A case report of biallelic CHEK2 heterozygous variant presenting with breast cancer.

Pathogenic germline variants in the CHEK2 gene have been shown to cause a moderate increased risk of breast cancer. Here, we present a striking CHEK2 family with a biallelic carrier of two frameshift pathogenic variants, to draw attention and to encourage a comprehensive genetic and cancer risk education for biallelic carriers of CHEK2 pathogenic variants.

The CHEK2*1100delC Mutation and Adolescent Breast Cancer: A Case Report of Breast Cancer in a 19-Year-Old and a Review of the Literature.

Background: Breast cancer (BC) is the most common non-skin cancer affecting women but is extremely uncommon in the adolescent population. Genetic inheritance has been linked to <10% of BCs. CHEK2 is an uncommon genetic variant with a reported incidence of 0.3-1.6% in the general population and 4.9-5.7% in those with a family history of BC. Commonly, this mutation presents in females of European descent and is rare in North America. Case Presentation: A 19-year-old Caucasian female presented with breast pain and mass. She had an extensive family history of cancer, as well as a known CHEK2 gene mutation in 2 of her paternal aunts. Ultrasound and MRI confirmed a 4.5-cm mass with an enlarged right axillary lymph node. Image guided biopsy of the breast mass showed ER/PR-positive grade 1 invasive mucinous ductal cancer. Genetic testing confirmed an isolated CHEK2 mutation. After discussion by a multidisciplinary tumor board, the patient deferred bilateral mastectomy and underwent a right mastectomy with sentinel-lymph-node biopsy and immediate tissue-expander reconstruction. Final pathology confirmed ER/PR-positive Stage 1A (pT2 pN0 M0) invasive mucinous carcinoma. Chemotherapy was not recommended. Summary: Malignant adolescent breast masses are relatively rare and CHEK2 does not typically present at younger than 20 years of age. While there are many different differential diagnoses when evaluating an adolescent with a breast mass, we wish to increase providers' suspicion of malignancy, specifically in those individuals who have a strong family history of BC and the CHEK2*1100delC mutation.

Heller myotomy perforation: robotic visualization decreases perforation rate and revisional surgery is a perforation risk.

Minimally invasive surgery (MIS) has improved surgical access to the foregut. While the benefits of MIS versus open surgery are well accepted, the relative benefits of laparoscopic versus robotic approaches continue to be debated. Procedure-specific comparisons are difficult to obtain for Heller myotomy, due to the relative rarity of the procedure in most practices. A retrospective review of prospectively collected perioperative data of a single surgical practice from 2001 to 2019 was conducted for the rate of perforation during Heller myotomy laparoscopically compared to robotically. From 2001 through February 2012, a laparoscopic approach was employed and from October 2008 to 2019, a robotic approach was employed. All perforations were recorded, as well as secondary outcomes of perforation location (gastric or esophageal), postoperative imaging for evidence of leak, length of stay, and complications. Chi-square and simple t test were employed for data analysis. During the 11 years of laparoscopic Heller myotomy, 14 cases resulted in 7 instances of perforation (50%). During the 11 years of robotic Heller myotomy, 45 cases resulted in 11 instances of perforation (24%) (p value = 0.06). All perforations in both groups were tiny, recognized, and repaired immediately. The length of stay (LOS) was longer in the laparoscopic perforation group (3.4 days) compared to the laparoscopic non-perforation group (1.2 days) (p value = 0.06). LOS for robotic was not significantly longer in the perforation group (2.8 days) compared to the robotic non-perforation group (1.5 days) (p value = 0.18). First time Heller myotomies showed a higher rate of perforation with laparoscopic (50%) vs robotic (14%) (p value = 0.009) approach. In subgroup analysis of revisional procedures, all ten were performed robotically (p value < 0.001) with a 60% perforation rate (p value = 0.001) and one associated, radiographically confirmed leak. Primary laparoscopic Heller myotomy related to more than four times the frequency of perforation than did primary robotic myotomy. We propose that the robotic platform provided the surgeon with superior ability to avoid perforation. Interestingly, the robotic group in this study dealt with more complex redo cases. In fact, reoperation in the area of the hiatus was a separate risk factor for perforation during robotic Heller myotomy. We recommend further prospective trials be done to better evaluate the benefits of robotic platform in regard to revisional foregut surgery.

