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Frontiers in Cardiovascular Medicine 2024Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated...
Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.3 years (30%). With this longer lifespan, calcific aortic stenosis (AS) was identified as an emerging critical risk factor for cardiac death in older patients. Intervention to relieve critical AS has the potential for immediate improvement in healthspan and lifespan. However, HGPS patient-device size mismatch, pervasive peripheral arterial disease, skin and bone abnormalities, and lifelong failure to thrive present unique challenges to intervention. An international group of experts in HGPS, pediatric and adult cardiology, cardiac surgery, and pediatric critical care convened to identify strategies for successful treatment. Candidate procedures were evaluated by in-depth examination of 4 cases that typify HGPS clinical pathology. Modified transcatheter aortic valve replacement (TAVR) and left ventricular Apico-Aortic Conduit (AAC) placement were deemed high risk but viable options. Two cases received TAVR and 2 received AAC post-summit. Three were successful and 1 patient died perioperatively due to cardiovascular disease severity, highlighting the importance of intervention timing and comparative risk stratification. These breakthrough interventions for treating critical aortic stenosis in HGPS patients could rewrite the current clinical perspective on disease course by greatly improving late-stage quality of life and increasing lifespan. Expanding worldwide medical and surgical competency for this ultra-rare disease through expert information-sharing could have high impact on treatment success.
PubMed: 38725831
DOI: 10.3389/fcvm.2024.1356010 -
Database : the Journal of Biological... May 2024Cancer immunotherapy has brought about a revolutionary breakthrough in the field of cancer treatment. Immunotherapy has changed the treatment landscape for a variety of...
Cancer immunotherapy has brought about a revolutionary breakthrough in the field of cancer treatment. Immunotherapy has changed the treatment landscape for a variety of solid and hematologic malignancies. To assist researchers in efficiently uncovering valuable information related to cancer immunotherapy, we have presented a manually curated comprehensive database called DIRMC, which focuses on molecular features involved in cancer immunotherapy. All the content was collected manually from published literature, authoritative clinical trial data submitted by clinicians, some databases for drug target prediction such as DrugBank, and some experimentally confirmed high-throughput data sets for the characterization of immune-related molecular interactions in cancer, such as a curated database of T-cell receptor sequences with known antigen specificity (VDJdb), a pathology-associated TCR database (McPAS-TCR) et al. By constructing a fully connected functional network, ranging from cancer-related gene mutations to target genes to translated target proteins to protein regions or sites that may specifically affect protein function, we aim to comprehensively characterize molecular features related to cancer immunotherapy. We have developed the scoring criteria to assess the reliability of each MHC-peptide-T-cell receptor (TCR) interaction item to provide a reference for users. The database provides a user-friendly interface to browse and retrieve data by genes, target proteins, diseases and more. DIRMC also provides a download and submission page for researchers to access data of interest for further investigation or submit new interactions related to cancer immunotherapy targets. Furthermore, DIRMC provides a graphical interface to help users predict the binding affinity between their own peptide of interest and MHC or TCR. This database will provide researchers with a one-stop resource to understand cancer immunotherapy-related targets as well as data on MHC-peptide-TCR interactions. It aims to offer reliable molecular characteristics support for both the analysis of the current status of cancer immunotherapy and the development of new immunotherapy. DIRMC is available at http://www.dirmc.tech/. Database URL: http://www.dirmc.tech/.
Topics: Immunotherapy; Humans; Neoplasms; Receptors, Antigen, T-Cell; Databases, Protein; User-Computer Interface
PubMed: 38713861
DOI: 10.1093/database/baae032 -
Frontiers in Medicine 2024Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments....
OBJECTIVE
Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis.
METHODS
We retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome ( = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results.
RESULTS
According to the inverse variance-weighted estimation, we identified that ten bacterial traits (, , , , , , , and ) were negatively correlated with skin fibrosis while five bacterial traits (, , , ), and ) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis.
OBJECTIVE CONCLUSION
There is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.
PubMed: 38695027
DOI: 10.3389/fmed.2024.1380938 -
Cancers Apr 2024Painful pelvic and spinal bone metastases are a considerable challenge for doctors and patients. Conventional therapies include morphine-equivalent medication (MeM) and...
Painful pelvic and spinal bone metastases are a considerable challenge for doctors and patients. Conventional therapies include morphine-equivalent medication (MeM) and local radiotherapy (RT), but these interventions are not always successful. More recently, hyperthermia (HT) has been applied to complement RT and MeM, and this complex approach has shown promising synergistic results. The objective of our study was to present the results of RT combined with a special kind of HT (modulated electrohyperthermia, mEHT), in which some of the thermal effect is contributed by equivalent nonthermal components, drastically reducing the necessary power and energy. This retrospective study included 61 patients divided into three groups with pelvic and spinal bone metastases to compare the effects of RT and mEHT alone and in combination (RT + mEHT). A detailed evaluation of pain intensity, measured by the brief pain inventory score, MeM use, and breakthrough pain episodes, revealed no significant differences between RT and mEHT alone; thus, these individual methods were considered equivalent. However, RT + mEHT yielded significantly better results in terms of the above parameters. Clinically, mEHT has a lower risk of adverse thermal effects, and due to its efficacy, mEHT can be used to treat RT-resistant lesions.
