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The SUB-urothelial DUrvalumab InjEction-1 (SUBDUE-1) trial: first-in-human trial in patients with bladder cancer

BJU Int. 2024 Mar 12. doi: 10.1111/bju.16325. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations.

PATIENTS AND METHODS: The patients were chemotherapy and immunotherapy naïve (bacille Calmette-Guérin allowed) with non-metastatic muscle-invasive bladder cancer or non-muscle-invasive bladder cancer planned for radical cystectomy (RC). The study was a Phase Ib 3 + 3 dose-escalation design with sub-urothelial injection of durvalumab at three pre-determined doses (25, 75, 150 mg) diluted in 25 mL normal saline, injected at 25 locations (25 × 1 mL injections), at least 2 weeks before RC.

RESULTS: A total of 11 patients were recruited (10 male, one female). No significant changes were reported on American Urological Association Symptom Score or O’Leary Interstitial Cystitis Scale. In all, 14 adverse events (AEs) were reported (10 Grade 1, three Grade 2, one Grade 3), none considered immune-related. No Grade 4 or 5 AEs were recorded. All the patients underwent RC. Tissue immune populations changed following durvalumab injection (P = 0.012), with a statistically significant increase in M2-macrophage (CD163) when comparing the 25-150 mg dose (P = 0.021). Basal/mixed cancers showed a larger CD163 increase than luminal cancers (P = 0.033).

CONCLUSION: Sub-urothelial injection of durvalumab is feasible and safe without immune-related AEs and shows local immunological effects.

PMID:38469652 | DOI:10.1111/bju.16325

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Reporting outcome measures in veterinary physiotherapy with particular reference to the treatment of canine and equine joint cases in the UK

Vet Rec. 2024 Mar 12:e3900. doi: 10.1002/vetr.3900. Online ahead of print.

ABSTRACT

BACKGROUND: Outcome measures are extensively used within human physiotherapy, but a widely accepted issue in veterinary physiotherapy is that outcome measures lack sufficient evaluation and standardisation in terms of how they are implemented. This cross-sectional study aimed to provide clarity on (1) the current selection of outcome measures in canine and equine physiotherapy and (2) investigate external influences on outcome measure selection, including comparative literature availability, professional memberships and background.

METHODS: A structured scoping literature review consolidated current understanding and limitations. This informed a survey of qualified veterinary physiotherapists (n = 40). The statistical analysis comprised descriptive statistics.

RESULTS: Key observations included (1) a lack of difference in outcome measure application between veterinary physiotherapists with and without a human physiotherapy background, (2) enhanced outcome measure utilisation by registry body members and (3) an overall skew towards subjective, rather than objective, outcome measure use.

LIMITATIONS: The study was limited by the absence of a defined veterinary physiotherapist population and subsequent convenience sample size.

CONCLUSION: The apparent skew towards subjective outcome measures highlights objective outcome measure underutilisation and the need for a more extensive evidence base. In conclusion, there is a need to develop comprehensive professional development resources promoting the use of repeatable outcome measures such as goniometers and the Liverpool osteoarthritis scoring.

PMID:38469651 | DOI:10.1002/vetr.3900

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Association Between Pro-inflammatory Cytokine Levels (IL-1β, IL-6, and TNF-α) in Human Colostrum and Maternal Body Composition Components

Breastfeed Med. 2024 Mar 12. doi: 10.1089/bfm.2023.0263. Online ahead of print.

ABSTRACT

Background: Obesity is characterized as a low-grade chronic inflammatory state, marked by elevated inflammatory biomarkers. Breast milk (BM) is rich in nutritional elements, vitamins, minerals, immunological factors, and bioactive components. These bioactive components, capable of influencing biological processes, may vary in concentration based on maternal body composition. Research Aim/Question(s): This study aimed to explore the association between pro-inflammatory cytokine levels (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) in human colostrum and maternal body composition, as analyzed through bioelectrical impedance vector analysis (BIVA). Method: In this cross-sectional study, 117 healthy postpartum participants were included, with each group (normal weight, overweight, and obese) comprising 39 individuals, as classified by BIVA. Colostrum samples were collected within the first 24 hours postpartum. Results: IL-1β levels did not significantly differ across the groups, with concentrations of 69.5 ± 103 pg/mL in normal-weight, 79.7 ± 97.9 pg/mL in overweight, and 68.7 ± 108 pg/mL in obese women. IL-6 levels were significantly higher in the overweight group (55 ± 72.4 pg/mL) than in the normal-weight (48.1 ± 74.1 pg/mL) and obese groups (28.9 ± 36.2 pg/mL) (p = 0.02). Similarly, TNF-α levels were higher in the overweight group, with concentrations of 58.7 ± 74.9 pg/mL, than in the normal-weight group, with concentrations of 38.6 ± 95.4 pg/mL, and 52.6 ± 115 pg/mL in obese women (p = 0.02). Conclusion: This study shows that IL-6 and TNF-α concentrations were statistically higher in the colostrum of overweight women, suggesting that maternal body composition may influence the inflammatory profile of BM.

