Course Of Disease Research Articles

Spontaneous regression of head and neck squamous cell carcinoma: a systematic review and meta-analysis of case reports.

A systematic review of case reports in spontaneous regression of head and neck squamous cell carcinoma (SCC) was carried out to investigate the pattern and characteristics of this phenomenon. A systematic search of case studies of spontaneously regressed head and neck SCC was carried out in Ovid Embase, Ovid Medline and Pubmed. Methodological quality was assessed by ascertainment of diagnosis and overall details of reports. Outcomes included patient demographics, head and neck SCC characteristics and clinical course of disease. A total of 8 cases were included and 50 per cent (n = 4) of the reported cases were SCC of the vocal folds. All cases received a surgical biopsy and three cases had possible febrile episodes preceding regression. The mean length of time to regression was 4.3 months. Spontaneous regression in head and neck SCC is likely to be under-reported. A better understanding of how the host immune system can instigate an antitumour response will shed light on the development of novel treatments.

Protocol for the systematic review of age and sex in preclinical models of age-correlated diseases

The translation of animal-based biomedical research into clinical research is often inadequate. Maximizing translation should be central to animal research on human diseases, guiding researchers in study design and animal model selection. However, practical considerations often drive the choice of animal model, which may not always reflect key patient characteristics, such as sex and age, impacting the disease's course. Despite diseases affecting both sexes, researchers frequently use male mice. To address this imbalance, journals and funding agencies have begun questioning the sex of animals used in studies and issued new guidelines. Conversely, the age of rodents is rarely discussed, even though many diseases primarily affect older patients. Young mice are commonly used, even in studies of diseases affecting older adults. Systematic comparisons between the age of rodents used and the age of patients in clinical trials are lacking. In this review, we systematically analyze the age and sex of mice used to model the five leading causes of global disability-adjusted life-years over the age of 75. We compare the results with the age and sex of patients in clinical trials focusing on Alzheimer's disease, stroke, type 2 diabetes mellitus, ischemic heart disease, and chronic obstructive pulmonary disease. We also analyze whether the age of the mice used has changed over the past decade. By systematically assessing the age and sex of the mice, we aim to initiate a discussion on the appropriate choice of animal model to improve the translatability of research results.

Pulmonary involvement in systemic sclerosis: can sex play a role?

Systemic sclerosis (SSc) is a rare and complex autoimmune disease with significant complications. During the last few years, research interest focuses on the differences between female and male patients. However, there is a lack of data regarding the role of sex in the presence of small airway disease (SAD). Therefore, we aimed to investigate the impact of sex on pulmonary involvement in a cohort of SSc patients, focusing primarily on small airways. For this retrospective study, consecutive patients with a diagnosis of SSc, that visited our department until January 2024, were recruited. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared between the two groups. In total 393 patients (female-to-male ratio 6:1) were included. Median time to diagnosis after the onset of Raynaud's was significantly longer for female patients. Electrocardiogram abnormalities were more common in male patients, while telangiectasias, calcinosis and arthralgias were more common in female individuals. Moreover, male SSc patients exhibited a higher prevalence of ILD and shorter time until the diagnosis of ILD. However, female individuals demonstrated a lower maximal-mid expiratory flow rate (MMEF) and higher ratio of residual volume to total lung capacity. Interestingly, sex remained an independent predictor of MMEF, in the multivariate analysis. Our results showed that, although ILD is more common in male SSc patients, SAD was more prevalent among female individuals. Importantly, female sex remained an independent predictor of SAD. This study further supports the presence of sex-related differences in SSc, with important implications in disease course and management.

A fluorescence immunochromatography method for detection of human papillomavirus type 16 E6 and L1 proteins

