Avaliação tomográfica das dimensões verticais dos tecidos periodontais supracrestais em dentes anteriores da maxila / Tomographic evaluation of the vertical dimensions of periodontal supracrestal tissues in maxillary anterior teeth

O objetivo do presente estudo foi avaliar em tomografias computadorizadas as dimensões dos tecidos periodontais supracrestais (TPSC). Cem pacientes, 600 dentes anteriores da maxila (200 incisivos centrais, 200 incisivos laterais e 200 caninos), foram avaliados. A distância média da margem gengival até a crista óssea alveolar (COA) foi de 3.25mm (95% IC: 3.20-3.30), enquanto que da junção cemento-esmalte até a COA foi de 1.77mm (95% IC: 1.72-182mm). As medidas foram significativamente diferentes entre os grupos de dentes (ANOVA, p < 0.001). A tomografia, pode representar uma importante ferramenta para a avaliação das dimensões dos TPSC.

The aim of this study was to evaluate the dimensions of the supracrestal periodontal tissues (SPT) on tomographic scans. One hundred patients, 600 maxillary anterior teeth (200 central incisors, 200 lateral incisors and 200 canines), were evaluated. The average distance from the gingival margin to the alveolar bone crest (ABC) was 3.25mm (95% CI: 3.20-3.30), while the distance from the cemento-enamel junction to ABC was 1.77mm (95% CI: 1.72-182mm). The measurements were significantly different between the tooth groups (ANOVA, p < 0.001). When properly indicated, tomography can be an important tool for assessing the dimensions of TPSCs on a case-by-case basis.

O emprego da moldagem digital na prática odontológica - relato de caso / The use of digital molding in dental practice ­ case report

O avanço da tecnologia de digitalização de imagens e desenvolvimento de dispositivos de fresagem possibilitaram a otimização de diversos processos na Odontologia. O emprego do escaneamento intraoral e do sistema CAD-CAM (CAD - Computer Aided Design; CAM - Computer Aided Manufacturing) aprimorou a realização de reabilitações protéticas, permitindo a obtenção de peças de alta qualidade em tempo reduzido. O objetivo deste trabalho é relatar um caso de reabilitação de um incisivo central inferior a partir de escaneamento intraoral, com scanner Omnicam (DentsplySirona Charlotte, NC, EUA) e aplicação do sistema CAD-CAM.

The advancement of image digitization technology and the development of milling devices have made it possible to optimize various processes in Dentistry. The use of intraoral scanning and the CAD-CAM system (CAD - Computer Aided Design; CAM - Computer Aided Manufacturing) has improved the performance of prosthetic rehabilitations, allowing the obtaining of high quality parts in a reduced time. The objective of this work is to report a case of rehabilitation of a lower central incisor using intraoral scanning, with an Omnicam scanner (Dentsply Sirona) and application of the CAD-CAM system.

Patient-Reported Outcomes of Bicruciate Multiligament Versus Single Cruciate Multiligament Knee Injuries.

BACKGROUND: Multiligament knee injuries (MLKIs) are heterogeneous, and bicruciate knee ligament injuries are considered a serious form of this injury. The current literature tends not to distinguish between single and bicruciate MLKI when reporting outcomes. PURPOSE: To investigate patient-reported outcomes after surgical treatment of MLKI comparing single cruciate MLKI with bicruciate MLKI. The secondary aim was to investigate the influence of different factors on patient-reported outcomes after surgery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study was designed as a cross-sectional cohort study. Patients who underwent surgical treatment for MLKI at a single level 1 trauma center between January 2013 and December 2020 were included in this study. Patient-reported outcomes included the Tegner score, Lysholm score, International Knee Documentation Committee (IKDC) subjective knee form, Knee injury and Osteoarthritis Outcome Survey (KOOS), and a visual analog scale for pain. RESULTS: Of the 191 patients meeting the inclusion criteria, 124 (65%) agreed to participate and had a complete data set with a follow-up time at a mean 74 ± 27 months. Patients with single cruciate MLKI (type I) had significantly higher scores for IKDC (P = .007), Lysholm (P = .012), KOOS Pain (P = .04), KOOS Activities of Daily Living (P = .01), KOOS Sport and Recreation (P = .005), KOOS Quality of Life (P = .04), KOOS4 (which considers the subscales of Pain, Symptoms, Sport and Recreation, and Quality of Life) (P = .01), Tegner (P = .04), and visual analog scale for pain during activity (P = .004) when compared with patients with bicruciate MLKI (type II-type IV). Furthermore, age was significantly associated with a lower IKDC (P = .001), and an increased severity of injury was significantly associated with IKDC (P = .015), KOOS4 (P = .022), and Lysholm (P = .029) scores. CONCLUSION: MLKIs involving a single cruciate ligament had significantly higher patient-reported postoperative outcome measures compared with bicruciate MLKIs. Age and type of injury were important predictors for outcomes. Patients presenting with dislocated knees had lower patient-reported outcomes; however, there was no significant difference in outcomes between bicruciate MLKIs and patients presenting with dislocated knees.

Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial.

OBJECTIVE: Depression varies along a difficulty-to-treat spectrum. Patients whose illness fails to respond to at least five treatments may be considered to have severely treatment-resistant depression (TRD). The objective of this study was to document the safety and efficacy of psilocybin in patients with severe TRD. METHODS: This was a 12-week, open-label trial conducted at Sheppard Pratt Hospital. Participants were 18-65 years of age, in a major depressive episode with documented insufficient benefit from at least five treatments during the current episode. A single dose of synthetic psilocybin (25 mg) was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing through at least 3 weeks post-dosing. Therapists met with patients for three sessions during pretreatment, during the 8-hour dosing day, and for three integration sessions posttreatment. The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures including MADRS scores up to 12 weeks posttreatment, and subject-rated scales capturing depression and level of function were completed at baseline and all subsequent visits. RESULTS: Twelve participants (six male, six female; mean age=40.6 years [SD=9.6]) with severe TRD were followed over the study period. Depressive symptoms were significantly decreased at week 3 (MADRS least-squares mean change=-15.8, 95% CI=-25.4 to -6.3) and Week 12 (MADRS least-squares mean change=-17.2, 95% CI=-25.2 to -9.1). In exploratory analyses, the Oceanic Boundlessness (OB) dimension of the psychedelic experience correlated with post-dosing antidepressant responses. Patients with comorbid PTSD (N=5) showed significantly less antidepressant effect of psilocybin. CONCLUSIONS: This open-label study suggests efficacy and safety of psilocybin in severe TRD and supports further study of psychedelics in this population, including consideration of PTSD interaction effects.

Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking. METHODS: Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback. RESULTS: Relative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session. CONCLUSIONS: PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.

Posterolateral Knee Ligament Reconstruction Using the Arciero Technique Provides Greater Rotational Stability Than the Modified Larson Technique: A Biomechanical Study.

BACKGROUND: It is still unknown if the double-femoral tunnel technique (Arciero [ARC]) provides better stability as compared with the single-femoral tunnel technique (modified Larson [LAR]) in posterolateral corner reconstruction. The ideal angle of fixation of the popliteofibular strand in ARC is also unknown. HYPOTHESES: The ARC provides greater external rotation (ER) stability than the LAR (hypothesis 1); there is no difference in varus rotation (VR) stability between LAR and ARC (hypothesis 2); and femoral fixation of the popliteofibular strand at 60° during the ARC leads to greater ER stability than fixation at 30° or 90° of knee flexion (hypothesis 3). STUDY DESIGN: Controlled laboratory study. METHODS: Eight fresh-frozen human knees were tested in a knee test bench in 4 states: native, posterolateral deficiency, LAR, and ARC. With the ARC, the popliteofibular strand was fixed at 30°, 60°, and 90° (ARC30, ARC60, ARC90). The order of testing (LAR/ARC) was randomized. A tibial ER and VR torque of 5 N·m was applied at 0°, 30°, 60°, and 90°. Rotation degrees were captured using an ultrasound-based analysis system. Wilcoxon signed rank tests were used to assess statistical significance between paired groups in different states. RESULTS: The ARC and LAR significantly improved VR and ER stability at all flexion angles in comparison with posterolateral deficiency (P < .05). At 60° and 90°, ARC30 showed significantly greater ER stability in comparison with the LAR (mean ± SD; ARC30 vs LAR at 60°, 21.2°± 5.1° vs 15.4°± 5.6° [P < .05]; ARC30 vs LAR at 90°, 23.7°± 5.6° vs 16.8°± 6.3° [P < .05]). At 90°, the LAR showed significantly greater VR instability in comparison with the native state (3.5°± 1.5° vs 2.5°± 1.0°; P = .012), and ARC30 was not significantly different from the native state with respect to VR (2.9°± 1.5° vs 2.5°± 1.0°; P = .327). No significant differences in ER and VR were found among ARC30, ARC60, and ARC90 at any flexion angle (P≥ .05). CONCLUSION: The ARC technique provided greater tibial ER stability in comparison with the LAR at higher flexion angles (hypothesis 1 accepted). There were no differences between LAR and ARC in restoring VR stability, except at 90° (hypothesis 2 partly accepted). Different femoral flexion angles for fixation of the popliteofibular strand during the ARC did not show any significant differences in relation to knee stability (hypothesis 3 rejected). CLINICAL RELEVANCE: Posterolateral corner reconstruction using the ARC technique provides greater ER stability at higher flexion angles than the modified LAR technique.

