Diagnostic and Prognostic Performance of Metabolic Signatures in Pancreatic Ductal Adenocarcinoma: The Clinical Application of Quantitative NextGen Mass Spectrometry.

With 64,050 new diagnoses and 50,550 deaths in the US in 2023, pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all human malignancies. Early detection and improved prognostication remain critical unmet needs. We applied next-generation metabolomics, using quantitative tandem mass spectrometry on plasma, to develop biochemical signatures that identify PDAC. We first compared plasma from 10 PDAC patients to 169 samples from healthy controls. Using metabolomic algorithms and machine learning, we identified ratios that incorporate amino acids, biogenic amines, lysophosphatidylcholines, phosphatidylcholines and acylcarnitines that distinguished PDAC from normal controls. A confirmatory analysis then applied the algorithms to 30 PDACs compared with 60 age- and sex-matched controls. Metabolic signatures were then analyzed to compare survival, measured in months, from date of diagnosis to date of death that identified metabolite ratios that stratified PDACs into distinct survival groups. The results suggest that metabolic signatures could provide PDAC diagnoses earlier than tumor markers or radiographic measures and offer insights into disease severity that could allow more judicious use of therapy by stratifying patients into metabolic-risk subgroups.

Unicortical versus bicortical plate fixation for midshaft clavicular fractures.

BACKGROUND: The aim of this study was to compare the functional and radiological outcomes of unicortical vs bicortical fixation in patients with midshaft clavicular fractures who were treated using pre-contoured locking plates. METHODS: We performed a prospective multicenter study of 45 individuals who underwent open reduction and internal fixation of midshaft clavicular fractures with precontoured locking plates between March 2017 and December 2019. Twenty-five patients were treated with bicortical screws and 20 patients with unicortical screws. Functional outcomes were assessed at 6 months and 12 months after surgery using the Constant score, the 11-item version of the Disabilities of Arm, Shoulder and Hand (Quick- DASH) score and the Single Assessment Numeric Evaluation (SANE) score. Pain was evaluated using a visual analog scale (VAS). The rate of return to work and sports was also recorded. Radiologic evaluation was obtained in the immediate postoperative day, monthly until fracture consolidation, at 6 months and 12 months. All intraoperative and postoperative complications were documented. RESULTS: At both 6 and 12 months, the follow-up rates were 100%, and the mean age was 28.5 years (range, 20 to 45 years). The mean postoperative Constant score, Quick DASH, and SANE score at 12 months were 93.5 (±6), 2.3 (±3), and 92% (±7), respectively. There were no significant differences in the functional scores between the groups neither at 6 months nor at 12 months. Of the 30 active workers, 97% were able to return to their previous working routine and from the 25 patients who practiced sports before the injury,92% returned to sports all at the same level. All the fractures healed in both groups. There were 6 complications (13%). CONCLUSION: In young, active patients with displaced midshaft clavicular fractures, both unicortical and bicortical locked plates achieved 100% bone consolidation, with excellent functional outcomes and a low rate of complications without significant differences between the groups. Therefore, locked plates with unicortical fixation could be a very good alternative for the management of young patients with midshaft clavicular fractures, potentially avoiding severe neurovascular complications. LEVEL OF EVIDENCE: Prospective comparative (Level II).

Therapeutic Targeting of P53: A Comparative Analysis of APR-246 and COTI-2 in Human Tumor Primary Culture 3-D Explants.

