Feasibility and Safety of Intrathoracic Biopsy and Repeat Biopsy for Evaluation of Programmed Cell Death Ligand-1 Expression for Immunotherapy in Non-Small Cell Lung Cancer.

Purpose To determine feasibility and safety of biopsy and repeat biopsy for assessment of programmed cell death ligand-1 (PD-L1) status. Materials and Methods This retrospective analysis reviewed 101 patients who underwent transthoracic core needle biopsy for the KEYNOTE-001 (MK-3475) clinical trial of pembrolizumab, an antiprogrammed cell death-1 therapy for non-small cell lung cancer, from May 2012 to September 2014. Sixty-one male patients (mean age, 66.1 years; range 36-83 years) and 40 female patients (mean age, 66.8 years; age range, 36-90 years) were included. Data collected included population characteristics, treatment history, target location, size, and depth from pleura. Adequacy of the tissue sample for diagnostic testing and rates of biopsy-related complications were assessed. Statistical analysis was performed by using univariate and multivariate generalized linear models to determine significant risk factors for biopsy complications. Results A total of 110 intrathoracic biopsies were performed, and 101 (91.8%) were performed as repeat biopsies subsequent to a previous percutaneous or bronchoscopic biopsy or previous surgical biopsy or resection. More than 84.5% (93 of 110) of biopsies were performed in patients who had undergone previous local or systemic therapy. Specimens were adequate for evaluation of PD-L1 expression in 96.4% of biopsies. Procedure-related complications occurred in 28 biopsies (25.4%); pneumothorax was most common (22.7%). Overall mean number of core needle biopsy samples obtained was 7.9 samples. Conclusion Image-guided transthoracic core needle biopsy is an effective method for obtaining tissue for PD-L1 expression analysis. © RSNA, 2017.

Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges.

BACKGROUND: Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated. METHODS: The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. RESULTS: In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. CONCLUSIONS: Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800-7. © 2017 American Cancer Society.

Evaluating Casama: Contextualized semantic maps for summarization of lung cancer studies.

OBJECTIVE: It is crucial for clinicians to stay up to date on current literature in order to apply recent evidence to clinical decision making. Automatic summarization systems can help clinicians quickly view an aggregated summary of literature on a topic. Casama, a representation and summarization system based on "contextualized semantic maps," captures the findings of biomedical studies as well as the contexts associated with patient population and study design. This paper presents a user-oriented evaluation of Casama in comparison to a context-free representation, SemRep. MATERIALS AND METHODS: The effectiveness of the representation was evaluated by presenting users with manually annotated Casama and SemRep summaries of ten articles on driver mutations in cancer. Automatic annotations were evaluated on a collection of articles on EGFR mutation in lung cancer. Seven users completed a questionnaire rating the summarization quality for various topics and applications. RESULTS: Casama had higher median scores than SemRep for the majority of the topics (p≤ 0.00032), all of the applications (p≤ 0.00089), and in overall summarization quality (p≤ 1.5e-05). Casama's manual annotations outperformed Casama's automatic annotations (p = 0.00061). DISCUSSION: Casama performed particularly well in the representation of strength of evidence, which was highly rated both quantitatively and qualitatively. Users noted that Casama's less granular, more targeted representation improved usability compared to SemRep. CONCLUSION: This evaluation demonstrated the benefits of a contextualized representation for summarizing biomedical literature on cancer. Iteration on specific areas of Casama's representation, further development of its algorithms, and a clinically-oriented evaluation are warranted.

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center.

We retrospectively analyzed non-small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related. AEs labeled as possibly/probably related were considered trAEs for this analysis. The relationship between the incidence of a trAE and clinical outcomes was evaluated. Ninety-seven NSCLC patients treated on KEYNOTE-001 at the University of California, Los Angeles were evaluated. Ten percent (85/826) of AEs were trAEs, occurring in 40% (39/97) of patients. The most frequent trAEs were rash (21% patients), fatigue (6% patients), and hypothyroidism (6% patients). The 39 patients that experienced a trAE had increased objective response rate (ORR, 38.5%), progression-free survival (PFS: median, 248 days), and overall survival (OS: median, 493 days), compared with the 58 patients that did not (ORR: 8.9%, PFS: median 60 days, OS: median 144.5 days). The observed association between trAEs and improved clinical outcome persisted when using Cox proportional hazards regression models to assess the confounding effect of covariates and mitigate guarantee-time bias. The association also remained when data were substratified by grade, degree of association, and treatment-related select AE designation. This single-center analysis revealed that trAEs predicted for improved clinical outcome with pembrolizumab, and when controlling for guarantee-time bias and plausible confounders, this association remained. This observed relationship adds to our understanding of anti-PD-1 therapy and could aid clinicians in identifying patients most likely to benefit from therapy. Cancer Immunol Res; 6(3); 288-94. ©2018 AACR.

Arthroscopic disc fixation to the condylar head. Use of resorbable pins for internal derangement of the temporomandibular joint (stage II-IV). Preliminary report of 34 joints.

