Intra-arterial chemotherapy combined with BCG immunotherapy is more effective than intra-arterial chemotherapy plus intravesical chemotherapy or standard BCG immunotherapy in preventing the recurrence and progression of high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Up to 45% of patients with high-risk non-muscle-invasive bladder cancer (NMIBC) will not benefit from adjuvant intravesical instillation. We aimed to introduce intra-arterial chemotherapy (IAC) to existing intravesical treatment and evaluate its feasibility and safety. MATERIALS AND METHODS: We collected data from 170 patients who had been diagnosed with high-risk NMIBC and underwent transurethral resection of bladder tumor (TURBT) over the last 5 years. Twenty-seven patients were excluded according to specific exclusion criteria. The remaining 143 patients were divided into 3 groups according to their treatment: intravesical instillation of Bacillus Calmette - Guerin (BCG), BCG+ intra-arterial chemotherapy (IAC), and intravesical chemotherapy (IVC)+IAC groups. All groups received standard intravesical instillation of BCG or chemotherapeutic agents. In contrast, both the BCG+IAC and IVC+IAC groups received four courses of IAC (injection of cisplatin [60 mg/m2] and epirubicin [50 mg/m2] in the internal iliac arteries via Seldinger's percutaneous technique). RESULTS: The median follow-up time was 47 months, ranging from 20 to 60 months. The restricted mean survival time (RMST), which represents the recurrence and progression rate of the BCG+IAC group, differed significantly when compared with the BCG group (P = 0.029 and 0.004, respectively) and the IVC+IAC group (P = 0.004 and 0.006, respectively). Kaplan-Meier plots revealed that the recurrence and progression-free survival of the BCG+IAC group were significantly higher than the BCG and IVC+IAC groups (P = 0.033 and 0.028, respectively). In contrast, the BCG and IVC+IAC groups showed similar RMST (P = 0.156 and 0.935, respectively), recurrence (P = 0.627), and progression-free (P = 0.931) survival. A small proportion of patients (20%) suffered from the adverse effects of IAC while 65% suffered from adverse reactions to intravesical instillation. Most adverse effects were ranked as grade I or II according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. CONCLUSION: Analysis showed that tumor recurrence and progression rate in the BCG+IAC group was lower than the BCG and IVC+IAC groups while patients in the IVC+IAC group suffered from milder adverse effects in cystitis and flu-like symptoms. Our findings may provide a new perspective for urologists when treating patients with high-risk NMIBC.

Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan-cancer analysis.

Objectives: Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T-cell activation, is a negative prognostic factor. However, its impact on tumours has yet to be comprehensively elucidated on a pan-cancer scale. Thus, we aim to reveal its role at the pan-cancer level. Methods: We performed IHC staining on a retrospective cohort of 370 patients. Then we assessed the prognostic effect of LAG3 using Kaplan-Meier survival analysis and multivariate Cox regression analysis. In pan-cancer analysis, we constructed competing endogenous RNA and protein-protein interaction networks, conducted gene set enrichment analysis and identified correlations between LAG3 gene expression and various factors, including clinical characteristics, tumour purity, mutations, tumour immunity and drug sensitivity across 33 cancer types. Results: LAG3 was expressed higher in normal kidney tissues than in tumours. A high level of LAG3 gene expression was an independent prognostic factor for OS (HR = 6.60, 95% CI = 2.43-17.90, P < 0.001) and PFS (HR = 3.44, 95% CI = 1.68-7.10, P < 0.001). In pan-cancer analysis, LAG3 exhibited robust correlations with survival and tumour stages in various cancers. Moreover, LAG3 was strongly associated with immune-related genes, proteins and signalling pathways. LAG3 gene expression was positively associated with increased infiltration of activated immune cells and decreased infiltration of several resting cells. LAG3 gene expression was associated with tumour mutation burden and microsatellite instability in multiple cancers. Conclusion: High LAG3 gene expression was an independent risk factor in kidney neoplasms. It also functioned as a biomarker for prognosis, TIME and immunotherapy efficacy in the pan-cancer dimension.

Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination: a two-year follow-up of the prospective clinical trial COVAXID.

BACKGROUND: Immunocompromised patients with primary and secondary immunodeficiencies have shown impaired responses to SARS-CoV-2 mRNA vaccines, necessitating recommendations for additional booster doses. However, longitudinal data reflecting the real-world impact of such recommendations remains limited. METHODS: This study represents a two-year follow-up of the COVAXID clinical trial, where 364 of the original 539 subjects consented to participate. 355 individuals provided blood samples for evaluation of binding antibody (Ab) titers and pseudo-neutralisation capacity against both the ancestral SARS-CoV-2 strain and prevalent Omicron variants. T cell responses were assessed in a subset of these individuals. A multivariate analysis determined the correlation between Ab responses and the number of vaccine doses received, documented infection events, immunoglobulin replacement therapy (IGRT), and specific immunosuppressive drugs. The original COVAXID clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659). FINDINGS: Several of the patient groups that responded poorly to the initial primary vaccine schedule and early booster doses presented with stronger immunogenicity-related responses including binding Ab titres and pseudo-neutralisation at the 18- and 24-month sampling time point. Responses correlated positively with the number of vaccine doses and infection. The vaccine response was blunted by an immunosuppressive state due to the underlying specific disease and/or to specific immunosuppressive treatment. INTERPRETATION: The study results highlight the importance of continuous SARS-CoV-2 vaccine booster doses in building up and sustaining Ab responses in specific immunocompromised patient populations. FUNDING: The present studies were supported by the European Research Council, Karolinska Institutet, Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and the Swedish Research Council.

