pathway, and mitogen-activated protein kinases (MAPKs). These effects eventually caused the diminished expression level of the master transcriptional factor of osteoclastogenesis, nuclear factor of activated T cells 1 (NFATc1), and its downstream osteoclast-specific proteins. Furthermore, our data revealed that OB alleviated estrogen deficiency-induced osteoporosis by targeting MIF and thus inhibiting hyperactive osteoclasts in vivo. ConclusionThese results together implicated that OB may represent as a therapeutic candidate for bone disorders caused by osteoclasts, such as osteoporosis.

Short- and Long-term side effects of Concomitant Chemoradiation treatment for Cervical Cancer

Concomitant chemoradiation (CRT) for locally advanced cervical cancer has become an established treatment based on randomised trials. Major concerns, however, remain over the acute and late toxicity and hence the generalisability of the conclusions of these studies. The study period was from October 2020 to May 2022. A total of 126 patients with Stage IIB to IIIB Cervical Cancer were taken for the study from Patna Medical College Hospital, Patna, Bihar with consent from the patients. Most of the patients were of stage IIIB (47.60%) in group A and (54%) in group B. Most of the patients had parity ˃5 (68.30%) in group A and (87.30%) in group B. Most of the patients (58.73%) in group A and (66.66%) in group B completed EBRT within the schedule time of 35 days. Twenty seven (42.85%) patients in group A and twenty three (36.50%) patients in group B had break during EBRT due to toxicity. In conclusion, observation during follow up after 6 months group A patients 74.60% had no evidence of disease and in group B 76.19% had no evidence of disease or no residual disease. In group A 25.40% had residual disease and in group B 24.60% had residual disease.

Parents' perceptions and experiences of physical activity in childhood cancer survivors in Singapore: a qualitative study.

The survival rate for childhood cancer has increased with advances in medical care. Along with this comes the growing burden of long-term side effects of cancer treatment and cancer survivorship. Childhood cancer survivors are more likely to be sedentary and have a lower quality of life. Physical activity (PA) can promote health and well-being in childhood cancer survivors, but few studies have explored the role of parents of childhood cancer survivors (PCCS) in promoting PA. This qualitative study aims to explore the perceptions of PCCS in Singapore and the role they may have with regard to PA. Participants were recruited through a local charity via email, social media and posters. One-hour semi-structured interviews were conducted online with seven parents. With consent, the interviews were recorded, transcribed verbatim and analysed using thematic analysis. Our study discussed thematically parents' accounts on (1) the barriers and enablers of PA and (2) the complications of cancer that potentially affect the levels of PA in childhood cancer survivors. Parents reported that childhood cancer negatively affects the quality of life and participation in PA. The determinants of participation in PA were multifaceted, and socioecological and health belief models were used to demonstrate how these factors were interlinked. Participation in PA is influenced at an individual, family, community and societal level. The improved understanding facilitated by this research can be used to shape paediatric cancer care practices in Singapore and guide institutional or national policy interventions.

Side effects of long-term treatment with chloroquine for rheumatoid arthritis - a review of the literature

Background: Chloroquine is a 4-aminoquinoline derivative. Initially the substance was used as an antimalarial drug, but now chloroquine is also used to treat connective tissue diseases. It is a widely used drug in rheumatological diseases, especially in rheumatoid arthritis and systemic lupus erythematosus. A number of side effects have been reported in the public literature among patients using this drug. This article reviews side effects during long-term treatment of patients with rheumatoid arthritis. Materials and methods: A review of the literature available in the PubMed database was performed, using the key words: "Chloroquin" ; "Chloroquin rheumatoid" ; "Chloroquin toxicity" ; "Chloroquine" ; "Chloroquine rheumatoid" ; "Chloroquine toxicity". Results: Chloroquine is a quinine derivative, originally used in the prevention and treatment of malaria. It is now being successfully used to treat patients with certain connective tissue diseases, including rheumatoid arthritis. A number of publications have described various side effects of this drug. Serious and major problems arise from the drug's toxicity with long-term use, such as in the treatment of rheumatoid arthritis. Long-term use of the drug results in retinopathy and cardiotoxicity (conduction disturbances, cardiomyopathy). The available literature also mentions neuromyotoxicity which is rarely reported by patients. Conclusion: Long-term use of chloroquine carries serious side effects. The main complications of long-term use of the drug affect the visual, cardiovascular and nervous systems. The use of chloroquine in patients with rheumatoid arthritis should emphasize the need for accurate dosing and periodic cardiovascular, ophthalmologic and neurologic monitoring.

