ResearchPad - general https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Patients’ views on involving general practice in bowel cancer screening: a South Australian focus group study]]> https://www.researchpad.co/article/elastic_article_12554 To explore patients’ experiences of bowel cancer screening and its promotion, and perspectives on possible input from general practice for improving screening rates.DesignQualitative focus group study underpinned by a phenomenological approach.SettingThree general practice clinics in metropolitan South Australia.ParticipantsThirty active general practice patients, aged 50–74 years (60% female) who were eligible for the National Bowel Cancer Screening Program.FindingsFactors affecting screening were described, with particular concerns regarding the nature of the test, screening process and culture. There were mixed views on the role for general practice in bowel cancer screening; some participants appreciated the current process and viewed screening as out of scope of primary care services, while others were in support of general practice involvement. Roles for general practice were proposed that comprised actions across the continuum from providing information through to reminders and the provision and collection of screening kits. With a view that multifaceted strategies are required to encourage participation, community-based solutions were suggested that centred on improving screening culture and education.ConclusionsThere was a view among participants that general practice could play a useful role in supporting the uptake of the National Bowel Cancer Screening Program, however participants saw a need for multiple strategies at different levels and under different jurisdictions. ]]> <![CDATA[Physicians' Difficulties Due to Patient Safety Incidents in Korea: a Cross-Sectional Study]]> https://www.researchpad.co/article/elastic_article_10905

]]>
<![CDATA[Successful Conservative Management of Acute Appendicitis in a Coronavirus Disease 2019 (COVID-19) Patient]]> https://www.researchpad.co/article/elastic_article_10711 Appendectomy is the gold standard of treatment for acute appendicitis; however, recent evidence suggests conservative management with intravenous antibiotics may provide similar outcomes and can be used as an alternative in selected patients. Performing appendectomy in acute appendicitis patients with 2019 novel Coronavirus Disease (COVID-19) is challenging, as it involves considerable operative risks for the patients and risks for health care professionals (HCPs) exposed to COVID-19. Medical management eliminates the morbidity and mortality associated with surgery but involves significant risks of treatment failures that, in turn, may lead to perforation, peritonitis, and death. We are reporting a case of a middle-aged man with multiple co-morbidities, who was diagnosed with COVID-19 and acute appendicitis. Our patient received intravenous antibiotics for seven days with a significant improvement in symptoms. Our case report illustrates the implementation of successful conservative treatment for acute appendicitis in COVID-19 patients.

]]>
<![CDATA[Postrenal Acute Renal Failure Due to Giant Fecaloma-related Bilateral Hydronephrosis: A Case Report and Brief Literature Review]]> https://www.researchpad.co/article/elastic_article_10544 An 88-year-old woman presented to the emergency department with abdominal distention, fever, and constipation of about a week's duration. Laboratory tests showed impaired kidney function tests and fluid electrolyte values. Bilateral hydroureteronephrosis was observed on non-contrasted abdominal CT. Imaging revealed no intrinsic urological pathology (ureteral stones, etc.) that could lead to obstruction in the urinary system; however, excessively dilated and feces-loaded rectum and colon were observed. The patient was treated with conservative methods. Unfortunately, she passed away due to general condition disorder.

]]>
<![CDATA[Clinico-radiological Outcomes of Using Modified Stoppa Approach for Treating Acetabular Fractures: An Institutional Review]]> https://www.researchpad.co/article/elastic_article_10538 Introduction

Acetabular fractures are complex intra-articular fractures. The extra-pelvic ilioinguinal (IL) has been the workhorse for the anterior approach and remains the gold standard. The major difference between the IL and the Stoppa approaches is that Stoppa allows for the avoidance of the middle window of the IL approach. Hence, the modified Stoppa approach (MSA) can be adopted by a comparatively less experienced surgeon with minimal complications. The purpose of this study is to evaluate the radiological and functional outcomes of patients operated on using the MSA.

Materials and methods

Patients operated on by the MSA for acetabular fractures with a minimum of one year of clinical and radiographic follow-ups were reviewed. CT scans and radiographs were evaluated for the fracture pattern, time to surgery, operative time, blood loss, quality of reduction (Matta criterion), FO [Harris hip score (HHS) and Nach Merle d'Aubigné and Postel score (NMAPS)] and complications (perioperative and follow-up). Twenty-three of 26 patients with 45 acetabular fractures operated between January 2016 and November 2018 were included. Descriptive statistics were used for demographic data, and Pearson’s chi-squared statistic was calculated for the association between radiological and functional outcomes.

