The Influence of Kinesiophobia and Pain Catastrophizing on Disease-Specific Quality of Life in Patients With Recurrent Patellofemoral Instability.

BACKGROUND: The Banff Patellofemoral Instability Instrument 2.0 (BPII 2.0) is a disease-specific, quality of life patient-reported outcome measure (PROM) that is valid and reliable in patients with recurrent lateral patellofemoral instability (LPI). Quality of life encompasses the physical, emotional, and psychological aspects of patient functioning and recovery. PURPOSES: To concurrently validate the BPII 2.0 to the Tampa Scale for Kinesiophobia (TSK-11), the Pain Catastrophizing Scale (PCS), and the Anterior Cruciate Ligament-Return to Sport after Injury Scale (ACL-RSI) in patients presenting with recurrent LPI and to assess baseline values for the PROMs in patients with LPI. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2. METHODS: A total of 107 consecutive patients with recurrent LPI were assessed between January and October 2021. Patients completed the BPII 2.0, TSK-11, PCS, and ACL-RSI. A Pearson r correlation coefficient was employed to examine relationships between the PROMs. Baseline values, as well as floor and ceiling effects and Cronbach alpha, were assessed for all PROMs. RESULTS: All 107 patients completed the 4 PROMs. Patients included 28 men (26.2%) and 79 women (73.8%), with a mean (SD) age of 25.7 (9.8) years. The mean (SD) age at first dislocation was 14.8 (6.3) years. The TSK-11, PCS, and ACL-RSI were all statistically significantly correlated with the BPII 2.0 (P < .01; 2-tailed), with moderate correlations (r = -0.361-0.628) The R2 values indicated an overlap of the constructs measured by the PROMs. CONCLUSION: A statistically significant correlation was evident between the BPII 2.0 and the other PROMs. The BPII 2.0 does not explicitly measure kinesiophobia or pain catastrophizing; however, the significant statistical relationship of the TSK-11 and PCS to the BPII 2.0 suggests that this information is being captured and reflected.

The influence of preoperative 12-item veterans rand physical component scores on outcomes following cervical disc replacement.

PURPOSE: To evaluate the influence of preoperative VR-12 physical component scores (PCS) on outcomes following cervical disc replacement (CDR). METHODS: Patients undergoing elective CDR were retrospectively identified. Patient-reported outcomes (PROs) of interest included VR-12 PCS/VR-12 Mental Component Score (MCS)/9-Item Patient Health Questionnaire (PHQ-9)/Short Form-12 (SF-12) PCS and MCS/Patient-Reported Outcome Measurement Information System-Physical Function (PROMIS-PF)/Visual Analog Scale-Neck Pain (VAS-NP)/VAS-Arm Pain (VAS-AP)/Neck Disability Index (NDI). Baseline up to two-year postoperative scores were obtained (average follow-up: 9.2 ± 6.8months). Two cohorts were created: VR-12 PCS < 35 or VR-12 PCS ≥ 35. Improvements in scores from baseline to six weeks postoperatively and to final follow-up were calculated. Changes in scores were compared to previously reported thresholds to determine rates of minimum clinically important difference (MCID). RESULTS: Of 127 patients, 64 were in the worse VR-12 PCS group. Patients with better VR-12 PCS were more likely to have private insurance (p = 0.034). When accounting for insurance differences, the worse VR-12 PCS group reported inferior NDI/VAS-NP/PHQ-9/PROMIS-PF/VR-12 PCS/SF-12 PCS at six weeks and final follow-up (p ≤ 0.015, all). The worse VR-12 PCS group reported greater improvements in VAS-AP and VR-12 PCS by six weeks and in NDI/VR-12 MCS/VR-12 PCS/SF-12 PCS by final follow-up (p ≤ 0.026, all). Patients with worse VR-12 PCS reported greater MCID achievement for VR-12 MCS and SF-12 PCS (p ≤ 0.034, both). CONCLUSION: Following surgery, patients with worse VR-12 PCS report greater improvements in PROs, highlighting the increased relative impact of surgery for patients with worse baseline physical function. These findings can be used to optimize patient experience perioperatively and inform postoperative expectations.

