Infiltrative Intramuscular Lipoma with Overlying Fascial Defect in the Anterior Thigh: A Case Report.

This case report details a unique presentation of an infiltrative intramuscular lipoma in the anterior thigh of a 51-year-old female with an overlying fascial defect. The patient reported a progressively enlarging left thigh mass associated with pain exacerbated by knee movement and exercise. MRI revealed a homogeneous intramuscular lipoma without contrast enhancement with a fascial defect. An 8 cm longitudinal incision exposed a 7 x 4 cm fascial defect overlying the lipomatous mass within the rectus femoris muscle. Pathological analysis confirmed an intramuscular lipoma without malignancy. Follow-ups at two, six, and 12 weeks demonstrated pain resolution and no soft tissue bulge. This case underscores the importance of distinguishing intramuscular lipomas from other neoplasms, such as lipomatosis and liposarcomas. The association of a fascial defect with intramuscular lipomas is unprecedented and may be due to the increased pressure on the fascia by the lipoma. The report emphasizes the role of MRI in diagnosis and appropriate surgical management, and highlights the need for further exploration into the etiology of fascial defects associated with intramuscular lipomas.

Differentiating Between Obturator and Inferior Epigastric Arterial Injury in Traumatic Pelvic Hemorrhage: A Case Report.

The pubic branches of the inferior epigastric and obturator arteries are subject to injury from pelvic trauma or surgery within the retropubic space. Such injuries can result in severe internal hemorrhage that can lead to hemodynamic instability if not adequately controlled. Due to their anatomical proximity and anastomosis, it is critical to determine which artery is hemorrhaging in order to provide accurate embolization. In the presented case, a geriatric patient suffered a fall from standing height that resulted in bilateral and multiple pelvic fractures. CT angiography of the abdomen demonstrated active left-sided pelvic hemorrhage and a resultant 10 cm anterior extraperitoneal hematoma, likely exacerbated by existing anticoagulant usage. Urgent embolization of the inferior epigastric artery was performed in addition to multiple transfusions. The patient recovered without any procedural complications and was later discharged for rehabilitation.

Biliary Outlet Obstruction Due to Pancreatic Calculi in a Post-cholecystectomy Patient.

Chronic pancreatitis has been shown to cause various pathologies, such as biliary strictures and pancreatic malignancies, which can in turn result in biliary outlet obstruction. However, a pancreatic calculus itself resulting in biliary obstruction has been far less observed. The patient in question had a documented history of chronic alcoholism and received a cholecystectomy decades prior to the onset of cholestatic symptoms. Cholangiography demonstrated no indication of biliary stricture formation, nor was there radiological evidence of pancreatic pseudocyst or malignant formation. CT evidence across a decade of time established a storyline of pancreatic calculi formation, migration, and resultant biliary obstruction. Subsequent endoscopic sphincterectomy, pancreatic calculi removal, and biliary tree stent placement resulted in laboratory value normalization and clinical symptom resolution.

Adult Radiographic Presentation of Corpus Callosal Agenesis With a Single Interhemispheric Cyst and Dandy-Walker Malformation: A Case Report.

Agenesis or dysgenesis of the corpus callosum may occur due to ischemic, toxic, traumatic, or another insult to the fetus in the first trimester. Occasionally, such a malformation is associated with an interhemispheric cyst, among other central nervous system anomalies. Holoprosencephaly tends to mimic this radiographic presentation, which is where key imaging findings are helpful to differentiate between these entities. We present a 56-year-old male patient who was found to have a monoventricle, corpus callosum agenesis, interhemispheric cyst, and a Dandy-Walker malformation. The patient presented with a right acetabular fracture with computed tomography (CT) of the brain revealing the congenital brain abnormalities. The patient's past medical history was notable for a seizure disorder identified during early adulthood. The CT scan of the head revealed a large monoventricle with an associated midline dorsal interhemispheric cyst and a Dandy-Walker malformation. The absence of both the corpus callosum and septum pellucidum was noted, with the presence of a monoventricle, leading to an initial differential of holoprosencephaly. Further review of the findings suggested instead a rare congenital presentation consisting of corpus callosum agenesis and an interhemispheric cyst. This case highlights a unique radiographic presentation of multiple brain anomalies, rarely presented in non-pediatric literature, which may help determine appropriate surgical and medical management for similarly affected adult individuals.