Secondary matrix-associated autologous chondrocyte implantation after failed cartilage repair shows superior results when combined with autologous bone grafting: Findings from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: The aim of this study was to evaluate whether additive autologous bone grafting (ABG) improves clinical outcome and survival in revision matrix-associated autologous chondrocyte implantation (M-ACI) after failed cartilage repair (CR). METHODS: A retrospective, registry-based, matched-pair analysis was performed to compare patient-reported outcomes and survival in secondary M-ACI with or without additional bone grafting for focal full-thickness cartilage defects of the knee and to compare it with those in primary M-ACI. Patients were matched for age, sex, body mass index, defect size and localization, and number of previous CRs. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was assessed over a follow-up period of 36 months. The patient acceptable symptomatic state, the clinical response rate and the survival of the subgroups were determined. RESULTS: A total of 818 patients were matched. Revision M-ACI (n = 238) with concomitant bone grafting was associated with significantly higher PRO as measured by KOOS (80.8 ± 16.8 vs. 72.0 ± 17.5, p = 0.032) and higher CRR (81.4% vs. 52.0%, p = 0.018) at 36 months compared to patients with revision M-ACI alone. KOOS and KOOS improvement in these patients did not differ from those who underwent primary M-ACI (p = n.s.). The combination of M-ACI and ABG resulted in a significantly higher KOOS at 36 months than M-ACI alone, regardless of whether bone marrow stimulation (89.6 ± 12.5 vs. 68.1 ± 17.9, p = 0.003) or ACI (82.6 ± 17.0 vs. 72.8 ± 16.0, p = 0.021) was performed before. Additional bone grafting results in equivalent survival rates at 7 years in secondary compared to primary M-ACI (83% vs. 84%, p = n.s.). CONCLUSIONS: Regardless of the type of previous CR, additional bone grafting in secondary M-ACI improves the clinical outcome, response rate and survival at 36 months compared to M-ACI alone. Secondary M-ACI with ABG had comparable clinical response and survival rates to primary M-ACI. Therefore, subchondral bone should be treated even in cases of mild bone involvement in revision M-ACI. LEVEL OF EVIDENCE: Level III.

The potential of retinoic acid receptors as prognostic biomarkers and therapeutic targets in gastric cancer.

Background: Gastric cancer is a heterogeneous collection of tumors characterized by low survival rates. All-trans retinoic acid (retinoic-acid) is a clinically useful therapeutic agent belonging to the chemical family of retinoids, which consists of both natural and synthetic derivatives of vitamin-A. Retinoids are essential components of the normal diet and they regulate different physiological processes. From a therapeutic point of view, retinoic-acid is the first example of clinically useful differentiating agent. Indeed, the differentiating properties of this compound have promoted the use of retinoic-acid as a standard of care in Acute-Promyelocytic-Leukemia, a rare form of acute myeloid leukemia. In this study, we determine the RNA expression of the six isoforms of Retinoic-Acid-Receptors (RARα/RARß/RARγ/RXRα/RXRß/RXRγ) in view of their potential use as gastric cancer progression markers and/or therapeutic targets. In addition, we evaluate associations between the expression of these receptors and a simplified molecular classification of stomach tumors as well as the clinical characteristics of the cohort of patients analyzed. Finally, we define the prognostic value of the various Retinoic-Acid-Receptors in gastric cancer. Methods: In this single institution and retrospective RAR-GASTRIC study, we consider 55 consecutive gastric cancer patients. We extract total RNA from the pathological specimens and we perform a NanoString Assay using a customized panel of genes. This allows us to determine the expression levels of the RAR and RXR mRNAs as well as other transcripts of interest. Results: Our data demonstrate ubiquitous expression of the RAR and RXR mRNAs in gastric cancers. High levels of RARα, RARß, RXRα and RXRß show a significant association with stage IV tumors, "de novo" metastatic disease, microsatellite-stable-status, epithelial-to-mesenchymal-transition, as well as PIK3CA and TP53 expression. Finally, we observe a worse overall-survival in gastric cancer patients characterized by high RARα/RARß/RARγ/RXRß mRNA levels. Conclusions: In gastric cancer, high expression levels of RARα/RARß/RARγ/RXRß transcripts are associated with poor clinical and molecular characteristics as well as with reduced overall-survival. Our data are consistent with the idea that RARα, RARß, RARγ and RXRß represent potential prognostic markers and therapeutic targets of gastric cancer.