Quality of life and abdominal wall functionality after abdominal wall reconstruction: A prospective single center follow-up study.

BACKGROUND: Fascial breakdown with the occurrence of an incisional hernia (IH) is an important and challenging complication of any laparotomy. For a long time, the success of the abdominal wall reconstruction (AWR) was measured only from the surgeon's perspective by defining outcome measures such as wound morbidity and recurrence. The understanding that complete recovery is difficult to assess without considering patients has shifted the paradigm of optimal outcomes to Patient Reported Outcome Measures (PROMS) and Quality of Life (QoL), which are pivotal to evaluate the success and efficacy of AWR. METHODS: We conducted a prospective follow-up study of 91 patients undergoing mesh-augmented abdominal wall reconstruction for primary or recurrent incisional hernia between January 2021 and December 2023. Demographic data, comorbidities, and hernia characteristics were recorded. All patients were evaluated preoperatively by a native abdomino-pelvic CT scan to assess the characteristics of hernia (length, width, surface, and volume of the incisional hernia sac and of peritoneal cavity), the presence of mesh (if previously inserted), and abdominal wall muscles status. All intervention were performed by the same surgical team according to the techniques described by Rives - Stoppa (RS), Ramirez (ACS), and Novitsky (PCS). Abdominal wall function was assessed using trunk raising (TR) and double leg lowering (DLL) measurements performed preoperatively, 1 month, 6 months, and 1 year postoperatively. At the same time, pre- and post-operative quality of life was analysed using the EQ-5D score. RESULTS: Mean age of 59.42 ± 12.28 years and a male/female ratio of 35/56 were recorded, most of them being obese. There were 36 (42%) patients with defects larger than 10 cm. The distribution of the type of surgical intervention was: RS 35 patients, ACS 13 patients, and PCS 43 patients. The mean value of combined score for the preoperative abdominal wall functionality was 4.41 ± 1.67 (2-8) while the mean value of preoperative EQ-5D index was 0.652 ± 0.026 (-0.32-1.00). QoL was poor and very poor for 48% (44) of the patients who recorded index values less than 0.56 (50% percentile). Preoperative EQ-5D index was highly correlated with Combined AWF score (r = 0.620; p < 0.0001) and the correlation was specific (AUC = 0.799; p < 0.0001; asymptotic 95%CI = 0.711-0.923). At 12 months, the AWF score increased to 8.13 ± 2.58 (1-10) and the QoL total score to 0.979 ± 0.007 (0.71-1). Good and very good total scores for QoL were recorded for 47 patients (84%) compared to 33 (36%) in the preoperative evaluation (χ2 with Yates continuity correction for two degrees of liberty = 46.04; p < 0.00001). CONCLUSION: Our results suggest that patients can expect to see a significant overall improvement in all five components of QoL measured with the help of Eq. 5D questionnaire. This improvement is dependent by hernia size, and some individual patient's factors (diabetes, cardiovascular diseases, and age over 60 years).

Translation, cross-cultural adaptation and psychometric properties of the Urdu version of the avoidance endurance behavior questionnaire in patients with chronic musculoskeletal pain.

BACKGROUND: The Avoidance Endurance Questionnaire (AEQ) successfully measures the fear-avoidance and endurance-related responses to chronic pain. OBJECTIVE: The objective of this study was to translate, cross-culturally adapt AEQ into Urdu and assess the reliability and validity of the Urdu version. METHOD: For the translation and cross-cultural adaptation process, the Beaton Guidelines were followed. A total of 103 participants responded to the Urdu version of the AEQ SF-12, Pain Catastrophizing Scale (PCS) and Numeric Pain Rating Scale (NPRS) at baseline and after 48 hours. The test-retest reliability was assessed using the intraclass correlation coefficient (ICC). Cronbach's alpha was used to measure internal consistency. To measure validity, Pearson's correlation between the subscales of AEQ-Urdu and other outcome measures (SF-12, PCS and NPRS scores) were used (p< 0.05). RESULTS: The mean age of the total 103 participants was 32.7 ± 10.90 among which 45 (43.6%) were male and 58 (56.3%) were female. The pre-final version of the translated AEQ was tested on 40 Urdu speaking participants and no major changes were made. The Cronbach's alpha for all subscales of the AEQ-Urdu ranged from 0.848-0.990. AEQ-U showed an excellent test-retest reliability with the ICC ranging from 0.775-0.996. The majority of the subscales of AEQ showed significant (p< 0.05) positive correlation with pain scales (PCS and NPRS) and negative correlation with the domains of SF-12. CONCLUSION: The AEQ-U has reliable and valid construct validity, good internal consistency, and test-retest reliability, indicating that it has adequate psychometric features and can be a useful tool for evaluating pain responses in patients with chronic musculoskeletal pain.