Vestibular Implant Surgery: How to Deal With Obstructed Semicircular Canals-A Diagnostic and Surgical Guide.

BACKGROUND: A vestibular implant can partially restore vestibular function by providing motion information through implanted electrodes. During vestibular implantation, various obstructions of the semicircular canals, such as protein deposits, fibrosis, and ossification, can be encountered. The objective was to explore the relationship between preoperative imaging and intraoperative findings of semicircular canal obstruction and to develop surgical strategies for dealing with obstructions of the semicircular canal(s) in patients eligible for vestibular implantation. METHODS: Patients undergoing vestibulocochlear implantation (in an active clinical trial) were included in the current study when preoperative imaging indicated an obstruction in the semicircular canal. Preoperative imaging consisted of CT and MRI scans. During surgery, the bony semicircular canals were skeletonized ("bluelined") to identify the course of the canals and create a fenestration to insert the electrodes. The aim was to place the electrodes in the semicircular canal ampullae. Surgical strategies were developed to deal with the soft tissue obstructions. These procedures were evaluated intraoperatively with microscopic visualization, postoperatively with CT imaging. RESULTS: The three included patients suffered from bilateral vestibulopathy and hearing loss due to autosomal dominant nonsyndromic sensorineural deafness 9 (DFNA9). A soft tissue obstruction was predicted in one semicircular canal (2 patients) or two semicircular canals (1 patient), based on preoperative imaging. Intraoperatively, bluelining the semicircular canals aided in identifying these locations, by revealing a "whiteline" instead of blueline. Depending on the nature and location of the obstruction, different surgical procedures were employed to facilitate proper electrode insertion. These were as follows: a dummy electrode was used to probe the soft tissue, the obstructive tissue was removed, and/or a bypass fenestration was created. In all patients, the electrodes could be implanted in the semicircular canal ampullae. Based on these first experiences, a diagnostic and surgical guide to deal with obstructions of the semicircular canals during vestibular implantation was developed. CONCLUSIONS: Preoperative imaging can indicate locations of obstructions in the SCCs. Different surgical procedures can be applied to enable appropriate electrode positioning in the SCC ampulla. This article describes the first experiences with obstructions of the semicircular canals during intralabyrinthine vestibular implantation and presents a diagnostic and surgical guide. TRIAL REGISTRATION: ABR NL73492.068.20, METC20-087 (Maastricht University Medical Center) and NAC 11-080 (Geneva University Hospitals).

Development and assessment of a novel magnetic nanoparticle antibody-conjugate and aptamer-based assay (MNp-Ab-Ap assay) for the rapid diagnosis of pleural tuberculosis.