Raman Spectroscopy for Instant Bladder Tumor Diagnosis: System Development and In Vivo Proof-Of-Principle Study in Accordance with the European Medical Device Regulation (MDR2017/745).

This work reports on an in vivo Raman-based endoscopy system, invaScope, enabling Raman measurements of healthy and tumor bladder tissue during an endoscopic procedure in the operating theatre. The presented study outlines the progression from the initial concept (validated through previously performed ex vivo studies) to the approval and implementation of a clinical investigational device according to the requirement within the framework of the European Medical Device Regulation (MDR2017/745). The study's primary objective was to employ the invaScope Raman system within the bladder, capturing in vivo spectroscopic Raman data followed by standard histo- and cytopathological examinations of urological tissue (considered the gold standard). The collected data were analyzed and correlated with histopathological findings post-procedure. Additionally, the study aimed to assess the feasibility of using diagnostic equipment, probes, and software for application in a clinical setting, evaluating usability aspects that are important during surgical procedures. This research represents a pivotal step toward advancing Raman spectroscopy for routine clinical use in characterizing bladder lesions.

Limb Perfusion Delivery of a rAAV1 Alpha-1 Antitrypsin Vector in Non-Human Primates Is Safe but Insufficient for Therapy.

BACKGROUND/OBJECTIVES: α-1 antitrypsin (AAT) deficiency is an inherited, genetic condition characterized by reduced serum levels of AAT and increased risk of developing emphysema and liver disease. AAT is normally synthesized primarily in the liver, but muscle-targeting with a recombinant adeno-associated virus (rAAV) vector for α-1 antitrypsin (AAT) gene therapy has been used to minimize liver exposure to the virus and hepatotoxicity. Clinical trials of direct intramuscular (IM) administration of rAAV1-hAAT have demonstrated its overall safety and transgene expression for 5 years. However, the failure to reach the therapeutic target level after 100 large-volume (1.5 mL) IM injections of maximally concentrated vector led us to pursue a muscle-targeting approach using isolated limb perfusion. This targets the rAAV to a greater muscle mass and allows for a higher total volume (and thereby a higher dose) than is tolerable by multiple direct IM injections. Limb perfusion has been shown to be feasible in non-human primates using the rAAV1 serotype and a ubiquitous promoter expressing an epitope-tagged AAT matched to the host species. METHODS: In this study, we performed a biodistribution and preclinical safety study in non-human primates with a clinical candidate rAAV1-human AAT (hAAT) vector at doses ranging from 3.0 × 1012 to 1.3 × 1013 vg/kg, bracketing those used in our clinical trials. RESULTS: We found that limb perfusion delivery of rAAV1-hAAT was safe and showed a biodistribution pattern similar to previous studies. However, serum levels of AAT obtained with high-dose limb perfusion still reached only ~50% of the target serum levels. CONCLUSIONS: Our results suggest that clinically effective AAT gene therapy may ultimately require delivery at doses between 3.5 × 1013-1 × 1014 vg/kg, which is within the dose range used for approved rAAV gene therapies. Muscle-targeting strategies could be incorporated when delivering systemic administration of high-dose rAAV gene therapies to increase transduction of muscle tissues and reduce the burden on the liver, especially in diseases that can present with hepatotoxicity such as AAT deficiency.

Blood endocan as a biomarker for breast cancer recurrence.

BACKGROUND: Endocan was reported to affect breast cancer patients negatively and was able to be detected from patients' blood. OBJECTIVE: This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers. METHODS: Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20 patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3). RESULTS: Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan. CONCLUSIONS: Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence.

Clinical outcomes of guided tissue regeneration with carbonate apatite granules and poly(lactic acid/caprolactone) membrane for the treatment of intrabony defects and mandibular Class II furcation involvements: A 12-month prospective pilot clinical study.