Results 

Among the 23 patients, the mean age was 38.5 years (range: 15-65) with a male-to-female ratio of 18:5. The average time to surgery was 11.5 days (range: 2-32), operating time was 155 minutes (range: 90-243), and average blood loss was 650 ml (range: 500-1,250). A supplemental lateral window was used in 20 patients (87%), and three underwent the combined anterior and posterior [Kocher Langenbacks (KL)] approach. All cases were unilateral. The transverse fracture was the most common pattern (eight patients) followed by the associated both-column fracture in six and T-type, isolated anterior column fracture, and anterior column and posterior hemi-transverse fractures seen in three patients each. Iliac blade (high anterior column) fracture was seen in 14 cases and one patient had associated sacral type II fracture. Road traffic accidents accounted for 61% of the injuries and injury severity score (ISS) of >15 (polytrauma) was seen in more than 50% of the cases (associated with other organ injuries). The radiological outcome was anatomical in 52% of the cases, imperfect in 39%, and poor in 9%. The functional outcomes were good to excellent in 74% (HHS) and 79% (NMAPS) of the cases. The association and correlation between them were nonsignificant (p-value: >0.5). Two patients developed a superficial infection and three had iatrogenic obturator nerve palsy. One patient had a direct inguinal hernia, one had grade 3 bedsores, and two patients developed grade 2 arthritic changes during the follow-up. No case of vessel injury was encountered.

Conclusion

Adoption of the MSA for the treatment of acetabular fractures leads to a good-to-excellent anatomical reduction in most cases while providing direct visualization of the quadrilateral plate and posterior column. The learning curve is smaller for less-experienced surgeons in terms of complications and results. We recommend this technique as a viable alternative to the IL approach for anterior acetabular fixation.

]]>
<![CDATA[Subterranean biodiversity and depth distribution of myriapods in forested scree slopes of Central Europe]]> https://www.researchpad.co/article/elastic_article_9853 The shallow underground of rock debris is a unique animal refuge. Nevertheless, the research of this habitat lags far behind the study of caves and soil, due to technical and time-consuming demands. Data on in scree habitat from eleven localities in seven different geomorphological units of the Czech and Slovak Republics were processed. Based on previous studies, as well as knowledge of cave and soil fauna, it was hypothesised that the occurrence of a varied and peculiar fauna would show a pattern of depth distribution with variations due to local specificities. From 2005–2016 (at least one year on each site), macrofauna was collected via sets of three long-term exposed subterranean traps consisting of 110 cm long perforated tube, with ten cups located in a gradient at 5–95 cm below the soil surface. In total, 14 symphylans (not identified to species level), 271 centipedes (23 spp.) and 572 millipedes (32 spp.) were sampled. The overall depth distribution of centipedes and millipedes appeared to have relatively similar pattern, with both groups being found at all depth levels. Nevertheless, this pattern depends on locations. The depth distribution trend lines are mostly in the form of an asymmetric ‘U’, with decreased abundance until the middle of the gradient, followed by increase in the deepest levels. Epigeic species were sporadically distributed along the whole depth gradient, but concentrated at the soil surface, while some subterranean species, such as the centipede and the millipedes , and , were recorded in the deepest parts of the gradient. This characterises the debris community as a mixture of soil and subterranean species with an absence of species exclusively found in caves. The use of different fixation methods in traps had a significant and selective impact on samples; millipedes were either attracted by ethylene glycol or repelled by formaldehyde. Centipedes were also captured more frequently in ethylene glycol; however, the species composition varied in each of the fixatives. Depth distribution of myriapods was similar in both fixative solutions. Traps with these fixatives could be recommended for similar ecological studies.

