Radiation with platinum-based chemotherapy is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall ...survival remain poor. It is unclear whether any tumor genetic mutations are associated with response to chemoradiation therapy.
We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation who had undergone tumor molecular profiling through a next-generation DNA sequencing platform. Cox proportional hazards model was used to investigate associations between clinical outcomes and genetic mutations detected by next-generation sequencing.
110 patients were identified with stage III NSCLC and underwent definitive radiation between 2013 and 2017 and tumor molecular profiling. Concurrent or sequential chemotherapy was given in 104 patients (95%). Unbiased genomic analyses revealed a significant association between AKT2 mutations and decreased local-regional tumor control and overall survival (hazard ratios HR 12.5 and 13.7, P = .003 and P = .003, respectively). Analyses restricted to loss-of-function mutations identified KMT2C and KMT2D deleterious mutations as negative prognostic factors for overall survival (HR 13.4 and 7.0, P < .001 and P < .001, respectively). Deleterious mutations in a panel of 38 DNA damage response and repair pathway genes were associated with improved local-regional control (HR 0.32, P = .049).
This study coupled multiplexed targeted sequencing with clinical outcome and identified mutations in AKT2, KMT2C, and KMT2D as negative predictors of local-regional control and survival, and deleterious mutations in damage response and repair pathway genes were associated with improved local-regional disease control after chemoradiation therapy. These findings will require validation in a larger cohort of patients with prospectively collected and detailed clinical information.
Parietal block, defined as intra right ventricular (RV) conduction slowing, is a major diagnostic criterion for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C).
We evaluated the ...utility of total RV endocardial activation duration (EAD) measured by 3-dimensional electroanatomic mapping during sinus rhythm in the diagnosis of ARVD/C.
Twenty-five consecutive patients with frequent left bundle branch block morphology premature ventricular complexes who underwent electroanatomic mapping as a part of the evaluation for ARVD/C were included in the study. All patients were evaluated using standard protocol that included electrocardiogram (ECG), signal-averaged ECG, Holter monitoring, echocardiography, and magnetic resonance imaging. Invasive testing was performed as indicated. Total RV EAD was measured as the time interval between the onset of RV activation to the latest activated region in the RV.
The mean age of the study subjects was 38 +/- 11 years, and 32% were men. Fourteen subjects were diagnosed with ARVD/C using task force criteria, and the remainder had idiopathic ventricular tachycardia. Although the surface QRS durations were similar, the total RV EAD was significantly prolonged in ARVD/C compared with idiopathic VT (83.9 +/- 10 ms vs. 50.8 +/- 7 ms, P <.001). None of the idiopathic VT subjects had RV EAD of >65 ms. RV EAD also showed significant negative correlation with RV ejection fraction.
Total RV EAD obtained by 3-dimensional electroanatomic mapping is a sensitive marker of intra-RV conduction delay in ARVD/C, and a total RV EAD of >65 ms accurately differentiates ARVD/C from idiopathic VT.
Abstract Objectives We examined the effect of access to epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) therapy on survival for Asian female (AF) EGFR mutation enriched ...patients(EGFR E) with advanced lung adenocarcinoma. Materials/Methods We used the SEER 18 database to study patients with stage IV lung adenocarcinoma diagnosed 1998-2012. We compared survival(lung cancer specificLCSS and overall OS) between AF and non-Asian males (NAM), EGFR E or EGFR unenriched(EGFR U) populations, respectively, diagnosed in the pre-EGFR TKI(1998-2004) and EGFR TKI(2005-2012) eras. We used Cox proportional hazards models to examine the interaction of access to TKI treatment and EGFR enrichment status. Results Among 3029 AF and 35352 NAM patients, we found that LCSS was best for AF diagnosed in the TKI era(median 14 months) followed by AF diagnosed pre-TKI era(8 months) followed by NAM diagnosed in the TKI era(5 months), followed by NAM diagnosed pre-TKI era(4 months)(log-rank p<0.0001). In a multivariable model the effect of being diagnosed in the TKI era on survival was greater for AF than NAM(LCSS p=0.0020; OS p=0.0007). Being diagnosed in the TKI era was associated with an overall mortality decrease of 26% for AF(HR 0.740 CI 0.682-0.80), and 15.9% for NAM(HR 0.841 CI 0.822-0.860). Conclusion We found increased survival for lung adenocarcinoma diagnoses made after widespread access to EGFR TKIs, with the greatest increase among AF patients enriched for EGFR mutations. This analysis eliminates the effect of crossover which has complicated assessments of survival advantage in EGFR TKI randomized trials.
Nelson Syndrome: A Case Report and Literature Review Esparza-Salazar, Felipe J.; Hernández-González, Jhosue A.; Lezama-Toledo, Alma R. ...
AACE clinical case reports,
03/2021, Letnik:
7, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Nelson syndrome (NS) is a rare clinical disorder that can occur after total bilateral adrenalectomy (TBA), performed as a treatment for Cushing disease. NS is defined as the accelerated growth of an ...adrenocorticotropic hormone-producing pituitary adenoma. Our objective is to describe a case of NS and discuss it based on existing knowledge of this syndrome.
We describe the case of a woman diagnosed with NS at our facility in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran and review published cases of NS.
The patient, a 35-year-old woman with Cushing disease, had been diagnosed in 2006 at the endocrinology department in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. In 2007, a laparoscopic TBA was performed, and 2 years later, she presented with hyperpigmentation and adrenocorticotropic hormone levels of up to 11 846 pg/mL. NS was suspected, and as magnetic resonance imaging showed macroadenoma, transsphenoidal surgery was performed. The patient remained asymptomatic until 2012, when she presented with a right hemicranial headache, photophobia, and phonophobia. A fresh magnetic resonance imaging was performed, which documented tumor growth. She was referred to the Instituto Nacional de Neurologia y Neurocirugia, where she underwent surgery.
NS develops as a complication of TBA, which is used as a treatment of Cushing disease. The main treatment is surgery and radiotherapy.
Paper 223: Etiology of Shoulder Injuries in SA Tennis Players Morkel, Daniel Francois, MD, South Africa; de Villiers, Richard, South Africa; Barnard, Justhinus, Phd, South Africa ...
Arthroscopy,
September 2012, Letnik:
28, Številka:
9
Journal Article
Objectives The purpose of this study was to determine the extent of left ventricular (LV) involvement in individuals predisposed to developing arrhythmogenic right ventricular ...dysplasia/cardiomyopathy (ARVD/C), and to investigate novel morphologic variants of ARVD/C. Background The discovery of desmosomal mutations associated with ARVD/C has led researchers to hypothesize equal right ventricular (RV) and LV affliction in the disease process. Methods Thirty-eight (age 30 ± 17 years; 18 males) family members of 12 desmosomal mutation-carrying ARVD/C probands underwent genotyping and cardiac magnetic resonance imaging (CMR). The CMR investigators were blinded to clinical and genetic data. Results Twenty-five individuals had mutations in PKP2 , DSP , and/or DSG2 genes. RV abnormalities were associated with the presence of mutation(s) and with disease severity determined by criteria (minor = 1; major = 2) points for ARVD/C diagnosis. The only LV abnormality detected, the presence of intramyocardial fat, was present in 4 individuals. Each of these individuals was a mutation carrier, whereas 1 had no previously described ARVD/C-related abnormality. On detailed CMR, a focal “crinkling” of the RV outflow tract and subtricuspid regions (“accordion sign”) was observed in 60% of the mutation carriers and none of the noncarriers (p < 0.001). The sign was present in 0%, 37%, 71%, and 75% of individuals who met 1, 2, 3, and 4+ criteria points, respectively (p < 0.01). Conclusions Despite a possible LV involvement in ARVD/C, the overall LV structure and function are well preserved. Independent LV involvement is of rare occurrence. The accordion sign is a promising tool for early diagnosis of ARVD/C. Its diagnostic utility should be confirmed in larger cohorts.
Ophthalmic manifestations of tetrasomy 18p White, W. Abraham, MD; Schatz, Martha P., MD; Sebold, Courtney ...
Journal of AAPOS,
06/2011, Letnik:
15, Številka:
3
Journal Article
Recenzirano
Purpose To characterize ophthalmic findings in patients with tetrasomy 18p, a rare chromosomal anomaly that has been previously associated with strabismus. Methods All subjects underwent a complete ...eye examination to screen for ocular pathology. Results A total of 25 subjects (13 female) were examined after they were diagnosed with tetrasomy 18p. The average age of subjects was 8.2 years (range, 13 months to 22 years). Of the 25 subjects, 18 (72% of examined subjects, 42% of the cohort) showed evidence of strabismus; 16 had esotropia (8 uncategorized, 5 infantile, and 3 accommodative), 1 had esophoria, and 1 was diagnosed with intermittent exotropia. Conclusions The coincidence of esotropia with tetrasomy 18p indicates the need to routinely screen these patients for strabismus at the time of diagnosis.
Metal Plates and Foils for Closure of Oroantral Fistulae Steiner, Martin, DDS; Gould, Alan R., DDS, MS; Madion, Daniel C., DDS, MD ...
Journal of oral and maxillofacial surgery,
07/2008, Letnik:
66, Številka:
7
Journal Article
Abstract Purpose Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The ...synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively ( P < .001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS + IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio HR, 0.48; 95% confidence interval CI, 0.29-0.80; P = .003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P = .001).One-year local control for SRS, SRS + IMT, and SRS + targeted therapy was 66%, 85%, and 72%, respectively ( P = .044). On multivariate analysis, after adjusting for dose, SRS + IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P = .04). Conclusions SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result.
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