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Dysregulated appetite is common in autism spectrum disorder (ASD) and it includes excessive interest in tasty foods. Overconsumption of palatable fluids has been found in the valproic acid-induced ASD rat. Though ASD has a strong genetic component, the link between ASD-related genes and appetite for palatable foods remains elusive. We focused on the CNTNAP2 gene whose deletion in mice recapitulates human ASD symptoms. We investigated whether Cntnap2-/- male mice consume greater amounts of palatable 10% sucrose, 0.1% saccharin, and 4.1% intralipid solutions offered in episodic meals either in a no-choice paradigm or a two-bottle choice test. We examined how sucrose intake affects c-Fos immunoreactivity in feeding-related brain areas. Finally, we determined doses at which intraperitoneal oxytocin decreases sucrose intake in mutants. In the single-bottle tests, Cntnap2-/- mice drank more sucrose, saccharin, and intralipid compared to WTs. Given a choice between two tastants, Cntnap2-/- mice had a higher preference for sucrose than intralipid. While the standard 1â mg/kg oxytocin dose reduced sucrose intake in WTs, a low oxytocin dose (0.1â mg/kg) decreased sucrose intake in Cntnap2-/- mice. Sucrose intake induced a more robust c-Fos response in wild-type (WT) than Cntnap2-/- mice in the reward and hypothalamic sites and it increased the percentage of Fos-immunoreactivity oxytocin neurons in WTs, but not in mutants. We conclude that Cntnap2-/- mice overconsume palatable solutions, especially sucrose, beyond levels seen in WTs. This excessive consumption is associated with blunted c-Fos immunoreactivity in feeding-related brain sites, and it can be reversed by low-dose oxytocin.
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BACKGROUND: Germline genetic testing, previously restricted to familial and young-onset breast cancer, is now offered increasingly broadly to patients with 'population-type' breast cancer in mainstream oncology clinics, with wide variation in the genes included. PATIENTS AND METHODS: Weighted meta-analysis was carried out for three population-based case-control studies (BRIDGES, CARRIERS and UK Biobank) comprising in total 101 397 women with breast cancer and 312 944 women without breast cancer, to quantify 37 putative breast cancer susceptibility genes (BCSGs) for the frequency of pathogenic variants (PVs) in unselected, 'population-type' breast cancer cases and their association with breast cancer and its subtypes. RESULTS: Meta-analysed odds ratios (ORs) and frequencies of PVs in 'population-type' breast cancer cases were generated for BRCA1 (OR 8.73, 95% confidence interval (CI) 7.47-10.20; 1 in 101), BRCA2 (OR 5.68, 95% CI 5.13-6.30; 1 in 68) and PALB2 (OR 4.30, 95% CI 3.68-5.03; 1 in 187). For both CHEK2 (OR 2.40, 95% CI 2.21-2.62; 1 in 73) and ATM (OR 2.16, 95% CI 1.93-2.41; 1 in 132) subgroup analysis showed a stronger association with oestrogen receptor-positive disease. The magnitude of association and frequency of PVs were low for RAD51C (OR 1.53, 95% CI 1.29-2.04; 1 in 913), RAD51D (OR 1.76, 95% CI 1.29-2.41; 1 in 1079) and BARD1 (OR 2.34, 95% CI 1.85-2.97; 1 in 672); frequencies and associations were higher when the analysis was restricted to triple-negative breast cancers. The PV frequency in 'population-type' breast cancer cases was very low for 'syndromic' BCSGs TP53 (1 in 1844), STK11 (1 in 11 525), CDH1 (1 in 2668), PTEN (1 in 3755) and NF1 (1 in 1470), with metrics of association also modest ranging from OR 3.62 (95% CI 1.98-6.61) for TP53 down to OR 1.60 (95% CI 0.48-5.30) for STK11. CONCLUSIONS: These metrics reflecting 'population-type' breast cancer will be informative in defining the appropriate gene set as we continue to expand to germline testing to an increasingly unselected group of breast cancer cases.