Introduction: For deep intrabony defects or Class II furcation involvements (FI), periodontal tissue regenerative therapy combined with bone graft materials and a barrier membrane is recommended. The objective of this study was to assess the safety and efficacy of using carbonate apatite (CO3Ap) granules and absorbable poly(lactic acid/caprolactone) (PLCL) membranes for periodontal regeneration in the treatment of intrabony defects and mandibular Class II FI. Methods: This prospective pilot clinical study, conducted at a single center with a single-arm design, aimed to assess the safety and efficacy of CO3Ap and PLCL membranes in patients with periodontitis. A total of 9 patients with 10 teeth, including seven deep intrabony defects and three Class II FI, were treated with CO3Ap granules and PLCL membranes. Clinical parameters such as probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), tooth mobility (Mo), Plaque Index (PI), and Gingival Index (GI) were assessed at baseline, 6 and 12 months post-surgery. Radiographic analysis was performed using dental X-rays and cone beam computed tomography (CBCT) images taken at baseline, 6, and 12 months post-surgery. Results: Postoperative healing was uneventful in most of the cases. In some cases, membrane exposures were observed. However, there were no signs of inflammation, such as abnormal bleeding, pain, swelling, or pus. These exposures eventually healed well in the end. The mean reductions in PPD at 6 and 12 months were 4.5 ± 1.6 mm and 4.9 ± 1.4 mm, respectively, while the mean gains in CAL were 4.4 ± 1.7 mm at 6 months and 4.6 ± 1.2 mm at 12 months. Radiographic analysis showed improvements in linear bone height within intrabony defects and in the vertical subclassification of FI in Class II FI. Conclusions: Despite the limitations of this study, periodontal regenerative therapy using CO3Ap granules and a PLCL membrane demonstrated promising clinical safety and efficacy for treating intrabony defects and mandibular Class II furcation involvement.

Tyrosine and tryptophan in urine as biomarkers for prostate cancer: A validation study.

Prostate cancer (PCa) is a common male malignancy and early diagnosis is crucial for successful treatment. The current study aims to validate results from a pilot study that demonstrated an inverse association between urine tyrosine and tryptophan levels and the severity of PCa. This study comprised a cohort of 97 patients with benign prostatic hyperplasia, 93 patients diagnosed with localized PCa, 75 patients diagnosed with locally advanced PCa, and 68 patients diagnosed with metastatic PCa. The tyrosine and tryptophan levels in the samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electrochemical sensors in accordance with the pilot to maintain uniformity for accurately evaluating the data. One-way ANOVA with post Tukey test as well as the Wilcoxon Rank Sum Test were performed. Analyzing 333 patients across PCa stages with consistent methods, we observed no significant differences in tyrosine and tryptophan levels between PCa patients and controls, finally rejecting the use of tyrosine and tryptophan as PCa biomarkers. We did, however, verify the strong correlation between the urinary concentrations of tyrosine and tryptophan found in the pilot study.

Cannabidiol plus krill oil supplementation improves chronic stifle osteoarthritis in dogs: A double-blind randomized controlled trial.

Osteoarthritis (OA) is the most common orthopedic disorder characterized by chronic inflammation and pain in dogs and cats. Cannabis spp. contains cannabidiol (CBD), a substance with pain relief and anti-inflammatory properties in different animals including dogs with OA. The use of CBD supplements has been increasingly intertwining in veterinary medicine. This study aimed to evaluate the clinical efficacy of CBD + krill oil-supplemented biscuit against canine OA. In total, 30 dogs with stifle OA were randomized and divided into the placebo, krill oil, and CBD + krill oil groups. The Canine Brief Pain Inventory questionnaire was used to evaluate the efficacy of each treatment against pain. Stifle temperature was monitored to identify degrees of stifle inflammation. Two and one dogs in the placebo group were excluded from the study due to worsening lameness and increased pain interference score (PIS) and pain severity score (PSS) at days 14 and 28, respectively. The PIS and PSS scores of the krill oil and CBD + krill oil groups gradually and significantly improved after two weeks of treatment. The CBD + krill oil group had better PIS and PSS scores than the placebo and krill oil groups. However, there was no statistically significant difference in the PIS and PSS scores between the krill oil and CBD + krill oil groups. The stifle temperature of the three groups at different periods did not significantly differ. In conclusion, CBD + krill oil supplements are safe against canine OA. CBD can reduce pain and inflammation.

Effectiveness and Safety of Vertebral Body Stenting for Acute Spinal Compression Fractures due to Primary Osteoporosis: A Multicenter Prospective Clinical Study.

Introduction: Segmental spinal deformity results from vertebral compression fracture (VCF) and progressive collapse of the fractured vertebral body (VB). The VB stenting (VBS) systemⓇ comprises a balloon-assisted, expandable, intrasomatic, metal stent that helps maintain the restored VB during balloon removal and cement injection, which minimizes cement leakage. We performed a prospective, multicenter, clinical trial of the VBS system in Japanese patients with acute VCF owing to primary osteoporosis. Methods: Herein, 88 patients, 25 men and 63 women aged 77.4±8.3 years, with low back pain, numerical rating scale (NRS) score of ≥4, and mean VB compression percentage (VBCP) of <60% were enrolled. The primary endpoints were the VBCP restoration rate and reduction in low back pain 1 month and 7 days after VBS surgery, respectively. Secondary endpoints included changes in VBCP, NRS pain score, Beck index, kyphosis angle, and quality of life according to the short form 36 (v2) score. Safety was assessed as adverse events, device malfunctions, and new vertebral fractures. Results: Overall, 70 patients completed the study. VBS surgery increased the restoration rates of anterior and midline VBCP by 31.7%±26.5% (lower 95% confidence intervals (CI): 26.8) and 31.8%±24.6% (lower 95% CI: 27.2), respectively, and the reduction in NRS pain score was -4.5±2.4 (upper 95% CI: -4.0). As these changes were greater than the predetermined primary endpoint values (20% for VBCP and -2 for NRS score), they were judged clinically significant; these changes were maintained throughout the 12-month follow-up (p<0.001). Likewise, significant improvement was observed in the Beck index, kyphosis angle, and quality of life score, which were maintained throughout the follow-up. There were three serious adverse events. New fractures occurred in 12 patients-all in the adjacent VB. Conclusions: VBS surgery effectively restored the collapsed VB, relieved low back pain, and was tolerable in patients with acute osteoporotic VB fracture.