Phytochelatin Synthase: An In Silico Comparative Analysis in Cyanobacteria and Eukaryotic Microalgae.

Phytochelatins (PCs) are small cysteine-rich peptides involved in metal detoxification, not genetically encoded but enzymatically synthesized by phytochelatin synthases (PCSs) starting from glutathione. The constitutive PCS expression even in the absence of metal contamination, the wide phylogenetic distribution and the similarity between PCSs and the papain-type cysteine protease catalytic domain suggest a wide range of functions for PCSs. These proteins, widely studied in land plants, have not been fully analyzed in algae and cyanobacteria, although these organisms are the first to cope with heavy-metal stress in aquatic environments and can be exploited for phytoremediation. To fill this gap, we compared the features of the PCS proteins of different cyanobacterial and algal taxa by phylogenetic linkage. The analyzed sequences fall into two main, already known groups of PCS-like proteins. Contrary to previous assumptions, they are not classed as prokaryotic and eukaryotic sequences, but rather as sequences characterized by the alternative presence of asparagine and aspartic/glutamic acid residues in proximity of the catalytic cysteine. The presence of these enzymes with peculiar features suggests differences in their post-translational regulation related to cell/environmental requirements or different cell functions rather than to differences due to their belonging to different phylogenetic taxa.

Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review.

Post-COVID syndrome (PCS) describes a persistent complex of symptoms following a COVID-19 episode, lasting at least 4 to 12 weeks, depending on the specific criteria used for its definition. It is often associated with moderate to severe impairments of daily life and represents a major burden for many people worldwide. However, especially during the first two years of the COVID-19 pandemic, therapeutic and diagnostic uncertainties were prominent due to the novelty of the disease and non-specific definitions that overlooked functional deficits and lacked objective assessment. The present work comprehensively examines the status of PCS definitions as depicted in recent reviews and meta-analyses, alongside exploring associated symptoms and functional impairments. We searched the database Pubmed for reviews and meta-analysis evaluating PCS in the period between May 31, 2022, to December 31, 2023. Out of 95 studies, 33 were selected for inclusion in our analyses. Furthermore, we extended upon prior research by systematically recording the symptoms linked with PCS as identified in the studies. We found that fatigue, neurological complaints, and exercise intolerance were the most frequently reported symptoms. In conclusion, over the past eighteen months, there has been a notable increase in quantity and quality of research studies on PCS. However, there still remains a clear need for improvement, particularly with regard to the definition of the symptoms necessary for diagnosing this syndrome. Enhancing this aspect will render future research more comparable and precise, thereby advancing and understanding PCS.

A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity.