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BACKGROUND: As a surrogate of malnutrition, degree of weight loss and recovery from head and neck cancer (HNC) treatment is understudied. The influence of modifiable factors that affect weight, including speech/language pathology (SLP) and nutrition counseling, is also poorly defined. We characterize weight loss trends, baseline weight recovery (BWR), and the impact of interdisciplinary care on oncologic outcomes. METHODS: Retrospective cohort study assessing 266 newly diagnosed patients with HNC who completed curative-intent radiation (definitive or adjuvant) between January 2016 to January 2022. Relevant treatment factors were analyzed using multivariable Cox regression models. RESULTS: Altogether, 266 patients completed full-course radiation therapy (RT), encompassing definitive chemoRT (53.0%), surgery with chemoRT (18.4%), surgery with RT (17.7%), and RT alone (10.9%). Patient weight reached a nadir at median 3.0 months (IQR 3.0-11.3) after radiation, with a median weight loss of 12.6% (IQR 7.9-18.7). Notably, only 47.4% exhibited BWR. For those who recovered, median time to BWR was 10.5 months (IQR 3.0-24.0). On multivariable analysis, BWR by 6 months was significantly associated with overall survival (HR 0.28 [95% CI 0.10-0.76], p = 0.013), as was SLP consultation (HR 0.40 [95% CI 0.17-0.92], p = 0.031) and nutrition consultation (HR 0.34 [95% CI 0.13-0.89], p = 0.028). CONCLUSION: A high proportion of patients with HNC fail to recover baseline weight after treatment; those that do can take longer than expected to return. Failure to recover baseline weight is associated with a notable decrease in survival. Similarly, SLP and nutrition consultation are independent, modifiable determinants correlated with outcomes, supporting the emphasis on multidisciplinary management. Measures to promote BWR may reduce mortality.
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OBJECTIVE: Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC). METHODS: Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay. RESULTS: Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety. CONCLUSION: ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines.
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ADN Tumoral Circulante , Neoplasias Orofaríngeas , Humanos , Masculino , Neoplasias Orofaríngeas/psicología , Neoplasias Orofaríngeas/virología , Femenino , Persona de Mediana Edad , Anciano , ADN Tumoral Circulante/sangre , Infecciones por Papillomavirus/psicología , Infecciones por Papillomavirus/virología , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/psicología , Carcinoma de Células Escamosas/sangreRESUMEN
Importance: Although patient-reported outcomes provide valuable insights, these subjective data may not align with objective test results. Hearing loss is a pervasive problem, such that concordance between subjective perceptions of hearing ability and objective audiogram assessments would be beneficial. Objectives: To determine (1) whether psychological status is an effect modifier of the association between subjective patient reports of hearing ability and objective audiometry results, and (2) whether any effect modification observed in standard static questionnaires would be either mitigated or exacerbated by adaptive testing based on Item Response Theory analyses. Design, Setting, and Participants: This diagnostic study at a tertiary care center and community-based practice included consecutive adults who presented with queries related to hearing loss. Participants were recruited and enrolled and data analyses occurred from 2022 to 2024. Exposures: Participants prospectively reported their hearing-specific abilities through either a standard static or adaptive version of the Inner Effectiveness of Auditory Rehabilitation (EAR) scale, alongside validated measures of their mental health and audiometry. Word recognition scores (WRS) and pure tone averages (PTA) were used to analyze audiometric testing. Main Outcomes and Measures: The association between subjective Inner EAR results and audiometry was evaluated. Stratified analyses were used to assess for effect modification by psychological status. The results of standard static and adaptive testing were compared. Results: In this study of 395 patients (mean [range] age, 55.9 [18-89] years; 210 [53.2%] female), standard static Inner EAR mean scores were appropriately higher in patients with higher (better) WRS (50.7, 95% CI, 46.4-54.9), compared with patients with lower (worse) WRS (34.7, 95% CI, 24.3-45.1). However, among patients with worse mental health, there was no association between standard static Inner EAR scores and WRS. In contrast, adaptive Inner EAR mean scores were significantly higher for those with better WRS, regardless of mental health status. Thus, effect modification was observed in standard static assessments, whereas adaptive testing remained durably associated with audiometry, regardless of mental health. Conclusions and Relevance: Psychological status was an effect modifier of the association between standard Inner EAR scale scores and audiometry, with a positive association observed only in those with better mental health. Adaptive testing scores, however, remained significantly associated with audiometry, even when mental status was worse. Adaptive testing may stabilize the association between subjective and objective hearing outcomes.