Postoperative Infection and Revision Surgery Rates in Foot and Ankle Surgery Without Routine Prescription of Prophylactic Antibiotics.

INTRODUCTION: Surgical site infections (SSIs) are associated with patient morbidity and increased healthcare costs. Limited literature in foot and ankle surgery provides guidance about routine administration of postoperative antibiotic prophylaxis. The purpose of this study was to examine the incidence and revision surgery rates of SSI in outpatient foot and ankle surgeries in patients not receiving oral postoperative antibiotic prophylaxis. METHODS: A retrospective review of all outpatient surgeries (n = 1517) conducted by a single surgeon in a tertiary referral academic center was conducted through electronic medical records. Incidence of SSI, revision surgery rate, and associated risk factors were determined. The median follow-up was 6 months. RESULTS: Postoperative infection occurred in 2.9% (n = 44) of the surgeries conducted, with 0.9% of patients (n = 14) requiring return to the operating room. Thirty patients (2.0%) were diagnosed with simple superficial infections, which resolved with local wound care and oral antibiotics. Diabetes (adjusted odds ratio, 2.09; 95% confidence interval, 1.00 to 4.38; P = 0.049) and increasing age (adjusted odds ratio, 1.02; 95% confidence interval, 1.00 to 1.04; P = 0.016) were significantly associated with postoperative infection. DISCUSSION: This study demonstrated low postoperative infection and revision surgery rates without the routine prescription of prophylactic postoperative antibiotics. Increasing age and diabetes are signficant risk factors for developing a postoperative infection.

MmCMS: mouse models' consensus molecular subtypes of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1-4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems to test new drug treatments. Despite its importance, dual-species classification has been limited by the lack of a reliable approach. Here we utilise, develop and test a set of options for human-to-mouse CMS classifications of CRC tissue. METHODS: Using transcriptional data from established collections of CRC tumours, including human (TCGA cohort; n = 577) and mouse (n = 57 across n = 8 genotypes) tumours with combinations of random forest and nearest template prediction algorithms, alongside gene ontology collections, we comprehensively assess the performance of a suite of new dual-species classifiers. RESULTS: We developed three approaches: MmCMS-A; a gene-level classifier, MmCMS-B; an ontology-level approach and MmCMS-C; a combined pathway system encompassing multiple biological and histological signalling cascades. Although all options could identify tumours associated with stromal-rich CMS4-like biology, MmCMS-A was unable to accurately classify the biology underpinning epithelial-like subtypes (CMS2/3) in mouse tumours. CONCLUSIONS: When applying human-based transcriptional classifiers to mouse tumour data, a pathway-level classifier, rather than an individual gene-level system, is optimal. Our R package enables researchers to select suitable mouse models of human CRC subtype for their experimental testing.

Recurrent Retroperitoneal Lymphatic Malformation in a Pediatric Patient: A Case Report.

Retroperitoneal lymphatic malformations are rare, benign, cystic tumors of the lymphatic system, accounting for 1% of all lymphatic malformation manifestations. Lymphatic malformations are often asymptomatic, but may clinically present with abdominal pain and a palpable mass. Initial diagnostic workup is challenging due to the difficulty of differentiating from masses that may arise from the pancreas, liver, and kidney. This report describes a recurrent retroperitoneal lymphatic malformation in a 15-year-old male. The patient presented with abdominal pain and radiological imaging demonstrated abdominal fluid collection. Following conservative management using aspiration, the patient presented three months later with recurrent abdominal pain. Radiological imaging identified a large thin-walled cystic lesion in the right hemiabdomen containing minimal thin internal septations. Histological analysis confirmed the lymphatic malformation following computed tomography-guided biopsy. The patient underwent aspiration and was referred for outpatient sclerotherapy to prevent future abdominal fluid collection. This case highlights conservative management of recurrent retroperitoneal lymphatic malformation, both on the initial and subsequent presentation.