The lack of success in clinical trials for HIV vaccines highlights the need to explore novel strategies for vaccine development. Research on highly exposed seronegative (HESN) HIV-resistant Kenyan female sex workers revealed naturally protective immunity is correlated with a focused immune response mediated by virus-specific CD8 T cells. Further studies indicated that the immune response is unconventionally focused on highly conserved sequences around HIV viral protease cleavage sites (VPCS). Thus, taking an unconventional approach to HIV vaccine development, we designed lipid nanoparticles loaded with mRNA that encodes multi-epitopes of VPCS (MEVPCS-mRNA LNP), a strategic design to boost antigen presentation by dendritic cells, promoting effective cellular immunity. Furthermore, we developed a novel cold-chain compatible mRNA LNP formulation, ensuring long-term stability and compatibility with cold-chain storage/transport, widening accessibility of mRNA LNP vaccine in low-income countries. The in-vivo mouse study demonstrated that the vaccinated group generated VPCS-specific CD8 memory T cells, both systemically and at mucosal sites of viral entry. The MEVPCS-mRNA LNP vaccine-induced CD8 T cell immunity closely resembled that of the HESN group and displayed a polyfunctional profile. Notably, it induced minimal to no activation of CD4 T cells. This proof-of-concept study underscores the potential of the MEVPCS-mRNA LNP vaccine in eliciting CD8 T cell memory specific to the highly conserved multiple VPCS, consequently having a broad coverage in human populations and limiting viral escape mutation. The MEVPCS-mRNA LNP vaccine holds promise as a candidate for an effective prophylactic HIV vaccine.

Effectiveness and safety of coils plus glue in slope embankment technology versus coils plus sclerosant in embolization therapy for reflux-type pelvic venous disorders.

OBJECTIVE: This study aimed to evaluate the effectiveness and safety of coils plus glue (CPG) in slope embankment technology vs coils plus sclerosant (CPS) in treating reflux-type pelvic venous disorders. METHODS: The analysis included patients diagnosed with reflux-type pelvic venous disorders who were treated with CPG or CPS from 2019 to 2021. The inclusion criteria were noncyclic pain lasting more than 6 months, atypical varicose, and transvaginal Doppler ultrasound (TVDUS) and computed tomographic venography confirming the diagnosis and excluding compression factors and other diseases. Propensity score matching was performed at a 1:1.1 ratio based on the following covariates: age, pregnancy, body mass index, pretreatment visual analog scale (VAS), dysmenorrhea, dyspareunia, urinary urgency, tenesmus, low back pain, vulvar varicosities, vaginal varicosities, and lower limb varices. The pain was relieved by embolizing the target lesions with different embolic materials. The efficacy and safety of the different embolization materials were compared by VAS and TVDUS examinations at 1, 3, 6, 12, 24, and 36 months. RESULTS: From a total of 495 patients, 88 patients were selected from the CPG group and 77 patients from the CPS group by propensity score matching. The patients were followed up for 36 months. The preoperative VAS score of the CPG group was 8 (range, 6-8), and the CPS score was 8 (range, 7-8; P = .64). The postembolization VAS score of the CPG group was 2.05 ± 0.37, and the CPS score was 2.14 ± 0.35 (P = .55). A total of 28 cases (16.9%) showed complications, most of which were transient pain after embolization. No serious complications such as coil embolization to the lungs occurred. In addition, the CPG group used fewer coils than the CPS group by using the slope embankment technique. The mean coil length of the CPG group was 77.18 ± 33.82 cm, and the CPS group was 105.29 ± 71 cm (P = .001). The CPG group had an average operative time of 44.49 ± 5.72 minutes, whereas the CPS group took 43.45 ± 4.18 minutes on average (P = .19). The radiation dose in the CPG group was 398.40 ± 76.16 mGy, and the radiation dose in the CPS group was 388 ± 44.23 mGy (P = .30). The median recurrence-free survival in the CPG group was 34.23 months (95% confidence interval, 33.2-35.2), and the median recurrence-free survival in the CPS group was 30.39 months (95% confidence interval, 28.2-32.6; log rank P = .018). CONCLUSIONS: Embolization therapy for refluxing PeVD was safe and effective, and proficient use of slope embankment technique with CPG increased efficacy and reduced complications.

Guessability of Indian picture symbols for communication (IPSC) and picture communication symbols (PCS) among Malayalam-speaking typical adults.