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Pérdida Auditiva , Humanos , Femenino , Masculino , Persona de Mediana Edad , Pérdida Auditiva/psicología , Anciano , Audiometría de Tonos Puros , Adulto , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Encuestas y Cuestionarios , Audiometría , Salud MentalRESUMEN
Background: Patients with isolated anterior cruciate ligament (ACL) reconstruction have demonstrated an increased risk of ACL graft failure and lower patient-reported outcome (PRO) scores when increased posterior tibial slope (PTS) is present. However, there is a paucity of literature evaluating the effect of PTS on outcomes after combined bicruciate multiligamentous knee reconstruction. Purpose: To determine whether differences exist for graft failure rates or PRO scores based on PTS after combined bicruciate multiligamentous knee reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: All patients who underwent combined ACL and posterior cruciate ligament (PCL) reconstruction between 2000 and 2020 at our institution were identified. Exclusion criteria were age <18 years, knee dislocation grade 5 injuries, concomitant osteotomy procedures, and <2 years of clinical follow-up. Demographic and outcomes data were collected from our prospectively gathered multiligamentous knee injury database. Lysholm and International Knee Documentation Committee (IKDC) scores were analyzed in relation to PTS. Outcomes were compared for patients with a PTS above and below the mean for the total cohort, PTS >12° versus <12°, positive versus negative Lachman test at follow-up, and positive versus negative posterior drawer test at follow-up. Results: A total of 98 knees in 98 patients were included in the study, with a mean clinical follow-up of 5.1 years (median, 4.6 years; range, 2-16 years). The mean PTS was 8.7° (range, 0.4°-16.9°). Linear regression analysis showed no significant correlation between PTS and IKDC or Lysholm scores. Patients with a PTS above the mean of 8.7° trended toward lower IKDC (P = .08) and Lysholm (P = .06) scores. Four patients experienced ACL graft failure and 5 patients experienced PCL graft failure. There were no differences in graft failure rates or PRO scores for patients with a PTS >12°. Patients with a positive Lachman test trended toward higher PTS (9.6° vs 8.5°, P = .15). Conclusion: In this series of bicruciate multiligamentous knee reconstructions at midterm follow-up, no differences in graft failures, complications, reoperations, revisions, or PRO scores based on PTS were identified. Patients with a positive Lachman test were found to have a slightly higher PTS, although this did not reach statistical significance.
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Anterior cruciate ligament (ACL) reconstruction using the quadriceps tendon (QT) autograft is an increasingly utilized technique that confers less donor site morbidity and comparable outcomes to other historically used graft options. The graft harvest and implantation process present vast variability-particularly regarding the achievement of adequate graft site visualization, consistently attaining a uniform and appropriately sized graft, and subsequent reconstruction of the ACL with the all-soft tissue graft. The purpose of this Technical Note and video is to describe and demonstrate minimally invasive quadriceps tendon autograft harvesting using the Quadriceps Tendon Harvest Guide System (QUADTRAC), and its subsequent implantation within a single-bundle ACL reconstruction with suspensory fixation.
