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Congenital myasthenic syndrome (CMS) is a group of 32 disorders involving genetic dysfunction at the neuromuscular junction resulting in skeletal muscle weakness that worsens with physical activity. Precise diagnosis and molecular subtype identification are critical for treatment as medication for one subtype may exacerbate disease in another (Engel et al.

De novo deleterious and heritable biallelic mutations in the DNA binding domain (DBD) of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of disorders termed DEAF1-associated neurodevelopmental disorders (DAND). RNA-sequencing using hippocampal RNA from mice with conditional deletion of Deaf1 in the central nervous system indicate that loss of Deaf1 activity results in the altered expression of genes involved in neuronal function, dendritic spine maintenance, development, and activity, with reduced dendritic spines in hippocampal regions. Since DEAF1 is not a dosage-sensitive gene, we assessed the dominant negative activity of previously identified de novo variants and a heritable recessive DEAF1 variant on selected DEAF1-regulated genes in 2 different cell models. While no altered gene expression was observed in cells over-expressing the recessive heritable variant, the gene expression profiles of cells over-expressing de novo variants resulted in similar gene expression changes as observed in CRISPR-Cas9-mediated DEAF1-deleted cells. Altered expression of DEAF1-regulated genes was rescued by exogenous expression of WT-DEAF1 but not by de novo variants in cells lacking endogenous DEAF1. De novo heterozygous variants within the DBD of DEAF1 were identified in 10 individuals with a phenotypic spectrum including autism spectrum disorder, developmental delays, sleep disturbance, high pain tolerance, and mild dysmorphic features. Functional assays demonstrate these variants alter DEAF1 transcriptional activity. Taken together, this study expands the clinical phenotypic spectrum of individuals with DAND, furthers our understanding of potential roles of DEAF1 on neuronal function, and demonstrates dominant negative activity of identified de novo variants.

Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by pathogenic biallelic variants in the ETHE1 gene. The phenotype of this disease has been attributed to deficiency in the mitochondrial sulfur dioxygenase leading to many downstream effects. Ethylmalonic encephalopathy classically presents with developmental regression, petechiae, acrocyanosis, and chronic diarrhea. The neurologic phenotype includes hypotonia, spastic diplegia, ataxia, and developmental delay. As more patients with this condition are described, the neurologic phenotype continues to expand. Although strokelike episodes or metabolic strokes have been studied in other mitochondrial disorders, they have not been thoroughly reported in this disorder. Herein, we describe 3 patients with ethylmalonic encephalopathy who presented clinically with strokelike episodes and strokelike abnormalities on brain magnetic resonance imaging in the setting of acute illness, and the long-term sequelae with evolution into cystic changes in one of these subjects.

Robinow syndrome (RS) is a genetically heterogeneous skeletal dysplasia with recent reports suggesting an osteosclerotic form of the disease. We endeavored to investigate the full spectrum of skeletal anomalies in a genetically diverse cohort of RS patients with a focus on the bone micro-architecture. Seven individuals with molecularly confirmed RS, including four with DVL1 variants and single individuals with variants in WNT5A, ROR2, and GPC4 underwent a musculoskeletal focused physical examination, dual-energy X-ray absorptiometry (DEXA) scan, and high-resolution peripheral quantitative computed tomography (HR-pQCT). Skeletal examination revealed variability in limb shortening anomalies consistent with recent reports. DEXA scan measures revealed increased total body bone mineral density (BMD) (3/7), cranial BMD (5/7), and non-cranial BMD (1/7). Cranial osteosclerosis was only observed in DVL1-RS (4/4) and GPC4-RS (1/1) subjects and in one case was complicated by choanal atresia, bilateral conductive hearing loss, and cranial nerve III, VI, and VII palsy. HR-pQCT revealed a unique pattern of low cortical BMD, increased trabecular BMD, decreased number of trabeculations, and increased thickness of the trabeculations for the DVL1-RS subjects. The spectrum of skeletal anomalies including the micro-architecture of the bones observed in RS has considerable variability with some osteosclerosis genotype-phenotype correlations more frequent with DVL1 variants.