A Wireless Implantable Passive Intra-Abdominal Pressure Sensing Scheme via Ultrasonic Imaging of a Microfluidic Device.

In this article, we demonstrate a wireless and passive physiological pressure sensing scheme that utilizes ultrasound imaging of an implantable microfluidic based pressure sensitive transducer. The transducer consists of a sub-mm scale pressure sensitive membrane that covers a reservoir filled with water and is connected to a hydrophobic micro-channel. Applied pressure onto the transducer deflects the membrane and pushes the water from the reservoir into the channel; the water's travelling distance in the channel is a function of the applied pressure, which is quantitatively measured by using a 40 MHz ultrasound imaging system. The sensor presents a linear sensitivity of 42 kPa/mm and a spatial resolution of 1.2 kPa/30 µm in the physiological range of abdominal compartment syndrome. Reliability assessments of the transducer confirm its ability to remain functional after more than 600 cycles of pressure up to 55 kPa over the course of 2 days. Ex vivo experimental results verify the practical capability of the technology to effectively measure pressures under a 15 mm thick porcine skin. It is anticipated that this technology can be applied to a broad range of implantable pressure measurement, by simply tuning the thickness of the thin polydimethylsiloxane membrane and the geometry of the reservoir.

Delayed Intracranial Hemorrhage After Blunt Head Injury With Direct Oral Anticoagulants.

INTRODUCTION: Patients presenting to the Emergency Department (ED) following head injury are frequently evaluated with an initial computed tomography scan (CT) of the brain. Imaging is particularly important in patients who are receiving medications that alter normal blood hemostasis. As an imaging modality, CT has a high negative predictive value when used to rule out clinically significant acute intracranial hemorrhage. Patients receiving anticoagulant or antiplatelet therapy have both an increased risk of initial hemorrhage, as well as an increased risk of mortality above nonanticoagulated patients, should they suffer hemorrhage. Multiple studies of delayed intracranial hemorrhage have placed the risk among the patients taking warfarin at the time of head injury in the range of 0.6-6.0%. However, data regarding the risk of delayed intracranial hemorrhage in patients taking the class of agents referred to as Direct-Acting Oral Anticoagulants (DOACs) remains limited. This study aims to estimate this risk. METHODS: A retrospective chart review was performed to identify patients on DOACs who presented to our Level I trauma center following blunt head injury between January 2017 and August 2018. Patients with a negative initial head CT were selected. From this subset, data regarding demographics, injury characteristics, anticoagulant use, and antiplatelet use were collected. RESULTS: Overall, 314 patients were included; 129 patients taking rivaroxaban, 182 patients taking apixaban, and four patients taking dabigatran. In approximately 29% of the patients, the sole indication for admission was close monitoring following head injury while taking an anticoagulant agent. The mechanism of injury for the majority of the patients was fall. Of the 314 patients, three were found to have delayed intracranial hemorrhage on the repeated head CT (0.95%). Two of these three patients were on concomitant antiplatelet medication. None of the three individuals required neurosurgical intervention. CONCLUSIONS: at the time of submission, this is the largest study estimating the risk of delayed intracranial hemorrhage among patients on DOACs. Based on the results of this study, patients who sustain a blunt head injury while taking only DOACs; that is, without concurrent antiplatelet medication, admission, and repeat head CT may not be necessary after confirming a negative initial CT scan.

Lower Post Myocardial Infarction Mortality Among Women Treated at Veterans Affairs Hospitals Compared to Men.

BACKGROUND: There is conflicting evidence about whether mortality after myocardial infarction is higher among women than among men. This study aimed to compare sex differences in post myocardial infarction mortality in the Veterans Affairs system, a setting where the predominant subjects are men. MATERIALS AND METHODS: The Veterans Affairs Corporate Data Warehouse inpatient and laboratory chemistry databases were used to identify patients diagnosed with acute myocardial infarction from inpatient records from January 1st, 2005 to April 25th, 2015. Mortality data was obtained through the Veterans Affairs death registry. RESULTS: A total of 130,241 patients were identified; 127,711 men (98%) and 2,530 women (2%). Men typically had more comorbidities including congestive heart failure (54% vs. 46%, P value < 0.001), diabetes mellitus (54% vs. 48%, P value < 0.001), and chronic kidney disease (39% vs. 28%, P value < 0.001). The peak troponin-I was significantly higher among men (16.0 vs. 10.7 ng/mL, P value = 0.03). The mean follow-up time was 1490.67 ± 8 days. After adjusting for differences in demographics and comorbidities, women had a significantly lower risk of mortality (hazard ration [HR]: 0.747, P value < 0.0001) as compared to men. CONCLUSIONS: In a health care system where the predominant subjects are men, women had better short- and long-term survival than men after an acute myocardial infarction. Further investigation is warranted to determine the reasons behind the improved outcomes in women post myocardial infarction in the veteran population.

