Individualized Treatment Regimens Research Articles

AI-Driven Real-Time Classification of ECG Signals for Cardiac Monitoring Using i-AlexNet Architecture.

The healthcare industry has evolved with the advent of artificial intelligence (AI), which uses advanced computational methods and algorithms, leading to quicker inspection, forecasting, evaluation and treatment. In the context of healthcare, artificial intelligence (AI) uses sophisticated computational methods to evaluate, decipher and draw conclusions from patient data. AI has the potential to revolutionize the healthcare industry in several ways, including better managerial effectiveness, individualized treatment regimens and diagnostic improvements. In this research, the ECG signals are preprocessed for noise elimination and heartbeat segmentation. Multi-feature extraction is employed to extract features from preprocessed data, and an optimization technique is used to choose the most feasible features. The i-AlexNet classifier, which is an improved version of the AlexNet model, is used to classify between normal and anomalous signals. For experimental evaluation, the proposed approach is applied to PTB and MIT_BIH databases, and it is observed that the suggested method achieves a higher accuracy of 98.8% compared to other works in the literature.

A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma

A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma

Effectiveness and safety analysis of serplulimab-based regimens in patients with HER2-negative advanced gastric cancer from a real-world retrospective study.

e16058 Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy are currently the preferred regimen for the treatment of HER-2 negative advanced gastric cancer. Serplulimab, an anti-PD-1 inhibitor, has been conditionally approved for the treatment of adult advanced gastric cancer. Because of the diverse nature of patients (pts), patient-centered, individualized treatment require accumulation of experience for real-world applications. Methods: We retrospectively studied 42 HER2-negative advanced gastric adenocarcinoma pts whose safety profiles of regimen containing serplulimab could be evaluated from April 2022 to October 2023 in the First Affiliated Hospital of Soochow University. Individualized treatment regimens mainly included serplulimab combined with one or two selected drug(s) from platinum, taxanes, and fluoropyrimidines. Results: Cut-off on January 30th, 2024, 30 pts (71.4%) received serplulimab based regimens as the first line (1L), 12 pts (28.6%) received the second or more line (≥2L) therapy. The characteristics were as follows: the median age, 66 years (range 35-80 years); male/female 33 (78.6%)/9(21.4%); ECOG performance status 0-1/38, ≥2/4. The median follow-up was 5.7 months (range 0.2-22.3 mos). A total of 227 cycles of treatment was administrated with a median of 4 cycles (range 1-17). Among the pts evaluable for RECIST 1.1, ORR and DCR were 42.9% and 69.0% respectively. There were 3 pts with 3 or more metastatic lesions achieved PR. Nine 1L pts and one 2L pt receiving serplulimab combined with dual chemotherapy containing platinum achieved disease control more than a year. We also tracked 11 pts who experienced grade 1-2 immune-related adverse events (irAEs) reaped over 6 months PFS. Two of four pts who stopped immunotherapy but maintained 1 or 2 cycles of original combined chemotherapy obtained PFS for more than a year. Median PFS and DoR have not reached. The most common grade 3/4 AEs was myelosuppression (7.1%), increased aminotransferases (4.7%) and elevated creatinine (2.3%). 15 (35.7%) pts experienced immune-related adverse events (irAEs) of any grade including aminotransferase elevation, increased creatinine, but no grade 3 or higher irAEs observed. Conclusions: The real-world data analysis shows that serplulimab-based flexibly combination according to patient status, achieving tumor control in diverse pts while ensuring drug safety. We successfully validated the effectiveness and safety of chemo-immunotherapy strategy in real-world practice. [Table: see text]

Trends in mortality from secondary malignancy in the United States, 1999-2019.