The purpose of this study was to investigate the perceived symbol referent relationship for selected symbols in typical adults for two different symbol sets: Indian Picture Symbols for Communication (IPSC) and Picture Communication Symbols (PCS) to identify cultural influences on symbol recognition. A total of 240 typical adults, including 120 nonprofessionals, and 120 health professionals, from Kerala, a southern state in India, participated in the study. A guessability task involving IPSC and PCS symbols for 30 target referents was utilized. Guessability scores for each participant as well as each symbol stimuli across two symbol sets were determined. The guessability scores for IPSC were significantly (p <.001) higher than PCS. For both symbol sets, nouns were the most accurately guessed, followed by verbs, adjectives, and prepositions. The results also revealed that prompting and previous exposure to symbols tend to influence the transparency of symbols. Error analyses revealed that visual and conceptual cues within a symbol tend to influence guessability. The results indicate that cultural and linguistic factors play a role in symbol guessability. The study highlights the importance of investigating the iconicity of IPSC and PCS symbols across different populations within India, before using symbols for educational/clinical purposes.

Utilizing machine learning to facilitate the early diagnosis of posterior circulation stroke.

BACKGROUND: Posterior Circulation Syndrome (PCS) presents a diagnostic challenge characterized by its variable and nonspecific symptoms. Timely and accurate diagnosis is crucial for improving patient outcomes. This study aims to enhance the early diagnosis of PCS by employing clinical and demographic data and machine learning. This approach targets a significant research gap in the field of stroke diagnosis and management. METHODS: We collected and analyzed data from a large national Stroke Registry spanning from January 2014 to July 2022. The dataset included 15,859 adult patients admitted with a primary diagnosis of stroke. Five machine learning models were trained: XGBoost, Random Forest, Support Vector Machine, Classification and Regression Trees, and Logistic Regression. Multiple performance metrics, such as accuracy, precision, recall, F1-score, AUC, Matthew's correlation coefficient, log loss, and Brier score, were utilized to evaluate model performance. RESULTS: The XGBoost model emerged as the top performer with an AUC of 0.81, accuracy of 0.79, precision of 0.5, recall of 0.62, and F1-score of 0.55. SHAP (SHapley Additive exPlanations) analysis identified key variables associated with PCS, including Body Mass Index, Random Blood Sugar, ataxia, dysarthria, and diastolic blood pressure and body temperature. These variables played a significant role in facilitating the early diagnosis of PCS, emphasizing their diagnostic value. CONCLUSION: This study pioneers the use of clinical data and machine learning models to facilitate the early diagnosis of PCS, filling a crucial gap in stroke research. Using simple clinical metrics such as BMI, RBS, ataxia, dysarthria, DBP, and body temperature will help clinicians diagnose PCS early. Despite limitations, such as data biases and regional specificity, our research contributes to advancing PCS understanding, potentially enhancing clinical decision-making and patient outcomes early in the patient's clinical journey. Further investigations are warranted to elucidate the underlying physiological mechanisms and validate these findings in broader populations and healthcare settings.

Osimertinib Resistance via Histologic Transformation From Non-small Cell Lung Carcinoma to Carcinosarcoma.

Resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung carcinoma (NSCLC) remains a significant clinical challenge. Osimertinib, a third-generation TKI, has demonstrated efficacy in overcoming resistance, but novel resistance mechanisms continue to emerge. This case report presents a unique instance of histologic transformation from NSCLC to carcinosarcoma, representing a previously unreported manifestation of osimertinib resistance. We describe the clinical course of a 63-year-old female with epidermal growth factor receptor (EGFR)-mutant NSCLC who initially responded to osimertinib but eventually developed carcinosarcoma. The transformation was associated with additional EGFR mutations and alterations in RB and TP53. Despite aggressive treatment, the patient's condition deteriorated, emphasizing the limited therapeutic options for carcinosarcoma. This case underscores the need for further research to elucidate the molecular mechanisms behind histologic transformation and explore novel therapeutic strategies to address osimertinib resistance in NSCLC. Understanding and addressing these mechanisms are crucial for improving outcomes in patients facing this challenging form of resistance.

Premature Chromatid Separation Trait Found During the Diagnosis of Male Infertility: A Case Report.