PubMed: 38672685
DOI: 10.3390/cancers16081604 -
Children (Basel, Switzerland) Apr 2024Infants, children and young people with life-limiting or life-threatening conditions often experience acute, transient pain episodes known as breakthrough pain. There is...
Infants, children and young people with life-limiting or life-threatening conditions often experience acute, transient pain episodes known as breakthrough pain. There is currently no established way to assess breakthrough pain in paediatric palliative care. Anecdotal evidence suggests that it is frequently underdiagnosed and undertreated, resulting in reduced quality of life. The development of a standardised paediatric breakthrough pain assessment, based on healthcare professionals' insights, could improve patient outcomes. This study aimed to explore how healthcare professionals define and assess breakthrough pain in paediatric palliative care and their attitudes towards a validated paediatric breakthrough pain assessment. This was a descriptive qualitative interview study. Semi-structured interviews were conducted with 29 healthcare professionals working in paediatric palliative care across the UK. An inductive thematic analysis was conducted on the data. Five themes were generated: 'the elusive nature of breakthrough pain', 'breakthrough pain assessment', 'positive attitudes towards', 'reservations towards' and 'features to include in' a paediatric breakthrough pain assessment. The definition and assessment of breakthrough pain is inconsistent in paediatric palliative care. There is a clear need for a validated assessment questionnaire to improve assessment, diagnosis and management of breakthrough pain followed by increased healthcare professional education on the concept.
PubMed: 38671702
DOI: 10.3390/children11040485 -
Clinical Drug Investigation May 2024Recombinant zoster vaccine (RZV) is approved in adults for the prevention of herpes zoster. The effect of RZV in moderating the severity of breakthrough cases of herpes... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Recombinant zoster vaccine (RZV) is approved in adults for the prevention of herpes zoster. The effect of RZV in moderating the severity of breakthrough cases of herpes zoster has been noted but not explicitly quantified before. In this study, a meta-analysis was undertaken to estimate differential utility losses between unvaccinated (Placebo) and vaccinated (RZV) subjects in breakthrough cases of herpes zoster from three RZV clinical trials.
METHODS
Differential utility losses between the two groups were estimated in units of quality-adjusted life-years (QALYs), leveraging aggregate patient data from the ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) clinical trials. Differential utility losses and the ratio of mean utility losses were analyzed using random-effects and fixed-effects meta-regression models.
RESULTS
The mean QALY loss differences between the unvaccinated (Placebo) and vaccinated (RZV) groups were 0.008, 0.004, and 0.011 in the ZOE-50, ZOE-70, and ZOE-HSCT studies, respectively, yielding an overall estimated difference of 0.007 (95% confidence interval 0.002-0.012) QALYs. Quality-adjusted life-year loss in the vaccinated group was estimated to be 35.5% of the value in the placebo group. A sensitivity analysis estimated an overall difference of 0.005 (95% confidence interval 0.001-0.009) QALYs, corresponding to 48.6% of the QALY loss value in the placebo group.
CONCLUSIONS
Recombinant zoster vaccine is effective in alleviating disease severity in breakthrough cases of herpes zoster. The results may be useful in distinguishing QALY losses between vaccinated and unvaccinated cohorts in health economics studies, particularly cost-effectiveness analyses.
Topics: Humans; Herpes Zoster; Herpes Zoster Vaccine; Quality-Adjusted Life Years; Vaccination; Clinical Trials as Topic
PubMed: 38662318
DOI: 10.1007/s40261-024-01355-1 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Apr 2024To compare the early analgesic effects and the impact on knee joint function recovery after unicompartmental knee arthroplasty (UKA) between single adductor canal block... (Randomized Controlled Trial)
Randomized Controlled Trial
[A prospective comparative study on effectiveness of single versus continuous adductor canal block combined with local infiltration anesthesia in unicompartmental knee arthroplasty].
OBJECTIVE
To compare the early analgesic effects and the impact on knee joint function recovery after unicompartmental knee arthroplasty (UKA) between single adductor canal block (SACB) and continuous adductor canal block (CACB) combined with local infiltration anesthesia (LIA) using a prospective study.