11166 Background: Recent advancements in cancer diagnosis, treatment, and supportive care increased the survivorship of cancer patients. However, the risk of secondary malignancy (SM), associated most commonly with side effects of radiation and chemotherapies, has emerged as a looming threat to childhood and adult-onset cancer survivors. Recognizing the recent trends in malignancy-related deaths and the risk factors associated could assist healthcare professionals and policymakers in constructing appropriate guidelines for timely diagnosis and individual patient-dependent treatment regimens. Hence, our CDC analysis focuses on highlighting trends in mortality from SM from “1999 to 2019”. Methods: Using the deidentified death certificate data from the CDC WONDER database, we analyzed mortality trends from 1999 to 2019 for SM. Age-adjusted mortality rates (AAMRs) per 100,000 people were calculated for the total population, stratified by gender, race, age, and site of SM. Annual percent change (APC) was calculated using the Joinpoint regression software. Results: A total of 1,499,108 deaths occurred from 1999 to 2019 in the US. The overall AAMR showed a decrease from 27.5 in 1999 to 18.83 in 2007 (APC: -4.71), remained at a relatively constant level of 19.11 till 2013 (APC: 0.48), followed by a rapid rise to 23.29 in 2017 (APC: 5.37), and finally a gradual rise to 24.29 in 2019 (APC: 1.97). Men showed consistently higher AAMR than women throughout the study period between 1999 (AAMR Men: 33.31 vs Women: 23.78) and 2019 (AAMR Men: 28.03 vs Women: 21.51). Moreover, Black (AAMR: 23.89) showed the highest mortality rate, followed by Whites (AAMR: 21.46). American Indian (AAMR: 13.93), Asian (AAMR: 13.89), and Hispanic (AAMR: 15.9) showing similar mortality trends. Furthermore, AAMR increased with age, showing the highest mortality rates in patients 75+ yrs (148.3), followed by 55-74 yrs (61.6), 35-54 yrs (9.23), 15-34 yrs (0.7), and ≤ 14 yrs (0.19). More recently the greatest rise in SM from 2013-2019 was observed in adrenal glands (APC: 11.8), bone and bone marrow (APC: 8.7), kidney and renal pelvis (APC: 7.6), and small intestine (APC: 6.9). Less prominent rise was seen in all other types of SM. Conclusions: Despite recent advances in cancer treatments, SM remains one of the most common causes of death in cancer survivors. Our analysis shows that age, gender, race, and site are important factors influencing the risk of SM-related mortality. Although the risk of SM varies across the spectrum of age, findings from one age group could be translated into preventive and screening strategies across other age groups. Guidelines for survivors should be taken into account based on prior treated malignancy and the risk of future ones. Large population based studies are imperative to understand factors behind the recent rise in SM-related mortalities from 2013 onwards.

Risk-aware restricted outcome learning for individualized treatment regimes of schizophrenia

Risk-aware restricted outcome learning for individualized treatment regimes of schizophrenia

Integrated Diagnosis, Treatment and Prognosis in Healthcare using Artificial Intelligence

Artificial Intelligence (AI) has revolutionized healthcare by integrating treatment, diagnosis, and prognosis into a cohesive and patient-centric approach. This study examines how utilising AI technology in healthcare might improve patient management and have a transformational impact. Huge volumes of patient data, including as genetic data, medical records, and treatment outcomes are analysed by AI algorithms, allowing for the creation of individualised treatment regimens based on precise prognostic assessments and diagnoses. Utilising AI-driven decision-making promotes proactive and preventative actions, improving healthcare outcomes. To ensure ethical AI adoption, however, concerns about data privacy, algorithmic bias, and ethical issues must be addressed. In order to demonstrate how AI-driven therapy approaches are successful, case examples are reviewed in this article, demonstrating how they might potentially enhance patient care. As AI develops, its seamless integration with healthcare systems has enormous promise for revolutionising medical practise. It will usher in a new era of accurate, effective, and data-driven patient management, which will ultimately be advantageous to both patients and healthcare professionals.its capacity to enhance patient care.