PMID:38469624 | DOI:10.1089/bfm.2023.0263

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The relationship between fear of old age, loneliness and death anxiety in adults

Psychogeriatrics. 2024 Mar 12. doi: 10.1111/psyg.13106. Online ahead of print.

ABSTRACT

BACKGROUND: The increase in the number of elderly people in the world, individuals’ perspectives on older adults, and false beliefs and ideas about old age negatively affect adults in terms of ageing. This study was conducted to determine the relationship between fear of old age, loneliness and death anxiety in adults.

METHOD: This study, which was designed in a correlational cross-sectional descriptive model, was conducted with 1074 adult individuals living in one province in eastern Turkey. Data were collected using Personal Information Form, Fear of Old Age Scale, UCLA Loneliness Scale and Turkish Death Anxiety Scale. Data were analyzed using SPSS 25.0, AMOS 24.0, G*Power 3.1 statistical package programs.

RESULTS: In our study, it was determined that the model created in line with the hypotheses was compatible and the model fit indices were within the desired limits as χ2 /df = 4.737, root mean square error of approximation = 0.05, comparative fit index = 0.93, goodness-of-fit index = 0.92, adjusted goodness-of-fit index = 0.90, IFI = 0.93. There is a significant relationship between loneliness and death anxiety (P < 0.05). There is a significant relationship between loneliness and fear of old age (P < 0.05). There is a significant relationship between death anxiety and fear of old age (P < 0.05). It was determined that death anxiety has a mediating role in the effect of loneliness on fear of old age (95% confidence interval: 0.112-0.226; P < 0.05).

CONCLUSION: As the level of loneliness increases, the level of death anxiety and fear of old age increases. Fear of old age also increases in the mediating role of death anxiety. It is recommended to conduct intervention studies to reduce fear of old age. Longitudinal study on fear of old age is recommended.

PMID:38469620 | DOI:10.1111/psyg.13106

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The Relationship between the Duration of Surgery for Thoracoscopic Lobectomy and Postoperative Complications in Patients with Stage I Non-small Cell Lung Cancer

Ann Ital Chir. 2024;95(1):64-69.

ABSTRACT

OBJECTIVE: To investigate the relationship between the duration of surgery for thoracoscopic lobectomy and postoperative complications in patients with stage I non-small cell lung cancer (NSCLC).

METHODS: The clinical data of patients who underwent thoracoscopic lobectomy in the Department of Cardiothoracic Surgery, Shaoxing Central Hospital from September 2018 to September 2023 were retrospectively analyzed.

RESULTS: A total of 263 patients with thoracoscopic lobectomy were enrolled in this study. The duration of surgery was longer for patients with postoperative hospital stay >7 days, atrial fibrillation, postoperative pulmonary air leakage (>5 days), pleural effusion, or pneumonia compared to patients without corresponding complications, and the differences were statistically significant. Further regression analysis showed that prolonged duration of surgery was a risk factor for pneumonia, pleural effusion, atrial fibrillation, and postoperative hospital stay >7 days, and the predictive value of prolonged duration of surgery for the above complications was moderate. The results of chi-square tests showed that pneumonia, atelectasis, urinary tract infection, liver dysfunction, postoperative pulmonary air leakage (>5 days), pleural effusion, and atrial fibrillation were associated with postoperative hospital stay >7 days.

CONCLUSION: Prolonged duration of surgery is a risk factor for complications such as pneumonia, pleural effusion, atrial fibrillation, and postoperative hospital stay >7 days.

PMID:38469614

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The Prognostic Importance of Cancer Stem Cells in Colorectal Polyps

Ann Ital Chir. 2024;95(1):70-77.

ABSTRACT

BACKGROUND: This purpose aims to investigate the usefulness of CD133, a stem cell marker, for the prognosis of colon polyps. This study aimed to assess the adenomatous polyps that have an essential role in the development of colorectal cancer. The risk of colorectal carcinogenesis can be reduced by polypectomy and close medical supervision of the patients with adenomatous polyps. The prominence of stem cells in carcinoma development is also a recognized verdict. It must be noted that stem cell evaluation in adenomatous polyps may provide information about carcinoma development.