Inborn errors of metabolism (IEM) involving the non-oxidative pentose phosphate pathway (PPP) include the two relatively rare conditions, transketolase deficiency and transaldolase deficiency, both of which can be difficult to diagnosis given their non-specific clinical presentations. Current biochemical testing approaches require an index of suspicion to consider targeted urine polyol testing. To determine whether a broad-spectrum biochemical test could accurately identify a specific metabolic pattern defining IEMs of the non-oxidative PPP, we employed the use of clinical metabolomic profiling as an unbiased novel approach to diagnosis. Subjects with molecularly confirmed IEMs of the PPP were included in this study. Targeted quantitative analysis of polyols in urine and plasma samples was accomplished with chromatography and mass spectrometry. Semi-quantitative unbiased metabolomic analysis of urine and plasma samples was achieved by assessing small molecules via liquid chromatography and high-resolution mass spectrometry. Results from untargeted and targeted analyses were then compared and analyzed for diagnostic acuity. Two siblings with transketolase (TKT) deficiency and three unrelated individuals with transaldolase (TALDO) deficiency were identified for inclusion in the study. For both IEMs, targeted polyol testing and untargeted metabolomic testing on urine and/or plasma samples identified typical perturbations of the respective disorder. Additionally, untargeted metabolomic testing revealed elevations in other PPP metabolites not typically measured with targeted polyol testing, including ribonate, ribose, and erythronate for TKT deficiency and ribonate, erythronate, and sedoheptulose 7-phosphate in TALDO deficiency. Non-PPP alternations were also noted involving tryptophan, purine, and pyrimidine metabolism for both TKT and TALDO deficient patients. Targeted polyol testing and untargeted metabolomic testing methods were both able to identify specific biochemical patterns indicative of TKT and TALDO deficiency in both plasma and urine samples. In addition, untargeted metabolomics was able to identify novel biomarkers, thereby expanding the current knowledge of both conditions and providing further insight into potential underlying pathophysiological mechanisms. Furthermore, untargeted metabolomic testing offers the advantage of having a single effective biochemical screening test for identification of rare IEMs, like TKT and TALDO deficiencies, that may otherwise go undiagnosed due to their generally non-specific clinical presentations.

Summary Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. To further explore the genetic heterogeneity, paralog contribution, and phenotypic variability of RS, we investigated a cohort of 22 individuals clinically diagnosed with RS from 18 unrelated families. Pathogenic or likely pathogenic variants in genes associated with RS or RS phenocopies were identified in all 22 individuals, including the first variant to be reported in DVL2. We retrospectively collected medical records of 16 individuals from this cohort and extracted clinical descriptions from 52 previously published cases. We performed Human Phenotype Ontology (HPO) based quantitative phenotypic analyses to dissect allele-specific phenotypic differences. Individuals with FZD2 variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic NXN variants clustered together with the majority of probands carrying DVL1, DVL2, and DVL3 variants, demonstrating no phenotypic distinction between the NXN-autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing WNT5A, FZD2, and ROR2 apart from non-RS-associated paralogs. Through human phenotype analyses of this RS cohort and OMIM clinical synopses of Mendelian disease, this study begins to tease apart specific biologic roles for non-canonical WNT-pathway proteins., Robinow syndrome (RS) is a genetically heterogeneous disorder caused by WNT/PCP-signaling dysfunction. We identified pathogenic variants in RS individuals (n = 22), including the first DVL2 variant. Quantitative HPO-term-based analyses unveiled gene/allele-specific correlations to disease traits, providing a model for delineating the phenotypic consequences of variants affecting paralogs in the same pathway.

Key Points Question Is untargeted metabolomic profiling associated with a significant increase in the diagnostic rate of screening for inborn errors of metabolism (IEMs) compared with the traditional metabolic screening approach? Findings This cross-sectional analysis of 4464 traditional metabolic screening samples and 2000 plasma metabolomic screening samples received at a clinical biochemical laboratory between July 2014 and February 2019 found a 1.3% diagnostic rate for traditional metabolic screening, whereas clinical metabolomics supported diagnosis in 7.1% of cases, providing an approximately 6-fold higher diagnostic rate in screening for IEMs and identifying more disorders and more disease types compared with the traditional screening approach. Meaning With expanded newborn screening available in all states in the US, a broader approach to primary screening for IEMs is needed, and these data support the application of untargeted clinical metabolomics to serve as a primary screening approach., This cross-sectional study examines the utility of untargeted metabolomics as a primary screening tool for inborn errors of metabolism by comparing the diagnostic rate of clinical metabolomics with the recommended traditional metabolic screening approach., Importance Recent advances in newborn screening (NBS) have improved the diagnosis of inborn errors of metabolism (IEMs); however, many potentially treatable IEMs are not included on NBS panels, nor are they covered in standard, first-line biochemical testing. Objective To examine the utility of untargeted metabolomics as a primary screening tool for IEMs by comparing the diagnostic rate of clinical metabolomics with the recommended traditional metabolic screening approach. Design, Setting, and Participants This cross-sectional study compares data from 4464 clinical samples received from 1483 unrelated families referred for trio testing of plasma amino acids, plasma acylcarnitine profiling, and urine organic acids (June 2014 to October 2018) and 2000 consecutive plasma samples from 1807 unrelated families (July 2014 to February 2019) received for clinical metabolomic screening at a College of American Pathologists and Clinical Laboratory Improvement Amendments–certified biochemical genetics laboratory. Data analysis was performed from September 2019 to August 2020. Exposures Metabolic and molecular tests performed at a genetic testing reference laboratory in the US and available clinical information for each patient were assessed to determine diagnostic rate. Main Outcomes and Measures The diagnostic rate of traditional metabolic screening compared with clinical metabolomic profiling was assessed in the context of expanded NBS. Results Of 1483 cases screened by the traditional approach, 912 patients (61.5%) were male and 1465 (98.8%) were pediatric (mean [SD] age, 4.1 [6.0] years; range, 0-65 years). A total of 19 families were identified with IEMs, resulting in a 1.3% diagnostic rate. A total of 14 IEMs were detected, including 3 conditions not included in the Recommended Uniform Screening Panel for NBS. Of the 1807 unrelated families undergoing plasma metabolomic profiling, 1059 patients (58.6%) were male, and 1665 (92.1%) were pediatric (mean [SD] age, 8.1 [10.4] years; range, 0-80 years). Screening identified 128 unique cases with IEMs, giving an overall diagnostic rate of 7.1%. In total, 70 different metabolic conditions were identified, including 49 conditions not presently included on the Recommended Uniform Screening Panel for NBS. Conclusions and Relevance These findings suggest that untargeted metabolomics provided a 6-fold higher diagnostic yield compared with the conventional screening approach and identified a broader spectrum of IEMs. Notably, with the expansion of NBS programs, traditional metabolic testing approaches identify few disorders beyond those covered on the NBS. These data support the capability of clinical untargeted metabolomics in screening for IEMs and suggest that broader screening approaches should be considered in the initial evaluation for metabolic disorders.