#1993 Analysis of the characteristics of IgA nephropathy patients using real-world data from five European countries

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally; it has a significant health burden and a highly variable disease course. As IgAN is a heterogeneous disease, it is important to appreciate the associated patient characteristics in order to understand disease progression and how best to implement individualised treatment regimens. To determine the patient characteristics associated with IgAN, a physician questionnaire and patient chart audit were conducted. Method From 21 December 2022 to 6 February 2023, physicians from five European countries (France, Germany, Spain, Italy and the UK) completed a questionnaire and patient chart review of their IgAN patients. Physicians were required to have ≥50 patients with stage 1–4 chronic kidney disease (CKD); at least four of these were required to be non-dialysis IgAN patients. Patients whose charts were included were required to be aged 12 years or older, non-dialysis IgAN patients and have an estimated glomerular filtration rate of ≥15 mL/min/1.72 m2. The charts included were required to be from patients who had seen a participating physician within the prior 6 months. Results 261 physicians answered the questionnaire and completed chart audits on 473 of their most recently seen patients. Patient charts audited were largely from male (71%) Caucasian (78%) patients from 31–49 years of age (38%). 22% of patients were referred to their current physician within the past year. Most patients (70%) were referred by a primary care physician and 9% by another nephrologist. Of those referred by a nephrologist, 32% were referred for specialised care. Participating physicians perceived that close to 30% of patients were referred to them late or extremely late, with contributing factors including lack of engagement from patients with annual follow-ups and patients remaining asymptomatic for a long time. At the most recent visit, 24.3% had CKD stage 1 or 2, 26.6% of patients had CKD stage 3a, 30.4% had stage 3b and 18.6% had stage 4 disease. Nephrologists characterised 53% of their CKD stage 4 patients as having severe IgAN. The symptoms reported with greatest frequency at the most recent visit included fatigue (59%), blood in the urine (41%) and increased weight gain (41%). In total, 71% of patients had proteinuria >0.5 g/day (8% had no values available) and 8% of patients had nephrotic syndrome (urine protein >3.5 g/day and low serum albumin). In total, 28% of patients had no co-morbid conditions. More than half (54%) of the patients whose charts were audited had comorbid hypertension. Other comorbidities included hyperlipidaemia (22%), obesity (17%), type 2 diabetes (15%) and peripheral oedema (7%). Counterintuitively, when asked about the overall health of their patients, physicians perceived the majority (98%) of patients to be in good or excellent overall health. Patients were prescribed five medications on average, with most (92%) taking an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, or both. The number of medications prescribed increased after the age of 50. Two-thirds (66%) of physicians felt that patients completely adhered to their treatment regimen. However, 54% of physicians reported some form of dissatisfaction with the response of their patients to their overall treatment regimen; though, levels of satisfaction varied between individual treatment options. Conclusion Despite high rates of proteinuria and patients often in late-stage CKD at referral, physicians perceived the majority of patients to be in good or excellent overall health, revealing a potential gap in physicians’ perceptions of patients’ health and their risk of progression to kidney failure. As a result, patients were often diagnosed or referred late and their perception of their own health may have led to a lack of engagement with physicians. These data indicate that there is an unmet need for early diagnosis and treatment of IgAN to ensure that patients receive appropriate care.

Predictors of Fatal Outcome in Newly Diagnosed Tuberculosis/HIV Co-Infection with Chronic Alcoholism (Clinical Case)