Acetyl zingerone methyl ether protects hair against oxidative damage incurred during and after treatment with permanent dyes and helps extend longevity of newly developed hair colour.

BACKGROUND: Use of permanent hair dyes causes unintended oxidative damage during the short time frame of the dyeing process that leads to perceivable changes in the feel, manageability and appearance of hair. Moreover, after hair has been dyed, regular exposure to the sun as a key environmental stressor continues to stimulate additional oxidative damage and to induce newly developed hair colours to fade prematurely or undergo changes in colour quality. OBJECTIVE: To document the utility of acetyl zingerone methyl ether (MAZ) as a newly designed haircare ingredient to afford extra protection against oxidative damage and safeguard the integrity of hair colour. RESULTS: We demonstrate that MAZ is compatible chemically with the high alkaline conditions required for the colouring process and from theoretical calculations preferentially binds Fe and Cu ions relative to Ca or Zn ions. In model Fenton reactions MAZ effectively chelated active redox metals (Fe and Cu ions) in the presence of excess Ca+2 ions to inhibit the production of hydroxyl radicals, and in separate studies, MAZ neutralized singlet oxygen with greater efficiency than α-tocopherol by a factor of 2.5. When mixed into permanent dyes prior to hair tress application, MAZ significantly reduced combing forces, and SEM images led to substantial reductions in visual signs of surface damage. In a 28-day clinical study, relative to controls, mixing MAZ into hair dyes prior to application interfered neither with colour development nor with ability to cover grey hair and led to significant improvements in perceived attributes associated with hair's condition immediately following the dyeing process. Over a 28-day maintenance phase, especially between Day 14 and Day 28, continued use of shampoo and conditioner containing MAZ significantly preserved gloss measurements and hair colour in terms of longevity and colour quality as remaining desired and fresh compared to use of control shampoo and conditioner. CONCLUSION: This work establishes MAZ as a next-generation hair care ingredient for use in permanent dyes to attenuate oxidative damage and in shampoos and conditioners to promote longevity of hair colour and to maintain overall health and appearance of hair on a daily basis.

CONTEXTE: L'utilisation de colorants capillaires permanents provoque des dommages oxydatifs involontaires pendant la courte période du processus de teinture, ce qui entraîne des changements perceptibles dans la texture, la maniabilité et l'aspect des cheveux. De plus, après la teinture des cheveux, une exposition régulière au soleil comme facteur de stress environnemental clé continue de stimuler des dommages oxydatifs supplémentaires et d'induire une décoloration prématurée des nouvelles couleurs de cheveux ou des changements dans la qualité de la couleur. OBJECTIF: Documenter l'utilité de l'éther méthylique d'acétyl zingérone (MAZ) en tant qu'ingrédient de soin capillaire nouvellement conçu pour offrir une protection supplémentaire contre les dommages oxydatifs et sauvegarder l'intégrité de la couleur des cheveux. RÉSULTATS: Nous démontrons que le MAZ est chimiquement compatible avec les conditions alcalines élevées requises pour le processus de coloration et, d'après les calculs théoriques, lie de préférence les ions Fe et Cu aux ions Ca ou Zn. Dans les réactions de Fenton, le MAZ chélate efficacement les métaux redox actifs (atomes de Fe et de Cu) en présence d'un excès d'ions Ca+2 pour inhiber la production de radicaux hydroxyles et, dans des études séparées, le MAZ neutralise l'oxygène seul avec une efficacité supérieure à celle de l'α­tocophérol, d'un facteur de 2.5. Lorsqu'il est mélangé à des teintures permanentes avant l'application de la coiffure, le MAZ réduit de manière significative les forces de peignage et, d'après les images SEM, conduit à des réductions substantielles des signes visuels de dommages à la surface. Dans une étude clinique de 28 jours, le mélange de MAZ dans les teintures capillaires avant l'application n'interfère pas avec le développement de la couleur ni avec la capacité à couvrir les cheveux gris et conduit à des améliorations significatives des attributs perçus associés à l'état des cheveux immédiatement après le processus de teinture. Au cours d'une phase d'entretien de 28 jours, en particulier entre le 14ème et le 28ème jour, l'utilisation continue du shampooing et de l'après­shampooing contenant du MAZ a permis de préserver de manière significative les mesures de brillance et la couleur des cheveux en termes de longévité et de qualité de la couleur, qui reste telle que désirée et nette, par rapport à l'utilisation du shampooing et de l'après­shampooing de contrôle. CONCLUSION: Ces travaux font du MAZ un ingrédient de nouvelle génération pour les soins capillaires, à utiliser dans les teintures permanentes pour atténuer les dommages oxydatifs et dans les shampooings, et après­shampooings pour promouvoir la longévité de la couleur des cheveux et maintenir la santé et l'apparence générales des cheveux au quotidien.