METHODS
The patients with knee osteoarthritis admitted between April 2022 and December 2023 were enrolled as a subject. Among them, 60 patients met the selection criteria and were enrolled in the study. They were randomly assigned to the SACB group or CACB group in a ratio of 1:1 using a random number table method. There was no significant difference between the two groups ( >0.05) in terms of age, gender, height, body mass, body mass index, affected side, and preoperative resting visual analogue scale (VAS) score and active VAS score, Oxford knee score (OKS), and American Hospital of Special Surgery (HSS) score. All patients received multimodal analgesia management using LIA combined with SACB or CACB. The operation time, pain related indicators (resting and activity VAS scores, number and timing of breakthrough pain, opioid consumption), joint function related indicators (quadriceps muscle strength, knee range of motion, OKS score, and HSS score), as well as postoperative block complications and adverse events were recorded and compared between the two groups.
RESULTS
There was no significant difference in the operation time between the two groups ( <0.05). All patients in the two groups were followed up with a follow-up time of (9.70±4.93) months in the SACB group and (12.23±5.05) months in the CACB group, and the difference was not significant ( >0.05). The CACB group had a significant lower resting VAS score at 24 hours after operation compared to the SACB group ( <0.05). There was no significant difference in resting and active VAS scores between the two groups at other time points ( >0.05). The CACB group had a significantly lower incidence of breakthrough pain compared to the SACB group [9 cases (30.00%) . 17 cases (56.67%); <0.05). However, there was no significant difference in the timing of breakthrough pain occurrence and opioid consumption between the two groups ( >0.05). Four cases in the SACB group and 7 cases in the CACB group experienced adverse events, with no significant difference in the incidence of adverse events between the two groups ( >0.05). The CACB group had significantly better knee joint mobility than the SACB group at 1 and 2 days after operation ( <0.05). There was no significant difference between the two groups in knee joint mobility on 0 day after operation and quadriceps muscle strength and OKS and HSS scores at different time points ( >0.05).
CONCLUSION
In UKA, the analgesic effects and knee joint function recovery are similar when compared between LIA combined with SACB and LIA combined with CACB. However, SACB is simpler to perform and can avoid adverse events such as catheter displacement and dislocation. Therefore, SACB may be a better choice.
Topics: Humans; Analgesics, Opioid; Anesthesia, Local; Arthroplasty, Replacement, Knee; Breakthrough Pain; Nerve Block; Pain, Postoperative; Postoperative Complications; Prospective Studies
PubMed: 38632065
DOI: 10.7507/1002-1892.202312103 -
Journal of Pain Research 2024Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain...
BACKGROUND
Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain.
PATIENTS AND METHODS
Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST).
RESULTS
A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5-11.5] hours vs.16.0 [95% CI:11.5-22.5] hours; <0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0-3.5) than in the oxycontin group.(3.0; 2.5-4.5) (=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5-3.0) vs 4.5;3.0-6.0) (=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (=0.29), but there was a significant improvement in quality of life (QoL) in both groups (=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (=0.32).
CONCLUSION
Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (<0.001), without significantly increasing adverse events (=0.32).
PubMed: 38628430
DOI: 10.2147/JPR.S451698 -
Journal of Pain Research 2024This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in...
PURPOSE
This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai.
METHODS
From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China.
RESULTS
A total of 238 responses participated in the survey. This survey reports physicians' understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors' knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff's understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training.
CONCLUSION
Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.
PubMed: 38618294
DOI: 10.2147/JPR.S452605 -
Frontiers in Pharmacology 2024The aim of our study was to administer adequate local anesthetic in programmed intermittent epidural bolus (PIEB) to avoid breakthrough pain and decrease the use of...
Optimum programmed intermittent epidural bolus interval time of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL: a randomized controlled trial.
BACKGROUND
The aim of our study was to administer adequate local anesthetic in programmed intermittent epidural bolus (PIEB) to avoid breakthrough pain and decrease the use of manual and PCEA boluses. We, therefore, conducted this study to determine the effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL in 90% of subjects (EI), without the use of patient-controlled epidural analgesia (PCEA).
METHODS
A total of 80 subjects were included in the final statistical analysis from 23 August 2022 to 22 November 2022. The subjects were randomly assigned to one of four different PIEB time intervals: 40, 50, 60, and 70 min (groups 40, 50, 60, and 70), respectively. The primary outcome was the effective epidural labor analgesia, defined as no use of PCEA bolus or a manual bolus until the end of the first stage of labor or within 6 hours after loading dose administration. The PIEB EI (95% CI) between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL was estimated using probit regression.
RESULTS
The effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL in 90% of subjects without the use of PCEA was 45.4 (35.5-50.5) minutes using probit regression. No statistical differences were found in the proportion of subjects with Bromage score > 0, hypotension, pruritus, nausea, and vomiting between groups. However, the highest sensory block (pinprick) in the 40-min group was significantly higher than that in the other groups.
CONCLUSION
The estimated value for EI for PIEB between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL using probit regression was 45.4 (35.5-50.5) minutes. Furthermore, future studies are warranted to be established to determine the optimal parameters for different regimens in clinical practice.
PubMed: 38595925
DOI: 10.3389/fphar.2024.1368222