Background: Pleural tuberculosis (pTB) is a diagnostic challenge because of its non-specific clinical features, lack of accurate diagnostic tools and paucibacillary nature of the disease. Methods: We, here describe the development of a novel magnetic nanoparticle antibody-conjugate and aptamer-based assay (MNp-Ab-Ap assay) targeting 4 different Mycobacterium tuberculosis (M. tb.) antigens (GlcB, MPT51, MPT64 and CFP-10) for pTB diagnosis. The MNp-Ab-Ap assay was developed by conjugating polyclonal antibodies on the surface of magnetic nanoparticles (MNPs) by using EDC-NHS chemistry. These conjugated MNPs were used to capture M. tb. antigens present in the pleural fluid samples. The resulting antigen-antibody complex was detected by antigen-specific 5'-biotinylated aptamers. All assays were standardized using samples of the 'Development set' (n=17) and evaluated in the 'Validation set' (n=114) in a blinded manner. Patient categorization was done using a 'Composite Reference Standard'. Assay cut-offs were determined from the 'Development set' (n=17; 'Definite & Probable' pTB; n=9 and 'Non-TB'; n=8) by calculating mean+3SD of OD450 values of the 'Non-TB' group and applied to 'Validation set' (n=114; 'Definite' pTB; n=8, 'Probable' pTB; n=34, 'Possible' pTB; n=28 and 'Non-TB'; n=44). Results: Out of the 4 assays, MPT51-based MNp-Ab-Ap assay performed the best with 66.6% (95%CI;50.4-80.4) sensitivity and 95.4% (95%CI;85.1-99.4) specificity in the combined 'Definite and Probable' pTB group. Xpert MTB/RIF assay detected only six samples in the 'Validation set'. Binary logistic regression analysis indicated that MPT51-based MNp-Ab-Ap assay provided an incremental advantage over the existing diagnostic algorithm for pTB. Conclusions: We conclude that MPT51-based MNp-Ab-Ap assay is a novel technique that can pave the way towards rapid and accurate diagnosis of pTB.

Therapeutic potential of Astragalus-based Eefooton in patients with chronic kidney disease: from clinical to bench study.

Objective: Chronic kidney disease (CKD) is a global health concern, and recent clinical evidence suggests the potential of traditional Chinese medicine (TCM) to slow CKD progression. This offers alternative strategies for CKD patients, mitigating risks related to polypharmacy and adverse drug reactions. Our self-controlled, prospective study aims to assess the impact of Eefooton (EFT), a TCM-based regimen, on kidney health in stage 3-5 CKD patients. Additionally, we conduct a cell culture study to explore the potential mechanisms of EFT in protecting renal function. Materials and methods: Between 2021 and 2022, 75 stage 3-5 CKD patients (56% males; mean age 68.20y) at Kaohsiung Veterans General Hospital and Wu San-Chiang Medical Clinic received six months of EFT treatment alongside conventional CKD medications. The primary outcome assessed was the change in estimated glomerular filtration rate (eGFR) at 6 months, with secondary outcomes including kidney size and blood biomarker changes. Adverse events were monitored. In an in vitro study, EFT effects on HK-2 cell viability and clonogenicity, as well as analysis of apoptosis and fibrosis-related proteins through Western blot, were investigated. Results: Median eGFR significantly improved from 34.37 ± 13.58 to 42.47 ± 18.82 mL/min/1.73 m2 (p < 0.001) at month 6 post-treatment. Notably, improvements were observed across different baseline CKD stages (stage 3: p < 0.001, stage 4: p = 0.037). Ultrasonography scans indicated a slight increase in mean kidney size. In vitro, EFT enhanced HK-2 cell viability and increased clonogenicity. Indoxyl sulfate exposure raised cleaved and total PARP-1 activity. Co-treatment with EFT and IS reduced cleaved PARP-1 activity. EFT decreased IS-induced expression of fibrosis-related proteins (α-smooth muscle actin) without affecting apoptosis-related proteins (Caspase 3). Conclusions: When combined with conventional CKD medications, EFT has shown effectiveness in enhancing kidney function in individuals with stage 3-5 CKD, with no reported safety concerns. The PARP-1 inhibition and anti-fibrosis properties of EFT present potential benefits in the context of CKD.

Identification and validation of Novel Estrogen Biosynthesis Biomarkers in Sinonasal Inverted Papilloma.

