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In this review, recent key publications related to acute coronary syndrome (ACS) are summarized and placed into context of contemporary practice. Landmark trials examining vascular access in ST-elevation myocardial infarction, the management of multivessel disease, acute myocardial infarction and cardiac arrest are discussed. An update in pharmacology for ACS provides updates in major trials relating to P2Y12 inhibitor initiation, deescalation, and use in special populations. Additional updates in the use of lipid-lowering agents and adjunctive medications in ACS are reviewed. Finally, cardiac pathology related to coronavirus disease 2019 (COVID-19), as well as the impact of the COVID-19 global pandemic on the care of patients with ACS, is summarized.

Highlights • Brachytherapy boost is a standard of care for locally advanced cervical cancer. • High-dose-rate brachytherapy (HDR-BT) boost procedure is not standardized. • The number of implants, fractions, doses and imaging differ in literature. • Bi-fractionated HDR-BT in 1 implant is feasible with good oncological outcome. • Bi-fractionated HDR-BT dose escalation slightly increases acute toxicity., Purpose Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT. Patients and methods This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported. Results From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45–132] and median EQD210D90CTVHR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81–90], 83% [79–86], 70% [67–73], 61% [57–64] and 75% [69–78] respectively, with no significant difference between the groups. EQD210D90CTVHR

Background Numerous case reports and case series have described brain Magnetic Resonance Imaging (MRI) findings in Coronavirus disease 2019 (COVID-19) patients with concurrent posterior reversible encephalopathy syndrome (PRES). Purpose We aim to compile and analyze brain MRI findings in patients with COVID-19 disease and PRES. Methods PubMed and Embase were searched on April 5th, 2021 using the terms “COVID-19”, “PRES”, “SARS-CoV-2” for peer-reviewed publications describing brain MRI findings in patients 21 years of age or older with evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and PRES. Results Twenty manuscripts were included in the analysis, which included descriptions of 30 patients. The average age was 57 years old. Twenty-four patients (80%) required mechanical ventilation. On brain MRI examinations, 15 (50%) and 7 (23%) of patients exhibited superimposed foci of hemorrhage and restricted diffusion respectively. Conclusions PRES is a potential neurological complication of COVID-19 related disease. COVID-19 patients with PRES may exhibit similar to mildly greater rates of superimposed hemorrhage compared to non-COVID-19 PRES patients.

Background Achilles tendon rupture is one of the most common serious injuries in athletes. Various studies to accelerate the healing process of the Achilles tendon have been performed as it takes a longer time to repair the tissue compared to other tendons. Here, we report a case of an acute Achilles tendon rupture in a male basketball player treated by a combination of an intra-tissue injection of freeze-dried platelet-derived factor concentrate, which included a platelet-derived growth factor with an early rehabilitation protocol after the operative treatment to facilitate the biological healing of the injured tendon tissue. To the best of our knowledge, this case is the first instance that enabled the athlete to return to original sport activity at only 3-months after the injury. Case report A 23-year-old male basketball player who belonged to a university basketball team sustained an Achilles tendon rupture during running in a training match. The remaining time period until the final tournament of the university league as a senior player was only 3 months. The patient received a combination of an intra-tissue injection of freeze-dried platelet-derived factor concentrate and early rehabilitation protocol after operative treatment. Surgery was performed 4 days after the injury and the early rehabilitation protocols were applied postoperatively. A freeze-dried platelet-derived factor concentrate was injected into the ruptured site of the Achilles tendon under ultrasound guide at 4 weeks postoperatively. The patient could return to play at the pre-injury level without any symptoms and disfunctions at 3 months after surgery. At two years postoperatively, the patient could play basketball without symptoms or rerupture. Conclusions We reported a case of an Achilles tendon rupture which was treated by a combination of intra-tissue injection of freeze-dried platelet-derived factor concentrate and an early rehabilitation protocol after the operative treatment. The patient could return to play basketball at the pre-injury activity level at only 3-months after the injury, suggesting that the role of applying excessively early rehabilitation of mechanical loading could facilitate tendon tissue healing when combined with an intra-tissue injection of freeze-dried platelet-derived factor concentrate., Highlights • FD-PFC has rich growth factors such as PDGF-BB, which is a part of the PDGF growth family. • An achilles tendon rupture was treated by a combination of injection of FD-PFC and excessively postoperative rehabilitation. • The patient could return to play basketball at the pre-injury activity level at only 3-months after the injury.

Gestational choriocarcinoma is a malignant trophoblastic tumor arising from any gestational event, even with a long latency period, generally in the reproductive female. It is associated with a high level of beta-human chorionic gonadotropin. Its primary site is usually the uterus but not all patients have a detectable lesion in this site. Regression of the primary tumor after it has metastasized is not uncommon, and one-third of cases manifest as complications of metastatic disease. In this report we present an uncommon case of gestational choriocarcinoma with lung, liver and jejunal metastases at the time of diagnosis without evidence of pelvic disease, in 34-year-old woman. The main points of interest of our case were the development of the ovarian hyperstimulation syndrome with massive multicystic ovarian enlargement induced by high level of beta-human chorionic gonadotropin and the bleeding of jejunal and liver metastases, due to the high vascularity of the tumor tissue, a condition known as “Choriocarcinoma Syndrome”. We will focus on the radiological findings of metastases, bleeding complications and ovarian hyperstimulation syndrome.