]]>
<![CDATA[SAT-141 Glycoprotein NMB (GPNMB) Is Pro-Tumorigenic in TSC2-Null Cancer Cells and Is a Potential Drug Target and Biomarker for Lymphangioleiomyomatosis (LAM)]]> https://www.researchpad.co/article/elastic_article_9551 Lymphangioleiomyomatosis (LAM) is an estrogen-sensitive lung disease found almost exclusively in women that is characterized by hyperproliferation of smooth muscle cells forming small tumors, or LAM lesions throughout the lungs of patients. Growth of these tumors leads to progressive loss of pulmonary function, and sometimes subsequent lung transplantation. LAM tumor cells contain mutations in either the TSC1 or TSC2 genes, leading to activation of the mTORC1 pathway. In fact, mTOR inhibitors such as sirolimus are commonly used to treat LAM; however, these drugs are not always effective and have significant side effects, suggesting the need for new therapeutic targets. Interestingly, another important feature of LAM cells is that they express melanocytic markers that are normally found in melanocytes or melanoma cells. From RNASeq analysis of a mouse model for LAM that we designed, we discovered significant upregulation of the melanocytic marker Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB), a type I transmembrane protein. GPNMB was not only highly expressed in our mouse model (a uterine specific TSC2-null mouse), it was also expressed in TSC2-null cell lines, and human LAM patient lung samples. In our hands, knocking down GPNMB expression by siRNA directed against GPNMB mRNA decreased migration and proliferation in TSC2-null cells. Additionally, we found that GPNMB’s large ectodomain is shed by TSC2-null cells and can be detected in the blood of human patients with LAM. Finally, MMP 2 and 9 can be secreted as a result of ectodomain shedding and its interaction with integrins. Accordingly, we did indeed see a decrease in MMP 2/9 expression in TSC2-null cells with reduced GPNMB expression from treatment with siRNA directed against GPNMB mRNA. Overall, our results demonstrate the potential importance of GPNMB in LAM tumor progression, and suggest that GPNMB may be a possible LAM biomarker and target for its treatment.

]]>
<![CDATA[Amyand's Hernia: Perforated Appendix in an Incarcerated Inguinal Hernia]]> https://www.researchpad.co/article/elastic_article_9470 Amyand’s hernia is an unusual condition characterized by the presence of a normal or inflamed appendix located within an inguinal hernia. We present a rare situation wherein a 56-year-old male patient presented with an incarcerated inflamed appendix in a right inguinal hernia. He was emergently taken to the operating room, with diagnostic laparoscopy changed to open, due to incarcerated cecum and terminal ileum. The incarcerated segment had to be resected with primary anastomosis. The inflamed and purulent contents were washed out, and the hernia defect was left unrepaired due to the presence of abscess in the inguinal canal. 

]]>
<![CDATA[Unusual Chemotherapeutic Resistant Testicular Embryonal Germ Cell Tumor with Widespread Metastasis in a Case of Klinefelter Syndrome: A Case Report]]> https://www.researchpad.co/article/elastic_article_9446 Cryptorchidism is an undeniable risk factor for testicular germ cell tumors (TGCTs) and is also commonly associated with Klinefelter syndrome (KS) patients. Embryonal cell carcinoma usually shows strong expression of CD30 and OCT3/4, with patchy staining of PLAP1. Most patients with nonseminomatous GCTs (NSGCTs) can achieve total remission with proactive chemotherapy, and most can be cured. We present an extremely rare case of a testicular embryonal germ cell tumor that is atypical in its gene expression and response to chemotherapy treatment.

A 71-year-old male patient presented in July 2019 with abdominal pain of unknown duration, weight loss for one year, and recent history of altered bowel habits. His past medical history is significant for KS and congenital unilateral cryptorchidism. Physical examination yielded mild abdominal distention and bilateral inguinal lymphadenopathy. Imaging revealed a posterior mediastinal mass and large retroperitoneal masses. The above features, in addition to the history of KS and unilateral cryptorchidism, were highly suggestive of a testicular retroperitoneal germ cell tumor. Serologic studies revealed elevated lactate dehydrogenase (LDH) while other tumor markers were normal. Excisional biopsy of inguinal lymph nodes revealed poorly differentiated embryonal cell carcinoma with strong expression of SALL4, a rare expression of OCT 3/4, and the absence of expression of CD30 and placental alkaline phosphatase (PLAP). The patient was given four cycles of bleomycin, etoposide and platinum (BEP) chemotherapy, as is the standard chemotherapy regimen for these tumors, without any significant change in the size of the masses or lymph nodes.

Unfortunately, there are no specific guidelines when it comes to the management of KS patients with testicular GCTs (embryonal cell carcinoma) with aberrant histological markers and normal serum tumor markers. These findings in combination with chemotherapeutic resistance indicate a need for more specific treatment modalities and follow-up for unusual testicular embryonal GCTs in KS patients.