This study aims to establish a time-resolved fluorescence immunochromatography method for simultaneous determination of human papillomavirus (HPV) type 16 E6 and L1 protein concentrations. The amount of lanthanide microsphere-labeled antibodies, the concentration of coated antibodies, and the reaction time were optimized, and then a test strip for the simultaneous determination of the protein concentrations was prepared. The performance of the detection method was evaluated based on the concordance of the results from clinical practice. The optimal conditions were 8 μg and 10 μg of HPV16 L1 and E6-labeled antibodies, respectively, 1.5 mg/mL coated antibodies, and reaction for 10 min. The detection with the established method for L1 and E6 proteins showed the linear ranges of 5-320 ng/mL and 2-64 ng/mL and the lowest limits of detection of 1.78 ng/mL and 1.09 ng/mL, respectively. There was no cross reaction with human immunodeficiency virus (HIV), treponema pallidum (TP), or HPV18 E6 and L1 proteins. The average recovery rate of the established method was between 97% and 107%. The test strip prepared in this study showed the sensitivity, specificity, and diagnostic accuracy of 97.46%, 90.57%, and 95.32%, respectively, in distinguishing patients with cervical cancer and precancerous lesions from healthy subjects, with the area under the curve (AUC) of 0.980 1 and 95% Confidence Interval (CI) of 0.956 5 to 1.000 0. The time-resolved fluorescence immunochromatography combined with the test strips prepared in this study showed high sensitivity, high accuracy, simple operation, and rapid reaction in the quantitation of HPV16 E6 and L1 proteins. It thus can be used as an auxiliary method for the diagnosis and early screening of cervical cancer and precancerous lesions and the assessment of disease course.

Dravet Syndrome – Clinical and Developmental Characteristics: A Case Report

Introduction: Dravet syndrome is a rare, genetically determined epilepsy and epileptic encephalopathy primarily caused by a loss-of-function mutation in the SCN1A gene, also associated with autism spectrum disorder. Follow-ing birth, patients have typical neurodevelopment, but the regression of cognitive, motor and speech abilities become noticeable after the onset of seizures.Aims and case report: We report on the case of a five-year-old girl with characteristic clinical features of Dravet syndrome, detailing her basic clinical and developmental characteristics, disease course and treatment. The first seizure occured at four months of age, coinciding with increased body temperature, and by the end of first year she developed recurrent seizures. While the baseline electroencephagram was nomal, follow-up examinations revealed continuous high-amplitude and sharp, multifocal spike waves. During her second year of life, significant delay in psychomotor development became apparent. The Bayley-III scale was used to assess psychomotor de-velopment in cognition area, comprehension and quality of speech, as well as fine and gross motor skills. The results indicated that her cognitive abilities corresponded to those of an eight-month-old child, while her motor skills were at the level of an 18-month-old. Notable gait impairment was observed, with a wide-based crouch gait. The patient was also diagnosed with an autism spectrum disorder.Conclusion: Although rare, Dravet syndrome is an important differential diagnosis in children presenting with early-onset epilepsy and progressive developmental delays. It is essential to evaluate patients for common comor-bidities, such as autism, gait disorders, and intellectual disability, important determinants of patients’ quality of life.

A multicenter study on the sex difference of dysfunctions among rehabilitation outpatients in China

Dysfunction is a common clinical symptom among rehabilitation patients; however, whether there are sex differences in dysfunctions remains unclear. Therefore, this study aimed to explore this issue by examining a large sample of the population with dysfunctional problems. A multi-stage sampling scheme was used to select the rehabilitation outpatients as study participants. A total of 3415 participants from 21 medical institutions in seven cities in China were included in the final analysis. The measurement included general characteristics (age, sex, educational level, marital status, and household income) and disease-related characteristics (dysfunctions, self-care ability, vital signs, disease status, and disease course). The logistic regression was used to analyse the sex difference in dysfunctions among rehabilitation outpatients. Among 3415 rehabilitation outpatients, the mean age of participants was 45.3 years (SD:24.9), and more than half (54.0%) were male. The male patients were more likely to have cognitive impairment (OR = 1.74; 95% CI = 1.42, 2.13), speech disorders (OR = 2.00; 95% CI = 1.62, 2.48), dysphagia (OR = 1.55; 95% CI = 1.12, 2.16), and multiple dysfunctions (OR = 2.00; 95% CI = 1.57, 2.54) than female. Female patients were more likely to have motor dysfunctions (OR = 0.63; 95% CI = 0.50, 0.78). There are sex differences in dysfunctions among rehabilitation outpatients. This sex difference may provide potential clinical value for the treatment of rehabilitation patients.

Skin and Soft Tissue Nontuberculous Mycobacteria Infection: A Retrospective Case Series of 49 Patients.