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BACKGROUND: Anatomic landmarks such as the tympanomastoid suture line, posterior belly of the digastric muscle, tragal pointer, and styloid process can assist the parotid surgeon in identifying and preserving the facial nerve. Vascular structures such as the posterior auricular artery and its branch, the stylomastoid artery, lay in close proximity to the facial nerve and have been proposed as landmarks for the identification of the facial nerve. In this case report, we describe an anatomic variation in which the stylomastoid artery has fenestrated the main trunk of the facial nerve, dividing it in two. METHODS: Two patients underwent parotidectomy (one for a pleomorphic adenoma, the second for a parotid cyst) through a standard anterograde approach with identification of the usual facial nerve landmarks. RESULTS: The appearance of the main trunk of the facial nerve was unusual in both patients due to its being fenestrated by the stylomastoid artery. The stylomastoid artery was divided, and the remainder of the facial nerve dissection was performed uneventfully with subsequent resection of the parotid mass in both patients. CONCLUSIONS: In rare instances, the stylomastoid artery can penetrate through the common trunk of the facial nerve. This is an important anatomic variant for the parotid surgeon to be aware of, as it can increase the difficulty of facial nerve dissection.
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Nervio Facial , Glándula Parótida , Neoplasias de la Parótida , Humanos , Nervio Facial/cirugía , Nervio Facial/anatomía & histología , Glándula Parótida/cirugía , Neoplasias de la Parótida/cirugía , Neoplasias de la Parótida/patología , Masculino , Femenino , Adenoma Pleomórfico/cirugía , Adenoma Pleomórfico/patología , Persona de Mediana Edad , Variación Anatómica , Disección , Puntos Anatómicos de Referencia , Adulto , Hueso Temporal/cirugía , Hueso Temporal/anomalíasRESUMEN
Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.
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Carcinoma de Células Escamosas , Interferón gamma , Animales , Humanos , Ratones , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Linfocitos T CD8-positivos , Línea Celular Tumoral , Inmunidad , Interferón gamma/metabolismo , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Factores de Transcripción/metabolismo , Microambiente Tumoral , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
BACKGROUND: Hip arthroscopy is rapidly advancing, with positive published outcomes at short- and midterm follow-up; however, available long-term data remain limited. PURPOSE: To evaluate outcomes of primary hip arthroscopy at a minimum 10-year follow-up at 2 academic centers by describing patient-reported outcomes and determining reoperation and total hip arthroplasty (THA) rates. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with primary hip arthroscopy performed between January 1988 and April 2013 at 2 academic centers were evaluated for postoperative patient-reported outcomes-including the visual analog scale, Tegner Activity Scale score, Hip Outcome Score Activities of Daily Living and Sport Specific subscales, modified Harris Hip Score, Nonarthritic Hip Score, 12-item International Hip Outcome Tool, surgery satisfaction, and reoperations. RESULTS: A total of 294 patients undergoing primary hip arthroscopy (age, 40 ± 14 years; 66% women; body mass index, 27 ± 6) were followed for 12 ± 3 years (range, 10-24 years) postoperatively. Labral debridement and repair were performed in 41% and 59% of patients, respectively. Of all patients who underwent interportal capsulotomy, 2% were extended to a T-capsulotomy, and 11% underwent capsular repair. At final follow-up, patients reported a mean visual analog scale at rest of 2 ± 2 and with use of 3 ± 3, a 12-item International Hip Outcome Tool of 68 ± 27, a Nonarthritic Hip Score of 81 ± 18, a modified Harris Hip Score of 79 ± 17, and a Hip Outcome Score Activities of Daily Living of 82 ± 19 and Sport Specific subscale of 74 ± 25. The mean surgical satisfaction was 8.4 ± 2.4 on a 10-point scale, with 10 representing the highest level of satisfaction. In total, 96 hips (33%) underwent reoperation-including 65 hips (22%) converting to THA. THA risk factors included older age, higher body mass index, lower lateral center-edge angle, larger alpha angle, higher preoperative Tönnis grade, as well as labral debridement and capsular nonrepair (P≤ .039). Patients undergoing combined labral and capsular repair demonstrated a THA conversion rate of 3% compared with 31% for patients undergoing combined labral debridement and capsular nonrepair (P = .006). Labral repair trended toward increased 10-year THA-free survival (84% vs 77%; P = .085), while capsular repair demonstrated significantly increased 10-year THA-free survival (97% vs 79%; P = .033). CONCLUSION: At a minimum 10-year follow-up, patients undergoing primary hip arthroscopy demonstrated high satisfaction and acceptable outcome scores. In total, 33% of patients underwent reoperation-including 22% who underwent THA. Conversion to THA was associated with patient factors including older age, higher Tönnis grade, and potentially modifiable surgical factors such as labral debridement and capsular nonrepair.