Introduction Low anterior resection syndrome (LARS) is the most common complication after total mesorectal excision (TME) in patients with low rectal cancer and has been a challenge in colorectal surgery that severely impacts the quality of life of patients. This study aimed to introduce a revised surgical procedure which could effectively maintain rectal compliance and significantly improve LARS after the operation. Methods We performed mesorectal reconstruction after routine Dixon TME using greater omental pedicle flap transplantation in 11 patients with low rectal cancer (5 cases of preoperative neoadjuvant chemoradiotherapy, 5 cases of preoperative neoadjuvant chemotherapy, and 1 case of postoperative adjuvant chemotherapy), thereby simulating the initial anatomical structure of the mesorectum and significantly reducing the postoperative anterior resection syndrome. The lars precision syndrome assessment scale (LARSS) was used to access the LARS. Results At 12 weeks after the 11 patients recovered from the anal defecation function, the average score on the LARS questionnaire was 25.5 ± 1.5 (minor). The average time at which anal function began to recover was 6.2 ± 2.6 weeks after surgery. The recovery was rapid, as the rectal and anal function of all patients generally returned to normal levels within 12 weeks, and the quality of life was close to that before surgery. Conclusion Greater omental flap transplantation can significantly improve LARS after Dixon TME in patients with low rectal cancer., Highlights • Omental pedicle flap transplantation is a revised and promising surgical procedure. • The procedure reconstructing the mesorectum could maintain rectal compliance. • The procedure can significantly improve low anterior resection syndrome.

Objective: Diabetes insipidus (DI) can be classified into 2 types: central/neurogenic DI and nephrogenic DI. Most cases of central DI occur after brain surgery, trauma, tumor, or infection. Here we report a rare case of familial central DI due to a heterozygous AVP gene mutation. Methods: A case of familial neurogenic DI has been described with thorough clinical, laboratory, and genetic workup. PubMed and Google scholar databases were used for literature discussion. Results: A 22-year-old man presented with polyuria and polydipsia. He drank about 4 gallons of water everyday and urinated large volumes very frequently. His physical examination was unremarkable. After 2 hours of water-deprivation, his serum sodium level was 147 mmol/L, serum osmolality was 302 mOsm/kg with concurrent urine osmolality of 78 mOsm/kg, vasopressin level was

Abnormalities of an athlete’s electrocardiogram may be the result of an underlying heart disease and may carry a risk of sudden death. It is important that electrocardiographic abnormalities are correctly distinguished. We present the case of a young marathon athlete presenting with syncope and incomplete right bundle block pattern suggestive of a type 2 Brugada pattern. (Level of Difficulty: Advanced.), Central Illustration

Rotational vertebral artery occlusion is a rare cause of ischemic stroke in the vertebrobasilar arteries. While computed tomography angiography (CTA) is less invasive for the diagnosis of rational vertebral artery occlusion than digital subtraction angiography and more useful for elucidating the correlation between vertebrobasilar arteries and the surrounding structure, carotid ultrasound is noninvasive and more beneficial for the real-time evaluation of the hemodynamic change with neck rotation compared to CTA. Here, we reported 2 cases of rotational vertebral artery occlusion in patients aged 81 and 38 years and proposed a novel technique for its diagnosis using ultrasound-guided CTA. We suggest that the combination of ultrasound and CTA is useful for diagnosing rotational vertebral artery occlusion, which would compensate for the disadvantages of CTA alone.

MALT lymphoma is a non-Hodgkin lymphoma developing from B cells and is a type of marginal zone lymphoma. It can develop in any organs, but no case of primary cardiac location has yet been reported. We report the first observation of a primary epicardial MALT lymphoma mimicking a compressive pericardial syndrome. (Level of Difficulty: Advanced.), Central Illustration

Highlights • The entire brain is susceptible to dose-dependent volume loss after RT. • Future studies should examine the impact of cerebral volume loss on cognition. • Current sparing strategies in RT for brain tumours may need to be reconsidered., Purpose Numerous brain MR imaging studies have been performed to understand radiation-induced cognitive decline. However, many of them focus on a single region of interest, e.g. cerebral cortex or hippocampus. In this study, we use deformation-based morphometry (DBM) and voxel-based morphometry (VBM) to measure the morphological changes in patients receiving fractionated photon RT, and relate these to the dose. Additionally, we study tissue specific volume changes in white matter (WM), grey matter (GM), cerebrospinal fluid and total intracranial volume (TIV). Methods and materials From our database, we selected 28 patients with MRI of high quality available at baseline and 1 year after RT. Scans were rigidly registered to each other, and to the planning CT and dose file. We used DBM to study non-tissue-specific volumetric changes, and VBM to study volume loss in grey matter. Observed changes were then related to the applied radiation dose (in EQD2). Additionally, brain tissue was segmented into WM, GM and cerebrospinal fluid, and changes in these volumes and TIV were tested. Results Performing DBM resulted in clusters of dose-dependent volume loss 1 year after RT seen throughout the brain. Both WM and GM were affected; within the latter both cerebral cortex and subcortical nuclei show volume loss. Volume loss rates ranging from 5.3 to 15.3%/30 Gy were seen in the cerebral cortical regions in which more than 40% of voxels were affected. In VBM, similar loss rates were seen in the cortex and nuclei. The total volume of WM and GM significantly decreased with rates of 5.8% and 2.1%, while TIV remained unchanged as expected. Conclusions Radiotherapy is associated with dose-dependent intracranial morphological changes throughout the entire brain. Therefore, we will consider to revise sparing of organs at risk based on future cognitive and neurofunctional data.