The incidence of skin and soft tissue nontuberculous mycobacteria infection (SSTNI) is increasing. But it may be challenging to diagnose and treat SSTNI. To summarize course, clinical features, diagnosis and treatment of SSTNI and discuss the association between SSTNI and procedures. A retrospective case series study was conducted among patients diagnosed with SSTNI after surgical procedures. Medical history was collected, disease course and characteristics were analyzed. 49 patients were collected. Among them, 39 (80%) patients were infected with Mycobacterium abscesses. 40 (82%) patients had a history of fat-related procedures. The median and interquartile range of onset time were 15 and 43 days (1-100). Time from first visit to diagnosis was 82±57 days (23-308). Wound healing time was 161±92 days (30-545). The most common symptom were redness (96%), followed by swelling (96%), abscess (84%), pain (80%) and induration (76%). The most common infected site were head and neck (56%), followed by breasts (20%). 6 (12.5%) patients were diagnosed clearly before admission to our department. 10 (28%) patients showed positive acid-fast bacilli (AFB) smears among 36 patients. Treatment included debridement surgeries, drainage and antibiotics. Patient with the above symptoms should be considered as SSTNI. Results of AFB smears are frequently negative after empirical antibiotic treatment so that molecular diagnostic techniques are required for rapid and accurate identification. Debridement surgeries, drainage and sensitive antibiotics are effective. Drug safety and psychological status should be paid attention. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer’s disease, positive for plasma p-tau217

BackgroundThe spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer’s disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1, an active immunotherapy targeting the microtubule-binding region (MTBR) of tau, in a subgroup of participants with elevated plasma p-tau217, indicating AD-related neuropathological changes.MethodsADAMANT was a 24-month, randomized, placebo-controlled, parallel-group, double-blinded, multicenter, phase 2 clinical trial in subjects with mild AD. The trial participants were randomized 3:2 to receive six doses of AADvac1 or placebo at 4-week intervals, followed by five booster doses at 14-week intervals. The primary outcome was safety. The secondary outcomes were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer’s Disease Cooperative Study – Activities of Daily Living score for Mild Cognitive Impairment 18-item version (ADCS-ADL-MCI-18), and immunogenicity. Volumetric MRI, plasma neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were exploratory outcomes. The inclusion criterion for this post-hoc analysis was a baseline plasma p-tau217 level above the cutoff for AD.ResultsAmong 196 ADAMANT participants, 137 were positive for plasma p-tau217 (mean age 71.4 years, 59% women). AADvac1 was safe and well tolerated in this subgroup. AADvac1 reduced the rate of accumulation of log-plasma NfL by 56% and that of GFAP by 73%. The treatment differences in the CDR-SB and ADCS-ADL-MCI-18 scores favored AADvac1 but were not statistically significant. AADvac1 had no effect on whole-brain volume but nonsignificantly reduced the loss of brain cortical tissue in several regions. Importantly, the impact on the study outcomes was more pronounced in participants with higher anti-tau antibody levels.ConclusionsThese results suggest that AADvac1 tau immunotherapy can reduce plasma biomarkers of neurodegeneration and neuroinflammation. These findings and possible observations on brain atrophy and cognition are hypothesis-generating and warrant further evaluation in a larger clinical trial.Trial registrationEudraCT 2015–000630-30 (primary) and NCT02579252.

EANM perspective on clinical PET and SPECT imaging in schizophrenia-spectrum disorders: a systematic review of longitudinal studies.

There is a need for biomarkers in psychiatry to improve diagnosis, prognosis and management, and with confirmed value in follow-up care. Radionuclide imaging, given its molecular imaging characteristics, is well-positioned for translation to the clinic. This systematic review lays the groundwork for integrating PET and SPECT imaging in the clinical management of schizophrenia-spectrum disorders. Systematic search of PubMed, Embase, Web of Science and Cochrane library databases was conducted from the earliest date available until February 2024. The focus was on longitudinal studies evaluating PET or SPECT imaging in individuals with a schizophrenia-spectrum or another psychotic disorders. Quality assessment was done using the Newcastle-Ottawa Scale (NOS), NIH scale for before-after studies and Cochrane Risk of Bias tool version 2 (Cochrane RoB2). Studies were further categorised into three groups: preclinical and diagnosis, predicting disease course or personalising treatment. Fifty-six studies were included in the systematic review investigating in total 1329 patients over a median of 3 months. Over two-thirds used PET tracers, whereas the remaining studies employed SPECT tracers. The most frequently investigated system was dopaminergic transmission, followed by cerebral metabolism and blood flow. [18F]FDOPA demonstrated large effect size in predicting conversion of subjects at risk and treatment response. Additionally, treatment dosage could be optimised to reduce side effects using [123I]IBZM or [11C]raclopride. Molecular imaging holds significant promise for real-life application in schizophrenia, with two particularly encouraging avenues being the prediction of conversion/response to antipsychotic medication and the improved management of antipsychotic dosage. Further longitudinal studies and clinical trials will be essential for validating both the clinical effectiveness and economic sustainability, as well as for exploring new applications.