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Pinzamiento Femoroacetabular , Satisfacción del Paciente , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Resultado del Tratamiento , Estudios de Seguimiento , Artroscopía/efectos adversos , Actividades Cotidianas , Articulación de la Cadera/cirugía , Medición de Resultados Informados por el Paciente , Pinzamiento Femoroacetabular/cirugía , Pinzamiento Femoroacetabular/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Osteochondral allograft transplantation (OCAT) is an accepted knee joint-preserving treatment strategy for focal osteochondral lesions that is often conducted in combination with meniscal allograft transplantation (MAT). Despite its frequent and simultaneous utilization, there remains a lack in the literature reporting on outcomes and failure rates after concomitant procedures. PURPOSE: To determine (1) the midterm clinical success rate after OCAT+MAT in comparison with a matched-pair cohort undergoing isolated OCAT, (2) whether patient-specific and procedural variables influence the risk of failure, and (3) patient-reported outcome measures over time. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A single-center matched-pair cohort study was conducted investigating outcomes in patients who underwent OCAT of the medial or lateral femoral condyle with and without MAT between 2004 and 2020. Patients were matched 1:1 by age (±5 years), sex (male or female), body mass index (±5), and grouped Kellgren and Lawrence grade (grades 0-1 or 2-4). The minimum follow-up time was 2 years. Radiographic variables (International Cartilage Regeneration & Joint Preservation Society [ICRS] grade and Kellgren and Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery for graft failure or conversion to total knee arthroplasty. Patient-reported, clinical, and radiographic outcomes were compared between groups. RESULTS: In total, 66 patients (33 treated with isolated OCAT, 33 treated with OCAT+MAT; 57.6% male) with a mean age of 26.3 years (range, 18-62 years) were followed for a mean of 5.6 years (minimum, 2 years; range, 24-218 months). The 2 cohorts showed no difference in Kellgren and Lawrence grade postoperatively (P = .59). There was a significantly higher ICRS grade detected at follow-up in the OCAT+MAT group (2.81 ± 1.10) compared with the OCAT group (2.04 ± 0.96) (P < .05). There were no statistically significant differences between the groups regarding reoperation rate (OCAT: n = 6; OCAT+MAT: n = 13; P = .116), time to reoperation (OCAT: 46.67 ± 47.27 months vs OCAT+MAT: 28.08 ± 30.16 months; P = .061), and failure rate (OCAT: n = 4 [12.1%] vs OCAT+MAT: n = 5 [15.2%]; P = .66). In the OCAT+MAT group, an increase of tibial slope by 1° conferred a 1.65-fold increase in the hazard for failure over decreased slope (hazard ratio, 1.65; 95% CI, 1.10-2.50; P < .05). The overall survival rate was 86% at a mean follow-up of 5.6 years. Patient-reported outcome scores were significantly improved at the final follow-up compared with preoperative status. No significant differences were seen between groups with respect to subjective IKDC, Lysholm, Tegner, and KOOS results, except for the KOOS Symptoms subscale score, which was significantly higher in the OCAT+MAT group than in the OCAT group (mean difference, 14.6; P < .05) and did exceed the minimal clinically important difference threshold of 10.7. CONCLUSION: Midterm results after isolated OCAT and OCAT+MAT show high rates of healing and sustainable subjective improvement of knee function and quality of life. However, it should be noted that the difference in reoperation rate and time to reoperation between the groups is arguably clinically important and that lack of statistical significance may be because of low power. These results imply that isolated OCAT is an efficient joint-preserving treatment that can be combined with MAT in well-selected patients with meniscal insufficiency without negative influence on global clinical outcomes.