]]>
<![CDATA[Robotic versus Laparoscopic Cholecystectomy: Case-Control Outcome Analysis and Surgical Resident Training Implications]]> https://www.researchpad.co/article/elastic_article_9386 Background

The robotic approach in surgery is becoming more widely used in many subspecialties. Robot-assisted laparoscopic procedures provide potential improvements in clinical outcomes due to improved visualization and enhanced surgical ergonomics. In this study, we measured and compared outcomes of robot-assisted laparoscopic cholecystectomy with the conventional laparoscopic technique, as well as the implications for the training of surgical residents.

Method

We compared a total of 244 patients undergoing minimally invasive cholecystectomies performed by one surgeon between July 2013 and June 2016 examining relevant clinical outcomes including operative room (OR) time, length of hospital stay (LOS), readmission to the hospital, post-operative emergency department (ED) visits, and post-operative pain between laparoscopic single-incision cholecystectomy and robot-assisted laparoscopic cholecystectomy. A chi-square test and Student’s t-test were used to compare these variables between the two groups. Propensity score matching (PSM) was used using gender, age, and body mass index (BMI) as variables.

Results

From the total number of procedures of 244, 144 were included in the laparoscopic group and 100 in the robot-assisted group. The robot-assisted patients had a shorter post-operative LOS (mean: 0.8 vs. 1.6 days; p = 0.002). There was no significant difference in the OR time (mean: 64.8 vs. 65.0 minutes; p = 0.945), readmissions (4.0% vs. 3.5%; p = 0.830), post-operative ED visits (7.0% vs. 7.6%; p = 0.851), or post-operative pain (13.0% vs. 21.3%; p= 0.137). Robotic cholecystectomy patients were younger (mean: 46 vs. 52 years; p = 0.023) and had lower BMIs (mean: 31 vs. 33; p = 0.038). Because of these differences, we compared the two groups using PSM that confirmed the shorter LOS in the robotic group (mean: 0.9 vs. 1.9; p = 0.009).

Conclusions

These results demonstrate that robotic cholecystectomies can reduce LOS for patients undergoing laparoscopic cholecystectomy, without increasing OR time. Increased surgeon experience with robotic procedures and improved OR efficiency will allow greater opportunities for resident participation. Robotic training curricula need to be employed and objectively evaluated to improve surgical resident skill acquisition and provide earlier and progressive clinical participation in robotic procedures.

]]>
<![CDATA[Lymph Node Ratio as a Prognostic Marker in Rectal Cancer Survival: A Systematic Review and Meta-Analysis]]> https://www.researchpad.co/article/elastic_article_9385 Introduction 

The lymph node ratio (LNR) is defined as the ratio of the number of positive lymph nodes to the total number of nodes retrieved. LNR has recently emerged as a prognostic factor in rectal cancer. The objective of our study was to pool eligible studies to elucidate the prognostic role of LNR on overall survival (OS) and disease-free survival (DFS) in rectal cancer patients using a meta-analysis.

Methods

A systematic database search was performed in MEDLINE and Embase for relevant studies that reported LNR in rectal cancer. Two authors independently screened the relevant articles for selection and data extraction. As a result, a list of such studies and references, published in English up to December 2019, was obtained, and a total of 4,486 node-positive patients in 18 studies were included in this meta-analysis. RevMan software 5.3 (Cochrane Collaboration, the Nordic Cochrane Centre, Copenhagen) was used for conducting all statistical analyses.

Results

A higher LNR was significantly correlated with worse OS [hazard ratio (HR): 2.60; 95% confidence interval (CI): 2.21-3.06; p≤.00001] and DFS (HR: 2.43; 95% CI: 2.11-2.80; p≤.00001) in node-positive rectal cancer patients. Besides, LNR is an independent predictive and prognostic marker of OS and DFS (HR: 2.52; 95% CI: 2.17-2.94; p≤.00001 with I2=0%; p=.32 and HR: 2.63; 95% CI: 2.17-3.18; p≤.00001 with I2=0%; p=.63 respectively, irrespective of lymph nodal harvest).

Conclusions

Our present study demonstrates that LNR is an independent predictor of survival in rectal cancer. LNR should be considered as a parameter in future oncological staging systems. Further well-designed randomized control trials to prospectively assess LNR as an independent predictor of rectal cancer survival are necessary before its application in daily practice.