Background:TP53 is the most commonly mutated gene in human cancer with loss of function mutations largely concentrated in "hotspots" affecting DNA binding. APR-246 and COTI-2 are small molecules under investigation in P53 mutated cancers. APR binds to P53 cysteine residues, altering conformation, while COTI-2 showed activity in P53 mutant tumors by a computational platform. We compared APR-246 and COTI-2 activity in human tumor explants from 247 surgical specimens. Methods: Ex vivo analyses of programmed cell death measured drug-induced cell death by delayed-loss-of-membrane integrity and ATP content. The LC50s were compared by Z-Score. Synergy was conducted by the method of Chou and Talalay, and correlations were performed by Pearson moment. Results: APR-246 and COTI-2 activity favored hematologic neoplasms, but solid tumor activity varied by diagnosis. COTI-2 and APR-246 activity did not correlate (R = 0.1028) (NS). COTI-2 activity correlated with nitrogen mustard, cisplatin and gemcitabine, doxorubicin and selumetinib, with a trend for APR-246 with doxorubicin. For ovarian cancer, COTI-2 showed synergy with cisplatin at 25%. Conclusions: COTI-2 and APR-246 activity differ by diagnosis. A lack of correlation supports distinct modes of action. Cisplatin synergy is consistent with P53's role in DNA damage. Different mechanisms of action may underlie disease specificity and offer better disease targeting.

Tratamiento quirúrgico de las fracturas mediodiafisarias desplazadas de clavícula mediante placas precontorneadas con técnica mininvasiva / Surgical treatment of clavicle displaced midshaft fractures with pre-contoured plates using mini invasive technique (MIPO)

Introducción: Las fracturas mediodiafisarias de clavícula representan hasta el 10% de las fracturas del esqueleto. El tratamiento conservador brinda buenos resultados con baja incidencia de complicaciones. Sin embargo, en trazos desplazados, multifragmentarios o con deformidad significativa, se debe considerar la cirugía. El propósito de esta serie retrospectiva es exponer nuestra experiencia en el tratamiento de fracturas cerradas, desplazadas y mediodiafisarias de clavícula con placas precontorneadas mediante la técnica MIPO, describir la técnica y los resultados funcionales preliminares. Materiales y Métodos: Serie retrospectiva de 13 pacientes (11 varones [84,6%] y 2 mujeres [15,4%]), media de la edad: 31 años, con fracturas diafisarias cerradas desplazadas de clavícula de tipo 2B de Robinson (Edimburgo), tratadas mediante reducción y osteosíntesis con placas precontorneadas con MIPO, entre abril de 2010 y noviembre de 2013. Seguimiento promedio: 13 meses (rango 11-25). Se realizaron controles radiográficos y tomografías computarizadas, valorando la funcionalidad mediante las escalas de Constant-Murley modificada, QuickDASH y el dolor con la escala analógica visual. Resultados: El tiempo promedio hasta la cirugía fue de 8 días; la cirugía duró 35 minutos y el tiempo de internación posoperatoria fue de 1.28 días. La consolidación clínico-radiológica se registró en una media de 15.2 semanas. El puntaje promedio de Constant-Murley modificado fue 88; el de QuickDASH, 26,9 y la escala analógica visual arrojó un valor de 0,3. No hubo complicaciones sistémicas ni cosméticas. Conclusión: La osteosíntesis mínimamente invasiva en fracturas cerradas mediodiafisarias desplazadas de clavícula representó una técnica reproducible con un tiempo quirúrgico reducido y puntajes funcionales aceptables, sin complicaciones de relevancia. Nivel de Evidencia: IV

Introduction: Midshaft clavicular fractures represent up to 10% of skeleton fractures. Conservative treatment usually provides good results with low incidence of complications. However, surgical treatment should be considered in displaced, multifragmentary fractures or cases with significant deformity. The purpose of this retrospective case series is to report our experience in the treatment of closed and displaced midshaft clavicular fractures with pre-contoured plates using MIPO technique, to describe the technique and report preliminary functional results. Methods: Retrospective series of 13 patients (11 males [84.6%] and 2 females [15.4%], mean age: 31 years), with closed and displaced midshaft clavicle fractures classified as type 2B according to Robinson (Edinburgh) treated by reduction and internal fixation with pre-contoured plates osteosynthesis using minimally invasive technique (MIPO) between April 2010 and November 2013. Mean follow-up: 13 months (range 11-25). Radiographic and tomographic controls were carried out to assess function using modified Constant-Murley scale, QuickDASH Questionnaire and the visual analogue scale to evaluate pain. Results: Average time to surgery was 8 days, surgical time: 35 minutes, days in hospital after surgery: 1.28. Clinical and radiological consolidation was recorded at 15.2 weeks on average. The average modified Constant-Murley score was 88, QuickDASH 26.9 and visual analogue scale 0.3. No systemic or cosmetic complications were recorded. Conclusion: Minimally invasive plate osteosynthesis (MIPO) in displaced and closed midshaft clavicle fractures represented a reproducible technique with reduced surgical time and acceptable functional scores. Level of Evidence: IV