METHOD: Previously pathologically assessed colorectal polyps in 60 males and 40 females at Azerbaijan Medical University were reevaluated at the Pathology Department under the Meram Medical Faculty. Hematoxylin-eosin stained preparations were examined, and cases with and without dysplasia were determined. The image analysis program re-examined the preparations, and the same image analysis system automatically counted CD133 positive stained cells in the unit area. At the end of the follow-up period after polypectomy, the cases of malignancy were detected.

RESULTS: The relationship between CD133 expression of dysplasia and malignancy was statistically compared. During the investigation, the statistically significant relationship between CD133 expression and dysplasia, as well as malignancy development, was observed in this study.

CONCLUSION: During the examination, the statistical significance of CD133 expression was detected in cases with dysplasia and malignancy. The investigation of CD133 expression in colorectal polyps is crucial in determining the presence of dysplasia and malignancy development, particularly in obtaining prognostic data in colorectal polyps.

PMID:38469604

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Utility of three-dimensional printing in the surgical management of intra-articular distal humerus fractures: a systematic review and meta-analysis of randomized controlled trials

Clin Shoulder Elb. 2024 Mar;27(1):72-78. doi: 10.5397/cise.2023.00591. Epub 2024 Feb 8.

ABSTRACT

BACKGROUND: Clinical outcomes after fixation of distal humerus intraarticular fractures are directly related to the quality of reduction. The use of three-dimensional (3D)-printed fracture models can benefit preoperative planning to ensure good reduction. This review aims to determine if surgery performed with 3D printing assistance are faster and result in fewer complications and improved clinical outcomes than conventional methods. We also outline the benefits and drawbacks of this novel technique in surgical management of distal humerus fractures.

METHODS: A systematic literature search was carried out in various electronic databases. Search results were screened based on title and abstract. Data from eligible studies were extracted into spreadsheets. Meta-analysis was performed using appropriate computer software.

RESULTS: Three randomized controlled trials with 144 cases were included in the final analysis. The 3D-printed group had significantly shorter mean operating time (mean difference, 16.25 minutes; 95% confidence interval [CI], 12.74-19.76 minutes; P<0.001) and mean intraoperative blood loss (30.40 mL; 95% CI, 10.45-60.36 mL; P=0.005) compared with the conventional group. The 3D-printed group also tended to have fewer complications and a better likelihood of good or excellent outcomes as per the Mayo elbow performance score, but this did not reach statistical significance.

CONCLUSIONS: Three-dimensional-printing-assisted surgery in distal humerus fractures has several benefits in reduced operating time and lower blood loss, indirectly decreasing other complications such as infection and anemia-related issues. Future good-quality studies are required to conclusively demonstrate the benefits of 3D printing in improving clinical outcomes. Level of evidence: I.

PMID:38469596 | DOI:10.5397/cise.2023.00591

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Acute histological reactions in the otolith organs to inner ear drug delivery through a cochlear implant

Front Neurol. 2024 Feb 26;15:1363481. doi: 10.3389/fneur.2024.1363481. eCollection 2024.

ABSTRACT

INTRODUCTION: Cochlear implantation is currently regarded as a safe and minimally invasive procedure. However, cochlear implantation can have an impact on vestibular function, despite the lack of correlation between patient symptomatology and damage in vestibular tests. Thus, the present study aims to analyze the presence of hydrops and histological reactions at the level of the vestibule after cochlear implantation with dexamethasone pump delivery in Macaca fascicularis (Mf).

MATERIALS AND METHODS: A detailed histological study was conducted on a total of 11 Mf. All 11 Mf were divided into three groups: 5 Mf were implanted with an electrode array HL-14 connected to a pump delivering FITC-dextran for 24 h (Group A); 4 Mf were implanted with a CI electrode array attached to a pump for FITC-dextran delivery for 7 days (Group B); and 2 Mf were considered the control group, without any kind of cochlear device implantation (Group C). After drug deliver, the selected macaques were euthanized to collect tissue samples for histological analysis. An experienced observer, focusing on the utricle and saccule areas, conducted a blinded inner ear histology analysis.

RESULTS: Surgical procedures were successfully performed in all cases. No signs of cochlear reaction to the device were observed, including neither collapse nor fibrosis. Endolymphatic sinus dilatation was observed in Mf4A and Mf3B, while cochlear hydrops was observed in Mf3A. The mean areas of the utricle and saccule exhibited some statistically significant differences, specifically, in the saccule between groups C and both groups A (p = 0.028) and B (p = 0.029); however, no significant differences were observed between groups A and B or among comparisons of the utricle.