First-in-Human Phase I/II ICONIC Trial of the ICOS Agonist Vopratelimab Alone and with Nivolumab: ICOS-High CD4 T-Cell Populations and Predictors of Response.

PURPOSE: The first-in-human phase I/II ICONIC trial evaluated an investigational inducible costimulator (ICOS) agonist, vopratelimab, alone and in combination with nivolumab in patients with advanced solid tumors. PATIENTS AND METHODS: In phase I, patients were treated with escalating doses of intravenous vopratelimab alone or with nivolumab. Primary objectives were safety, tolerability, MTD, and recommended phase II dose (RP2D). Phase II enriched for ICOS-positive (ICOS+) tumors; patients were treated with vopratelimab at the monotherapy RP2D alone or with nivolumab. Pharmacokinetics, pharmacodynamics, and predictive biomarkers of response to vopratelimab were assessed. RESULTS: ICONIC enrolled 201 patients. Vopratelimab alone and with nivolumab was well tolerated; phase I established 0.3 mg/kg every 3 weeks as the vopratelimab RP2D. Vopratelimab resulted in modest objective response rates of 1.4% and with nivolumab of 2.3%. The prospective selection for ICOS+ tumors did not enrich for responses. A vopratelimab-specific peripheral blood pharmacodynamic biomarker, ICOS-high (ICOS-hi) CD4 T cells, was identified in a subset of patients who demonstrated greater clinical benefit versus those with no emergence of these cells [overall survival (OS), P = 0.0025]. A potential genomic predictive biomarker of ICOS-hi CD4 T-cell emergence was identified that demonstrated improvement in clinical outcomes, including OS (P = 0.0062). CONCLUSIONS: Vopratelimab demonstrated a favorable safety profile alone and in combination with nivolumab. Efficacy was observed only in a subset of patients with a vopratelimab-specific pharmacodynamic biomarker. A potential predictive biomarker of response was identified, which is being prospectively evaluated in a randomized phase II non-small cell lung cancer trial. See related commentary by Lee and Fong, p. 3633.

Malignant Pineal Parenchymal Tumors in Adults: A National Cancer Database Analysis.

BACKGROUND: Limited retrospective data exist on malignant pineal parenchymal tumors (PPTs) in adults, and there are no large previous studies that review clinical outcomes across the 3 treatment arms of surgery, radiotherapy, and chemotherapy. As a result, optimal disease management has yet to be defined. OBJECTIVE: To evaluate treatment trends and perform survival analysis in adult PPT. METHODS: The National Cancer Database was queried for histologically confirmed PPT diagnosed from 2007 to 2016. Univariate and multivariate Cox regressions were used to evaluate the prognostic impact of covariates. Kaplan-Meier survival curves were generated for comparative subanalyses. RESULTS: Of the 251 patients who met inclusion criteria, 172 had PPTs of intermediate differentiation (PPTID) and 79 had pineoblastoma. A plurality of patients with pineoblastoma were treated with trimodal therapy (39.1%), whereas patients with PPTID were commonly treated with either surgery alone or surgery and radiation (33.7% each). Factors independently associated with improved overall survival include younger patient age, female sex, lower comorbidity score, lower tumor grade, and treatment with surgery or radiation (each P < .05). Subanalyses confirm the effect of radiation on survival in patients with grade III PPTID with subtotal resection; however, no survival benefit of adjuvant radiation is demonstrated in patients with grade II PPTID with subtotal resection. CONCLUSION: Although radiotherapy and surgery were found to increase survival in all patients with PPT, there was no demonstrable survival benefit of adjuvant radiation in surgically treated patients with grade II PPTID. This suggests that adjuvant radiotherapy may not add significant survival benefit in many adult patients with grade II PPTID.

Nonrandom spatial clustering of spontaneous anterior fossa cerebrospinal fluid fistulas and predilection for the posterior cribriform plate.