Inferences for the distribution of the duration of response in a comparative clinical study.

Duration of response is an important endpoint used in drug development. Prolonged duration for response is often viewed as an early indication of treatment efficacy. However, there are numerous difficulties in studying the distribution of duration of response based on observed data subject to right censoring in practice. The most important obstacle is that the distribution of the duration of response is in general not identifiable in the presence of censoring due to the simple fact that there is no information on the joint distribution of time to response and time to progression beyond the largest follow-up time. In this article, we introduce the restricted duration of response as a replacement of the conventional duration of response. The distribution of restricted duration of response is estimable and we have proposed several nonparametric estimators in this article. The corresponding inference procedure and additional downstream analysis have been developed. Extensive numerical simulations have been conducted to examine the finite sample performance of the proposed estimators. It appears that a new regression-based two-step estimator for the survival function of the restricted duration of response tends to have a robust and superior performance, and we recommend its use in practice. A real data example from oncology has been used to illustrate the analysis for restricted duration of response.

Comparison of postoperative analgesia effects between subcostal anterior quadratus lumborum block and transversus abdominis plane block in bariatric surgery: a prospective randomized controlled study.

BACKGROUND: Currently, the prevalence of obesity is on the rise annually. Bariatric surgery stands out as the most efficacious approach for addressing obesity. Obese patients are more prone to experience moderate to severe pain after surgery due to lower pain thresholds. Regional block, as an important component of multimodal analgesia in bariatric surgery, is crucial in reducing opioid consumption and alleviating postoperative pain in patients undergoing bariatric surgery. Transversus abdominis plane block (TAPB) has gained widespread utilization in bariatric surgery; however, its limitation of inadequate reduction of visceral pain in obese patients remains a significant concern. Therefore, it is imperative to explore new and more efficient strategies for analgesia. Quadratus lumborum block (QLB) has emerged as a popular nerve block in recent years, frequently utilized in conjunction with general anesthesia for abdominal surgery. In the cadaver study of QLB, it was confirmed that the dye level could reach up to T6 when using the subcostal anterior quadratus lumborum muscle approach, which could effectively reduce the incision pain and visceral pain of bariatric surgery patients during the perioperative period. However, there is currently a lack of research on the use of subcostal anterior QLB in patients undergoing bariatric surgery. Our study aims to investigate whether subcostal anterior QLB can provide superior perioperative analgesic efficacy for bariatric surgery under general anesthesia compared to TAPB, leading to reduced postoperative opioid consumption and a lower incidence of postoperative nausea and vomiting (PONV). METHODS AND DESIGN: This study is a prospective, randomized controlled trial aiming to recruit 66 patients undergoing bariatric surgery. The participants will be randomly allocated into two groups in a 1:1 ratio: subcostal anterior QLB group (n = 33) and TAPB group (n = 33). The study aims to investigate the efficacy of subcostal anterior QLB and TAPB in obese patients who are scheduled to undergo bariatric surgery. Our primary outcome is to observe the amount of opioids used in the two groups 24 h after operation. The secondary outcomes included VAS of pain during rest/activity after operation, the type and dose of additional analgesics, the occurrence and severity of PONV, the type and dose of additional antiemetic drugs, postoperative anesthesia care unit (PACU) time, time of first postoperative exhaust, time to first out of bed activity, time to first liquid diet and postoperative admission days. DISCUSSION: Opioid analgesics are prone to causing adverse reactions such as nausea, vomiting, and respiratory depression, especially in obese patients. Multimodal analgesia, including nerve block, can effectively reduce the dose of opioids and alleviate their adverse effects. Currently, TAPB is the most prevalent nerve block analgesia method for abdominal surgery. Recent studies have indicated that subcostal anterior QLB offers advantages over TAPB, including a wider block plane, faster onset, and longer maintenance time. It is not clear which of the two nerve block analgesia techniques is better for postoperative analgesia in patients undergoing bariatric surgery. Our objective in this investigation is to elucidate the superior method between TAPB and subcostal anterior QLB for postoperative pain management in bariatric surgery. TRIAL REGISTRATION: ChiCTR ChiCTR2300070556. Registered on 17 April 2023.