]]>
<![CDATA[Independent medical evaluation of general practitioners’ follow-up of sick-listed patients: a cross-sectional study in Norway]]> https://www.researchpad.co/article/elastic_article_9110 The study was designed to examine the sufficiency of general practitioners’ (GPs) follow-up of patients on sick leave, assessed by independent medical evaluators.DesignCross-sectional studySettingPrimary health care in the Western part of Norway. The study reuses data from a randomised controlled trial—the Norwegian independent medical evaluation trial (NIME trial).ParticipantsThe intervention group in the NIME trial: Sick-listed workers having undergone an independent medical evaluation by an experienced GP at 6 months of unremitting sick leave (n=937; 57% women). In the current study, the participants were distributed into six exposure groups defined by gender and main sick leave diagnoses (women/musculoskeletal, men/musculoskeletal, women/mental, men/mental, women/all other diagnoses and men/all other diagnoses).Outcome measureThe independent medical evaluators assessment (yes/no) of the sufficiency of the regular GPs follow-up of their sick-listed patients.ResultsEstimates from generalised linear models demonstrate a robust association between men with mental sick leave diagnoses and insufficient follow-up by their regular GP first 6 months of sick leave (adjusted relative risk (RR)=1.8, 95% CI=1.15–1.68). Compared with the reference group, women with musculoskeletal sick leave diagnoses, this was the only significant finding. Men with musculoskeletal diagnoses (adjusted RR=1.4, 95% CI=0.92–2.09); men with other diagnoses (adjusted RR=1.0, 95% CI=0.58–1.73); women with mental diagnoses (adjusted RR=1.2, 95% CI=0.75–1.77) and women with other diagnoses (adjusted RR=1.3, 95% CI=0.58–1.73).ConclusionsAssessment by an independent medical evaluator showed that men with mental sick leave diagnoses may be at risk of insufficient follow-up by their GP. Efforts should be made to clarify unmet needs to initiate relevant actions in healthcare and work life. Avoiding marginalisation in work life is of the utmost importance.Trial registration number NCT02524392; Post-results. ]]> <![CDATA[Composition and Natural History of Snakes from Etá Farm region, Sete Barras, south-eastern Brazil]]> https://www.researchpad.co/article/elastic_article_8995 Approximately 140 snake species are known to occur in the Atlantic Forest with nearly half being endemic to this ecoregion. However, the Atlantic forest is one of the most threatened tropical ecoregions, with only 16% of its original area remaining as forest. This extensive habitat loss must have had a negative effect on its snake fauna. Indeed, 53% of the threatened snakes of Brazil occur in the Atlantic forest. Therefore, basic natural history information that can potentially contribute to the conservation of Atlantic forest snakes are urgently needed. Here the natural history of a snake assemblage at Etá Farm region, Sete Barras municipality, south-eastern Brazil is described, and a visual guide and an identification key provided that can be used by researchers and local people to identify snakes from this region. Most of the species found in the field use both open areas and forests, are primarily terrestrial, present diurnal activity, and include frogs in their diet. A higher number of enlarged follicles, eggs, and/or embryos were recorded during the warm and rainy season. Seventeen different types of defensive tactics were recorded in the species found in the field. This study provides useful information for understanding the structure of snake assemblages of the Atlantic Forest and is potentially useful for conservation assessments and for designing conservation plans.