Background: Sinonasal inverted papilloma (SNIP) is characterized by a high recurrence rate and potential for malignant transformation. Although metabolic reprogramming plays a role in benign neoplasms, the specific metabolic pathways and biomarkers involved in SNIP pathogenesis remain unclear. Methods: RNA sequencing on paired SNIP and normal tissues identified altered genes with enzyme annotations and metabolic pathways by intersecting our cohort data (GSE270193, N=2) with the GSE193016 (N=4) dataset using Ingenuity Pathway Analysis. Functional and interaction assessments were performed using Metascape and STRING, with further validation via tissue microarray from an independent SNIP cohort (N=30). Results: The estrogen biosynthesis pathway was significantly altered in both datasets. Five key biomarkers, AKR1B10, CYP1B1, CYP2C19, CYP3A5, and HSD17B13, were significantly altered in SNIP tissues. These markers, sharing Gene Ontology terms, showed significant correlations at both the transcript and protein levels. Functional analysis revealed enrichment in epithelial cell proliferation and regulation of EGFR signaling, suggesting a role in SNIP pathogenesis. Validation in an independent cohort confirmed elevated protein levels of these markers, all positively correlated with EGFR in SNIP tissues. Notably, AKR1B10, CYP2C19, and CYP3A5 exhibited specific expression patterns distinguishing SNIP from sinonasal squamous cell carcinoma. Conclusion: Altered estrogen biosynthesis signaling plays a role in SNIP pathogenesis, revealing distinct biomarkers that could serve as novel diagnostic markers and therapeutic targets for SNIP management.

Liver B Cells Promotes MASLD Progression via the Apelin/APLNR System.

Aims: Investigate the role of the apelin/APLNR axis in metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on the progression from metabolic dysfunction-associated simple steatotic liver (MASS) to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, with emphasis on liver B cells. Methods: Serum samples from MASLD patients and liver tissues from hepatocellular carcinoma patients were collected to measure apelin and APLNR protein expression. C57BL/6J mouse models of varying MASLD stages were developed using a high-fat diet and CCl4. RNA sequencing was used to study the apelin/APLNR axis's regulatory functions in the Raji B cell line. Results: Bioinformatic and clinical analyses show that apelin and APLNR are up-regulated in MASLD, correlating with disease severity. Animal models demonstrate that apelin and ML221 injections affect liver steatosis, inflammation, and fibrosis. Sequencing and RT-PCR in Raji cells indicate that the apelin/APLNR axis promotes the expression of inflammatory cytokines and extracellular matrix molecules. Conclusion: The apelin/APLNR axis is crucial in MASLD progression. Targeting this axis may offer therapeutic potential to modulate B cell function and mitigate MASLD advancement.

Cadherin 23 is a prognostic marker of pancreatic cancer and promotes cell viability in floating culture conditions.

Purpose: Pancreatic cancer has the worst prognosis of all common cancers worldwide. Cadherin plays important roles in cancer cell invasion and metastasis. This study investigated the role and mechanism of Cadherin 23 (CDH23) action in the viability of pancreatic cancer cells. Methods: We examined CDH23 expression in 70 surgical pancreatic cancer samples and examined relationships among the level of CDH23 expression, clinicopathological characteristics, and the prognosis of the pancreatic cancer patients. Furthermore, we silenced CDH23 expression in pancreatic cancer cell lines (Panc-1, SUIT-2, MIA PaCa-2, CFPAC-1, and Capan-2) and assessed the viability of these cells. CDH23 expression in pancreatic cancer patients and cell lines was examined using immunohistochemistry and western blotting. Results: High levels of CDH23 in pancreatic cancer patients led to shorter overall survival and correlated with local recurrence and distance metastasis. The viability of pancreatic cancer cells in floating culture conditions decreased sharply when CDH23 was silenced. The viability and migration of pancreatic cancer cells in monolayer culture conditions did not change when CDH23 was silenced. The level of phosphorylated AKT was significantly decreased in the CDH23 knockdown cells in floating culture conditions. Conclusion: High levels of CDH23 expression are correlated with a poor prognosis in pancreatic cancer and may serve as a novel prognostic marker.

HPV-Associated Gene Signatures in Bladder Cancer: A Comprehensive Prognostic Model and its Implications in Immunotherapy.