Artificial intelligence (AI) is a general term that refers to the use of a machine to imitate intelligent behavior for performing complex tasks with minimal human intervention, such as machine learning; this technology is revolutionizing and reshaping medicine. AI has considerable potential to perfect health-care systems in areas such as diagnostics, risk analysis, health information administration, lifestyle supervision, and virtual health assistance. In terms of immunotherapy, AI has been applied to the prediction of immunotherapy responses based on immune signatures, medical imaging and histological analysis. These features could also be highly useful in the management of cancer immunotherapy given their ever-increasing performance in improving diagnostic accuracy, optimizing treatment planning, predicting outcomes of care and reducing human resource costs. In this review, we present the details of AI and the current progression and state of the art in employing AI for cancer immunotherapy. Furthermore, we discuss the challenges, opportunities and corresponding strategies in applying the technology for widespread clinical deployment. Finally, we summarize the impact of AI on cancer immunotherapy and provide our perspectives about underlying applications of AI in the future., Graphical abstract With the increasing of clinical data and advanced AI methodologies, AI-based technologies have the potential to increase the functional roles in cancer immunotherapy response.Image 1

Menisci congenital anomalies are rare morphologic abnormalities including accessory meniscus, discoid meniscus, double-layered meniscus, hypoplastic meniscus and ring-shaped meniscus (RSM). In a 35 year-old male patient, MR arthrography showed a bridging accessory bundle connecting the anterior cruciate ligament and posterior cruciate ligament with the posterior horn of the lateral meniscus. Arthroscopic examination showed a fan-like obstacle embracing the posterior horn of the lateral meniscus. It would be important to correctly identify this anatomical variant, because the bundle connecting the external meniscus to the ligaments of the central pivot can be misinterpreted as a meniscal fragment.

Central thrombosis–associated chylothorax is underrecognized in children and frequently refractory to conservative management. Central venous catheterizations are the predominate cause. We present 3 cases highlighting endovascular techniques used to treat persistent chylous effusions. (Level of Difficulty: Advanced.), Central Illustration

Wolman disease is a lethal rare autosomal recessive disorder defined by the deficiency of acid lipase enzyme. The disease is a lysosomal storage disease. Multiple organs such as adrenal glands, liver, spleen, bone marrow, small bowel loops, and abdominal lymph nodes are infiltrated by the deposition of lipids. Infants generally present with failure to thrive, abdominal distention, vomiting, steatorrhea, and hepatosplenomegaly. Authors’ present a 1 month-old male infant with abdominal distention and failure to thrive who was referred for abdomen CT scan. The CT scan revealed stippled calcifications of both enlarged adrenal glands, without the distortion of the adreniform shape, fatty liver, splenomegaly and thickened small bowel loops; characteristic imaging findings of Wolman disease. CT scan is the imaging modality of choice for the recognition of the disease. There is no definite cure explained yet. Further studies are required to find the definite treatment of the disease.

Zinner syndrome is a rare congenital anomaly of the genitourinary tract, consisting of ipsilateral renal agenesis, seminal vesicle cysts, and ejaculatory duct obstruction. Besides, quadruplication of the ureter is the rarest anomaly composed of proximal four ureters ending with a single distal ureter. The authors present an adult male patient with left flank pain and dysuria who was referred for abdomen CT scan. The CT scan revealed renal agenesis, seminal vesicle cysts, and obstructed ejaculatory duct, all in the right side (Zinner syndrome), and quadruplication of the ureter on the left side. The additional finding of hemivertebra was present resulting in kyphoscoliosis. Zinner syndrome and quadrupled ureter, are both rare anomalies, and the occurrence of both entities at the same patient is exceptionally rare, and have not been reported yet in the English literature. Furthermore, standard treatment protocols have to be pursued, as such patients hold a single kidney with the quadrupled ureter.

Does oligometastatic breast cancer (OMBC) deserve a dedicated treatment? Although some authors recommend multidisciplinary management of OMBC with a curative intent, there is no evidence proving this strategy beneficial in the absence of a randomized trial. The existing literature sheds little light on OMBC. Incidence is unknown; data available are either obsolete or biased; there is no consensus on the definition of OMBC and metastatic sites, nor on necessary imaging techniques. However, certain proposals merit consideration. Knowledge of eventual specific OMBC biological characteristics is limited to circulating tumor cell (CTC) counts. Given the data available for other cancers, studies on microRNAs (miRNAs), circulating tumor DNA (ctDNA) and genomic alterations should be developed Finally, safe and effective therapies do exist, but results of randomized trials will not be available for many years. Prospective observational cohort studies need to be implemented., Highlights • The incidence of oligometastatic breast cancer is unknown. • Only one publication provides information regarding the biology of these cancers. • Oligometastatic breast cancer and metastatic site definitions should be harmonized. • Prospective observational cohort studies are needed.

Objective Neurosurgical patients are at a higher risk of having a severe course of coronavirus disease 2019 (COVID-19). The objective of this study was to determine morbidity, hospital course, and mortality of neurosurgical patients during the coronavirus disease 2019 (COVID-19) pandemic in a multicenter health care system. Methods A retrospective observational study was conducted to identify all hospitalized neurosurgical patients positive for COVID-19 from March 11, 2020 to November 2, 2020 at Mayo Clinic and the Mayo Clinic Health System. Results Eleven hospitalized neurosurgical patients (0.68%) were positive for COVID-19. Four patients (36.6%) were men and 7 (63.3%) were women. The mean age was 65.7 years (range, 35–81 years). All patients had comorbidities. The mean length of stay was 13.4 days (range, 4–30 days). Seven patients had a central nervous system malignancy (4 metastases, 1 meningioma, 1 glioblastoma, and 1 schwannoma). Three patients presented with cerebrovascular complications, comprising 2 spontaneous intraparenchymal hemorrhages and 1 ischemic large-vessel stroke. One patient presented with an unstable traumatic spinal burst fracture. Four patients underwent neurosurgical/neuroendovascular interventions. Discharge disposition was to home in 5 patients, rehabilitation facility in 3, and hospice in 3. Five patients had died at follow-up, 3 within 30 days from COVID-19 complications and 2 from progression of their metastatic cancer. Conclusions COVID-19 is rare among the inpatient neurosurgical population. In all cases, patients had multiple comorbidities. All symptomatic patients from the respiratory standpoint had complications during their hospitalization. Deaths of 3 patients who died within 30 days of hospitalization were all related to COVID-19 complications. Neurosurgical procedures were performed only if deemed emergent.