OBJECTIVE The anterior skull base is a common site for the spontaneous development of meningoceles, encephaloceles, and meningoencephaloceles that can lead to cerebrospinal fluid (CSF) fistula formation, particularly in association with idiopathic intracranial hypertension. In some circumstances the lesions are difficult to localize. Whether all sites in the anterior skull base are equally prone to fistula formation or whether they are distributed randomly throughout the anterior skull base is unknown, although the anterior cribriform plate has been proposed as the most frequent location. The purpose of this study was to identify sites of predilection in order to provide assistance for clinicians in finding occult leaks and increase the understanding of the etiology of this pathology. METHODS The authors performed a retrospective review of a prospectively acquired surgical database of all endonasal endoscopic surgeries performed at Weill Cornell Medical College by the senior authors. Spontaneous CSF fistulas of the anterior skull base were identified. The anatomical sites of the defects were located on radiographic images and normalized to a theoretical 4 × 2 grid representing the anterior midline skull base. Data from the left and right skull base were combined to increase statistical power. This grid was then used to analyze the distribution of defects. Frequency analysis was performed by means of a chi-square test, with a subsequent Monte Carlo simulation to further strengthen the statistical support of the conclusions. RESULTS Nineteen cases of spontaneous CSF fistulas were identified. Frequency analysis using chi-square indicated a nonrandom distribution of sites (p = 0.035). Monte Carlo simulation supported this conclusion (p = 0.034). Seventy-four percent of cases occurred in the cribriform plate (p = 0.086). Moreover, 37% of all defects occurred in the posterior third of the cribriform plate. CONCLUSIONS Anterior skull base spontaneous CSF leaks are distributed in a nonrandom fashion. The most likely site of origin of the spontaneous CSF leaks of the anterior midline skull base is the cribriform plate, particularly the posterior third of the plate, likely because of the lack of significant thick bony buttressing. Clinicians searching for occult spontaneous leaks of the anterior skull base should examine the cribriform plate, especially the posterior third with particularly close scrutiny.

Incidence of malignant mesothelioma in Aboriginal people in Western Australia.

OBJECTIVES: To describe the incidence of malignant mesothelioma (MM) in Aboriginal people in Western Australia (WA) and determine the main routes of exposure to asbestos in this population. METHODS: All MM cases in Western Australia, as well as the primary source of asbestos exposure, are recorded in the WA Mesothelioma Register. Aboriginal cases up to the end of 2013 were extracted from the register and compared with non-Aboriginal cases with respect to the primary means/source of exposure. Age-standardised incidence rates for each decade from 1980 were calculated for both Aboriginals and non-Aboriginals. Age-standardised mortality rates were calculated for the period 1994-2008 and compared with international rates. RESULTS: There were 39 cases (77% male) of MM among WA Aboriginal people. Twenty-six (67%) were a direct result of the mining of crocidolite at Wittenoom and the subsequent contamination of the surrounding lands. Of the non-Aboriginal MM cases (n = 2070, 86.3% male), fewer than 25% can be attributed to Wittenoom. Aboriginals had consistently higher 10-year incidence rates than non-Aboriginals and, when compared to world populations, the highest mortality rate internationally. CONCLUSION: When incidence rates in Aboriginal people are compared with non-Aboriginal people, the Wittenoom mining operation has had a disproportionate effect on MM incidence in the local Aboriginal population.

James Cook University's decentralised medical training model: an important part of the rural workforce pipeline in northern Australia.