Acetaminophen improves tardive akathisia induced by dopamine D2 receptor antagonists

Tardive akathisia is a movement disorder characterized by internal restlessness with an uncontrollable urge to move, leading to repetitive movements. It is a common side effect of long-term treatment with dopamine D2 receptor antagonists. In the present study, we analyzed the FDA Adverse Event Reporting System and IBM MarketScan Research Database to find a drug that can be used concomitantly with dopamine D2 receptor antagonists and still reduce the risk of akathisia. Acetaminophen was determined to be the most effective akathisia-suppressing drug. In an experimental validation of the hypothesis, chronic treatment of rats with haloperidol caused akathisia symptoms, including increased stereotyped behavior and locomotor activity, and decreased immobility time. Acute treatment with acetaminophen significantly attenuated haloperidol-induced akathisia. In the ventral striata of these rats, acetaminophen prevented haloperidol-induced decrease in the number of c-Fos+ preproenkephalin+ neurons. These results suggest that acetaminophen is effective in suppressing tardive akathisia by activating indirect-pathway medium spiny neurons.

Applications of the Grading Scales for the Detection of Ototoxicity in Children after Treatment of Neuroblastoma and Extracranial Germinal Tumor

Introduction: Advances in treatment have resulted in a significant increase in survival rates for patients cured of malignant diseases such as neuroblastoma (NBL) and extracranial germ cell tumor (GCT). NBL is one of the pediatric cancers during which potentially ototoxic cytostatic drugs (cisplatin and carboplatin) are used for treatment. Other cancers include germinal tumors, hepatoblastoma, sarcomas, and brain tumors. Often, this very aggressive treatment has a high risk of causing long-term side effects, including hearing loss. Hence, the present study aimed to evaluate the usefulness of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Brock, Chang, and International Society of Pediatric Oncology (SIOP) Boston scales in terms of detecting the high-frequency nature of hearing loss induced by ototoxic drugs and monitoring hearing status in children after completion of oncological treatment. Additionally, the frequency of hearing loss in children treated for NBL and extracranial GCT was assessed, and the principles of monitoring hearing in these patients were indicated. Methods: The study group consisted of 78 patients diagnosed with NBL (n = 47) and GCT (n = 31). There were 23 boys and 24 girls in the NBL group, aged 0–16 years, and 21 boys and 10 girls in the GCT group, aged 0–18 years. The control group consisted of 54 patients who had never received oncological treatment, were not taking potentially ototoxic drugs, and appeared socially efficient in the subjective audiological assessment. Audiometric examinations and DP-acoustic otoemission measurements were performed. Additionally, impedance audiometry tests were done to exclude a possible conductive component of the hearing loss. Results: The analysis shows that ototoxicity-induced hearing loss was observed in 13.8–65.5% of children. 75.9% of patients showed hearing loss in the 16 kHz frequency range, and at least 56.8% of patients showed hearing loss in the frequency range above 12.5 kHz. Hearing impairment, relevant to speech understanding, was displayed by more than 40% of children treated for NBL and GCT. Conclusions: The confirmation of hearing loss in nearly 65% of cases in both patients indicates the necessity to monitor the long-term side effects of anticancer treatment. Acoustic otoemission measurements, the adoption of articulatory indices based on an audiogram, or the use of arbitrary ototoxicity assessment scales such as Brock, Chang, or SIOP Boston are fully justified techniques for studying ototoxicity induced by cytostatic drugs. However, they all require continuous improvement to increase their sensitivity and specificity, especially in the pediatric group.

Psychosocial well-being and mental adjustment of patients with stage III melanoma in the re-entry phase: a scoping review

Abstract Background: The number of patients with stage III melanoma is rising because of increasing incidence and improved survival thanks to newly available adjuvant treatments. Patients may face specific challenges in the re-entry phase, the first 18 months after treatment, because of a high risk of recurrence and the intensity and long-term side effects of adjuvant treatment. The aims of this scoping review included summarizing the current state of evidence concerning patient psychosocial well-being and mental adjustment to the re-entry phase, as well as identifying knowledge gaps. Methods: A systematic literature search was conducted in PubMed and CINAHL using the PRISMA-ScR checklist. Results: Two qualitative and seven quantitative studies were included. Some studies found no evidence of diminished social and emotional functioning compared with the general population, while others reported emotional distress and impairment in psychological health. Regarding existential health, frequently expressed concerns encompassed fear of recurrence, hopelessness, and uncertainty about the future. Patients typically used behavioral coping, cognitive coping, and meaning-making to manage challenges in the re-entry phase. Only one study considered the effects of adjuvant therapy use on the re-entry phase. Conclusions: Limited evidence is available on the psychosocial status of patients with stage III melanoma in the re-entry phase, a phase in which patients face existential concerns. It may be beneficial to provide patients with support regarding existential concerns and meaning-making, for example by developing a practical tool to help set meaningful goals for the re-entry phase. A better understanding of the psychosocial well-being of these patients, the impact of adjuvant therapy, and the relationship between emotional distress, existential concerns, and meaning-making will require further research.