Urate lowering therapy in patients starting hemodialysis limit gout flares occurrence: ten years retrospective study.

BACKGROUND: Uncontrolled gout can cause articular impairment but is also associated with a global and cardiovascular excess mortality, especially in dialysis population. Data documented within existing research is not conclusive regarding gout flares evolution during hemodialysis and their control by urate lowering therapy (ULT). Without clear guidelines concerning hemodialysis patients management with chronic gout, this study proposes to investigate whether gout flare incidence reduction could be observed on this population treated by urate lowering therapy versus patients without treatment. METHODS: We performed a retrospective cohort study in two hemodialysis centers in France. Were selected patients over 18 years old with a gout history who started hemodialysis between January 2005 and September 2015. Demographics and clinicals data were recorded at hemodialysis start and throughout 5 years of follow up. Gout flare was defined as presence of uric acid crystal in joint punction or clinically diagnosed as such with a colchicine prescription. All statistical analysis were performed in SAS® version 9.4 (SAS Institute Inc., Cary, NC). RESULTS: One hundred eighty-one patients have been included, mean age at dialysis initiation was 68.6 years (± 12.4) with 72% of men, 54% were treated by ULT: 89.7% by allopurinol and 9.3% by febuxostat. One patient received both treatments successively. After hemodialysis initiation, 35.36% patients had experienced at least one gout flare. The appearance of at least one gout flare concerned 50% of patients in no ULT group and 22.68% patients in ULT group (p = 0.0002). Dialysis efficiency was measured at regular interval during follow-up and was similar in both groups. To study the association strength between clinical factors and gout flares occurrences, a Cox model was performed; ULT is a protector factor of gout flare (HR:0,42, CI 95: 0,25-0,71). The proportion of serum urate values within the target (median 53% vs 29.3%, p < 0.0001) was significantly higher in ULT group versus no ULT group (median 53% vs 29.3%, p < 0.0001). CONCLUSION: Urate lowering therapy limit new gout flares occurrence in hemodialysis patients with gout historyCollaboration between rheumatologists and nephrologists may help to update guidelines for urate-lowering therapies in patients on dialysis.

Forgotten joint score associated with prosthesis weight in cementless total hip arthroplasty: a prospective clinical study.

Background: This prospective study aimed to investigate the influence of weight difference between implanted prosthesis and removed bone in cementless total hip arthroplasty (THA) on hip awareness and patient-reported outcomes. Methods: A total of 48 patients (56 hips) who underwent primary THA were prospectively enrolled. Implanted prosthesis and removed bone were weighed intraoperatively. Forgotten Joint Score (FJS) and Western Ontario and McMaster Universities (WOMAC) scores were obtained before and at 1 and 3 months after surgery. Patients were divided into groups A, B, and C according to the percentile of the weight difference. Results: The mean weight difference of the implanted prosthesis and removed bone was 117.97 ± 47.35 g. A negative correlation was found among the weight differences of the three groups and 1- and 3-month postoperative FJS (correlation coefficients, -0.331 and -0.734, respectively). A positive correlation was found among the weight difference of the three groups and 3-month postoperative WOMAC (correlation coefficient, 0.403). A significant difference in 3-month postoperative FJS and WOMAC scores was found among the three groups. The mean 3-month postoperative FJS (79.00) of group C was significantly lower than that of group A (93.32) (P < 0.05). The mean WOMAC score (15.83) of group A was significantly lower than that of group C (23.67) (P < 0.05). Conclusion: The implanted prosthesis is larger than the removed bone in cementless THA. The weight difference is negatively correlated with hip function. The weight difference should be minimized to achieve optimal hip joint awareness.

Distribution and influencing factors of pulp stones based on CBCT: a retrospective observational study from southwest China.

BACKGROUND: Pulp stones are a type of pulp calcification, the presence of which tends to hinder endodontic treatment. Thus, this retrospective study aimed to analyze the distribution of pulp stones in the population in southwest China and identify the influencing factors. MATERIALS: Cone-beam computed tomography (CBCT) scans of 5066 teeth of 200 patients (91 males and 109 females) aged 16-45 years were evaluated. Pulp stones were marked as either present or absent when distinct radiopaque masses were found in the pulp cavity, then evaluated the occurrence of pulp stones with regard to tooth type, sex, age group, and contact it with tooth status. The Pearson chi-square test and nonparametric test were used for statistical analysis. RESULTS: Pulp stones were detected in 49.0% of patients and 7.4% of teeth, respectively. The incidence in females was 1.9 times higher than in males (OR = 1.9, 95% CI = 1.1-3.3, p = 0.001). Pulp stones were most prevalent in patients 36-45 years of age. Furthermore, in the age range of 16-45 years, the likelihood of finding pulp stones increased 1.1 times per year with age (OR = 1.1, 95% CI = 1.0-1.1, p = 0.032). A higher incidence of pulp stones was observed in the maxilla and molars. Of the 5066 teeth studied, pulp stones were more common in non-intact teeth. CONCLUSION: Nearly half of the population in southwest China had pulp stones. Pulp stones were found significantly more often in females, maxilla, and non-intact teeth, and their frequency increased with age. For dentists, understanding the distribution of pulp stones is crucial for the proper design of root canal treatment (RCT). TRIAL REGISTRATION: This study was approved by the Ethics Committee of the Affiliated Hospital of Stomatology, Southwest Medical University (certificate number: 20220818001).