Premature chromatid separation (PCS)/mosaic variegated aneuploidy (MVA) syndrome is a rare chromosome instability syndrome. This syndrome is inherited in an autosomal recessive pattern. Although heterozygous carriers of a monoallelic mutation reportedly have a normal phenotype, PCS-positive cells are found at a higher rate in such carriers than in the general population. We herein report a case in which a PCS carrier was incidentally diagnosed during investigation of male infertility. A diagnosis of nonobstructive azoospermia was made, and chromosome analysis revealed the PCS trait in 81 of 200 cells (40.5%), indicating that the patient was a PCS carrier. PCS carriers are not uncommon, and if both members of a couple are carriers, there would be a 25% likelihood of the child presenting with PCS syndrome. Therefore, a clinical psychological approach that includes genetic counseling should be considered before proceeding to microsurgical testicular sperm extraction.

Parenting and Gender as Impact Factors for Social Participation, Quality of Life, and Mental Health in Long COVID.

OBJECTIVES: This study aims to investigate the impact of gender and parental tasks on social participation, health-related quality of life (hrQoL), and mental health in persons with long COVID. METHODS: A mixed-methods approach was followed including a cross-sectional web-based survey and semi-structured interviews. Multivariable linear regressions were used to quantify the effect of gender and parenting tasks on social participation, hrQoL, and mental health. Qualitative data from interviews with participants experiencing long COVID symptoms was analyzed using content analysis. RESULTS: Data from 920 participants in the quantitative study and 25 participants in the qualitative study was analyzed. Parenting tasks were associated with increased impairments in family and domestic responsibilities in persons with long COVID compared to lower impairments in persons without long COVID (P = .02). The qualitative data indicate that coping with long COVID and pursuing parenting tasks limit participants' ability to perform leisure activities and attend social gatherings. In long COVID, men had higher anxiety symptoms than women, and in those without long COVID, the opposite was observed (P < .001). In the qualitative study, participants expressed feelings of dejection and pessimism about their future private, occupational, and health situations. No differences between the genders could be observed. CONCLUSIONS: Long COVID is associated with impairments in family and domestic responsibilities in individuals who have parenting tasks. Among participants with long COVID, anxiety symptoms are higher in men than women.

A systematic review of quantitative EEG findings in Fibromyalgia, Chronic Fatigue Syndrome and Long COVID.

Fibromyalgia Syndrome (FMS), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are similar multisymptom clinical syndromes but with difference in dominant symptoms in each individual. There is existing and emerging literature on possible functional alterations of the central nervous system in these conditions. This review aims to synthesise and appraise the literature on resting-state quantitative EEG (qEEG) in FMS, ME/CFS and LC, drawing on previous research on FMS and ME/CFS to help understand neuropathophysiology of the new condition LC. A systematic search of MEDLINE, Embase, CINHAL, PsycINFO and Web of Science databases for articles published between December 1994 and September 2023 was performed. Out of the initial 2510 studies identified, 17 articles were retrieved that met all the predetermined selection criteria, particularly of assessing qEEG changes in one of the three conditions compared to healthy controls. All studies scored moderate to high quality on the Newcastle-Ottawa scale. There was a general trend for decreased low-frequency EEG band activity (delta, theta, and alpha) and increased high-frequency EEG beta activity in FMS, differing to that found in ME/CFS. The limited LC studies included in this review focused mainly on cognitive impairments and showed mixed findings not consistent with patterns observed in FMS and ME/CFS. Our findings suggest different patterns of qEEG brainwave activity in FMS and ME/CFS. Further research is required to explore whether there are phenotypes within LC that have EEG signatures similar to FMS or ME/CFS. This could inform identification of reliable diagnostic markers and possible targets for neuromodulation therapies tailored to each clinical syndrome.

Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach.