Expression of Concern for Angelakis et al., "Abnormal Weight Gain and Gut Microbiota Modifications Are Side Effects of Long-Term Doxycycline and Hydroxychloroquine Treatment".

Expression of Concern for Angelakis et al., "Abnormal Weight Gain and Gut Microbiota Modifications Are Side Effects of Long-Term Doxycycline and Hydroxychloroquine Treatment".

The Role of Nutrition in Primary and Secondary Prevention of Cardiovascular Damage in Childhood Cancer Survivors.

Innovative therapeutic strategies in childhood cancer led to a significant reduction in cancer-related mortality. Cancer survivors are a growing fragile population, at risk of long-term side effects of cancer treatments, thus requiring customized clinical attention. Antineoplastic drugs have a wide toxicity profile that can limit their clinical usage and spoil patients’ life, even years after the end of treatment. The cardiovascular system is a well-known target of antineoplastic treatments, including anthracyclines, chest radiotherapy and new molecules, such as tyrosine kinase inhibitors. We investigated nutritional changes in children with cancer from the diagnosis to the end of treatment and dietary habits in cancer survivors. At diagnosis, children with cancer may present variable degrees of malnutrition, potentially affecting drug tolerability and prognosis. During cancer treatment, the usage of corticosteroids can lead to rapid weight gain, exposing children to overweight and obesity. Moreover, dietary habits and lifestyle often dramatically change in cancer survivors, who acquire sedentary behavior and weak adherence to dietary guidelines. Furthermore, we speculated on the role of nutrition in the primary prevention of cardiac damage, investigating the potential cardioprotective role of diet-derived compounds with antioxidative properties. Finally, we summarized practical advice to improve the dietary habits of cancer survivors and their families.

Psychosocial factors associated with the intention of breast cancer survivors to regularly practise moderate physical activity.

Regular physical activity (PA) can be beneficial to breast cancer survivors, although the majority do not devote sufficient time to the practice. The long-term side effects of cancer treatment represent barriers to adopting healthy lifestyle habits. Identify factors that influence the intention to practise regular PA among breast cancer survivors. A correlational study was conducted among my Active Health (Ma Santé Active) program participants (N = 136), using a self-administered questionnaire based on the theory of planned behaviour. Multiple regression analysis shows that attitude, perceived control, behavioural beliefs and control beliefs are the determinants of intention. It is recommended to design interventions based on these determinants to strengthen the behavioural intention of breast cancer survivors. The paper will also inform healthcare professionals about the intervention targets to be utilized to motivate women with a breast cancer diagnosis to engage in regular PA.

Rhinoplasty on Patients with von Willebrand's Disease

Von Willebrand's disease (VWD) is the most common hereditary bleeding disorder. Due to its frequency, occasionally, patients with this disease apply for rhinoplasty. Classically, desmopressin is used in emergent cases, and it is highly effective. However, the lack of long-term treatment and possible side effects limit the desmopressin treatment. Because the fibrinolytic activity in the nasal mucosa is high, antifibrinolytics such as tranexamic acid are beneficial in all types of VWD. An 18-year-old patient with Type 1 VWD who was operated without facing any complications is presented. Treatment involved 4 days of treatment starting the day before the surgery and healing process was uneventful. Patients with a diagnosis of VWD can be operated successfully with preoperative tranexamic acid treatment and using vasoconstrictor agents and avascular surgery planes. In Type 1 VWD or low von Willebrand's factor cases, tranexamic acid is a safe and successful treatment alternative due to its long-term use, local and systemic applicability, and regional affinity.