Our own case of tuberculosis/HIV co-infection’s diagnosis in chronic alcoholism and analysis of the fatal outcome predictors are presented. The patient abused alcohol for a long time in the presented case, he was hospitalised with acute psychosis in a psychoneurological dispensary, where pulmonary tuberculosis and HIV infection were diagnosed for the first time during additional examination. The patient was admitted to the department in serious condition after prolonged alcohol intoxication. The patient’s condition stabilized after detoxification therapy. Antimycobacterial therapy according to the scheme of an individual treatment regimen, antiretroviral therapy, treatment of hepatitis B and C, detoxification therapy, prophylaxis with Biseptol and Fluconazole and symptomatic therapy were prescribed. After 20 days immune reconstitution inflammatory syndrome developed. It was manifested with meningitis and cryptococci were detected in the cerebrospinal fluid 17 days later. Prescribed treatment of cryptococcal meningoencephalitis with fluconazole in high doses intravenously had a significant positive effect, which made it possible to reduce the dose of the drug to the maintenance level. The treatment was not stopped, but sterility of the liquor was not achieved. After 98 days the patient entered a coma and after 113 days he died from the progression of multiple organ failure and cryptococcal meningitis. It should be noted that the patient was diagnosed with tuberculosis with multiple drug resistance for the first time, the treatment of which had positive dynamics, despite the progression of multiple organ failure and the presence of cryptococcal meningoencephalitis. Therefore, although tuberculosis was not the direct cause of the patient’s death, the disease itself deepened the severity of the general condition. Considering the presented clinical case, it was established that predictors of the fatal outcome of newly diagnosed tuberculosis/HIV co-infection in chronic alcoholism are: antisocial lifestyle; concomitant diseases (tuberculosis, chronic viral hepatitis B and C); cryptococcal meningoencephalitis; fever, altered mental status, cryptococci in the cerebrospinal fluid; the number of CD4+ lymphocytes is less than 200/μL; lack of early screening for CrAg; early initiation of antiretroviral therapy before the diagnosis of cryptococcal meningoencephalitis, which provokes immune reconstitution inflammatory syndrome, against the background of which cryptococcal infection progresses; monotherapy of cryptococcal meningoencephalitis with Fluconazole. Knowledge and practice gaps among medical practitioners contribute to the high fatality rate of cryptococcal meningoencephalitis in tuberculosis/HIV co-infection in chronic alcoholism.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice

Background and purposeThe aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. MethodsWe conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. ResultsClinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. ConclusionsOur real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

P103 Centralised pain in early rheumatoid arthritis predicts worse bodily pain outcomes

Abstract Background/Aims Features of centralised pain, encompassing widespread pain and non-pain features such as multisensory hypersensitivity, fatigue, and sleep disturbance are common in RA. We hypothesise that centralised pain in early RA affects response to standard first-line treatment. Methods Prospective cohort study of adults with a clinical diagnosis of RA recruited from the early inflammatory arthritis clinic, Oxford University Hospitals, who completed an online assessment within two weeks of starting a DMARD. Centralised pain was assessed using three measures: the 2016 Fibromyalgia Survey Criteria (0-31), Central Sensitisation Inventory (CSI, 0-100), and PainDetect (0-38). The primary outcome, bodily pain, was assessed using the Short Form-36 Bodily Pain Scale (BPS), where lower scores indicate worse pain severity. During follow-up, participants completed three sets of follow-up questionnaires at 3-, 6- and 12-months. Linear mixed effects models were used to account for repeated measurements and patient variability. Three models were fitted, for an association between baseline values of each centralised pain measure with BPS over time. An interaction between centralised pain scores with time was fitted to assess for effect of the exposure on change over time. Age, sex, and symptom duration at baseline were included as confounding variables. Ethical approval was granted by South Central Oxford B Research Ethics Committee. Results Of 149 participants, 117 (79%) completed follow-up: median (IQR) age 59.8 (24.6) years; 36% male; 30% with symptoms >1 year at baseline. There were no significant baseline differences among those lost to follow-up, apart from a longer symptom duration (53% vs 30% symptom duration >1 year; P = 0.033). At baseline, median (IQR) Fibromyalgia Survey Criteria, CSI, and PainDetect scores were 12 (6), 36 (17), and 14 (9) respectively. The median (IQR) BPS at baseline was 32.5 (22.5). Measures of centralised pain were moderately-to-strongly correlated with each other, and with BPS. Individuals with symptoms for >1 year had higher scores on the PainDetect (P = 0.0015), but not the CSI (P = 0.0545) or Fibromyalgia Survey Criteria (P = 0.672). After adjusting for age, sex, and symptom duration, there was a significant association between centralised pain at baseline and BPS over follow-up, e.g.; for every unit increase in the fibromyalgia survey criteria at baseline, the BPS decreased by 2.40 (95%CI -3.29, -1.49; P < 0.001) points over follow-up. Similar relationships were seen with the CSI and PainDetect scores. Conclusion Centralised pain measures in early RA patients can be indicative of the severity of bodily pain experienced during the subsequent 12 months after starting a DMARD treatment. Recognising and assessing centralised pain in early RA patients may enable us to tailor more effective and individualised treatment regimens. Further studies, especially those utilising neuroimaging and QST, are essential to elucidate the neural mechanisms underlying the impact of centralised pain on treatment outcomes in RA. Disclosure E. Kelleher: None. A.J. Wall: None. M.T. Sanchez-Santos: None. V. Wanigasekera: None. A. Irani (nee Soni): None.