Favourable clinical outcomes and low revision rate after M-ACI in adolescents with immature cartilage compared to adult controls: Results at 10 years.

PURPOSE: The purpose of this study was to evaluate long-term survival, patient-reported outcomes (PROs) and radiographic results of matrix-associated autologous chondrocyte implantation (M-ACI) in adolescents with immature cartilage and compare them to adult controls. METHODS: A retrospective matched-pair analysis was performed comparing the PRO after M-ACI for focal cartilage defect of the knee in cartilaginous immature adolescents to mature adults. Groups were matched for sex, body mass index, defect site and size, symptom duration and the number of previous knee surgeries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART 2.0) scores were assessed at least 60 months postoperatively. Patient acceptable symptomatic state (PASS) and clinical response rate in KOOS and KOOS subscores were calculated. RESULTS: A total of 54 patients were matched. At a mean of 96 months (65-144 months), no surgical complications, graft hypertrophy or reoperations were noted in the cohorts studied. Adolescents showed superior PROs at the final follow-up (76.9 ± 14.1 vs. 66.4 ± 15.0, p = 0.03) and were significantly more likely to achieve PASS (74.1% vs. 55.6%; p = 0.02) compared to the adult cohort. The KOOS subscale analysis showed long-term benefits for adolescents in terms of symptom improvement, pain reduction, activities of daily living, sports and quality of life (p < 0.05). None of the patients in the adolescent group showed graft hypertrophy on magnet resonance imaging or signs of osteoarthritis on radiographs at long-term follow-ups. CONCLUSIONS: M-ACI is an effective treatment for chondral defects of the knee in patients with immature cartilage with low revision rates and high patient satisfaction over the long term. Adolescents showed comparable clinical and radiographic results in the short and medium term, with slightly more favourable, clinically relevant functional results in adolescents in the long term. M-ACI can be safely used in adolescents, and consideration should be given to expanding the indication to include these patients. LEVEL OF EVIDENCE: Level III.

Accuracy and safety of an autonomous artificial intelligence clinical assistant conducting telemedicine follow-up assessment for cataract surgery.

Background: Artificial intelligence deployed to triage patients post-cataract surgery could help to identify and prioritise individuals who need clinical input and to expand clinical capacity. This study investigated the accuracy and safety of an autonomous telemedicine call (Dora, version R1) in detecting cataract surgery patients who need further management and compared its performance against ophthalmic specialists. Methods: 225 participants were recruited from two UK public teaching hospitals after routine cataract surgery between 17 September 2021 and 31 January 2022. Eligible patients received a call from Dora R1 to conduct a follow-up assessment approximately 3 weeks post cataract surgery, which was supervised in real-time by an ophthalmologist. The primary analysis compared decisions made independently by Dora R1 and the supervising ophthalmologist about the clinical significance of five symptoms and whether the patient required further review. Secondary analyses used mixed methods to examine Dora R1's usability and acceptability and to assess cost impact compared to standard care. This study is registered with ClinicalTrials.gov (NCT05213390) and ISRCTN (16038063). Findings: 202 patients were included in the analysis, with data collection completed on 23 March 2022. Dora R1 demonstrated an overall outcome sensitivity of 94% and specificity of 86% and showed moderate to strong agreement (kappa: 0.758-0.970) with clinicians in all parameters. Safety was validated by assessing subsequent outcomes: 11 of the 117 patients (9%) recommended for discharge by Dora R1 had unexpected management changes, but all were also recommended for discharge by the supervising clinician. Four patients were recommended for discharge by Dora R1 but not the clinician; none required further review on callback. Acceptability, from interviews with 20 participants, was generally good in routine circumstances but patients were concerned about the lack of a 'human element' in cases with complications. Feasibility was demonstrated by the high proportion of calls completed autonomously (195/202, 96.5%). Staff cost benefits for Dora R1 compared to standard care were £35.18 per patient. Interpretation: The composite of mixed methods analysis provides preliminary evidence for the safety, acceptability, feasibility, and cost benefits for clinical adoption of an artificial intelligence conversational agent, Dora R1, to conduct follow-up assessment post-cataract surgery. Further evaluation in real-world implementation should be conducted to provide additional evidence around safety and effectiveness in a larger sample from a more diverse set of Trusts. Funding: This manuscript is independent research funded by the National Institute for Health Research and NHSX (Artificial Intelligence in Health and Care Award, AI_AWARD01852).