Unmet needs, anxiety, depression, and quality of life among caregivers of adolescents and young adults with cancer: A cross-sectional study

ObjectiveTo assess unmet needs, anxiety, depression, and quality of life of caregivers of adolescents and young adults with cancer and examine their associations. MethodsA total of 282 caregivers of adolescents and young adults with cancer were recruited by convenience sampling at a tertiary cancer hospital in Chinese Mainland. The participants’ unmet needs, anxiety, depression, and quality of life were assessed using self-reported questionnaires. Hierarchical regression analyses were conducted to examine associations between unmet needs and health outcomes. ResultsThe five most prevalent high unmet needs were related to ‘worries about future’ and ‘information’, including dealing with not knowing what lies in the future (n ​= ​161, 57.1%), dealing with worry about the cancer getting worse (n ​= ​151, 53.5%), dealing with worry about the cancer coming back (n ​= ​147, 52.1%), finding information about complementary or alternative therapies (n ​= ​137, 48.6%), and finding information about the long-term side effects of treatments and medicines (n ​= ​126, 44.7%). Around 40% of the caregivers reported moderate to severe anxiety and depression. After adjusting for sociodemographic and clinical characteristics, personal and emotional needs, healthcare access and continuity, and financial needs remained significantly associated with anxiety, depression, or quality of life. ConclusionsNurses need to be aware of the unmet needs of caregivers of adolescents and young adults with cancer. More effort is needed to identify services and interventions that address the unmet needs, particularly personal and emotional, healthcare access and continuity, and financial needs, to improve the caregivers’ health outcomes.

Abstract P4-11-19: Utilization of the RE-AIM frameworkfor evaluating the implementation of group medical visit for low-income breast cancer survivors

Abstract Introduction: Providing cost effective comprehensive survivorship care (SC) remains a major challenge for which optimal delivery models are needed. Group medical visits (GMV) are commonly used in chronic diseases to deliver medical care, education, and empower patients. Pilot GMV studies for breast cancer survivors (BCS) have shown increases in peer support and patient education. This pilot study uses the RE-AIM framework for evaluation of the GMV intervention to support breast cancer survivors. RE-AIM is an efficient framework for systematic evaluation of health care interventions. RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) is the evaluation methodology based on the framework developed by a working team of scholars from health care, public health, and implementation science. Methods: The study was conducted at a public hospital in California. GMV consisted of 4, 2-hour, weekly sessions focused on therapy side effects and prevention, emotional health, sexual health, physical activity, and diet. Patient navigator (PN) recruited 3 consecutive GMV groups of 6 English-speaking BCS (n=18). Results: The Reach was determined by the number and proportion of participants in this study. Our participants were primarily English-speaking and were within 1-5 years of completing active breast cancer treatment. Participants of the GMV were from diverse backgrounds and low-income neighborhoods in San Francisco and were representative of breast cancer survivors in our population. Effectiveness of GMV were assessed through self-reported changes with increased knowledge of survivorship care plans, recognition, and management of long-term side effects of cancer treatments and knowledge of community-based resources. There was an increase from baseline in all these domains and in confidence communicating with their primary care provider. Adoption involved initial stakeholder engagement in the intervention and Implementation was assessed by the consistent content and delivery of the intervention. We did not evaluate Maintenance as it was out of the scope of this study. We found that ongoing need for services is extremely high in our BCS, suggesting that this intervention has the potential to be widely adopted by cancer survivors and survivorship programs. Overall, consistent attendance and active participation indicated that GMV are feasible in this setting. 94% of BCS reported GMV increased their awareness and confidence of SC. Participants reported high satisfaction, felt well-informed, and supported through the availability of GMV. BCS highlighted the benefits of integrating treatment, services, emotional support, and education. BCS suggested GMV should be implemented at time of cancer diagnosis and emphasized the key role of PN in GMV and supporting SC. Conclusions: GMVs were specifically designed to address unmet needs for services that are necessary for SC but not readily available. Our pilot data suggests PN facilitated GMV are a feasible and acceptable model to integrate SC in public hospitals. The evaluation of our intervention using the RE-AIM framework can aid potential adopters in developing and implementing GMV intervention to support BCS. Citation Format: Evelin Trejo, Ana I. Velazquez, Elizabeth Castillo, Barbara Cicerelli, Robin McBride, Nancy J. Burke, Niharika Dixit. Utilization of the RE-AIM frameworkfor evaluating the implementation of group medical visit for low-income breast cancer survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-19.

Reduction of the Vertebral Bone Mineral Density in Patients with Hodgkin Lymphoma Correlates with Their Age and the Treatment Regimen They Received.