Remote Disease Diagnosis through IoMT-Enhanced Blood Cell Classification with Deep Learning

Background For the purpose of diagnosing diseases and developing treatment plans, blood cell pictures must be accurately classified. This procedure can be greatly enhanced by automated systems that make use of deep learning and the Internet of Medical Things (IoMT). Objective In order to improve illness detection and increase healthcare accessibility, this work suggests an IoMT-based system for remote blood cell picture transmission and classification utilizing deep learning algorithms. Methods High-resolution pictures of blood cells are captured by an IoMT tiny camera and wirelessly sent to a cloud-based infrastructure. The blood cells are divided into groups according to a, deeplearning classification algorithm, including neutrophils, lymphocytes, monocytes, and eosinophils. Results The IoMT-enabled system excels in transmitting and analyzing blood cell images, achieving precise classification. Utilizing deep learning models with multi-scale feature extraction and attention mechanisms, the system demonstrates robust performance. Numerical results showcase a high accuracy of approximately 97.21%, along with noteworthy precision, recall, and F1 scores for individual blood cell classes. Eosinophil, Lymphocyte, Monocyte, and Neutrophil classes exhibit strong performance metrics, emphasizing the system's effectiveness in accurate blood cell classification. Conclusion By combining IoMT and deep learning with blood cell image analysis, diagnostic accessibility and efficiency are improved. The suggested approach has the potential to completely transform healthcare by facilitating prompt interventions, individualized treatment regimens, and better patient outcomes. It is essential to continuously enhance and validate the system in order to maximize its efficacy and dependability in a variety of healthcare settings.

Conservative management of proximal hamstring avulsion: A clinical study

IntroductionThe management of proximal hamstring tear (PHT) is debated and consensus regarding recommended measures and individual treatment regimens is lacking. The present investigation evaluated the efficacy of a conservative management of partial and complete PHT. MethodsThe present observational study was conducted following the STROBE statement. In June 2018 the medical databases of the BG Klinikum Bergmannstrost Halle, Germany were accessed. All the patients with PHT were retrieved. The outcomes of interest were to evaluate the clinical examination, PROMs, imaging, and isokinetic muscle strength at the baseline and last follow-up. Results31 patients were enrolled in the present study. Nine patients (29 % (9 of 31) described local pain at the ischial tuberosity in sitting situations and also in manual palpation. A persistent gap in the tendon string beneath the tuberosity in manual palpation was reported in 25.8 % (8 of 31). The mean VAS at the last follow-up was 2.3 ± 2.3. The mean LEFS score was 50.9 ± 18.8.Control MRI at follow-up showed scarring restitution in the proximal tendon in all patients in the partial tear group. In the complete tear group, a persisting defect state of the proximal tendon course was found in 45 % (9 of 20). The injured side achieved 81.5 ± 22.2 % of the force of the uninjured side, measured in the flexion movement at 60°/s. At an angular velocity of 240°/s, 83.2 ± 26.3 % of the force of the uninjured side was achieved. ConclusionAccording to the main findings of the present study, conservative therapy of PTH tears is associated with good clinical outcomes. High-quality investigations are required to establish the proper therapeutic algorithm and advantages of conservative management compared to a surgical approach. Level of evidenceLevel III.