A Wireless Implantable Strain Sensing Scheme Using Ultrasound Imaging of Highly Stretchable Zinc Oxide/Poly Dimethylacrylamide Nanocomposite Hydrogel.

We are introducing a wireless and passive strain sensing scheme that utilizes ultrasound imaging of a highly stretchable hydrogel embedded with zinc oxide (ZnO) nanoparticles, named "ZnO-gel". The incorporation of ZnO nanoparticles into a polymer network of the hydrogel improves both its elasticity and strength. It also serves as an ideal biocompatible ultrasound contrast agent that allows remote interrogation of the changes in volume or dimensions of the hydrogel in response to mechanical strains through simple ultrasound imaging. A systematic study of various ratios of ZnO nanoparticle fillers (ranging from 0 to 40% w/w), cross-linked within the poly (DMA-co-MAA) hydrogel, was performed to identify the appropriate ZnO-to-gel ratio that provided the optimal mechanical and ultrasound imaging properties. The results of these investigations showed that 10% w/w of ZnO nanoparticles provided the highest stretchability of 260% with the effective amount of contrast agents to achieve clear visibility of the hydrogel dimension during ultrasound imaging. In general, the applied strain deforms the ZnO-gel specimens by reducing the cross-sectional area at a linear rate of 0.24% area change per % of applied strain for strain levels of up to 250%. Biocompatibility tests with stromal cells (fibroblasts) did not show any acute toxicity of the hydrogel and the ZnO nanoparticles used in this technology. It is anticipated that this technology can be applied to a broad range of wireless and passive monitoring of physiological functions for which microenvironmental strain matters throughout the body, simply by tuning both the mechanical properties of the hydrogel and ZnO nanoparticle concentration.

An Epidemiological Analysis of Pediatric Dog Bite Injuries Over a Decade.

BACKGROUND: An estimated 800,000 dog bites require medical attention every year. The purpose of this study is to review the characteristics of dog bite injuries in children and examine temporal trends. METHODS: The Kids' Inpatient Database was used to identify pediatric patients with dog bite injuries over a 10-y period. Demographic data, primary payer, injury characteristics, length of hospitalization, and treatments were recorded. Statistical analysis was performed in SAS 9.3 (SAS Institute Inc, Cary, NC). RESULTS: A total of 6308 patients were identified. Average age at time of injury was 6.4 ± 4.3 y. Children under age 5 y were the most affected subgroup (39.3% in 2000 versus 44.7% in 2009, P < 0.001). Most bites were to the head/neck and significantly increased from 53.9% in 2000 to 60.1% in 2009. Cellulitis complicated many injuries (33.7% in 2000 versus 44.8% in 2009, P < 0.001). Overall, 50% of patients underwent a procedure; 31% had an invasive surgical procedure; and 5.1% of patients required skin grafts or flaps. CONCLUSIONS: Dog bites are a common cause of pediatric injuries and are a significant burden on families and the health care system. Evaluating the characteristics of these injuries can guide educational efforts.

Regulatory networks upon neurogenesis induction in PC12 cell line by small molecules.

Alteration in the normal regulatory pathway of differentiation can lead to the induction of programmed cell death. Accordingly, some chemicals like staurosporine, nerve growth factor, pituitary adenylate cyclase activating peptide, and trimethyltin are shown to be able to induce differentiation in vitro, via different mechanisms in the PC12 cell line. Hence, understanding the details of the molecular mechanisms of differentiation induction by these small molecules are important for further application of these molecules in neurogenesis. Therefore, we sought to determine these signaling pathways, using gene regulatory networks analysis. Then, we have conducted a comparative analysis of the alterations in the gene expression pattern of the PC12 cell lines in response to these chemicals at the early stages. Based on the comparative analysis and previous knowledge, we have proposed the affected pathways during differentiation and apoptosis. Our findings could be useful in the development of protocols to reprogramming of neurons by such small molecules with high efficiency.