Simple SummaryHodgkin lymphoma (HL) is considered a largely curable disease (~80%). The young patient age at diagnosis and their long life expectancy make quality-of-life issues, including osteopenia, exceedingly important. This study aimed to assess treatment-related bone mineral density (BMD) changes that are overlooked in this young population. BMD was measured using PET/CT scans. Among 213 patients (median age 29 years), post-treatment BMD reduction of >15% was significantly more common in those aged ≥30 years and was also associated with a cumulative dose of steroids used. At 6 months post-therapy, BMD recovery was observed in ABVD (adriamycin/bleomycin/vinblastine/dacarbazine) treated patients, while individuals receiving EB (bleomycin/etoposide/adriamycin/cyclophosphamide/oncovin/procarbazine/prednisone) regimens demonstrated persistent BMD loss and higher rates of osteopenia. Our findings suggest that steroid use should be minimized and highly gonadotoxic drugs like procarbazine should be substituted with less toxic ones, due to their deleterious effect on BMD. Adequate vitamin D levels should be maintained.Nowadays, Hodgkin lymphoma (HL) has become highly curable. The young age at diagnosis and long life expectancy emphasize the importance of preventing long-term treatment side effects, including bone mineral density (BMD) loss, in these patients. We aimed to evaluate the effects of first-line therapeutic modalities on BMD dynamics in HL patients, intending to identify individuals at risk for osteopenia. Demographics, HL risk factors, treatment, including cumulative steroid doses, and BMD of 213 newly-diagnosed HL patients (median age 29 years), treated at Rambam between 2008–2016, were analyzed. The main chemotherapy regimens applied were: ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP (EB; bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, prednisone). BMD was measured using PET/CT scans. BMD loss >15% was revealed in 48% of patients at therapy completion, with osteopenia prevalence of 4% and 14% at baseline and post-therapy, respectively. Cumulative hydrocortisone equivalent doses >3400 mg/m2 correlated with significant BMD reduction. Multivariate analysis at 6 months post-therapy identified age ≥30 years and EB-regimens as significant risk factors for BMD decrease >15%. Therapy-related BMD loss is common in HL patients. Its persistence is associated with age ≥30 years and EB treatment. Reduction of cumulative steroid doses and switch to non-gonadotoxic drugs should be considered.

A Nomogram to Predict Critical Weight Loss in Patients with Nasopharyngeal Carcinoma During (Chemo) Radiotherapy.

Background:Weight loss is an important side effect of long-term anticancer treatment for nasopharyngeal carcinoma patients. The decline in body function will cause many adverse effects, such as local recurrence and distant metastasis, and reduce the patient’s quality of life. Therefore, this study developed a predictive model for the probability of critical weight loss to provide timely appropriate nutritional interventions and prevent serious side effects.Methods:A 20-week prospective follow-up study of 137 nasopharyngeal carcinoma patients in West China Hospital of Sichuan University undergoing radiotherapy and chemotherapy from February 2018 to March 2020 was conducted to collect relevant clinical data. The clinical usefulness and calibration of the prediction model were assessed using the C-index, calibration plot, receiver operating curve, and decision curve analysis. Internal validation was assessed using bootstrapping validation.Results:The nomogram consisted of sex, smoking status, physical status, chemotherapy regimen, and body mass index. Good calibration was observed for the cohort, with an area under the curve of 0.924. Five independent prognostic factors were included in the nomogram, which showed a high C-index value of 0.815 in the interval validation. Decision curve analysis showed that the nomogram was clinically useful when the intervention was decided at the critical weight loss possibility threshold in the 0% to 97% range.Conclusions:We constructed and validated a nomogram for predicting the incidence of critical weight loss in nasopharyngeal cancer patients undergoing chemotherapy and radiotherapy.

Dopaminergic co-transmission with sonic hedgehog inhibits abnormal involuntary movements in models of Parkinson\u2019s disease and L-Dopa induced dyskinesia

L-Dopa induced dyskinesia (LID) is a debilitating side effect of dopamine replacement therapy for Parkinson’s Disease. The mechanistic underpinnings of LID remain obscure. Here we report that diminished sonic hedgehog (Shh) signaling in the basal ganglia caused by the degeneration of midbrain dopamine neurons facilitates the formation and expression of LID. We find that the pharmacological activation of Smoothened, a downstream effector of Shh, attenuates LID in the neurotoxic 6-OHDA- and genetic aphakia mouse models of Parkinson’s Disease. Employing conditional genetic loss-of-function approaches, we show that reducing Shh secretion from dopamine neurons or Smoothened activity in cholinergic interneurons promotes LID. Conversely, the selective expression of constitutively active Smoothened in cholinergic interneurons is sufficient to render the sensitized aphakia model of Parkinson’s Disease resistant to LID. Furthermore, acute depletion of Shh from dopamine neurons through prolonged optogenetic stimulation in otherwise intact mice and in the absence of L-Dopa produces LID-like involuntary movements. These findings indicate that augmenting Shh signaling in the L-Dopa treated brain may be a promising therapeutic approach for mitigating the dyskinetic side effects of long-term treatment with L-Dopa.