Male patients with primary Sjögren's syndrome have unique clinical manifestations and circulating lymphocyte profiles.

We aimed to explore the relationship between clinical characteristics and circulating lymphocyte profiles in Chinese male patients with primary Sjögren's syndrome (pSS). Data from 397 patients with pSS were analyzed retrospectively. 37 were male, which is a prevalence of 9.3%. The clinical, laboratory, and immunophenotypic profiles of peripheral blood lymphocyte subsets were compared between male and female pSS patients. Male patients with primary Sjögren's syndrome have unique clinical manifestations and circulating lymphocyte profiles. Male patients complained more about xerophthalmia and presented with more extra-glandular manifestations as compared with female patients. The CD4+/CD8+ ratio (P = 0.030), the prevalence of CD4-CD8- T cells in lymphocytes (P = 0.020), the absolute number of CD4-CD8- T cells (P = 0.035), the prevalence of CD4+ T cells in lymphocytes (P < 0.001), and the absolute number of CD4+ T cells (P = 0.023) were significantly lower in male patients compared to female patients. On the other hand, the prevalence of CD8+CD28+ T cells (P = 0.030) and CD4+CD25high T cells (P = 0.040) in lymphocytes was significantly higher in male patients than in female patients. Moreover, compared to females with pSS, an elevated serum IgG level, low C3 and C4 levels, anti-SSB positivity, and ANA titers of ≥ 1:160 positivity were more frequent in male with pSS. Male patients with pSS have distinctive peripheral blood lymphocyte subpopulations, present with more severe clinical symptoms and immunological features, and have an unfavorable prognosis. Key Points • Male patients with pSS have more severe clinical symptoms and specific characteristics of peripheral blood lymphocyte subsets. • Male pSS patients exhibit a higher intensity of the disease (as evaluated by ESSDAI). • Male patients with pSS require individualized treatment regimens and closer follow-up.

Rationale for Using High-Frequency Ultrasound as a Routine Examination in Skin Cancer Surgery: A Practical Approach.

Ultrasound and high-frequency ultrasound assessment of melanoma and non-melanoma skin cancer in the pre-therapeutical setting is becoming increasingly popular in the field of dermatosurgery and dermatooncology, as it can provide clinicians with relevant, "in vivo" parameters regarding tumor lateral and depth extension as well as potential locoregional spread, cancelling the need of more extensive imaging methods and avoiding a delay in diagnosis. Furthermore, preoperative sonography and color Doppler can aid in orienting the clinical diagnosis, being able in numerous situations to differentiate between benign and malignant lesions, which require a different therapeutic approach. This preoperative knowledge is of paramount importance for planning an individualized treatment regimen. Using sonography at the time of diagnosis, important surgical complications, such as neurovascular damage, can be avoided by performing a preoperative neurovascular mapping. Furthermore, sonography can help reduce the number of surgical steps by identifying the lesions' extent prior to surgery, but it can also spare unnecessary surgical interventions in cases of locally advanced lesions, which infiltrate the bone or already present with locoregional metastases, which usually require modern radiooncological therapies in accordance to European guidelines. With this review, we intend to summarize the current indications of sonography in the field of skin cancer surgery, which can help us improve the therapeutic attitude toward our patients and enhance patient counseling. In the era of modern systemic radiooncological therapies, sonography can help better select patients who qualify for surgical procedures or require systemic treatments due to tumoral extension.

Exploring the Potentials of Hyaluronic Acid-coated Polymeric Nanoparticles in Enhanced Cancer Treatment by Precision Drug Delivery, Tackling Drug Resistance, and Reshaping the Tumour Micro Environment.

Cancer is a global health issue that requires modern treatments. Biocompatibility, variable size, and customisable targeting ligands make polymeric nanoparticles (PNPs) a flexible cancer therapy platform. Dynamic nanocarriers, Hyaluronic Acid (HA) coated PNPs, target the overexpressed CD44 receptor in cancer. Through improved permeability and retention, HA, a naturally occurring, biodegradable polymer, increases tumor accumulation and penetration. Hyaluronic acid-grafted polymeric nanoparticles (HA-PNPs) provide a number of advantages over other varieties due to their distinct characteristics. They used CD44 receptor upregulation on cancer cells for selective administration, leveraging the EPR effect for cancer site accumulation. Their natural composition improves biocompatibility while promoting conjugation with a variety of medicinal compounds and providing influence over size and surface features. HA-PNPs facilitate effective cellular uptake, safeguard their cargo, and have the possibility for regulated release, which leads to better delivery of drugs and therapeutic efficacy. While problems, such as CD44 expression variability and drug loading modification, persist, HA-PNPs offer a viable path for targeted and successful treatment of cancer due to their intrinsic benefits. HA-PNPs can be coupled with imaging agents to enable real-time tracking of the delivery of drugs and therapy response, hence enhancing individualized treatment regimens. HA-PNPs can be programmed to respond to particular environmental signals found in the tumor's microenvironment (such as pH, redox potential, and enzymes). This enables for controlled dispensing of therapeutic cargo only when it reaches the target site, reducing systemic exposure and associated negative effects. HA-PNPs have the ability to overcome common MDR processes used by cancer cells, thereby enhancing the efficiency of previously ineffective chemotherapeutic medicines. Recent advances in HA-functionalized PNP fabrication and cancer applications are covered in this article. It discusses complete treatment effectiveness and HA's targeting of tumors and receptors. The study describes production, clinical trials, and problems and prospects in turning HA-coated PNP platforms into viable therapeutic nanomedicines. HA-functionalized PNPs are versatile, targeted nanotherapeutics for various tumor types and disease stages, as shown in this comprehensive study.

A signature based on circadian rhythm-associated genes for the evaluation of prognosis and the tumour microenvironment in HNSCC

The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.

Development of a target concentration intervention to individualize paroxysmal nocturnal hemoglobinuria treatment with pegcetacoplan

Pegcetacoplan (Aspaveli®/Empaveli™) is a factor C3 inhibitor that is approved for the treatment of paroxysmal nocturnal hemoglobinuria. An individualized dosing strategy might be useful to improve patient-friendliness and cost-effectiveness of this very expensive drug. Therefore, the aim of this study was to develop an individualized treatment regimen for pegcetacoplan based on the pharmacokinetic-pharmacodynamic data of the manufacturer. We conducted a clinical trial simulation with the approved dosing regimen of 1080 mg twice-weekly and a target concentration intervention-based dosing regimen in patients with and without prior eculizumab use. For eculizumab-naïve patients, the target concentration intervention-based dosing regimen resulted in a comparable fraction of patients with LDH normalization (LDH < 226 U/L) and hemoglobulin normalization (> 12 g/dL) compared to the approved regimen (LDH 50.2% and 50.0% respectively and hemoglobulin 45.6% and 44.4%). A modest dose reduction of ~ 5% was possible with target concentration intervention-based dosing. An intensified dosing interval was necessary in 2.3% of the patients however an interval prolongation was possible in 28.2% of the patients. Similar results were obtained for patients prior treated with eculizumab. In this study we show the potential of an individualized dosing regimen of pegcetacoplan with can improve patient friendliness in approximately 30% of the patients and improve therapy in approximately 2% of the patients at slightly reduced costs.

Prognostic evaluation of a multi-target magnetic bead-enriched circulating tumor cell-enriched identification system for colorectal cancer.