Myxopapillary ependymoma (MPE) is a unique slow-growing benign (WHO grade 1) subtype of spinal cord ependymoma arising predominantly in the filum terminale. Despite its benign nature, it occasionally disseminates through the cerebrospinal fluid and metastasizes to distant sites. Here, we report an extremely rare case of MPE with interval CSF seeding and metachronous metastasis in a 47 -year-old female presented as a gradually increasing low back pain for three months with bilateral radiculopathy down to the knees. Magnetic resonance imaging (MRI) showed an intradural extramedullary spinal mass of iso-intense signal to the cord on T1 weighted-images (WIs), heterogeneous, predominantly hyperintense signal on T2WIs with homogenous enhancement after contrast administration. L2 laminectomy with gross total resection (GTR) was performed, and histopathological results confirmed the diagnosis of MPE. Adjuvant radiotherapy was administered, followed by series of MRI scans. 28 months after GTR, Lumbar MRI showed multiple tiny enhancing nodules in the cauda equina. 44 months follow-up whole spine MRI revealed multiple intradural extramedullary nodules throughout the entire spine. The largest one measures about 1.5cm opposite to T3 -T4 intervertebral disc space. The patient underwent T3 and T4 laminectomy and GTR under general anesthesia using microsurgical techniques, and the histopathological result came with the diagnosis of MPE.

Transient osteoporosis of the hip, also termed transient bone marrow edema, is a painful condition often occurring after trivial trauma. It can be diagnosed with MRI in patients whose radiographs are negative or inconclusive. In this case report we describe a 39-year-old female patient with this rare entity, who was successfully treated with oral Alendronate, active vitamin D and calcium supplementation combined with avoiding of weight bearing on the affected hip. She improved clinically within three months and on contrast enhanced MRI studies, as performed before and after treatment, complete regression of bone marrow edema was shown already after three months of treatment. The literature was reviewed regarding the pathophysiology of transient osteoporosis of the hip and the beneficial effects of Alendronate in this domain. The report is important because it will increase the awareness among clinicians and radiologists about this entity, as in neglected cases transient regional osteoporosis of the hip may progress to avascular necrosis with complete loss of hip function.

Hepatic splenosis, a rare entity, is the ectopic implantation of splenic tissue into the hepatic parenchyma, most often incidentally seen in patients with a history of splenic trauma and splenectomy. We present a unique case of hepatic splenosis in a patient with hemosiderosis and splenectomy following the incidental finding of hepatic masses on pretransplant imaging. Final diagnosis was made based on cross-sectional imaging characteristics matching that of the left upper quadrant splenules alone. We discuss common characteristics of hepatic splenosis on multiple modalities, the effect of iron deposition on the imaging characteristics of hepatic and splenic tissue and how that impacts the differential and diagnosis. This case highlights the unique imaging characteristics hepatic splenosis can have particularly in the setting of hemosiderosis. Hepatic splenosis imaging diagnosis has a significant advantage over tissue diagnosis in terms of decreased risk, time and cost.

Endovascular embolization is generally thought to be safe and effective for the cavernous sinus dural arteriovenous fistula (CS DAVF); however, some complications have been reported. We report an extremely rare brainstem hemorrhage associated with transvenous embolization (TVE) of CS DAVF. A 66-year-old man presented with right-sided conjunctival chemosis and exophthalmos. His brain magnetic resonance image showed right CS DAVF. Thus, emergent TVE was performed. Although his symptoms improved after the first TVE, magnetic resonance image showed brainstem edema, and venous congestion was suspected because of incomplete TVE. Second TVE was performed. Thereafter, computed tomography showed brainstem hemorrhage, resulting in the occurrence of right abducent nerve palsy, right-sided facial palsy, and ataxia. The patient's condition gradually improved, and a year has passed without recurrence. Incomplete TVE of CS DAVF can result in life-threatening complications, such as cerebral hemorrhage. To avoid these complications, the anatomical structure of the cavernous sinus should be understood accurately, and important drainage veins should be determined.

Peripheral neuroblastic tumors are extremely rare in the adult with less just over 20 cases involving adrenal gland described in the literature. We reported herewith the case of a 22-year-old young male who presented with epigastric pain and diarrhea. Imaging studies documented a 3.5cm x 3cm x 4cm solid well-circumscribed right adrenal mass, of heterogeneous structure and with fine calcifications. The lesion turned negative at MIBG scintigraphy. A right robotic-assisted adrenalectomy was performed leading to complete excision of the lesion without complications. Histology was consistent with intermixed stroma-rich ganglioneuroblastoma. A wait-and-see strategy was considered adequate. Two years after diagnosis patient is alive disease-free. Although the definitive diagnosis of a peripheral neuroblastic tumor is obtained after histopathological analysis, CT, and MRI are helpful to further characterize masses and useful in pretreatment risk stratification. Clinicians should be aware of the possibility of GNB development in adult population and its malignant potential.

Fibrous dysplasia, including McCune-Albright syndrome, is a genetic, non-inheritable benign bone disorder that may involve a single or multiple bone, typically occurring in the diaphysis or the metaphysis of long bones. In very rare instances polyostotic fibrous dysplasia present involvement of the epiphysis in long bones. Aneurysmal bone cysts are benign, expansile, lytic bone lesions formed by cystic cavities containing blood, that may occur de novo or secondary to other lesions of bone, including fibrous dysplasia. We report a case of an 18-year-old female with polyostotic fibrous dysplasia (McCune-Albright syndrome) with diaphyseal and unusual multiple foci of epiphyseal involvement of long bones as well as in the patella, and a simultaneous aneurysmal bone cyst of the left femoral neck with pathologic fracture. This is the first report of a simultaneous aneurysmal bone cyst in a patient with polyostotic fibrous dysplasia (McCune-Albright syndrome) with involvement of diaphysis and epiphysis of long bones, highlighting that fibrous dysplasia should be included in the differential diagnosis of polyostotic tumors involving the diaphysis as well as the epiphysis. In patients with polyostotic fibrous dysplasia there should be an active search for lesions in the epiphysis.