Background: Evidence increasingly indicates that HPV infection plays a pivotal role in the initiation and progression of bladder cancer (BC). Yet, determining the predictive value of HPV-associated genes in BC remains challenging. Methods: We identified differentially expressed HPV-associated genes of BC patients from the TCGA and GEO databases. We screened prognostic genes using COX and LASSO regression, subsequently establishing a risk prediction model. The model's precision and clinical relevance were gauged using Kaplan-Meier survival analyses and ROC curves. Functional enrichment, immune cell infiltration, and drug sensitivity analyses were performed across both high-risk and low-risk sets. PCR assays were utilized to measure the expression levels of genes. Results: We identified 13 HPV-associated genes for our risk model. Among these, FLRT2, HOXC5, LDLR, SCD, GRM7, DSC1, EMP1, and HMGA1 were identified as risk contributors, while LPA, SERPINA6, ZNF124, ETV7, and SCO2 were deemed protective. Cox regression analysis verified that our model provides an independent prediction of overall survival (OS) in bladder cancer (BC) patients. Gene Ontology (GO) analysis revealed predominant gene enrichment in wound healing, extracellular matrix composition, and collagen-rich extracellular matrices. KEGG pathway analysis highlighted primary enrichment areas, including focal adhesion, the PI3K-Akt signalling pathway, and ECM-receptor interaction. Risk scores were correlated with tumor microenvironment (TME) scores, immune cell infiltration, and sensitivities to both chemotherapy and immunotherapy. Conclusion: We have formulated a risk-assessment model pinpointing 13 central HPV-associated genes in BC. These genes present potential as prognostic indicators and therapeutic targets, emphasizing the intertwined relationship between HPV-induced BC progression and the immune landscape.

Investigating the Process of Autoimmune Inner Ear Disease: Unveiling the Intricacies of Pathogenesis and Therapeutic Strategies.

Autoimmune inner ear disease (AIED) is a rare condition characterized by immune-mediated damage to the inner ear, leading to progressive sensorineural hearing loss (SNHL) and vestibular symptoms such as vertigo and tinnitus. This study investigates the pathogenesis and therapeutic strategies for AIED through the analysis of three cases with different underlying autoimmune disorders: rheumatoid arthritis, relapsing polychondritis, and IgG4-related disease. The etiology of AIED involves complex immunopathological mechanisms, including molecular mimicry and the "bystander effect," with specific autoantibodies, such as those against heat shock protein 70 (HSP70), playing a potential role in cochlear damage. Diagnosis remains challenging due to nonspecific symptoms and the lack of distinct biomarkers, emphasizing the need for comprehensive clinical evaluation and exclusion of other hearing loss causes. Treatment primarily involves immunosuppressive therapies, with glucocorticoids as the first line, effective in 70% of cases. However, resistance or partial response necessitates the use of additional agents like methotrexate and biologics such as anti-TNF and IL-6 receptor antagonists. Early intervention is crucial for favorable outcomes, as demonstrated in the studied cases, where timely corticosteroid and immunosuppressive treatments led to significant hearing improvement. The study underscores the importance of personalized treatment strategies based on individual immunologic profiles and comorbidities. Our findings highlight the heterogeneity of AIED and the potential for biologic therapies in refractory cases.

CXCR4-directed endoradiotherapy with [177Lu]Pentixather added to total body irradiation for myeloablative conditioning in patients with relapsed/refractory acute myeloid leukemia.

Rationale: Despite recent advances in the targeted therapy of AML, the disease continues to have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (alloSCT) remains to be the curative therapy option for fit patients with high-risk disease. Especially patients with relapsed or refractory (r/r) AML continue to have poor outcomes. Myeloablative total body irradiation (TBI) based conditioning can be used in AML patients refractory to multiple lines of standard therapy, but the optimal conditioning regimen remains unclear for patients considered to be chemotherapy- refractory. Feasibility of C-X-C-motif chemokine receptor 4 (CXCR4)-directed endoradiotherapy (ERT) has previously been demonstrated in AML patients with CXCR4 expression on leukemic blasts. Methods: Here, we report on a small cohort of seven AML patients refractory to multiple lines (range 3-7) of therapy, who received CXCR4-directed ERT with [177Lu]Pentixather in combination with TBI and chemotherapy prior to alloSCT. We report outcomes with a focus on toxicity, engraftment, the impact on the bone marrow (BM) niche and efficacy. Results: In this intensively pre-treated group of patients, promising response (6 out of 7 patients) and engraftment (6 out of 7 patients) rates were observed. Histopathological analysis showed that niche compartments are spared and allow for engraftment to occur despite the combined ERT and TBI conditioning. Conclusion: To the best of our knowledge, we report on the first seven patients who received CXCR4-directed ERT in sequential combination with TBI and chemotherapy, providing an effective, individualized conditioning regimen for intensively pre-treated r/r AML patients.