Adrenocortical oncocytic neoplasm: A systematic review.

BACKGROUND: Adrenocortical oncocytic neoplasms are rare tumors, generally regarded as benign and hormonally nonfunctional. We performed a systematic review to update the literature on adrenocortical oncocytic neoplasms by reviewing patient and tumor characteristics, as well as management trends, because the literature is composed of predominately single-case reports. METHODS: A systematic search was performed in PubMed, Embase, and Cochrane Library through June 2017. Malignant potential was determined by applying the Lin-Weiss-Bisceglia criteria to cases. RESULTS: Included for analysis were 84 citations describing 140 adrenocortical oncocytic neoplasms, including our own case. These were diagnosed predominantly in females (66%), on the left side (64%), and were nonfunctional (66%). Average age at diagnosis was 44 years (2.5-77), and median tumor size was 80 mm (16-285). A total of 35% of adrenocortical oncocytic neoplasms were benign, 41% borderline, and 24% malignant. Male patients were more likely to have a malignant tumor compared with females (36% versus 18%, P = .035). The 5-year overall survival for benign adrenocortical oncocytic neoplasms was 100%, borderline 88%, and malignant 47%. Hormonal function did not discriminate malignant from benign lesions. Adrenocortical oncocytic neoplasms that stained positive for synaptophysin (50%, P < .001) and negative for vimentin (62%, P = .009) are more often benign. CONCLUSION: We found that the majority of adrenocortical oncocytic neoplasms (65%) were either malignant or had malignant potential, contrary to the previous literature. The Lin-Weiss-Bisceglia criteria are useful in identifying those patients for whom closer surveillance is warranted, because their prognosis is dependent on the Lin-Weiss-Bisceglia diagnosis.

Pyoderma gangrenosum demographics, treatments, and outcomes: an analysis of 2,273 cases.

OBJECTIVE: Pyoderma gangrenosum is a rare, neutrophil-mediated, auto-inflammatory dermatosis. This condition has clinical features analogous to infectious processes and must be quickly diagnosed to be properly treated. The purpose of this study was to characterise relevant clinical features associated with pyoderma gangrenosum based on a large inpatient cohort. METHOD: The National Inpatient Sample (US) was used to identify patients with the diagnosis of pyoderma gangrenosum using ICD-9 diagnosis code 686.01, during the years 2008-2010. Data was collected on demographics, associated diagnoses, treatments and outcomes. Data analysis was performed using SAS 9.3 software. RESULTS: A total of 2,273 adult patients were identified with pyoderma gangrenosum. Mean age was 56 years; 66.4% were female; 71.1% were Caucasian. Pyoderma gangrenosum was the primary diagnosis in 22.6% of patients, followed by cellulitis (9.4%), inflammatory bowel disease (IBD) (6.9%), wound/ulcer (5.4%), sepsis (4.7%), and postoperative infection/complication (2.7%). The most common procedures performed were wound debridement (5.3%), skin biopsy (5.1%), esophagogastroduodenoscopy (2%), large bowel biopsy (1.9%), and incision and drainage (1.1%). A total of 74 patients (3.2%) died during hospitalisation. CONCLUSION: Pyoderma gangrenosum is a serious skin condition, frequently associated with systemic disease, and often confused with other skin pathergies. Pyoderma gangrenosum should be considered when evaluating patients with ulcers, wounds, and post-operative complications. A high index of suspicion is necessary for early and accurate diagnosis and prompt treatment.

Safety and Utility of the Drainless Abdominoplasty in the Post-Bariatric Surgery Patient.