PURPOSE OF REVIEW: To provide an update of the most recent studies on Smith-Magenis syndrome (SMS) with a focus on the unique pattern of behavioral and sleep disturbances associated with the condition. RECENT FINDINGS: The recent literature on SMS has focused on the characteristic severe behavioral and sleep disturbances. A better understanding of the underlying pathophysiological mechanisms and common clinical course has helped further characterize SMS, while much is left to be discovered in regard to effective treatment/management. SUMMARY: SMS is a difficult to manage genetic condition defined by pervasive and progressive behavioral and sleep disturbances with a unique pattern that can often be easily discerned from other neurodevelopmental disorders. Common behavioral features include maladaptive/self-injurious, aggressive, stereotypic, and the newly appreciated food seeking behaviors associated with SMS. In addition, there is a sleep disturbance defined by an altered circadian rhythm with frequent nighttime waking and daytime sleepiness, causing patients and families significant distress. Small studies have suggested some treatment/management approaches to the behavioral and sleep disturbances, however, a lot remains to be discovered.

We report the clinical course of the first prenatally diagnosed cross-reactive immunologic material (CRIM)-negative infantile Pompe disease (IPD) patient [homozygous for c.2560C>T (p.Arg854X) variant in the GAA gene] to undergo prophylactic immune tolerance induction (ITI) and enzyme replacement therapy (ERT) within the first 2 days of life. Both parents were found to be carriers of the c.2560C>T (p.Arg854X) variant through prenatal carrier screening. Fetal echocardiogram at 31 weeks of gestation showed left ventricular hypertrophy. An echocardiogram on the 1st day of life revealed marked biventricular hypertrophy. Physical exam was significant for macroglossia and hypotonia. A short course of Prophylactic ITI with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) in conjunction with ERT at a dose of 20 mg/kg every other week was started on day 2 of life. The patient completed the ITI protocol safely and complete B-cell recovery, based on CD19 count, was noted by 3 months of age. The patient never developed anti-rhGAA IgG antibodies to ERT. Vaccinations were initiated at 9 months of age, with adequate response noted. Complete recovery of cardiac function and left ventricular mass was seen by 11 weeks of age. At 8 months of age, the patient developmentally measured at 75–90% on the Alberta Infant Motor Scale, walked at 11 months and continues to develop age-appropriately at 50 months of age based on the Early Learning Accomplishment Profile. ERT dosing was increased to 40 mg/kg every 2 weeks at 32 months of age and frequency increased to 40 mg/kg every week at 47 months of age. Patient continues to have undetectable antibody titers, most recently at age 50 months and urine Hex4 has remained normal. To our knowledge, this is the first report of successful early ERT and ITI in a prenatally diagnosed CRIM-negative IPD patient and the youngest IPD patient to receive ITI safely. With the addition of Pompe disease to the Recommended Uniform Screening Panel(RUSP) and its addition to multiple state newborn screening programs, our case highlights the benefits of early diagnosis and timely initiation of treatment in babies with Pompe disease, who represent the most severe end of the disease spectrum.