Highlights • A prospective pilot phase I/II study on metformin given concurrently with neoadjuvant chemoradiation (CRT) in non-diabetic rectal cancer patients. • Three patients had a clinical complete response (cCR) and did not have surgical resection. • Of the 12 patients who underwent surgery, there were two pCRs. For the combined pCR/cCR rate of 33% (95% CI 19–47%), a total of 85 patients will be required to yield a 95% CI with a 10% margin of error. • These pilot results are encouraging, and will serve to refine the design and conduct of a future phase 2 trial to determine whether adding metformin to CRT improves pCR/cCR rates., Purpose Neoadjuvant radiotherapy with or without chemotherapy decreases the risk of local recurrence after surgery for rectal cancer. Emerging data suggest that diabetic patients on metformin may have improved cancer outcome after radiotherapy. A single institutional pilot study was performed to determine if metformin given concurrently with long course chemoradiation (CRT) may improve pathologic complete response (pCR) in non-diabetic rectal cancer patients. The study was designed to construct a confidence interval (CI) for the pCR rate to determine the sample size for a phase 2 trial. Methods Non-diabetic patients with biopsy confirmed rectal cancer deemed candidates for long course neoadjuvant CRT were invited to participate. Radiation consisted of 50.4 Gy in 28 daily fractions with concurrent daily capecitabine (825 mg/m2 twice daily). Participants self-administered metformin (500 mg of twice daily) 2 weeks prior to, during and for 4 weeks after CRT. Results A total of 16 patients were accrued. One patient withdrew from the study. Only grade 1 or 2 adverse events were observed. Three patients had a clinical complete response (cCR) and did not undergo surgery. Of the 12 patients who underwent surgery, there were two pCRs. For the combined pCR/cCR rate of 33% (95% CI 19–47%), a total of 85 patients will be required to yield a 95% CI with a 10% margin of error. Conclusions Adding metformin to neoadjuvant CRT for rectal cancer does not appear to enhance toxicities. These results will be used to refine the design and conduct of a future phase 2 trial to determine whether adding metformin to CRT improves pCR/cCR rates.

A healthy 41-year-old man sustained cardiac arrest secondary to ventricular fibrillation. An extensive ischemic, structural, and genetic evaluation did not identify an attributable pathologic condition. Electrocardiograms were notable for early repolarization pattern. Here we review the diagnosis, prevalence, and prognostic significance of the early repolarization syndrome on sudden cardiac death. (Level of Difficulty: Intermediate.), Central Illustration

A previously healthy 39-year-old man presented in cardiogenic shock with evidence of multisystem inflammatory syndrome of adults 2 months after a mild case of coronavirus disease 2019. He was treated with intravenous immunoglobulin and pulse-dose corticosteroids with rapid resolution of his symptoms and normalization of biventricular function. (Level of Difficulty: Intermediate.), Central Illustration

Objectives COVID-19 is a multisystemic disease. Ophthalmological abnormalities are relatively rare among COVID-19-infected patients. The aim of our study was to report orbital and visual pathways MRI findings in a nationwide multicenter cohort of patients with severe COVID-19. Methods This IRB-approved retrospective multi-center study included participants presenting with severe COVID-19, who underwent brain MRI from March 4th to May 1st 2020. Two neuroradiologists (“blinded”), blinded to all data, individually analyzed morphological MRIs focusing on the orbits and the visual pathways. A second consensus reading session was performed in the case of disagreement between both readers. Clinical and ophthalmological data were compared to MRI findings. Descriptive statistical analysis and interobserver agreement for MRI reading using non-weighted Cohen kappa statistics were performed. Results 129 participants (43 [33%] women and 86 [67%] men, mean age 63 ± 14 years) were included in the study. 17/129 (13%) patients had abnormal MRI findings of the orbit or visual pathways. 11/17 (65%) patients had a FLAIR-WI hyperintense optic disc. 6/17 (35%) patients had abnormal signal of at least one of the visual pathway structures: 6/6 (100%) of the optic nerve, 1/6 (17%) of the optic chiasm, 2/6 (33%) of the optic tract and 1/6 (17%) of the optic radiations. Conclusions Our study showed that a substantial number of patients with severe COVID-19 presented with abnormal MRI findings of the orbit or visual pathways, which might lead to potentially severe visual impairment.

Foix-Alajouanine syndrome is a rare progressive form of spinal AVM predominantly affecting the lower thoracic and/or lumbosacral regions. This study aims to describe the imaging findings of spinal AVM causing Foix-Alajouanine syndrome and to review the literature. We present a 48-year-old man with progressive back pain, leg weakness, and gait imbalance without urinary retention. We discuss the clinical and imaging findings and the significance of MRI in establishing the diagnosis. A definitive diagnosis of spinal AVM requires radiographic demonstration of the vascular anomaly. Despite the high sensitivity of angiography for the diagnosis of spinal AVM, the result of the study may be inconclusive and/or negative. The key MRI findings are the presence of abnormally dilated perimedullary vessels with signal voids from a high-velocity flow on T1 and T2 weighted images.

Hepatic artery aneurysm (HAA) is a rare, yet clinically important, condition. While the causes of HAA are poorly understood, it is estimated that mortality following spontaneous rupture is as high as 40%. We discuss the case of a 77-year-old man who presented to our hospital due to a 10 mm pulmonary lesion in the left lower lung lobe, which was identified by a computed tomography scan of the lung at another institution. An examination with 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in our department, but no significant uptake of 18F-fluorodeoxyglucose was found in the lung, and HAA was diagnosed only incidentally. A magnetic resonance imaging angiography supported the differential diagnosis of HAA, and the aneurysm was confirmed by targeted angiography. It was located in the common hepatic artery and was coiled during an intervention session. HAA accounts for 20% of all visceral aneurysms and, with a poorly understood natural history, is difficult to diagnose clinically, but early detection and treatment of HAA can improve prognosis.

Blood–brain barrier (BBB) strictly controls matter exchange between blood and brain, and severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy of brain diseases. However, during the onset and progression of brain diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, traumatic brain injury and brain tumor. The advances on optimization of small molecules for BBB crossing and non-systemic administration routes (e.g., intranasal treatment) for BBB bypassing are not included in this review., Graphical abstract Blood–brain barrier (BBB) is evolving during the onset and progression of brain diseases. BBB evolution-based nanoscale brain-targeting drug delivery strategies are summarized in this review for various brain diseases.Image 1

Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted., Graphical abstract Pure drug nano-assemblies (PDNAs), fabricated by self-assembly or co-assembly of pure drug molecules, have attracted considerable attention in cancer treatment, indicating therapeutic advantages including carrier-free property, simple preparation, ultra-high drug loading and co-delivery behavior for combination therapy.Image 1

Herlyn–Werner–Wunderlich syndrome (HWWS) is a rare congenital malformation characterized by uterus didelphys, unilateral blind hemivagina, and ipsilateral renal agenesis. The obstructed vagina affects menstrual flow, leading to related clinical symptoms after menarche. However, the age of onset, initial symptoms, and clinical complications differ among patients owing to the different types of vaginal septum. Herein, we report 2 cases. The first case is of a 20-year-old woman who presented with fever; she was diagnosed with vaginitis and pelvic inflammation due to the vaginal septum with ostiole. The second case is of a 12-year-old girl who complained of abdominal pain; she was diagnosed as having pelvic inflammation, omentitis, and suppurative appendicitis due to the atretic vaginal septum.

Uterine rupture and postterm pregnancy pose a number of life-threatening complications to both mother and child, including severe intra-abdominal bleeding and peritonitis, birth injury, hypoxia, and fetal loss. This report presents a rare case of a 20-year-old female experiencing fetal demise at 60 weeks of pregnancy, with uterine rupture and bone tissue discharge from her vagina without severe intra-abdominal bleeding and peritonitis. The mild clinical course despite complete uterine rupture was due to the firm adhesion of the amniotic sac to the uterus caused by inflammation. The adhesion of the intestines to the rupture site prevented dehiscence of the ruptured wound. Suppuration and bone tissue discharge relieved the pressure on the patient's abdominal cavity and prevented subsequent occurrence of severe peritonitis. Radiologists mistakenly regarded the thick amniotic sac wall on the right side of the uterine wall as a right cornual pregnancy with uterine rupture caused by chronic inflammation. This report aims to bring awareness of this rare condition to medical students and radiologists.

Objective Pycnodysostosis is commonly associated with growth hormone (GH) deficiency and responds well to GH therapy with achievement of normal or near-normal height and restoration of body proportions. Case Report A 22-month-old extremely short (−4.05 height standard deviation score) disproportionate boy with skeletal dysplasia presented to clinic. Skeletal survey, genetic panel, magnetic resonance imaging, and an insulin-like growth factor generation tests were performed. Results Skeletal survey showed increased bone density with classic features of pycnodysostosis, subsequently confirmed to be due to a deleterious homozygous frameshift mutation in CTSK. Uniquely among skeletal dysplasias, GH deficiency is a common association, secondary to pituitary hypoplasia. Magnetic resonance imaging confirmed pituitary hypoplasia and he subsequently underwent an insulin-like growth factor generation test that demonstrated biochemical responsiveness to GH therapy. This was thought to be safer than a classic GH stimulation test, in view of his very small size. Subsequently, his height has markedly improved on GH therapy. His height is now −2.25 SD, with an annualized growth velocity of 9.65 cm/y over a period of 18 months . Conclusion It is important to consider GH therapy in children with pycnodysostosis, with the greatest benefit seen in children started at a young age.

A 58-year-old woman with nonischemic cardiomyopathy underwent an ablation for refractory ventricular fibrillation (VF). In addition to elimination of the premature ventricular contraction triggering VF, substrate ablation entailed elimination of dormant Purkinje potentials, which were unmasked in regions where local pacing revealed a narrow QRS with stimulus QRS latency. VF trigger and abnormal Purkinje ablation completely eliminated the refractory VF. (Level of Difficulty: Intermediate.), Central Illustration

While germ cell testicular cancer is rare and only accounts for 1% of cancers in males, it is the most common solid malignancy among men between 14 and 44 years of age. Testicular cancer can be surgically excised by orchiectomy and is highly responsive to both chemotherapy and radiation therapy. Therefore, testicular tumors generally have the best cancer prognoses, especially since the majority are localized in the initial stage. However, long-term outcome depends on the potential for germ cell testicular cancer to metastasize, both proximal to the testicles and distally throughout the body. Germ cell testicular cancer metastasis to soft tissue, including the trunk, and extremities, appears to be exceedingly rare, as reflected in the extremely limited number of published cases (total of seven patients reported in literature). Vague symptomatology, delayed medical attention, and inconsistent treatment compliance may contribute to testicular soft tissue metastasis and underreporting of these tumors. Here, we report a case of metastatic non–seminomatous germ cell testicular cancer with a large necrotizing, ulcerative mass in the left Iliopsoas muscle and posterior abdominal wall.