Medical treatment of primary sclerosing cholangitis: What have we learned and where are we going?

It has proven difficult to establish robust evidence for significant clinical benefits of medical treatment in primary sclerosing cholangitis (PSC). For ursodeoxycholic acid, clinical practice guidelines only offer vague recommendations, leading to a situation of variable prescription rates depending on local reimbursement policies and physician preference. The difficulty in drug development in PSC is partly related to poor understanding of critical disease processes with failure to identify relevant mechanisms of action of putative drugs. The variable disease course, both intra-individually and between individuals, and lack of robust definitions of what success looks like for clinical trials in PSC have also contributed to the negative outcomes of trials performed. In this review article we will discuss these uncertainties and challenges, building on key previous and ongoing clinical trials. Despite the lack of consensus for an ideal phase II and phase III study design, several trials for diverse compounds are currently ongoing, indicating a shift from therapeutic nihilism towards hope for people with PSC. While waiting for robust efficacy data for drugs currently being tested, the current lack of effective interventions should not motivate prescription of compounds to people with PSC based on low-quality evidence.

Modifiable risk factors for the development and severe course of diverticular disease: a review

Diverticulosis is a common condition of the bowel, particularly affecting the sigmoid colon with age-dependent increase in prevalence. While often asymptomatic and discovered incidentally during colonoscopies or imaging, some patients experience symptoms like left lower abdominal pain, bloating, and irregular bowel habits. When symptoms arise, it is termed diverticular disease (DD). Approximately 10% of diverticulosis cases progress to diverticulitis, which involves inflammation and can lead to complications like abscesses, perforation, or obstruction. In the U.S., acute diverticulitis accounts for 200,000 hospitalizations annually, costing about $2.2 billion in healthcare. The purpose of this paper is to review the current understanding of modifiable risk factors associated with the development and progression of diverticular disease

Clinical features and natural course of Hidradenitis Suppurativa in Turkey: a multicentre study.

The natural history, the progression of a disease process in an individual over time, has not yet been fully elucidated in hidradenitis suppurativa (HS). In this large multicenter study, we aimed to investigate the natural history of HS and its gender differences. This cross sectional study included 827 patients. The chronological order of the clinical manifestations for each patient were recorded retrospectively. Sociodemographic characteristics, triggering factors, clinical, treatment, and prognostic features were also evaluated. The mean age of disease onset was significantly younger in women than in men (22.42±9.28 vs. 27.06±20.56, p<0.001) and those with a family history (p<0.0001). The mean disease duration was 91.17±83.64 months. The most common symptom was purulent discharge (81%). The mean duration of abscess was shorter in women than in men (3.11±2.65 vs. 3.75±3.75, p=0.01). The axilla was the most common onset area followed by the inguinal and gluteal regions. The disease ran a more severe course in men. Abscess/inflammatory nodule was defined in the last 6 months in 88.6% of the patients; however, the first 5 years of the disease were the most active disease period in 67.5% of the patients. Multivariate analysis revealed being male, older age, family history, involvement of the axillary, inguinal and perianal regions independently associated with HS severity. While antibiotic use was the most important factor in improving the disease symptoms, stress was the most common aggravating factor. Biological therapy in men, laser epilation and pregnancy in women were significant alleviating factors. Whereas, weight gain was a more common aggravating factor for women. HS shows a relentlessly progressive course with inflammatory attacks, but the first years of the disease are the most active period. This study confirms that environmental and hormonal factors may play an important role in the disease course, probably with other endogenous or exogenous factors.