]]>
<![CDATA[SAT-147 Endogenous Expression of TCF21 by CRISPR/dCas9 System Results in Different Biological Responses in Adrenocortical Carcinoma and Hepatocarcinoma]]> https://www.researchpad.co/article/elastic_article_8780 Transcription factor 21 (TCF21/POD-1/Epicardin) inhibits the expression of SF-1 (NR5A1) by binding to the promoter E-box site in adrenocortical carcinoma (ACC). In contrast, TCF21 promotes increased expression of LRH-1 in hepatocarcinoma cell line, HepG2 cells, by binding to the Small Heterodimer Partner (SHP/NR0B2) promoter region, an LRH-1 negative regulator. Epigenetic alteration induced TCF21 loss of function and has been associated with increased of cellular migration and invasion. In ACC, TCF21 promoter is hypermethylated and less expressed. Our aim was to evaluate the effect of TCF21 by expressing or silencing TCF21 in adrenocortical pediatric adenoma, ACA-T7 cells, in ACC cell lines SW-13 and H295R cell line, and in HepG2 cell line. Were used CRISPR/dCas9/TCF21 and pCMVMycPOD1 or siRNATCF21 to express and silence TCF21, respectively. Increased expression of TCF21 in H295RpCMVMycPOD1 and SW-13CRISPR/dCas9/TCF21 cells resulted in significantly decreased cell migration and invasion (53.2±36.1%/70.8±26.5% and 82.6±4.2%/100%, respectively). In ACA-T7/siRNATCF21 cells, the inhibition of TCF21 resulted in significant increase migration and invasion capacity (45.0±12.7%/33.1±17.4%) compared with ACA-T7 cells. Higher TCF21 expression in HepG2CRISPR/dCas9/TCF21 increased invasion [147.08±16.54% (p<0.0001)]. Analysis of metalloproteinase genes expression showed that TCF21 significantly (p<0.01) increased MMP8 expression in SW-13CRISPR/dCas9/TCF21 and H295R/pCMVMycPod-1 whereas decreased MMP9 and MMP2 (p< 0.0001). The opposite effect was observed in ACA-T7/siRNATCF21. Moreover, in HepG2CRISPR/dCas9/TCF21 cells was observed an increase of MMP2 and MMP9 expression (p<0.001). These results suggest that TCF21 regulate epithelial mesenchymal transition and vice versa (EMT/MET) in tumors depending on cellular context. Supported by Fapesp and Capes.

]]>
<![CDATA[SUN-LB13 Idiopathic Infantile Hypercalcemia Secondary to CYP24A1 Mutation: A Rare Case Without Exogenous Vitamin D Supplementation]]> https://www.researchpad.co/article/elastic_article_8709 Background: Mutations in CYP24A1, which encodes 24-hydroxylase, the key enzyme for Vitamin D breakdown, cause symptomatic hypercalcemia and nephrocalcinosis in infants on Vitamin D supplementation. New, symptomatic diagnoses of idiopathic infantile hypercalcemia without exogenous supplementation are rare. Previous case reports describe a seasonal effect with worsening hypercalcemia and hypercalciuria during summertime, attributed to increased sun exposure and endogenous Vitamin D production. Clinical Case: A 10-month-old female presented to endocrine care with hypercalcemia and nephrocalcinosis, detected on renal ultrasound (US) due to history of UTI. Her first renal US and serum calcium (Ca) at 3mo of age were normal. Subsequent renal US at 6mo and 9mo of age demonstrated nephrocalcinosis, prompting nephrology and endocrine evaluation. History was significant for failure to thrive. She was born in the fall, with worsening hypercalcemia and nephrocalcinosis during the summer. Diet consisted of standard infant formula and age appropriate solid foods with no added Vitamin D supplementation (~300 IU/day in her formula). She had no family history of nephrocalcinosis, nephrolithiasis, bone disease, or disorders of Ca regulation. Initial labs were notable for Ca corrected for albumin 11.5 (7.8-11.1 mg/dL), PTH <4 (8.7-77.1 pg/mL), 25-OH-Vitamin D 81 (30-96 ng/mL), 1,25-OH-Vitamin D 23.1 (26.1-95 pg/mL), Urine Ca/creatinine ratio of 0.9 mg/mg (<0.81), normal chromosomal microarray, and normal thyroid function tests. She was started on reduced mineral formula PM 60/40. One week later, repeat Ca level increased to Ca corrected 14.2 (7.8-11.1 mg/dL). She was admitted for IV fluids and pamidronate, and was transitioned to a low Ca and Vitamin D formula (Calcilo), with improvement in Ca levels. Testing revealed an increased ratio of 25-OH-Vitamin D to 24,25-OH-Vitamin D of 192 (normal <25), and genetic testing showed 2 pathogenic missense mutations in CYP24A1 genes: c.1226T>C p.(Leu409Ser) and c.1186C>T p.(Arg396Trp). The Leu409Ser mutation has shown a small amount of 24-hydroxylase activity in previous in vitro analysis. She has continued a low Ca diet with stable Ca corrected of 10.7-10.8 (8.7-9.8 mg/dL) and significantly improved weight gain. Conclusion: This is one of the few documented cases of symptomatic idiopathic infantile hypercalcemia secondary to CYP24A1 mutation in an infant without exogeneous Vitamin D supplementation. Her nephrocalcinosis and hypercalcemia worsened over the summer, suggesting increased sun exposure may have been a contributing factor. This case demonstrates that 1,25-OH-Vitamin D levels may be normal or low in this condition, particularly for individuals with the Leu409Ser mutation who may retain partial 24-hydroxylase function.