Magnetic resonance imaging (MRI) has become the gold standard for the diagnosis of many pathologies. Using MRI in patients with auditory implants can however raise concerns due to mutual interactions between the implant and imaging device, resulting in potential patient risks. Several implant manufacturers have been working towards more MRI safe devices. Older devices are however often labelled for more stringent conditions, possibly creating confusion with patients and professionals. With this myriad of different devices that are implanted in patients for lifetimes of at least 20 years, it is crucial that both patients and professionals have a clear understanding of the safety of their devices. This work aims at providing an exhaustive overview on the MRI safety of active auditory implants. The available industry standards that are followed by manufacturers are outlined and an overview of the latest scientific developments focusing on the last five years is provided. In addition, based on the analysis of the adverse events reported to the Food and Drug Administration (FDA) and in literature within the past ten years, a systematic review of the most commonly occurring issues for patients with auditory implants in the MRI environment is provided. Results indicate that despite the release of more MRI conditional active hearing implants on the market, adverse events still occur. An extensive overview is provided on the MRI safety of active auditory implants, aiming to increase the understanding of the topic for healthcare professionals and contribute to safer scanning conditions for patients. ispartof: Journal of Otology vol:16 issue:3 pages:185-198 ispartof: location:China status: Published online

We describe the case of a 32-year-old man who developed a liver neoplasm due to previous Fontan surgery (FS) for a single ventricle anomaly and situs viscerum inversus. He was admitted to our hospital for suspected hepatocellular carcinoma during an Ultrasound (US) follow up. Computed tomography (CT) showed features of chronic liver disease and 7 cm hepatic nodule with arterial enhancement. Laboratory analyses documented preserved liver function and increased levels of alpha-fetoprotein. Trans-arterial-chemoembolization (TACE) was performed obtaining complete necrosis at 4 weeks of follow up and significant reduction of alpha-fetoprotein. The patient is currently in follow-up, being evaluated for further treatments and/or combined liver-heart transplantation. TACE is a therapeutic option for the treatment of patients with unresectable hepatocellular carcinoma (HCC) and with severe heart disease, like those submitted to FS and with also other vascular abnormalities like those correlated to situs viscerum inversus.

A 7-year-old boy was admitted to the Pediatric Cardiology Department with blood pressure of 160/120 mmHg accompanied by burning pain in his hands and feet and tachycardia, followed by a seizure attack for the first time in his life, which presented shortly after admission. The child underwent a widespread diagnostic process – including laboratory tests and imaging – showing inconclusive results. Acute autonomic neuropathy was eventually diagnosed and successfully treated with intravenous immunoglobulin. The described case illustrates the need for a careful and open-minded approach to patients with hypertension.

Objective: Tumor-induced osteomalacia (TIO) is a rare osteomalacia characterized by paraneoplastic secretion of fibroblast growth factor 23. Concomitant occurrence of TIO during pregnancy is rarer still. Our objective was to report a young patient with debilitating fractures diagnosed with TIO who became pregnant and subsequently had her tumor localized by gallium-68 (Ga-68) DOTATATE positron emission tomography/magnetic resonance imaging (PET/MRI). Case Report: A 28 year-old woman with a 2-year history of stress fractures was found to have the following: (1) alkaline phosphatase level, 220 (reference range, 30-95) U/L; (2) phosphorus level, 2.1 (2.5-5.0) mg/dL; (3) 1,25-dihydroxyvitamin D3 level

The blood-brain barrier (BBB) is a major anatomical and physiological barrier limiting the passage of drugs into brain. Central nervous system tumors can impair the BBB by changing the tumor microenvironment leading to the formation of a leaky barrier, known as the blood-tumor barrier (BTB). Despite the change in integrity, the BTB remains effective in preventing delivery of chemotherapy into brain tumors. Focused ultrasound is a unique noninvasive technique that can transiently disrupt the BBB and increase accumulation of drugs within targeted areas of the brain. Herein, we summarize the current understanding of different types of targeted ultrasound mediated BBB/BTB disruption techniques. We also discuss influence of the tumor microenvironment on BBB opening, as well as the role of immunological response following disruption. Lastly, we highlight the gaps between evaluation of the parameters governing opening of the BBB/BTB. A deeper understanding of physical opening of the BBB/BTB and the biological effects following disruption can potentially enhance treatment strategies for patients with brain tumors.

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.

The transcatheter approach is nowadays considered a cost-effective alternative to surgery in adults with “complex” aortic coarctation. The printed 3D model was crucial in planning transcatheter treatment of a complex case of postsurgical aortic re-coarctation, due to coexistence of transverse aortic arch stenosis and pseudoaneurysm as well as aneurysm of the descending aorta. (Level of Difficulty: Advanced.), Central Illustration

Graphical abstract, Highlights • Quantitative ultrasound (QUS) delta-radiomics to predict recurrence. • Machine learning model can predict recurrence with accuracy >80%. • Classification performances improve when features are taken from weeks 1 and 4., Purpose This study investigated the use of quantitative ultrasound (QUS) obtained during radical radiotherapy (RT) as a radiomics biomarker for predicting recurrence in patients with node-positive head-neck squamous cell carcinoma (HNSCC). Methods Fifty-one patients with HNSCC were treated with RT (70 Gy/33 fractions) (±concurrent chemotherapy) were included. QUS Data acquisition involved scanning an index neck node with a clinical ultrasound device. Radiofrequency data were collected before starting RT, and after weeks 1, and 4. From this data, 31 spectral and related-texture features were determined for each time and delta (difference) features were computed. Patients were categorized into two groups based on clinical outcomes (recurrence or non-recurrence). Three machine learning classifiers were used for the development of a radiomics model. Features were selected using a forward sequential selection method and validated using leave-one-out cross-validation. Results The median follow up for the entire group was 38 months (range 7–64 months). The disease sites involved neck masses in patients with oropharynx (39), larynx (5), carcinoma unknown primary (5), and hypopharynx carcinoma (2). Concurrent chemotherapy and cetuximab were used in 41 and 1 patient(s), respectively. Recurrence was seen in 17 patients. At week 1 of RT, the support vector machine classifier resulted in the best performance, with accuracy and area under the curve (AUC) of 80% and 0.75, respectively. The accuracy and AUC improved to 82% and 0.81, respectively, at week 4 of treatment. Conclusion QUS Delta-radiomics can predict higher risk of recurrence with reasonable accuracy in HNSCC. Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684.