Despite the recent and increasing knowledge surrounding COVID-19 infection, the underlying mechanisms of the persistence of symptoms for a long time after the acute infection are still not completely understood. Here, a multiplatform mass spectrometry-based approach was used for metabolomic and lipidomic profiling of human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered from acute mild COVID-19 (n = 40). Untargeted metabolomic analysis using CE-ESI(+/-)-TOF-MS and GC-Q-MS was performed. Additionally, a lipidomic analysis using LC-ESI(+/-)-QTOF-MS based on an in-house library revealed 447 lipid species identified with a high confidence annotation level. The integration of complementary analytical platforms has allowed a comprehensive metabolic and lipidomic characterization of plasma alterations in Long COVID disease that found 46 relevant metabolites which allowed to discriminate between Long COVID and fully recovered patients. We report specific metabolites altered in Long COVID, mainly related to a decrease in the amino acid metabolism and ceramide plasma levels and an increase in the tricarboxylic acid (TCA) cycle, reinforcing the evidence of an impaired mitochondrial function. The most relevant alterations shown in this study will help to better understand the insights of Long COVID syndrome by providing a deeper knowledge of the metabolomic basis of the pathology.

Longitudinal Assessment of Health-Related Quality of Life in Three Different Hyperphosphatemia Management Groups of Stage III and IV Chronic Kidney Disease Patients.

Introduction: Health-related quality of life (HRQoL) has emerged as an important outcome measure inpatients with CKD. The lack of prospective studies on HRQoL and its relation with hyperphosphatemia control measures among pre-dialysis patients necessitated the need for this study. Methods: This is a prospective, randomized, controlled, open-labelled studythat was conducted for one year on 120 CKD stages III and IV patients divided equally into three groups: Group 1, in which patients under went dietary phosphorus modification; Group 2, in which they were administered calcium-based phosphate binders; and Group 3, in which they were administered non-calcium-based phosphate binders. Patients were assessed for HRQoL, fibroblast growth factor 23 (FGF 23), intact parathyroid hormone (iPTH), phosphorus, and nutritional status, and dietary phosphorus control strategies at 0, 6, and 12 months. HRQoL was measured by using the 36-item Short Form Survey (SF-36) that included a physical component score (PCS) and mental component score (MCS). The scores is ranging from 0 to 100. Higher scores indicate better health status. Usingthe two-wayand one-way repeated measure ANOVA, we analyzed equality of group means, time intervals, and interactions. Results: At baseline, the mean PCS and MCS were equal in three groups. PCS improved significantly (P < 0.00) from baseline to one year in all the three groups: ingroup 1, the PCS score was 66.5 ± 13.5to 75.1 ± 9.76; in group 2, it was 68.9 ± 11.80 to 77.2 ± 7.50; and in group 3, it was 66.2 ± 12.16 to 73.8 ± 9.27. Initially, MCS declined substantially on the sixth month but recovered afterone year. Multiple regression analysis in 13 associated parameters yielded R2 of 13.7% and 18.1% in PCS and MCS, respectively, indicating little contribution of various parameters. Conclusion: There has been a significant positive change in PCSs in three hyperphosphatemia management groups over a period of 12 months. Among the three study groups, the incremental changes in PCS and MCS scores were insignificant.

Serum neurofilament light chain, inflammatory markers, and kynurenine metabolites in patients with persistent post-concussion symptoms: A cohort study.

BACKGROUND: Concussion leads to persistent post-concussion symptoms (PPCS) in up to one-third of those affected. While previous research has linked the initial trauma to elevated serum levels of neurofilament light chain (NFL), inflammatory markers, and neurotoxic metabolites within the kynurenine pathway, few studies have explored their relevance in PPCS. This study aims to investigate these biomarkers in PPCS patients, elucidating their relevance in the prolonged phase of concussion. METHODS: Serum samples from 86 PPCS individuals aged 18-30 years, 2-6 months post-trauma were analyzed, with 54 providing follow-up samples after seven months. NFL was measured using single-molecule array (Simoa) technology, 13 inflammatory markers via a Luminex immunoassay, and five kynurenine metabolites using liquid chromatography-mass spectrometry. A control group of 120 healthy anonymous blood donors was recruited for comparison. RESULTS: No significant NFL differences were found in PPCS participants compared with healthy individuals (p = 0.22). Intriguingly, a subset (9.3%) of PPCS participants initially exhibited abnormally high NFL levels (>9.7 pg/mL), which normalized upon follow-up (p = 0.032). Additionally, serum levels of the inflammatory markers, monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1/CCL11 were 25-40% lower than in healthy individuals (p ≤ 0.001). As hypothesized, PPCS participants exhibited a 22% reduction in the ratio of kynurenic acid to quinolinic acid (neuroprotective index) (p < 0.0001), indicating a shift towards the formation of neurotoxic metabolites. CONCLUSION: NFL may serve as a biomarker to monitor recovery, and future studies should investigate the potential therapeutic benefits of modulating the kynurenine pathway to improve PPCS.