INTRODUCTION: There has been much recent investment to improve the recruitment and retention of medical graduates in rural Australia. This paper describes the different outcomes of the strategies used at the James Cook University (JCU) medical school to improve the recruitment and retention of medical graduates in northern Australian towns: the decentralised model of four rural clinical schools, selecting students with a rural home town, enrolling students under the Bonded Medical Placements (BMP) scheme, and providing rurally orientated scholarships. METHODS: Home town at application to medical school, clinical school location, scholarship, BMP and postgraduate practice location data for JCU medical graduates were retrieved from an ongoing longitudinal cohort study. Multivariate logistic regression analysis was used to identify independent predictors of intern practice location from 2006 to 2013, and current (2014) practice location for postgraduate year 4-9 graduates for each of the four rural clinical school sites of Townsville, Cairns, Darwin and Mackay. RESULTS: The strongest predictor of JCU Bachelor of Medicine, Bachelor of Surgery (MBBS) graduates undertaking their internship in Townsville, Cairns, Mackay or Darwin hospitals was attending the JCU clinical school in that location (p<0.001, prevalence odds ratios (POR)=7.1; p<0.001, POR=11.5; p<0.001, POR=19.4; p<0.001, POR=85.7; respectively). Attending the JCU clinical school in the main town was also a strong predictor of JCU MBBS graduates currently practising (2014) in the Townsville, Cairns and Mackay health service districts (p<0.001, POR=2.9; p<0.001, POR=3.8; p=0.033, POR=3.6; respectively). CONCLUSIONS: While this study supports the effectiveness of improving the rural medical workforce via the targeted selection of students with a rural background, the JCU medical school's decentralised medical education program also appears to be significantly associated with rural recruitment and retention, including in districts of workforce shortage and/or geographically remote locations. These findings support other evidence that decentralised medical training can assist recruitment to underserved regions, and have implications for other jurisdictions looking to invest in a decentralised training model.

Cochlear implants in the etiopathogenesis of glioblastoma--an interesting observation or independent finding?

Various risk factors have been implicated in the pathogenesis of glioblastomas including ionizing radiation. Recent evidence has suggested a possible association between exposure to nonionizing radiofrequency electromagnetic fields (RF-EMF) generated from mobile phones and wireless devices to cause malignant transformation of the neuroglial cells, albeit this is widely debated. In this report, we discuss the development of glioblastoma in two geopolitically unrelated patients, an elderly male from the United States and a middle-aged woman from Sweden, with long-standing cochlear implants (CI). We hypothesize that the low-frequency RF-EMF emanating from the transcutaneous link of the CI prosthesis over a long period has potentially triggered tumor development in these patients.

Clinical and Radiologic Outcome of Gamma Knife Radiosurgery on Nonfunctioning Pituitary Adenomas.

Objective To elucidate the role of Gamma Knife radiosurgery (GKRS) in the management of nonfunctioning pituitary adenomas (NFAs). Materials and Methods A retrospective review of 57 consecutive patients spanning 2000 to 2013 with NFAs was performed. Of 57 patients, 53 patients had recurrent or residual tumors after microsurgical resection. The study population was evaluated clinically and radiographically after GKRS treatment. The median follow-up time was 45.57 months. Results GKRS in pituitary adenomas showed significant variations in tumor growth control (decreased in 32 patients [56.1%], arrested growth in 21 patients [36.1%], and increased tumor size in 4 patients [7%]). Progression-free survival after GKRS at 3, 7, and 10 years was 100%, 98%, and 90%, respectively. The neurologic signs and symptoms were significantly improved after GKRS (14% versus 107%) compared with pretreated signs and symptoms (p < 0.0001). Five patients (8.8%) required additional treatment. Conclusion Recent follow-up revealed that GKRS offers a high rate of tumor control and preservation of neurologic functions in both new and recurrent patients with NFAs. Thus GKRS is an effective treatment option for recurrent and residual as well as newly diagnosed patients with NFAs.

Atypical gunshot wound: Bullet trajectory analyzed by computed tomography.

INTRODUCTION: Gunshot injuries are a result of a bullet or projectile fired from a weapon that penetrates the body. Homicide, suicide, and occasionally, accidental events are a significant cause of firearm-related injuries. In rare cases, the damage from the gunshot injury can be masked due to an atypical bullet trajectory. PRESENTATION OF CASE: A 63-year-old male was found with a gunshot wound to the anterior left knee. Computed tomography (CT) scans revealed a bullet track extending from the anterior aspect of the left knee that traveled cephalad subcutaneously and entered into the peritoneal cavity, perforating the distal descending colon. The bullet was found to be at rest adjacent to the spleen and posterior chest wall, with no injury to the lungs, kidneys or the spleen. The patient required a sigmoid colectomy with descending colostomy and was subsequently discharged home without any complications. DISCUSSION: Intra-abdominal organ damage from a gunshot wound to the distal limb is a rare occurrence. Atypical gun shot wounds, such as this case, have the potential for multiple issues including: delayed diagnostic tests, inaccurate radiological readings, and inappropriate medical management. CONCLUSION: If an abnormal trajectory is maintained, it is possible for a bullet to traverse half the length of the body without the patient realizing it. Accurate CT analysis and quick decisions in surgical and medical management are critical takeaways to provide quality care to patients with these injuries.

Predictors of rural practice location for James Cook University MBBS graduates at postgraduate year 5.

OBJECTIVE: To describe factors predicting James Cook University (JCU) medical graduates having a rural practice location at postgraduate year (PGY) 5. PARTICIPANTS: JCU MBBS graduates who had completed their PGY 5 in Australia (n = 260). DESIGN: Multiple logistic regression analysis involving graduates' application data (age, gender, location of hometown, School Leaving Score, interview score, ethnicity), undergraduate data (scholarship awarded, honours program), and postgraduation data (internship location, specialty training undertaken). MAIN OUTCOME MEASURE: Predictors of practice in a 'rural' town (Australian Standard Geographic Classification Remoteness Area (ASGC-RA)) 3-5 at PGY 5. RESULTS: Practice in a 'rural' town in PGY 5 was predicted by 'internship in an ASGC-RA 3-5 location' (prevalence odds ratios (POR) = 3.9, P < 0.001), 'undertaken postgraduate training as a general practitioner or rural generalist' (POR = 3.4, P < 0.001), 'hometown at application located in ASGC-RA 3-5 area' (POR = 2.9, P = 0.023), 'Aboriginal & Torres Strait Islander ancestry' (POR = 5.6, P = 0.031), and NOT undertaken postgraduate training in surgery (POR = 5.4, P = 0.055). CONCLUSIONS: This study provides evidence that likelihood of early career rural medical practice in Australia is enhanced by education strategies, such as providing rurally located internship places, supporting rural general practice, and selecting applicants with rural origins, Aboriginal or Torres Strait Islander ancestry, and/or a genuine interest in rural, remote, Indigenous, and tropical medicine. This early evidence supports the proposition that investing in rural medical education will produce an appropriately trained medical workforce to meet the needs of rural Australia. Findings also suggest rural workforce may be further enhanced with additional specialty training opportunities in rural tertiary hospitals, in particular, surgery.

The Persian legend of ophthalmology: Ali Asghar Khodadoust and his everlasting lines.

This is a brief celebratory overview of the fruitful life and scientific endeavors of Professor Ali Asghar Khodadoust (b.1935), a world renowned ophthalmologist, Persian icon of modern ophthalmology and an international pioneer of eye research. The global reputation of Dr. Khodadoust is rooted in his extensive studies on corneal diseases and transplantation biology. As a result of his truly deserved world renown, several famous American ophthalmologists have recognized him as the world's best corneal graft surgeon. Due to his exceptionally impressive achievements in this field, a clinical finding has been named in his honor, the "Khodadoust rejection line", a sign indicative of a chronic focal transplant reaction.

Study of intracellular delivery of doxorubicin from poly(lactide-co-glycolide) nanoparticles by means of fluorescence lifetime imaging and confocal Raman microscopy.

The intracellular delivery of Doxorubicin (Dox) from poly(lactide-co-glycolide) (PLGA) nanoparticles stabilised with bovine serum albumin, in HepG2 cells, is studied via flow cytometry, fluorescence lifetime imaging microscopy (FLIM), confocal Raman microscopy (CRM) and cell viability studies. Flow cytometry shows that the initial uptake of PLGA and Dox follow the same kinetics. However, following 8 h of incubation, the fluorescence intensity and cellular uptake of Dox decreases, while in the case of PLGA both parameters remain constant. FLIM shows the presence of a single-lifetime species, with a lifetime of 1.15 ns when measured inside the cells. Cell viability decreases by approximately 20% when incubated for 24 h with PLGA loaded with Dox, with a particle concentration of 100 µg · mL(-1). At the single-cell level, CRM shows changes in the bands from DNA and proteins in the cell nucleus when incubated with PLGA loaded with Dox.