Inverted Meckel's diverticulum is an entity often discovered incidentally or through a clinical evaluation for gastrointestinal bleeding. While rare, inverted Meckel's diverticulum should be considered in the evaluation of a patient presenting with gastrointestinal bleeding, intestinal obstruction, or intussusception. In this case, a 67-year-old female with a remote history of surgically treated breast cancer presents to an urgent care facility with weakness and fatigue. She was found to be anemic with hemoglobin of 4. Imaging revealed a blind-ending pouch in the mid to distal ileum consistent with an inverted Meckel's diverticulum. Inverted Meckel's diverticulum is identified on computerized tomography as an intraluminal, blind-ending structure in the mid to distal ileum. The possibility of a lead point should be investigated and surgical resection is indicated to prevent intestinal obstruction.

An immune response for a nasal ovalbumin (OVA) powder formulation with an applied nasal delivery platform technology, consisting of a powdery nasal carrier and a device, was evaluated in monkeys with similar upper respiratory tracts and immune systems to those of humans, in order to assess the applicability to a vaccine antigen. Nasal distribution and retention studies using a 3D nasal cavity model and manganese-enhanced MRI were conducted by administering nasal dye and manganese powder formulations with the applied technology. Systemic and mucosal immune responses for the nasal OVA powder formulation were evaluated by determining serum IgG and nasal wash IgA antibody titers. The nasal dye and manganese powder formulations showed wider distribution and longer retention time than did a nasal liquid formulation. The nasal OVA powder formulation also showed comparable and higher antigen-specific IgG antibody titer to an injection and nasal liquid formulation, respectively. Furthermore, antigen-specific IgA antibody response was detected only for the nasal OVA powder formulation. The present study suggests that the technology, originally designed for drug absorption, is promising for nasal vaccines, enabling both a mucosal immunity response as the first line of defense and systemic immunity response as a second line of defense against infection.

Objective Primary hypophysitis refers to the isolated inflammation of the pituitary gland not associated with other secondary causes. Among its histopathologic subtypes, xanthomatous is the rarest. Methods We describe a 22-year-old woman with xanthomatous hypophysitis (XH), its clinical progression over 8 years as well as the treatment effects of prednisolone and azathioprine. Our patient was first referred for severe short stature and delayed puberty at the age of 14 years. Results Investigations revealed multiple pituitary deficiencies. Magnetic resonance imaging showed a pituitary mass whereby a partial resection was performed. A full resection was not feasible due to the location of the mass. The histopathologic analysis of the tissue was consistent with XH. The results of secondary workout for neoplasm, infection, autoimmune, and inflammatory disorders were negative. After surgery, a progressive enlargement of the mass was observed. Two courses of prednisolone were administered with a significant reduction in the mass size. Azathioprine was added due to the unsustained effects of prednisolone when tapered off and the concern of steroid toxicity with continued use. No further increase in the mass size was noted after 6 months on azathioprine. Conclusion Glucocorticoid and immunotherapy are treatment options for XH; however, more cases are needed to better understand its pathogenesis and clinical progression.

A 23-year-old man with sickle cell disease treated with splenectomy and allogenic stem cell transplantation presented with recurrent chest pain, elevated cardiac enzymes, and unremarkable electrocardiography. His work-up revealed eosinophilia, raising concern for eosinophilic myocarditis. Cardiac magnetic resonance imaging showed patchy late gadolinium enhancement of the left ventricular free wall, suggestive of myocarditis. He was treated with high-dose intravenous steroids followed by oral prednisone, with improvement in his symptoms and eosinophilia and a decrease in cardiac enhancement on follow-up imaging. (Level of Difficulty: Intermediate.), Central Illustration

Objective We report a case of pituitary apoplexy (PA) with negative radiographic findings for PA and cerebrospinal fluid (CSF) analysis consistent with neutrophilic meningitis. PA is a rare endocrinopathy requiring prompt diagnosis and treatment. Presentation with acute neutrophilic meningitis is uncommon. Methods The diagnostic modalities included pituitary function tests (adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, prolactin), brain computed tomography and magnetic resonance imaging (MRI), and CSF analysis. Results A 67-year-old man presented with worsening headache, nausea, and retching. He was somnolent with an overall normal neurologic examination other than a peripheral vision defect in the left eye. MRI showed a pituitary mass bulging into the suprasellar cistern with optic chiasm elevation, consistent with pituitary macroadenoma. Laboratory evaluation revealed decreased levels of adrenocorticotropic hormone, random cortisol, thyroid-stimulating hormone, thyroxine, luteinizing hormone, and testosterone. He had worsening encephalopathy with left eye ptosis and decreased vision, prompting a repeat computed tomography and MRI, showing no interval change in the pituitary adenoma or evidence of bleeding. CSF analysis revealed a leukocyte count of 1106/mm3 (89% neutrophils), a total protein level of 138 mg/dL, red blood cell count of 2040/mm3 without xanthochromia, and glucose level of 130 mg/dL. The CSF culture result was negative. Transsphenoidal resection revealed a necrotic pituitary adenoma with apoplexy. Conclusions Including PA in the differential diagnosis of acute headache is important, particularly in patients with visual disturbances. PA can present with sterile meningitis, mimicking acute bacterial meningitis. While neuroimaging can help detect PA, the diagnosis of PA remains largely clinical.