Impression life with pulmonary hypertension: clinically relevant characteristics and quality of life among patients in Gansu, China.

BACKGROUND: The adverse effects of pulmonary arterial hypertension (PAH) on physical, emotional, and health-related quality of life (HRQoL) remain primarily unrecognized, especially in resource-limited settings. OBJECTIVES: This study aims to characterize the HRQoL of patients with PAH in this area and also identify the potential role of clinically relevant characteristics, including the 6-min walk distance test (6MWD), WHO-Functional Classification (WHO-FC), and mental health in the occurrence of lowering quality of life. DESIGN: This was a cross-sectional observational study. METHODS: Inpatients with PAH were chosen from a tertiary hospital located in Gansu province, China. All participants were interviewed face-by-face by using questionnaires, including items from the 36-Item Short Form Health Survey (SF-36), the self-rating anxiety scale, and the self-rating depression scale. Data on demographic and clinically relevant characteristics, including WHO-FC and 6MWD, were also collected by tracing medical recorders. Multiple linear regression analysis was used to determine the association between demographic, clinically relevant characteristics data, and physical component summary (PCS) or mental component summary (MCS) in SF-36. RESULTS: Of the 152 participants, SF-36 differed significantly from Chinese norms in all eight domains, with role-physical (21.55 ± 9.87) less than one-third of the norm (88.79 ± 28.49). Multiple linear regression results showed that the factors with the greatest impact on PCS were anxiety scores (ß = -0.22, p = 0.001), followed by WHO-FC (ß = -0.16, p = 0.014) and 6MWD (ß = 0.15, p = 0.036). The factors with the greatest impact on MCS were WHO-FC (ß = -0.30, p < 0.001), followed by anxiety (ß = -0.23, p = 0.001) and depression scores (ß = -0.16, p = 0.013). CONCLUSION: HRQoL was substantially reduced among PAH patients in the resource-limited area, mainly the physiological functions. WHO-FC and anxiety scores were independently associated with both PCS and MCS in SF-36. Clinicians should make reasonable rehabilitation programs and plans for patients according to their cardiac function grade and the severity of clinical symptoms. In addition, psychological interventions should also be taken, especially for those with anxiety symptoms, so as to improve their HRQoL.

ETV6-NTRK2 Fusion in a Patient With Metastatic Pulmonary Atypical Carcinoid Successfully Treated With Entrectinib: A Case Report and Review of the Literature.

Pulmonary atypical carcinoid (AC) is an extremely rare neuroendocrine tumor. The neurotrophic tropomyosin receptor kinase (NTRK) fusions are reported in only 0.5% of nonsmall cell lung cancer, and are more rare in AC with only one previously reported case. Currently, there is little established evidence on the optimal therapeutic strategies and prognosis for advanced cases. We present a female patient with metastatic AC after complete resection. Due to low expression of somatostatin receptor in this case, somatostatin analogs and peptide receptor radionuclide therapy were not available. After pursuing other alternative treatments, including chemotherapy (ie, carboplatin, etoposide, capecitabine, temozolomide, and paclitaxel), everolimus, and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. New biopsy analysis revealed an ETV6-NTRK2 fusion. She was immediately administered the first-generation tropomyosin receptor kinase inhibitor entrectinib at a dose of 600 mg q.d. A subsequent month of treatment resulted in a complete response in all of the metastatic lung lesions. To date, she has maintained sustained benefit for at least 1 year from initiation of entrectinib. Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.

Enhancing drug development and clinical studies with patient-centric sampling using microsampling techniques: Opportunities, challenges, and insights into liquid chromatography-mass spectrometry strategies.

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient-centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography-mass spectrometry (LC-MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient-centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy.