Molecular Confirmation of t(6;11)(p21;q12) Renal Cell Carcinoma in Archival Paraffin-embedded Material Using a Break-apart TFEB FISH Assay Expands its Clinicopathologic Spectrum

A subset of renal cell carcinomas (RCCs) is characterized by t(6;11)(p21;q12), which results in fusion of the untranslated Alpha (MALAT1) gene to the TFEB gene. Only 21 genetically confirmed cases of t(6;11) RCCs have been reported. This neoplasm typically demonstrates a distinctive biphasic morphology, comprising larger epithelioid cells and smaller cells clustered around basement membrane material; however, the full spectrum of its morphologic appearances is not known. The t(6;11) RCCs differ from most conventional RCCs in that they consistently express melanocytic immunohistochemical (IHC) markers such as HMB45 and Melan A and the cysteine protease cathepsin K but are often negative for epithelial markers such as cytokeratins. TFEB IHC has been proven to be useful to confirm the diagnosis of t(6;11) RCCs in archival material, because native TFEB is upregulated through promoter substitution by the gene fusion. However, IHC is highly fixation dependent and has been proven to be particularly difficult for TFEB. A validated fluorescence in situ hybridization (FISH) assay for molecular confirmation of the t(6;11) RCC in archival formalin-fixed, paraffin-embedded material has not been previously reported. We report herein the development of a break-apart TFEB FISH assay for the diagnosis of t(6;11)(p21;q12) RCCs. We validated the assay on 4 genetically confirmed cases and 76 relevant expected negative control cases and used the assay to report 8 new cases that expand the clinicopathologic spectrum of t(6;11) RCCs. An additional previously reported TFEB IHC-positive case was confirmed by TFEB FISH in 46-year-old archival material. In conclusion, TFEB FISH is a robust, clinically validated assay that can confirm the diagnosis of t(6;11) RCC in archival material and should allow a more comprehensive clinicopathologic delineation of this recently recognized neoplastic entity.     

Exposure to Traumatic Events and the Behavioral Health of Children Enrolled in an Early Childhood System of Care

Children may be exposed to numerous types of traumatic events that can negatively affect their development. The scope to which studies have examined an array of events among young children has been limited, thereby restricting our understanding of exposure and its relationship to behavioral functioning. The current cross‐sectional study describes traumatic event exposure in detail and its relationship to behavioral health among an at‐risk sample of young children (N = 184), under 6 years of age, upon enrollment into an early childhood, family‐based, mental health system of care. Caregivers completed home‐based semistructured interviews that covered children's exposure to 24 different types of traumatic events and behavioral and emotional functioning. Findings indicated that nearly 72% of young children experienced 1 or more types of traumatic events. Multiple regression model results showed that exposure was significantly associated with greater behavioral and emotional challenges with children's age, gender, race/ethnicity, household income, and caregiver's education in the model. These findings highlight the prevalence of traumatic exposures among an at‐risk sample of young children in a system of care and suggest that this exposure is associated with behavioral and emotional challenges at a young age.     

Does physiologic response to loud tones change following cognitive–behavioral treatment for posttraumatic stress disorder?

This study examined responses to loud tones before and after cognitive-behavioral treatment for posttraumatic stress disorder (PTSD). Seventy-four women in a PTSD treatment outcome study for rape-related (n = 54) or physical assault-related PTSD (n = 20) were assessed in an auditory loud tone paradigm. Assessments were conducted before and after a 6-week period of cognitive-behavioral therapy. Physiologic responses to loud tones included heart rate (HR), skin conductance (SC), and eye-blink electromyogram (EMG). Groups were formed based upon treatment outcome and included a treatment responder group (no PTSD at posttreatment) and a nonresponder group (PTSD-positive at posttreatment). Treatment was successful for 53 of 74 women (72%) and unsuccessful for 21 women (28%). Responders and nonresponders were not significantly different from each other at pretreatment on the main outcome variables. Treatment responders showed a significant reduction in loud tone-related EMG, HR, and SC responses from pre- to posttreatment (partial η(2) = .24, .31, and .36, respectively; all p < .001) and the EMG and HR responses were significantly smaller than nonresponders at posttreatment (partial η(2) = .11, p = .004 and .19, p < .001, respectively). Successful cognitive-behavioral treatment of PTSD is associated with a quantifiable reduction in physiological responding to loud tones.     

A new member of the multidisciplinary ALS team: the otolaryngologist

The multidisciplinary approach to treatment of amyotrophic lateral sclerosis (ALS) has improved the overall care of patients suffering from this disease ( 1 , 2 ). This approach typically has included neurologists, physiatrists, occupational therapists, respiratory therapists and speech therapists. Dysphonia, dysarthria, and dysphagia are three of the most common bulbar manifestations of ALS, and are often the presenting symptoms in bulbar-onset patients. Despite this, otolaryngologists are often not included in ALS management until a tracheostomy is considered. The otolaryngologist can play an important role in early diagnosis and subsequent management of bulbar manifestations of ALS, and would be a valuable member of the multidisciplinary team.     

Door-to-Balloon Times from Freestanding Emergency Departments Meet ST-Segment Elevation Myocardial Infarction Reperfusion Guidelines

Background

Freestanding emergency departments (FEDs) introduce a challenge to physicians who care for the patient with an ST-segment elevation myocardial infarction (STEMI) because treatment is highly time dependent. FEDs have no percutaneous coronary intervention (PCI) capabilities, which necessitates transfer to a PCI-capable facility or fibrinolysis.

Study Objective

Our aim was to determine the proportion of STEMI patients who arrived to an FED and were subsequently transferred for PCI and met the door-to-balloon reperfusion guidelines of 90 min.

Methods

This was a dual-center retrospective cohort review of all patients 18 years and older who were diagnosed with an STEMI and presented to the main hospital−affiliated FEDs. Electronic medical records and emergency medical services documentation were reviewed for all cases since the opening of the FEDs in July 2007 and August 2009, respectively. Key time points were abstracted and statistical evaluation was performed using Fisher's exact test.

Results

A total of 47 patients met inclusion criteria. Median door-to-transport time was 34 min (interquartile range [IQR] 15 min). Median transport time from the FEDs to the main hospital catheterization laboratory was 21 min (IQR 5 min). Median arrival at the catheterization laboratory-to-balloon time was 25 min (IQR 13 min). Median total door-to-balloon time was 83 min (IQR 10.5 min), with 78.7% meeting the American Heart Association's recommended guidelines of ≤ 90 min.

Conclusion

STEMI patients initially seen at two FEDs achieved door-to-balloon time goals of < 90 min.     

Diffusion Tensor Imaging Study of the Response to Constraint-Induced Movement Therapy of Children With Hemiparetic Cerebral Palsy and Adults With Chronic Stroke

Objective

To investigate the relationship of white matter integrity and path of the corticospinal tract (CST) on arm function before and after constraint-induced (CI) movement therapy in children with hemiparetic cerebral palsy (CP) and adults with chronic stroke.

Design

Study 1 used a multiple-baseline pre-post design. Study 2 was a randomized controlled trial.

Setting

Outpatient rehabilitation laboratory.

Participants

Study 1 included children with hemiparetic CP (n=10; mean age ± SD, 3.2±1.7y). Study 2 included adults with chronic stroke (n=26; mean age ± SD, 65.4±13.6y) who received either CI therapy or a comparison therapy.

Interventions

Children in study 1 received CI therapy for 3.5h/d for 15 consecutive weekdays. Adults in study 2 received either CI therapy or a comparison therapy for 3.5h/d for 10 consecutive weekdays.

Main Outcome Measures

Diffusion tensor imaging was performed to quantify white matter integrity. Motor ability was assessed in children using the Pediatric Motor Activity Log–Revised and Pediatric Arm Function Test, and in adults with the Motor Activity Log and Wolf Motor Function Test.

Results

Participants in both studies improved in real-world arm function and motor capacity. Children and adults with disrupted/displaced CSTs and children with reduced fractional anisotropy values were worse on pretreatment tests of motor function than participants with unaltered CSTs. However, neither integrity (fractional anisotropy) nor distorted or disrupted path of the CST affected motor improvement after treatment.

Conclusions

Participants who had reduced integrity, displacement, or interruption of their CST performed worse on pretreatment motor testing. However, this had no effect on their ability to benefit from CI therapy. The results for children and adults are consistent with one another.     

Should peritoneal dialysis catheters be removed at the time of kidney transplantation?

Background:

Delayed graft function (DGF) following transplantation necessitates support in the form of hemodialyis (HD) or peritoneal dialysis (PD). However, post-transplant PD-related complication and failure rates are unknown.

Methods:

We studies patients who were on PD at the time of kidney transplantation over a 4-year period at two separate institutions.

Results:

Of the 137 PD patients, 19 had their catheters removed at the time of transplant. Of the remaining 118 patients, 89% had immediate graft function. PD-related complications in this group included peritonitis (n=5), catheter-related infections (n=2) and emergency laparotomy (n=1). Of the 15 patients requiring post-transplant PD, 33% developed peritonitis and 20% had fluid-leaks necessitating HD. Overall, leaving a PD catheter in situ post- transplantation is associated with 7% rate of peritonitis versus 0% if removed (p < 0.05).

Conclusions:

PD catheter removal should be considered at the time of renal transplantation, as postoperative PD-related failure/complication rates are high.     

Emergency Medical Services as a Strategy for Improving ST-Elevation Myocardial Infarction System Treatment Times

Background

Reducing delays in time to treatment is a key goal of ST-elevation myocardial infarction (STEMI) emergency care. Emergency medical services (EMS) are a critical component of the STEMI chain of survival.

Study Objective

We sought to assess the impact of the careful integration of EMS as a strategy for improving systemic treatment times for STEMI.

Methods

We conducted a study of all 747 nontransfer STEMI patients who underwent primary percutaneous coronary intervention (PCI) in Dallas County, Texas from October 1, 2010 through December 31, 2011. EMS leaders from 24 agencies and 15 major PCI receiving hospitals collected and shared common, de-identified patient data. We used 15 months of data to develop a generalized linear regression to assess the impact of EMS on two treatment metrics—hospital door to balloon (D2B) time, and symptom onset to arterial reperfusion (SOAR) time, a new metric we developed to assess total treatment times.

Results

We found statistically significant reductions in median D2B (11.1-min reduction) and SOAR (63.5-min reduction) treatment times when EMS transported patients to the receiving facility, compared to self-transport. In addition, when trained EMS paramedics field-activated the cardiac catheterization laboratory using predefined specified protocols, D2B times were reduced by 38% (43 min) after controlling for confounding variables, and field activation was associated with a 21.9% reduction (73 min) in the mean SOAR time (both with p < 0.001).

Conclusion

Active EMS engagement in STEMI treatment was associated with significantly lower D2B and total coronary reperfusion times.