Cigarette smoke-induced disordered microbiota aggravates the severity of influenza A virus infection.

Cigarette smoke (CS) promotes the development of chronic pulmonary disease and has been associated with increased risk for influenza-related illness. Here, we directly addressed the impact of CS disordered microbiota on the severity of influenza A virus (IAV) infection. Specific and opportunistic pathogen-free (SOPF) C57BL/6J mice were exposed to CS or room air (RA) for 5.5 months. Each exposed mouse was then cohoused with a group of recipient germ-free (GF) mice for 1 month for microbial transfer. Colonized GF mice were then infected intranasally with IAV and disease development was monitored. Upper and lower airway and fecal microbiota were longitudinally investigated by 16S rRNA gene sequencing and bacterial cultures in donor and recipient mice. The bacterial family Streptococcaceae accounted for the largest difference between CS- and RA-exposed microbiota in the oropharynx. Analysis of the oropharynx and fecal microbiota indicated an efficient transfer to coprophagic recipient mice, which replicated the differences in microbiota composition observed in donor mice. Subsequent IAV infection revealed significantly higher weight loss for CS microbiota recipient mice at 8-10 days post infection (dpi) compared to control recipient mice. In addition, H1N1 infection inflicted substantial changes in the microbiota composition, especially at days 4 and 8 after infection. In conclusion, mice with a CS-associated microbiota suffer from higher disease severity upon IAV infection compared to mice colonized with a normal SOPF microbiota. Our data suggest that independently of CS exposure and concomitant structural lung damage, microbial distortion due to CS exposure may impact the severity of IAV disease course.IMPORTANCEIt has been reported that chronic exposure to CS is associated with a disordered microbiota composition. In this study, we colonized germ-free (GF) mice with the microbiota from SOPF mice which were chronically exposed to CS or RA. This allowed disentangling the effect of the disordered microbiota from the immune-modulating effects of actual CS exposure. We observed a successful transfer of the microbiotas after cohousing including specific microbiota differences induced by CS exposure in formerly GF mice, which were never exposed to CS. We then investigated the effects of IAV infection on the disease course and microbiotas of formerly GF mice. We found that mice with CS-associated microbiota reveal worse disease course compared to the control group. We hypothesize that CS-induced disordering of the microbiota may, indeed, impact the severity of influenza A disease.

Short-term incremental prednisone therapy in patients with serologically active clinically quiescent lupus nephritis: a retrospective observational study

ObjectiveThis study investigated whether short-term incremental prednisone therapy decreases the risk of relapse without increasing adverse events (AEs) in patients with serologically active, clinically quiescent lupus nephritis (LN).MethodsAfter standardized treatment, 153 patients with serologically active, clinically quiescent LN were included. Clinical data were retrospectively reviewed. The patients were divided into two groups: the control group (n = 58) received prednisone or prednisone and immunosuppressant maintenance therapy, the prednisone increment group (n = 95) received additional prednisone doses of up to 10 mg/day as maintenance therapy, which were then gradually reduced back to the original dose at 3 months. Lupus activity, renal involvement, and AEs during follow-up in the two groups were analyzed within 18 months.ResultsNo significant differences in sex, age, disease course, maintenance treatment composition, or laboratory tests between the two groups were observed, except for serum complement C3 levels, which were significantly lower in patients in the prednisone increment group than in controls (P = 0.025). The prednisone increment group had significantly lower recurrence rates than the control group (P = 0.002), with only 3 patients (5.2%) in the prednisone increment group and 24 patients (25.3%) in the control group experiencing relapse. Renal recurrence was significantly lower in the prednisone increase group (P = 0.013). Nine AEs occurred in the prednisone-modulated group and 11 AEs occurred in controls, with infection being the main cause for both groups.ConclusionShort-term incremental prednisone therapy is safe in reducing recurrence rates in serologically active and clinically quiescent patients with LN.Key pointsIncremental prednisone is safe and effective for patients with serologically active clinically quiescent LN.