INTRODUCTION: Surgical drains are used in abdominoplasty patients to combat wound closure disruption by hematoma or seroma formation. Several recent publications have described techniques that allow abdominoplasty to be performed safely without the need for surgical drains. This has not, however, been described in the case of the bariatric patient, who is often considered to be of higher postoperative complication risk. Here, we describe our experience of the drainless abdominoplasty in patients who have undergone massive weight loss (MWL) after a bariatric procedure. METHODS: A retrospective review was conducted of 172 patients who had undergone drainless abdominoplasty using the progressive tension suture technique from 2011 to 2014. Thirty-five patients who had undergone MWL after bariatric surgery were assigned to group A. One hundred thirty-seven patients who had not undergone MWL with no history of bariatric surgery were assigned to group B. Demographics, intraoperative outcomes, and postoperative outcomes were compared. RESULTS: Patients in group A were older (mean age, 48.7 vs 42.7 years; P = 0.003) and had a higher body mass index (26.6 vs 24.6 kg/m, P = 0.01), a significantly larger tissue resection (2379 vs 1228 g, P = 0.0001), and a higher estimated blood loss (100 vs 120 mL, P = 0.049). There was also a significant group-to-group difference in the American Society of Anesthesiologists Physical Status Classification distribution, with a higher percentage of MWL patients having higher scores. Despite these differences, group A did not have a statistically higher incidence of complications. There was no statistically significant difference in the rate of seroma formation (11% vs 2%, P = 0.055), wound infection (2.9% vs 4.4%, P = 0.68), wound dehiscence (8.6% vs 8.0%, P = 0.91), meralgia paresthetica (2.8% vs 1.5%, P = 0.51), or rate of reoperation (11.4% vs 13.9%, P = 0.7) between the 2 groups. CONCLUSION: Despite post-bariatric surgery patients being considered higher risk for postoperative complications, drainless abdominoplasty can be safely offered to this population by using a progressive tension suture technique.

Dissection of Regulatory Elements During Direct Conversion of Somatic Cells Into Neurons.

A revolutionary approach that involves direct conversion of somatic cells into almost any other types of cells showed promising results for regenerative medicine. Currently, producing valuable cell types including neurons, cardiomyocytes, and hepatocytes through direct conversion of somatic cells appear to be a feasible option for regenerative medicine. The process involves inducing the cells by chemical cocktails or by expression of different types of transcription factors. In this concept, in vitro neurogenesis considered to be able to produce neuron cells to replace damaged neurons especially in Alzheimer and Parkinson disease. However, early successful experiments followed by major drawbacks such as low differentiation efficiency in producing neurons and detection of various undesirable types of cells in the culture. Therefore, there is not a single optimized common protocol for producing high quality neurons in vitro so far. This is partly due to the lack of our understanding about the precise cellular, genetic, and molecular mechanisms underlying neurogenesis via direct conversion. In the current work, we have employed meta-analysis tools and extensive gene regulatory network analysis on the high throughput gene expression data obtained from previous reprogramming protocols to identify central gene regulatory components involved in direct conversion of fibroblasts into neurons. Our results identified miR-9, miR-30 as the most important miRNA and TP53, MYC, JUN, SP1, and SMAD2 considered to be the most important transcription factors. These findings would be useful for direct targeting these hub regulatory elements in order to increase the efficacy and specificity of the conversion protocols. J. Cell. Biochem. 118: 3158-3170, 2017. © 2017 Wiley Periodicals, Inc.

Improving first case start times using Lean in an academic medical center.

BACKGROUND: Lean is a process improvement strategy that can improve efficiency of the perioperative process. The purpose of this study was to identify etiologies of late surgery start times, implement Lean interventions, and analyze their effects. METHODS: A retrospective review of all first-start surgery cases was performed. Lean was implemented in May 2015, and cases 7 months before and after implementation were analyzed. RESULTS: A total of 4,492 first-start cases were included; 2,181 were pre-Lean and 2,311 were post-Lean. The post-Lean group had significantly higher on-time starts than the pre-Lean group (69.0% vs 57.0%, P < .01). The most common delay etiology was surgeon-related for both groups. Delayed post-Lean cases were significantly less likely to be due to preoperative assessment (14.9% vs 9.9%, P < .01) and more likely due to patient-related (16.5% vs 22.3%, P < .01) or chaplain (1.8% vs 4.0%, P < .01) factors. Delayed starts occurred more often on snowy and cold days, and less often on didactic days (P < .01). CONCLUSIONS: Modifying preoperative tasks using Lean methods can improve operating room efficiency and increase on-time starts.