Optical molecular imaging in oral- and oropharyngeal squamous cell carcinoma using a novel uPAR-targeting near-infrared imaging agent FG001 (ICG-Glu-Glu-AE105): An explorative phase II clinical trial.

Background: In oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC), frequent inadequate surgical margins highlight the importance of precise intraoperative identification and delineation of cancerous tissue for improving patient outcomes. Methods: A prospective, open-label, single-center, single dose, exploratory phase II clinical trial (EudraCT 2022-001361-12) to assess the efficacy of the novel uPAR-targeting near-infrared imaging agent, FG001, for intraoperative detection of OSCC and OPSCC. Macroscopic tumor detection was quantified with sensitivity and intraoperative tumor-to-background ratio (TBR). Microscopic tumor-specificity was assessed by analysis of morphological co-localization between tumor tissue, uPAR-expression, and optical signal. Blood samples were collected up to 44 hours post-injection to further characterize the pharmacokinetic profile of the agent. The trial was conducted with close safety monitoring. Results: Sixteen patients undergoing primary surgical resection were systemically administered 36 mg (n = 4), 16 mg (n = 8), or 4 mg (n = 4) of FG001 the evening prior to surgery. Intraoperatively, using a near-infrared imaging system, real-time optical imaging successfully identified all 16 tumors (sensitivity: 100%, mean TBR: 2.99 range: 2.02 - 3.95), and tumor-specificity was confirmed by histology. Clinical neck metastasis was detected with optical imaging. The maximal plasma concentrations were measured after 1 hour, and the half-life of FG001 was 12 hours. No drug-related or serious adverse events were observed. Conclusions: FG001 holds great potential for optical molecular imaging of OSCC and OPSCC. Further trials are warranted to explore FG001 for intraoperative margin delineation and as a decision-making tool.

First clinical utility of sensing Ultrasound Localization Microscopy (sULM): identifying renal pseudotumors.

Rationale: Renal pseudotumors, which mimic tumors on imaging, pose diagnostic challenges that can lead to unnecessary interventions. Sensing ultrasound localization microscopy (sULM) is an advanced imaging technique that uses ultrasound imaging and microbubbles as sensors to visualize kidney functional units. This study aims to investigate whether sULM could differentiate between renal pseudotumors and tumors based on the presence of glomeruli. Methods: Eleven patients (6 tumors, 6 pseudotumors - 1 patient with 2 pseudotumors) were included. Data on patient demographics, tumor characteristics, and sULM metrics were collected. Glomeruli were quantified and compared among tumors, pseudotumors, and renal cortex using sULM. Additional metrics, i.e., normalized speed and dispersity, were also analyzed. Results: Renal tumors exhibited fewer detected glomeruli paths (mean: 10 ± 6 /cm2 [range: 4-20]) compared to pseudotumors (26 ± 5 /cm2 [19-32], p < 0.001) and normal renal cortex (26 ± 6 /cm2 [15-35], p < 0.01). Tumors displayed lower dispersity (0.13 ± 0.06 arbitrary units [a.u.] [0.07-0.20]) than both the renal cortex (0.3 ± 0.1 a.u. [0.1-0.4], p = 0.0012) and pseudotumors (0.22 ± 0.05 a.u. [0.16-0.25], p = 0.0389), and lower normalized speeds of 0.08 ± 0.04 without units (w.u.) [range: 0.03-0.17] compared to the renal cortex (0.18 ± 0.07 w.u. [0.11-0.28], p = 0.0014) and pseudotumors (0.14 ± 0.02 w.u. [0.12-0.16], p = 0.0497). sULM could effectively differentiate renal pseudotumors from tumors based on glomerular detection and metrics estimation. Conclusion: This initial exploration into the clinical utility of sULM suggests it could provide a noninvasive tool to support patient management, particularly for individuals with contraindications to conventional imaging methods. Further studies are needed to confirm these preliminary findings.