]]>
<![CDATA[SAT-LB26 A Dual Role for IGF-1R in Mammary Tumorigenesis]]> https://www.researchpad.co/article/elastic_article_8586 The insulin-like growth factor type 1 receptor (IGF-1R) is now thought to have a dual function in breast cancer. Several studies have shown overexpression of the IGF-1R pathway results in increased tumor cell proliferation and survival. Recent loss-of-function models have shown decreased mammary tumorigenesis latency and increased metastasis. These recent studies correlate with analyses of human patient datasets identifying worse overall survival with low IGF-1R expression. Similarly, inhibition of IGF-1R in the clinic has had no affect or has led to worse outcomes supporting the hypothesis that the IGF-1R may have tumor suppressive properties. Our prior published studies revealed loss of IGF-1R function results in heightened tumor epithelial stress, which alters the tumor microenvironment to be permissive for metastasis. Therefore, we asked does the loss of IGF-1R inherently change the tumor epithelium or is it simply the alterations of the microenvironment that lead to a metastatic primary tumor? We first analyzed cell invasion of primary tumor epithelial cells from a mouse tumor model driven by the Wnt1 oncogene (MMTV-Wnt1) and with reduced IGF-1R signaling by expression of a dominant-negative transgene (MMTV-dnIGF-1R). Epithelial cells from the MMTV-Wnt1/dnIGF-1R (bigenic) tumors invaded at the same rate as MMTV-Wnt1 tumor epithelial cells by tail vein injection suggesting invasive capacity is unchanged with reduced IGF-1R signaling. Interestingly, size of lung micrometastases from tail vein injected bigenic tumor epithelial cells was significantly reduced and the number also decreased over time in part due to a proliferative defect determined by immunostaining for pH3. Similarly, bigenic primary tumor epithelial cells injected into the mammary gland fat pad failed to form tumors suggesting alterations in cell adhesion. Consistent with this observation, E-cadherin gene and protein expression were decreased in the bigenic tumor epithelium compared to MMTV-Wnt1 tumors. In vitro analysis of cell adhesion in MMTV-Wnt1 primary epithelial cells resulted in both K8+ (luminal) and K14+ (basal) tumor epithelial cells adherence, while only K14+ cells from bigenic tumors adhered to collagen. Similarly, the lung micrometastases from tail vein injections exhibited predominantly K14+ cells. Analysis of MMTV-Wnt1 and bigenic primary tumors using single cell RNAseq revealed alterations in both stromal and epithelial populations that may contribute to bigenic primary tumor growth and metastasis. These data support the conclusion that inhibiting IGF-1R signaling results in both alterations to the tumor epithelium (partial EMT) and microenvironment that result in metastasis, but also, that the IGF-1R deficient metastatic cells need a niche or paracine signaling to proliferate.

]]>
<![CDATA[SAT-148 Ectopic ACTH Secretion Has Varied Presentation and Requires Individualized Treatment - One Size Does Not Fit All]]> https://www.researchpad.co/article/elastic_article_8565 Ectopic ACTH secretion (EAS) presents in myriad ways. We present five cases of EAS to highlight similarities and differences in presentation and treatment. The first woman with known metastatic lung neuroendocrine tumour (NET) for two years presented with facial fullness, proximal weakness, worsening hypertension and hypokalaemia. Random cortisol of 2742nmol/L (99.39mcg/dL), with adrenocorticotrophic hormone (ACTH) of 201ng/L (5-50), was in keeping with EAS. She received medical treatment followed by bilateral adrenalectomy with EAS resolution and development of adrenal insufficiency. She is doing well. The second woman with proximal weakness was evaluated by neurologists. All neurological tests were normal but facial fullness and easy bruising was noted. Random cortisol was 875nmol/L (31.71mcg/dL) and ACTH was 90 ng/L. Imaging revealed metastatic liver disease with unknown primary and biopsy confirmed NET. Cortisol rose despite medical treatment and she died within fifteen months. The third woman with significant smoking history presented with haemoptysis and breathlessness. A right lung mass was suspected on chest X-ray and confirmed with CT. Endobronchial ultrasound-guided biopsy revealed small cell lung cancer (SCLC). She developed generalised weakness and severe hypokalaemia. Random cortisol of 1645nmol/L (59.63mcg/dL) with ACTH of 282ng/L suggested EAS. Despite medical treatment, she died within two weeks. The fourth woman presented with confusion, hypertension and severe hypokalaemia. Morning cortisol of 8557nmol/L (310.19mcg/dL) and random ACTH of 73ng/L were suggestive of EAS. CT demonstrated left lung mass with widespread metastases. She deteriorated and died within 2 weeks. Our only man had incidentally discovered metastatic liver lesions on ultrasound. Further imaging revealed prostatic mass and biopsy showed small cell neuroendocrine cancer. He presented with severe hypokalaemia. Random cortisol was 1065nmol/L (38.61mcg/dL) and ACTH was 188ng/L. He was commenced on medical treatment but declined rapidly and died.