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Meniscos Tibiales , Calidad de Vida , Humanos , Masculino , Femenino , Adulto , Estudios de Cohortes , Estudios de Seguimiento , Meniscos Tibiales/trasplante , Análisis por Apareamiento , Articulación de la Rodilla/cirugía , Reoperación , AloinjertosRESUMEN
OBJECTIVE: In the West Midlands regional genetics service, cases of perinatal death with a possible genetic diagnosis are evaluated by the perinatal pathology genetic multidisciplinary team (MDT). The MDT assesses autopsy findings and suggests appropriate genomic assessment. The objective of this retrospective service evaluation was to determine the clinical utility of the MDT in assessing perinatal deaths associated with structural anomaly. This is the first evaluation since the introduction of whole-genome and whole-exome sequencing in routine clinical care. METHODS: This was a retrospective service evaluation including all cases of perinatal death with an associated structural anomaly and suspected genetic etiology that underwent perinatal MDT assessment between January and December 2021. All cases received a full or partial postmortem examination and at least a chromosomal microarray analysis. Demographic characteristics, phenotype, genotype, MDT recommendations, diagnoses, outcomes and impact of postmortem analysis and genetic testing data were collected from patient case notes. RESULTS: Overall, 123 cases were discussed at the MDT meetings in 2021. Genetic evaluation was recommended in 84 cases and accepted in 64 cases. A range of genetic tests were requested according to indication and availability. Thirty diagnoses were made in 29 cases from 26 unrelated families. The diagnostic yield was 24% (29/123) in all cases or 45% (29/64) in cases with a suspected genetic diagnosis who underwent genetic testing. Postmortem examination provided clinically actionable phenotypic data in 79% of cases. A genetic diagnosis enabled accurate recurrence risk counseling and provision of appropriate follow-up, including prenatal testing and preimplantation diagnosis for patients with inherited conditions. CONCLUSIONS: Genomic testing was a clinically useful addition to (but not a substitute for) postmortem examination in cases of perinatal death associated with structural anomaly. The MDT approach helped assess cases and plan appropriate follow-up. Expedited whole-genome sequencing or panel-agnostic analysis were most appropriate for heterogeneous presentations. This broad approach can also expand knowledge of prenatal phenotypes and detect novel disease genes, and should be a priority in future research. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
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BACKGROUND: H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma. METHODS: ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on 2 consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology high-grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.
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Neoplasias Encefálicas , Glioma , Mutación , Humanos , Glioma/genética , Glioma/tratamiento farmacológico , Glioma/patología , Método Doble Ciego , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Adulto , Masculino , Femenino , Histonas/genética , Adolescente , Niño , Adulto Joven , Pronóstico , Tasa de Supervivencia , Calidad de Vida , Persona de Mediana Edad , Estudios de Seguimiento , AncianoRESUMEN
The medial collateral ligament serves as the primary stabilizer to valgus stress on the medial side of the knee and is the most commonly injured ligament in the knee. Medial collateral ligament reconstruction can provide improved stability and clinical outcomes for patients. Advancements in techniques, including the use of an adjustable-length-loop suspensory fixation device through a longitudinal incision, have been introduced in recent years. The purpose of this Technical Note and video is to provide a minimally invasive method for medial collateral ligament reconstruction with adjustable-loop femoral fixation and posteromedial corner plication.
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Quadriceps tendon autografts are an increasingly popular choice for anterior cruciate ligament (ACL) reconstruction, with decreased donor-site morbidity alongside good patient outcomes. Although harvesting of the tendon can be done in a minimally invasive fashion, this introduces some difficulty with visualization and consistency of graft sizing. The purpose of this Technical Note and video is to provide a method of quadriceps tendon autograft harvesting using the Quadriceps Tendon Harvest Guide System (QUADTRAC) in a single-bundle ACL reconstruction.