DISCUSSION: A significant concern relates to the safety of cochlear implantation with regard to vestibular preservation and hearing. New advancements in electrode arrays, such as CI devices coupled with delivery pumps, pose a challenge in maintaining minimally traumatic surgical concept-based procedures without affecting the inner ear homeostasis. The implantation of this device may cause vestibular hydrops in the saccule, indicating that the longer the time of substance release, the greater the grade of hydrops evidenced at the saccular level. Apart from this finding, the risk of histological damage to the vestibule is low.

PMID:38469594 | PMC:PMC10926955 | DOI:10.3389/fneur.2024.1363481

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Clinical analysis of hyperbaric oxygen combined with subdural drilling and drainage in the management of subdural effusion type IV with intracranial infection in infant patients

Front Neurol. 2024 Feb 26;15:1340650. doi: 10.3389/fneur.2024.1340650. eCollection 2024.

ABSTRACT

BACKGROUND: To explore the therapeutic effect of hyperbaric oxygen combined with subdural drilling and drainage (SDD) on subdural effusion type IV with intracranial infection in infant patients.

METHODS: This retrospective controlled study included 328 infant patients with subdural effusion type 4 with intracranial infection between January 2005 and January 2023. 178 patients were treated by hyperbaric oxygen combined with SDD (group A). 142 cases were treated with SDD (group B). 97 infants were only received hyperbaric oxygen (group C). Clinical outcomes, the control time of intracranial infection, complications, and the degree of brain re-expansion after 6 months of treatment were compared among the three groups. According to the comprehensive evaluation of treatment effectiveness and imaging results, it is divided into four levels: cured, significantly effective, improved, and ineffective.

RESULTS: No patient died during follow-up. The three groups were similar regarding age, sex, the general information, and clinical symptoms (p > 0.05). All intracranial infections in the children were effectively controlled. There was no difference in infection control time between group A and group B, and there was no statistical significance. However, the control time of intracranial infection between the two groups was different from that of group C, which was statistically significant. Compared with group B and group C, the degree of brain re-expansion in group A has obvious advantages and significant differences. The effective rates of the three groups were 83.7%, 58.5%, and 56.7%, respectively. There were 28 cases of subcutaneous hydrops in group A and 22 cases of subcutaneous hydrops in group B after operation, and no other serious complications.

CONCLUSION: The SDD is safe and effective for infant patients with intracranial infections through fluid replacement and intrathecal antibacterial. Hyperbaric oxygen is effective as an adjuvant therapy to promote brain re-expansion.

PMID:38469593 | PMC:PMC10925761 | DOI:10.3389/fneur.2024.1340650

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Spasticity-Plus syndrome in multiple sclerosis patients in a tertiary hospital in Spain

Front Neurol. 2024 Feb 26;15:1360032. doi: 10.3389/fneur.2024.1360032. eCollection 2024.

ABSTRACT

INTRODUCTION: Spasticity is a common symptom in multiple sclerosis (MS) and it is often associated with other symptoms such as spasms/cramps and pain. The concept of Spasticity-Plus syndrome takes into account that spasticity is accompanied by one or more symptoms (spasms/cramps, pain, bladder dysfunction, sleep disorders, fatigue and/or tremor). As these symptoms share a common cannabinoid control, therapy acting on cannabinoid receptors may be useful. The main study objectives were to determine the number of MS patients who met Spasticity-Plus syndrome criteria and to identify the most common symptoms.

METHODS: Clinical records of MS patients treated with nabiximols in a tertiary hospital from 2002 to 2022 were reviewed retrospectively.

RESULTS: Of the 73 patients included in the study, 53.4% were women, and most had secondary progressive MS (64.4%). All patients met the criteria for Spasticity-Plus syndrome: 100% had spasticity and at least another symptom. Pain was the second most common symptom (91.8%), followed by spasms/cramps (79.4%), and fatigue (76.7%). Sleep disturbances (p < 0.0001) and tremor (p < 0.027) were more frequent in patients with relapsing-remitting MS than in patients with progressive MS. No statistically significant differences were found for spasticity, pain, spasms/cramps, and fatigue between MS phenotypes. Regarding symptoms clusters, 94.4% of the patients had three or more symptoms. Spasticity was more frequently associated with pain (91.8%) and spasms/cramps (79.4%).

CONCLUSION: Spasticity-Plus syndrome was present in all the study population of patients with different MS phenotypes, and treated with nabiximols.

PMID:38469589 | PMC:PMC10926473 | DOI:10.3389/fneur.2024.1360032