All our patients had profound hypokalaemia and metastatic disease at presentation. Many patients do not exhibit classical cushingoid features as EAS tends to develop acutely and underlying malignancy drives weight loss. A high index of suspicion is required to make a diagnosis. EAS should be considered in patients with proximal myopathy, pigmentation, resistant or severe hypokalaemia or hypertension and known or suspected malignancy. Early and quick control of cortisol excess is essential to minimise cardiometabolic abnormalities, severe infections and thromboembolic complications. Prognosis depends upon age, frailty, comorbidity, nature of neoplasm and extent of hypercortisolaemia. Adrenolytics with or without bilateral adrenalectomy, reduction in tumour burden and management of complications are the mainstay of treatment.

]]>
<![CDATA[SUN-065 Bone Health Outcomes in a Large, Diverse Pediatric Cohort Undergoing Hematopoietic Stem Cell Transplant]]> https://www.researchpad.co/article/elastic_article_8544 Background:

Impaired bone mineral density (BMD) is a known complication of hematopoietic stem cell transplantation (HSCT) in adults and may lead to increased fracture risk. Little is known in pediatrics about the risks for impaired BMD and fragility (low trauma) fractures after HSCT. Factors that may influence the risk of bone disease include underlying diagnosis, glucocorticoid exposure, and HSCT complications (e.g. graft versus host disease (GVHD)). Our study aims to describe the incidence of fragility fractures in a large diverse pediatric HSCT population and to identify risk factors of both fracture and impaired BMD.

Methods:

We reviewed the records of 237 patients (age ≤ 21 years at time of transplant) who underwent HSCT at our institution between January 2015 and March 2018. The primary endpoint was incidence of fragility fractures and the secondary endpoint was assessment of BMD on dual-energy X-ray absorptiometry (DXA). We analyzed DXA results at one-year post-HSCT in 72 out of 206 patients alive at 1 year.

Results:

There were 25/237 (10.5%) patients with evidence of fragility fracture on x-ray. Of those, 18/25 (72%) were spine fractures. For patients who had fractures, median time to fracture was 5.9 months after BMT. Mortality at one-year was proportionally higher, though not significant (p=0.11) in patients who had at least one fragility fracture (24%; 6/25) compared to patients without fragility fracture (12%; 25/212). Vitamin D status at one-year post transplant was sufficient (>20ng/mL) in 94% (160/171) of patients measured. There was no difference in incidence of fracture between vitamin D sufficient and insufficient patients. The median height-for-age adjusted Z-score (HAZ) for spine BMD at one-year post transplant was 0.13 in all patients. The median HAZ spine BMD Z-score in patients with fragility fracture was -1.64, though data was available for only 5 patients.

Conclusions:

The incidence of fragility fractures, especially vertebral compression fractures, after pediatric HSCT is striking and is higher than in adult populations. Furthermore, there are likely additional asymptomatic patients with occult fractures not detected in out cohort. Additional analysis will assess the associations between underlying medical diagnosis, GVHD, and chronic glucocorticoid exposure on fragility fracture risk. The high incidence of fragility fractures seen in this study advocates for establishing bone health screening protocols with attention toward spinal imaging in pediatric patients undergoing HSCT.

]]>
<![CDATA[Commentary: Differences of Perceived Image Generated through the Web Site: Empirical Evidence Obtained in Spanish Destinations]]> https://www.researchpad.co/article/elastic_article_7514 <![CDATA[Commentary: An enzymatic pathway in the human gut microbiome that converts A to universal O type blood]]> https://www.researchpad.co/article/elastic_article_7418