Colorectal cancer (CRC) is the third most prevalent cancer in the world. Traditional tissue biopsy cannot provide dynamic monitoring of patients' tumors or reflect the characteristics of tumors in real time because the sampling process is invasive and accompanied by risks. Circulating tumor cells (CTCs) are considered a major cause of tumor metastasis, and investigating CTCs helps to understand the biology and vulnerability of malignant tumors during hematogenous metastasis. We sequentially used epithelial cell adhesion molecule (EpCAM)-coated immunoliposomal magnetic beads (Ep-IMBs) and vimentin-coated immunoliposomal magnetic beads (Vi-IMBs) to capture and characterize CTCs from 110 CRC patients. We further constructed a Cox risk regression model, optimized the model composition using backward stepwise regression, and finally applied nomograms to show the effect of each variable on survival risk. The specificity of the CTCs enrichment and identification system was 100% and the sensitivity was 79.0%. Multivariate analysis indicated total CTC number was an important predictor for bad survival, whereas American Joint Committee on Cancer (AJCC) stage, lymph node metastasis, and carcinoembryonic antigen (CEA) level were associated with prognosis, and the risk of mortality was associated with the AJCC stage of the CRC. The CTC enrichment and identification system constructed in this research demonstrated superior accuracy. In addition, CTCs can be used as an important predictor for prognosis of patients with CRC, and the combination of other clinical predictive factors can help clinicians to better design individualized treatment regimens, which is of great clinical application value.

Global adoption of 6-month drug-resistant TB regimens: Projected uptake by 2026.

The WHO has issued a call to action urging countries to accelerate the rollout of new WHO-recommended shorter all-oral treatment regimens for drug-resistant TB (DR-TB), which remains a public-health crisis. The all-oral, 6-month BPaL/M regimen comprises 3-4 drugs: pretomanid used in combination with bedaquiline and linezolid, with or without moxifloxacin. This regimen has been recommended by the WHO for use in DR-TB patients instead of ≥9-month (up to 24-month) regimens. This study aims to project this regimen's use, along with its components bedaquiline, pretomanid and linezolid, and other treatments for DR-TB globally through 2026. It is intended to guide global health stakeholders in planning and budgeting for DR-TB interventions. Projected usage could help estimate cost of the individual components of DR-TB regimens over time. Semi-structured interviews were conducted with national TB programme participants in key countries to gather intelligence on established plans and targets for use of various DR-TB treatment regimens from 2023 to 2026. These data informed development of projections for the global use of regimens and drugs. Consistent global growth in the use of shorter regimens in DR-TB treatment was shown: BPaLM reaching 126,792 patients, BPaL reaching 43,716 patients, and the 9-11-month all-oral bedaquiline-based regimen reaching 13,119 patients by 2026. By 2026, the longer all-oral regimen is projected to be used by 19,262 patients, and individualised treatment regimens by 15,344 patients. The study shows BPaL/M will be used in majority of DR-TB patients by 2024, reaching 78% by 2026. However, national efforts to scale-up, case-finding, monitoring, drug-susceptibility testing, and implementation of new treatments will be essential for ensuring they are accessible to all eligible patients in the coming years and goals for ending TB are met. There is an urgent need to engage communities in capacity building and demand generation.

Learning Non-monotone Optimal Individualized Treatment Regimes

We propose a new modeling and estimation approach to select the optimal treatment regime from different options through constructing a robust estimating equation. The method is protected against misspecification of the propensity score model, the outcome regression model for the non-treated group, or the potential non-monotonic treatment difference model. Our method also allows residual errors to depend on covariates. A single index structure is incorporated to facilitate the nonparametric estimation of the treatment difference. We then identify the optimal treatment through maximizing the value function. Theoretical properties of the treatment assignment strategy are established. We illustrate the performance and effectiveness of our proposed estimators through extensive simulation studies and a real dataset on the effect of maternal smoking on baby birth weight.