AIM: The study describes the arthoscopic use of resorbable pins for the internal derangement of the temporomandibular joint with McCain's technique. Clinical and image features are reported retrospectively. METHODS: Twenty-seven consecutive patients (34 joints) were included. Symptomatic internal derangement and anterior-medial disc displacement with or without reduction in magnetic resonance images (MRI) were diagnosed in all cases. Two resorbable pins (SmartNail) were placed in each joint employing arthroscopic surgery with a third portal for disc recapture and fixation to condylar head. Clinical data 24 months after surgery are reported (movements, pain score, clicking, laterodeviation, occlusal changes). In eight joints a MRI control was required between 1 and 2 years after surgery. RESULTS: Visual analogue scale values (0-100) decreased from 70.8 to 11.9 (p < 0.001) in the first control (week) and kept down after 24 months of follow-up (VAS: 4.8). Movements began to recover in 3 months and mouth opening increased from 34 mm to 43.2 mm 1 year after surgery (p < 0.001). Clicking, laterodeviation and contralateral excursions improvement were statistically significant (p < 0.001). MRI showed disc fixation to condyle head in closed and opened mouth. CONCLUSION: Disc fixation to condylar head with resorbable pins is a safe and satisfactory procedure. Pain becomes drastically reduced and mandibular function recovers normal parameters in patients with internal derangement.

The posterior double pass suture in repositioning of the temporomandibular disc during arthroscopic surgery: a report of 16 cases.

AIM: Several procedures have been described to reposition and secure the disc during arthroscopic surgery of the temporomandibular joint. The usefulness of these procedures remains controversial since simple lysis and lavage shows a high percentage of clinical success and it is difficult to obtain radiological imaging of the surgically acquired new disc position. This report describes a new arthroscopic discopexy method, and the clinical as well as radiological results obtained with this new technique. METHODS: Sixteen patients with a clinical and radiological diagnosis of Temporomandibular Joint (TMJ) dysfunction (TMD) were treated using our discopexy method. Each patient was evaluated with a visual analogue scale (VAS) for pain, radiological and functional parameters. The evaluation also included a clinical examination. Each patient was recorded at baseline before surgery and at a one-year follow-up. Statistical analysis was performed to evaluate the differences in VAS, maximum opening and lateral movements before and after treatment and were considered statistically significant when p < 0.05. RESULTS: Patient evaluation showed an improvement in the clinical parameters. There were statistically significant reductions in the amount of pain according to the VAS (p < 0.01). Maximal interincisal opening (MIO) and contralateral translation movement (CTM) (p < 0.05) were substantially improved one-year after operation. In the post-surgical MRI study at the one-year follow-up, a significant improvement in the disc position was observed in 13 out of the 16 joints operated on. CONCLUSION: This method of arthroscopic disc repositioning is an effective surgical method for treating symptomatic patients with a diagnosis of TMJ disc displacement. Because of the minimally invasive character of the procedure, it should be considered in the surgical treatment of TMJ dysfunction.

Synovial chondromatosis of the temporomandibular joint: report of 2 patients whose joints were reconstructed with costochondral graft and alloplastic prosthesis.

Synovial chondromatosis of the temporomandibular joint (TMJ) is rare, and only about 100 cases have been reported. Among these, intracranial extension was reported in only 9. Although some patterns of clinical presentation and evolution, synovial histological changes, and diagnosis by computed tomography and magnetic resonance imaging have been described, there is little information about surgical treatment. We report two new cases that focus particularly on reconstruction with costochondral graft and alloplastic TMJ prosthesis. We report what is to our knowledge the youngest reported case of synovial chondromatosis of the TMJ, which is also the tenth reported case with extension into the middle cranial fossa.

Oxitocina: fundamentos teóricos e implicaciones / Oxytocin: theoretical basis and implications

Se revisan en este trabajo los aspectos más sobresalientes de la oxitocina, que son: historia, farmacocinética, concentraciones tisulares y séricas, mecanismo de acción, interacción con otras hormonas, indicaciones y uso clínico, contraindicaciones y complicaciones; cuando este medicamente se usa inadecuadamente puede generar graves complicaciones materno-fetales

Trauma obstétrico del neonato en el Hospital Civil de Guadalajara / Obstetrical trauma of the newborn infant at the Hospital Civil de Guadalajara

En el hospital Civil de Guadalajara en 1985 se analizaron 1,000 recién nacidos vivos de 32 semanas o más de gestación en los cuales se investigó trauma obstétrico (T.O.) 37.4% presentó un solo T. O., 2.8% presentó dos tipos de T.O. Los tipos de T.O. fueron: caput 307, hipoxia 55, huella de forceps 47, cefalohematoma 9, luxación de cadera 6, fractura de clavícula, parálisis braquial 1, parálisis facial 1 y fractura de cráneo 1. Las variables de mayor significancia estadística en su relación con el T. O. fueron: edad materna, paridad, apgar a los 5 minutos, uso de fórceps y líquido amniótico mecolos 5 minutos, uso de fórceps y líquido amniótico meconial (AL)

Síndrome premenstrual y piridoxina: ¿alternativa terapéutica? / Pre-menstrual syndrome and pyridoxine: A therapeutic alternative?

En 1987, 38 pacientes con síndrome premenstrual fueron estudiadas en dos grupos de 19 pacientes cada uno. Uno de los grupos ingirió piridoxina a las dosis de 100 mg diarios durante dos ciclos menstruales consecutivos mientras el otro grupo ingirió placebo a la misma dosis con cápsulas macroscópicamente iguales haciéndose un estudio prospectivo doblemente ciego. La mejoría de los síntomas (mastodinia, cefalea, tensión emocional, distensión abdominal y edema) varió de 33.3 a 71.4% con piridoxina y de 33.3 a 66.6% con el placebo, reflejando una Chi2 de 0.48 con una p<0.5, lo cual no tiene diferencia significativa.