Use of a Personalized Clinical Decision Support System for Dosing in Psychopharmacotherapy in Patients with Alcoholic Hallucinosis Based on Pharmacogenomic Markers.

Introduction: Alcoholic hallucinosis (AH) is one of the severe complications of chronic alcoholism, characterized by psychotic symptoms such as auditory hallucinations and delusions. Haloperidol is widely used to treat AH; however, its therapy is often complicated by side effects. A personalized approach using pharmacogenetic testing (particularly the CYP2D6 polymorphism) allows individualization of haloperidol dosage, improving both safety and efficacy of therapy. Materials and Methods: The study included 100 men diagnosed with "psychotic disorder induced by alcohol use." Patients were randomized into two groups: the main group (45 patients) received haloperidol based on the results of pharmacogenetic testing, while the control group (55 patients) received standard dosing. Genotyping was conducted for the CYP2D6 1846G > A polymorphism. The effectiveness was assessed using the PANSS, UKU, and SAS scales. Results: Genotyping showed an even distribution of CYP2D6 polymorphisms in both groups. The main group demonstrated a significant reduction in side effects and improvement in psychotic symptoms compared to the control group. Differences on the UKU, SAS, and PANSS scales reached statistical significance on days 3-5 of treatment. Conclusion: Using pharmacogenetic testing to adjust haloperidol dosage improves therapy tolerability and accelerates the resolution of psychotic symptoms in patients with alcoholic hallucinosis, confirming the feasibility of a personalized approach in psychopharmacotherapy.

Macrophage Migration Inhibitory Factor and Interleukin 1-ß mRNA Levels as Predictors of Antidepressant Treatment Response in Major Depression.

Background: Immunologic measures have been studied as predictors of who will respond to standard antidepressants. Two previous, small studies of pretreatment leukocyte mRNA expression levels of the cytokines macrophage migration inhibitory factor (MIF) and interleukin 1-beta (IL1-ß) identified antidepressant treatment responders. Methods: We tested these findings in 1,299 patients from the PRIME Care study, a multi-center pharmacogenetic depression treatment trial. Patients underwent 5 depression-symptom assessments over 24 weeks. mRNA was extracted from peripheral blood, purified, and assayed with TaqMan gene expression assays and a known copy number calibrator to yield relative quantification and copy numbers for each sample. In generalized estimating equations models, we regressed the repeated depression measures and a binary treatment response measure on the baseline MIF and IL-1ß measures and relevant covariates. Results: Participants' depression scores decreased monotonically during treatment, with the treatment response percentage increasing concomitantly. We found no significant associations of the cytokine concentrations with either the change in depression scores or the likelihood of a treatment response. A secondary analysis limited to a subsample of 126 participants selected to remove the potential for confounding also showed no significant associations. Limitations: Despite efforts to control for sample and assay method differences, these could have contributed to the lack of replication of prior research. Conclusions: We did not replicate prior findings that pre-treatment expression levels for two cytokines predicted antidepressant treatment response. This raises questions about the clinical utility of using these biomarkers in treating depression.

Prescribing Patterns of Gabapentinoids in Chronic Pain Management: A Single Institution Retrospective Chart Review.

Gabapentin and pregabalin are widely used in the management of neuropathic pain though their prescribing patterns, effectiveness, and safety profiles remain topics of ongoing research. This retrospective chart review analyzed the prevalence of gabapentinoid use in a chronic pain clinic over a one-year period from May 1, 2023, to April 30, 2024. The study examined patient records from four pain management physicians, focusing on those prescribed gabapentin or pregabalin. Of the 2,395 patients reviewed, 478 (19.96%) were prescribed gabapentin, while 236 (9.85%) received pregabalin. Combined, 714 patients (29.81%) were managed with either medication, highlighting the significant role gabapentinoids play in chronic pain treatment. The study found that gabapentin was prescribed more frequently than pregabalin. Although both medications are effective for neuropathic pain, their use comes with notable side effects, including dizziness, somnolence, and, in some cases, an increased risk of suicidal ideation. This review underscores the importance of careful patient monitoring and individualized treatment approaches when prescribing gabapentinoids. Future research across multiple sites and further stratification of patient demographics would enhance understanding of gabapentinoid use in clinical practice.