Pediatric pyoderma gangrenosum: is it just big wounds on little adults?

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon, ulcerative, cutaneous condition, often caused by surgical trauma that can masquerade as a pyogenic disease process requiring debridement and antibiotics. Treatment is, however, medical, with delay leading to significant morbidity. In addition, medical workup for coincident disorders has been suggested. The purpose of this study was to test the hypothesis that pediatric PG has differing disease associations and therefore requires a differing medical workup. METHODS: The National Inpatient Sample and the Kids' Inpatient Database were used to identify all hospitalized patients with PG. PG patients were identified using International Classification of Diseases-9 code and divided into adults and children. For each age group, the PG patients were compared with non-PG patients. The Breslow-Day test was used to determine the relationship between PG and associated diagnoses. RESULTS: There were 204 of 7,384,591 children and 10,154 of 89,674,318 adults with PG. Both adult and pediatric PG patients were more likely to be female and have arteritis, arthropathy, and colitis. The PG children had a significantly greater odds ratio for having arteritis, arthropathy, and colitis but not malignancy when compared to adults. CONCLUSIONS: This is the largest study of PG in adult and child populations. It validates the associations known regarding adult PG while demonstrating that pediatric PG is much more highly associated with gastroenterologic, rheumatologic, and vascular issues and less likely to be coincident with malignancy. These differences demonstrate a need to approach the disease differently in the pediatric population, with regard to associated diagnosis.

C-spine injury and mandibular fractures: lifesaver broken in two spots.

BACKGROUND: Trauma is a leading cause of injury and mortality and may involve mandibular fractures and cervical spine injuries. Manipulation of the spine during trauma protocols and operative treatment has the potential to cause serious spinal cord injuries. The purpose of this study was to identify risk factors associated with cervical spine injury (CSI) in patients with mandibular fractures. METHODS: The National Trauma Databank (2007-2010) was used to identify patients with mandibular fractures. RESULTS: A total of 59,028 patients were identified and separated into adult and pediatric cohorts. There were 50,711 adults (86%) and 8317 children (14%). There were statistically significant lower rates of associated CSI in pediatric patients than adults (3.5% versus 7.3%, P < 0.01). Predictors of associated CSI in mandible fractures for both adults and children were older age, lower Glasgow Coma Scale, thoracic injuries, firearm or motor vehicle accident mechanisms, and symphyseal fractures. In the pediatric cohort, body, ramus, and subcondylar fractures were significantly associated with CSI. In adults, female gender, and upper extremity, abdominopelvic, and head injuries were also significantly associated with CSI. CONCLUSIONS: Multiple mandibular fractures were inversely correlated with CSI. One possibility is that energy dissipation in the mandible with multiple fractures is protective of the C-spine leading to fewer fractures. Children and adults had different associations in the pattern of mandible fractures concomitant with CSI. This has implications in management, imaging, and workup of trauma patients.

Pediatric burns: Kids' Inpatient Database vs the National Burn Repository.

OBJECTIVE: Burn injuries are one of the leading causes of morbidity and mortality in young children. The Kids' Inpatient Database (KID) and National Burn Repository (NBR) are two large national databases that can be used to evaluate outcomes and help quality improvement in burn care. Differences in the design of the KID and NBR could lead to differing results affecting resultant conclusions and quality improvement programs. This study was designed to validate the use of KID for burn epidemiologic studies, as an adjunct to the NBR. METHODS: Using the KID (2003, 2006, and 2009), a total of 17,300 nonelective burn patients younger than 20 y old were identified. Data from 13,828 similar patients were collected from the NBR. Outcome variables were compared between the two databases. RESULTS: Comparisons revealed similar patient distribution by gender, race, and burn size. Inhalation injury was more common among the NBR patients and was associated with increased mortality. The rates of respiratory failure, wound infection, cellulitis, sepsis, and urinary tract infection were higher in the KID. Multiple regression analysis adjusting for potential confounders demonstrated similar mortality rate but significantly longer length of stay for patients in the NBR. CONCLUSIONS: Despite differences in the design and sampling of the KID and NBR, the overall demographic and mortality results are similar. The differences in complication rate and length of stay should be explored by further studies to clarify underlying causes. Investigations into these differences should also better inform strategies to improve burn prevention and treatment.