Artificial intelligence systems for predicting chronic ischemic heart disease outcomes in cardiac surgery patients based on presence of anemia: a literature review

BACKGROUND: In Russia, the number of people undergoing heart surgery exceeds 600 thousand annually. These include anemia in 30–70% of patients with a 4-fold increased risk of one-year death, a 5-fold increased risk of stent thrombosis, a 1.3-fold increased risk of recurrent acute coronary events, and a 2-fold increased risk of bleeding. However, among the prognostic systems developed using artificial intelligence (AI) technologies, few take the presence of anemia into account. Existing digital platforms are not designed to support clinical decision making. AIM: The review aimed to evaluate existing AI platforms for predicting the course of ischemic heart disease (IHD) and systems that take into account the presence of anemia. MATERIALS AND METHOD: The PubMed and Russian Science Citation Index databases from 2000 to January 2024 were analyzed. Using Keywords of “artificial intelligence”, “anemia”, “coronary heart disease”, “hemoglobin”, and “cardiac surgery”, 906 articles were found, of which 38 met the inclusion criteria for analysis. RESULTS: In some countries, AI platforms have been created to predict the course of IHD. This review analyzes published data on the development and use of AI-based digital products for the management of patients with IHD, including those that take into account key hemodynamic parameters. CONCLUSION: Analysis of existing developments revealed a focus on solving prognostic problems. However, in our opinion, the range of parameters analyzed is not wide enough. For example, anemia, which plays a key role in modifying the risk of adverse outcomes in IHD, has not been considered as a factor.

Correlation linking illness perception, negative emotions, and the post-operative recovery effect in patients with perianal disease.

Improvements in the standard of living have led to increased attention to perianal disease. Although surgical treatments are effective, the outcomes of post-operative recovery (POR) are influenced by various factors, including individual differences among patients, the characteristics of the disease itself, and the psychological state of the patient. Understanding these factors can help healthcare providers develop more personalized and effective post-operative care plans for patients with perianal disease. To investigate the effect of illness perception (IP) and negative emotions on POR outcomes in patients with perianal disease. A total of 146 patients with perianal disease admitted to the First People's Hospital of Changde City from March to December 2023 were recruited. We employed a general information questionnaire, the Brief Illness Perception Questionnaire (B-IPQ), and the Hospital Anxiety and Depression Scale (HADS). We used the 15-item Quality of Recovery Score (QoR-15) to measure patients' recovery effects. Finally, we conducted Pearson's correlation analysis to examine the relationship between pre-operative IP and anxiety and depression levels with POR quality. Fifty-three (36.3%) had poor knowledge of their disease. Thirty (20.5%) were suspected of having anxiety and 99 (67.8%) exhibited symptoms. Forty (27.4%) were suspected of having depression and 102 (69.9%) displayed symptoms. The B-IPQ, HADS-A, HADS-D, and QoR-15 scores were 46.82 ± 9.97, 12.99 ± 3.60, 12.58 ± 3.36, and 96.77 ± 9.85, respectively. There was a negative correlation between pre-operative IP, anxiety, and depression with POR quality. The influence of age and disease course on post-operative rehabilitation effect are both negative. The impact of B-IPQ, HADS-A, and HADS-D on POR was negative. Collectively, these variables accounted for 72.6% of the variance in POR. The quality of POR in patients with perianal disease is medium and is related to age, disease course, IP, anxiety, and depression.

Cellular Therapies for Multiple Myeloma: Engineering Hope.

Multiple myeloma (MM) treatment remains challenging due to its relapsed/refractory disease course as well as intra- and inter-patient heterogeneity. Cellular immunotherapies, especially chimeric antigen receptor (CAR)-T cells targeting B cell maturation antigen (BCMA), mark a major breakthrough, achieving long-lasting remissions and instilling hope for a potential cure. While ongoing clinical trials are increasingly driving approved cellular products towards earlier lines of therapy, novel targets as well as advanced approaches employing natural killer (NK) cells or dendritic cell (DC) vaccines are currently under investigation. Treatment resistance, driven by tumor-intrinsic factors such as antigen escape and the intricate dynamics of the tumor microenvironment (TME), along with emerging side effects such as movement and neurocognitive treatment-emergent adverse events (MNTs), are the major limitations of approved cellular therapies. To improve efficacy and overcome resistance, cutting-edge research is exploring strategies to target the microenvironment as well as synergistic combinatorial approaches. Recent advances in CAR-T cell production involve shortened manufacturing protocols and "off-the-shelf" CAR-T cells, aiming at decreasing socioeconomic barriers and thereby increasing patient access to this potential lifesaving therapy. In this review, we provide an extensive overview of the evolving field of cellular therapies for MM, underlining the potential to achieve long-lasting responses.

PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 30% of Western populations. While obesity is a recognized risk factor, MASLD does not develop in all obese individuals, highlighting the need to understand genetic and environmental interactions. The PNPLA3 I148M variant has been identified as a key genetic risk factor, significantly increasing the likelihood of MASLD development and progression. We reviewed current literature on the role of PNPLA3 I148M in MASLD, focusing on gene-environment interactions involving diet, physical activity, obesity, and insulin resistance. We included studies analysing ethnic differences in PNPLA3 I148M prevalence and its association with MASLD. Additionally, we reviewed data on how PNPLA3 I148M influences the response to therapies, including lipid-lowering medications and GLP-1 agonists. The PNPLA3 I148M variant markedly heightens MASLD risk, particularly in Hispanic populations, where a higher prevalence of MASLD is observed. Lifestyle factors such as high sugar intake, alcohol consumption, and physical inactivity exacerbate MASLD risk among I148M carriers. Evidence shows that insulin resistance amplifies MASLD risk associated with the I148M variant, especially in non-diabetic individuals. Moreover, the PNPLA3 I148M variant interacts with other genetic loci, further modifying MASLD risk and disease course. The variant also influences treatment response, with variability observed in effectiveness of lipid-lowering therapies and GLP-1 agonists among carriers. The interplay between PNPLA3 I148M and environmental factors underscores the need for personalized MASLD prevention and treatment strategies. Targeting both genetic and lifestyle contributors may enhance MASLD management, offering a tailored approach to reducing disease burden.

Carotid intima-media thickness and risk of atherosclerosis in multiple sclerosis: A cross-sectional study.

Multiple sclerosis (MS) is characterized by inflammation and demyelination in the central nervous system. Recent studies have suggested a potential association between MS and an increased risk of atherosclerosis, a systemic vascular disease involving arterial wall thickening. Understanding this relationship is crucial, given the heightened cardiovascular risk observed in MS patients. To investigate factors influencing the development of atherosclerosis in patients with multiple sclerosis (pwMS), focusing on carotid intima-media thickness (CIMT) as a marker. 114 pwMS (82 females and 32 males) and 127 control subjects (57 females and 70 males) were included. The mean CIMT between the two groups was compared. Additionally, the effects of annual relapse rate, EDSS (Expanded Disability Status Scale), MS duration, treatment duration, and type of Disease-modifying treatment (DMT) on CIMT were evaluated. This study included 241 participants with a mean (SD) age of 41.13 years (10.93). CIMT was significantly higher in pwMS compared to controls (p < 0.001). Even after adjusting for age, sex, and BMI (Body Mass Index), CIMT remained significantly higher in the pwMS group (p < 0.001). Spearman's correlation analysis revealed significant associations between CIMT and age, BMI, EDSS score, and disease duration (all p < 0.05). Additionally, the SPMS (Secondary Progressive Multiple Sclerosis) disease course was significantly associated with higher CIMT (p < 0.001). Linear regression analysis identified age as the most significant predictor of increased CIMT in pwMS (p < 0.001), followed by BMI (p = 0.054). This study demonstrates a significant association between MS and increased CIMT. Additionally, age emerged as the most prominent predictor of high CIMT in pwMS, followed by BMI. These findings suggest a potential link between MS and increased cardiovascular risk. Further research is warranted to explore the underlying mechanisms and investigate the long-term cardiovascular outcomes in this population.

The Interplay of Stress, Inflammation, and Metabolic Factors in the Course of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent neurodegenerative condition for which there are symptomatic treatments but no disease-modifying therapies (DMTs). Extensive research over the years has highlighted the need for a multi-target DMT approach in PD that recognizes the various risk factors and their intricate interplay in contributing to PD-related neurodegeneration. Widespread risk factors, such as emotional stress and metabolic factors, have increasingly become focal points of exploration. Our review aims to summarize interactions between emotional stress and selected key players in metabolism, such as insulin, as potential mechanisms underlying neurodegeneration in PD.