Transferencia de dorsal ancho para el tratamiento de las lesiones masivas e irreparables del manguito rotador / Latissimus dorsi transfer for treatment of massive and irreparable rotator cuff injuries

Introducción: el objetivo del trabajo fue realizar una valoración clínico-radiológica de pacientes con rupturas masivas e irreparables posterosuperiores del manguito rotador tratadas con transferencia del dorsal ancho. Materiales y Métodos: Estudio retrospectivo, descriptivo, de observación. Se incluyeron pacientes <70 años con lesión masiva e irreparable posterosuperior del manguito rotador tratados con transferencia del dorsal ancho y un seguimiento mínimo de 2 años. Se valoró la movilidad y la fuerza en abducción. Se emplearon la escala analógica visual y la de Constant-Murley modificada. En las radiografías, se analizaron la distancia acromiohumeral y el grado de artropatía. Resultados: Se incluyeron 17 pacientes (12 hombres, 5 mujeres; edad promedio: 54 años [rango 34-65]). El seguimiento promedio fue 46 meses (rango 24-71). En el grupo de cirugía primaria, la ganancia de movilidad promedio en flexión anterior fue de 53º, en abducción de 50º y en rotación externa de 19º. La fuerza en abducción registró una ganancia promedio de 1,4 kg. La escala de Constant-Murley modificada fue de 75,6 (rango 63-80) al final del seguimiento. En las cirugías de revisión, la ganancia de movilidad activa en flexión anterior fue de 48º, en abducción de 30º y en rotación externa de 10º. La fuerza en abducción tuvo una ganancia promedio de 1,1 kg. La escala analógica visual posoperatoria mejoró 5,1 puntos en el grupo con cirugía primaria y 3,4 en el otro grupo. Conclusión: La transferencia del dorsal ancho para lesiones posterosuperiores del manguito rotador mejoró el rango de movilidad, la fuerza, la función del hombro y alivió el dolor.

Introduction: the aim of the study was to analyze the clinical and radiological outcomes of a series of patients with massive ruptures of the rotator cuff treated with latissimus dorsi tendon transfer. Methods: A retrospective, descriptive and observational study was performed. Patients <70 years with massive and irreparable posterosuperior lesions of the rotator cuff were treated with latissimus dorsi transfer and with a minimum follow-up of 2 years. Range of motion and strength in abduction were assessed. In addition, the visual analogue scale and modified Constant-Murley scale were recorded. Acromio-humeral distance and arthropathy stage were radiographically analyzed. Results: Seventeen patients were included (12 males, 5 females), mean age 54 years (range 34-65), with a mean followup of 46 months (range 24-71). In the primary surgery group, the average motion gain was 53º in anterior flexion, 50º in abduction and 19º in external rotation. The abduction strength recorded an average gain of 1.4 kg. Modified Constant-Murley scale of 75.6 (range 63-80) at the end of follow-up. In the revision surgery group, the gain of active motion was 48º in anterior flexion, 30º in abduction and 10º in external rotation. Abduction strength had an average gain of 1.1 kg. Postoperative visual analogue scale improved 5.1 points in the primary surgery group and 3.4 in the other group. Conclusion: Latissimus dorsi tendon transfer for the treatment of massive posterosuperior rupture of the rotator cuff showed improvements in range of motion, strength, pain relief and shoulder function.