Background The nuclear encoded gene RMND1 (Required for Meiotic Nuclear Division 1 homolog) has recently been linked to RMND1‐related mitochondrial disease (RRMD). This autosomal recessive condition characteristically presents with an infantile‐onset multisystem disease characterized by severe hypotonia, global developmental delay, failure to thrive, sensorineural hearing loss, and lactic acidosis. Renal disease, however, appears to be one of the more prominent features of RRMD, affecting patients at significantly higher numbers compared to other mitochondrial diseases. We report the clinical, histological, and molecular findings of four RRMD patients across three academic institutions with a focus on the renal manifestations. Methods Four patients were identified for the purpose of this study, all of whom had molecular confirmation at the time of inclusion, which included the common pathogenic variant c.713A>G (p.N238S) as well as the three rare variants: c.485delC (p.P162fs), c.533C>T (p.T178M), and c.1317 + 1G>C splice donor variant. Medical history and laboratory findings were collected from the medical records and medical providers. Results In this study, all four patients developed renal disease characterized as tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end‐stage renal disease (4/4) necessitating renal transplantation (2/4). Histological evaluation of renal biopsy specimens revealed generalized tubular atrophy and on electron microscopy, abundant mitochondria with pleomorphism and abnormal cristae. Conclusion Our experience with RRMD demonstrates a specific pattern of renal disease manifestations and clinical course. Patients are unlikely to respond to traditional chronic kidney disease (CKD) treatments, making early diagnosis and consideration of renal transplantation paramount to the management of RRMD., RMND1‐related mitochondrial disease (RRMD) is a complex mitochondrial condition that has a particularly high risk of severe and early‐onset renal disease compared to other mitochondrial disorders. In this study of four patients, we have shown that the clinical phenotype may include tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end‐stage renal disease (ESRD) necessitating renal transplantation (4/4). Additionally, patients are unlikely to respond to traditional chronic kidney disease (CKD) treatments, making early diagnosis and consideration of renal transplantation paramount to the management of RRMD.

Background Organic acidemias, especially propionic acidemia (PA) and methylmalonic acidemia (MMA), may manifest clinically within the first few hours to days of life. The classic presentation in the newborn period includes metabolic acidosis, hyperlactatemia, and hyperammonemia that is precipitated by unrestricted protein intake. Implementation of newborn screening to diagnose and initiate early treatment has facilitated a reduction in neonatal mortality and improved survival. Despite early diagnosis and appropriate management, these individuals are prone to have recurrent episodes of metabolic acidosis and hyperammonemia resulting in frequent hospitalizations. Liver transplantation (LT) has been proposed as a treatment modality to reduce metabolic decompensations which are not controlled by medical management. Published reports on the outcome of LT show heterogeneous results regarding clinical and biochemical features in the post transplantation period. As a result, we evaluated the outcomes of LT in our institution and compared it to the previously published data. Study design/methods We performed a retrospective chart review of nine individuals with PA or MMA who underwent LT and two individuals with MMA who underwent LT and kidney transplantation (KT). Data including number of hospitalizations, laboratory measures, cardiac and neurological outcomes, dietary protein intake, and growth parameters were collected. Results The median age of transplantation for subjects with MMA was 7.2 years with a median follow up of 4.3 years. The median age of transplantation for subjects with PA was 1.9 years with a median follow up of 5.4 years. The survival rate at 1 year and 5 years post-LT was 100%. Most of our subjects did not have any episodes of hyperammonemia or pancreatitis post-LT. There was significant reduction in plasma glycine post-LT. One subject developed mild elevation in ammonia post-LT on an unrestricted protein diet, suggesting that protein restriction may be indicated even after LT. Conclusion In a large single center study of LT in MMA and PA, we show that LT may reduce the incidence of metabolic decompensation. Moreover, our data suggest that LT may be associated with reduced number of hospitalizations and improved linear growth in individuals with PA and MMA.

Hartnup disease is an autosomal recessive condition characterized by neutral aminoaciduria and behavioral problems. It is caused by a loss of B0 AT1, a neutral amino acid transporter in the kidney and intestine. CLTRN encodes the protein collectrin that functions in the transportation and activation of B0 AT1 in the renal apical brush bordered epithelium. Collectrin deficient mice have severe aminoaciduria. However, the phenotype associated with collectrin deficiency in humans has not been reported. Here we report two patients, an 11-year-old male who is hemizygous for a small, interstitial deletion on Xp22.2 that encompasses CLTRN and a 22-year-old male with a deletion spanning exons 1 to 3 of CLTRN. Both of them present with neuropsychiatric phenotypes including autistic features, anxiety, depression, compulsions, and motor tics, as well as neutral aminoaciduria leading to a clinical diagnosis of Hartnup disease and treatment with niacin supplementation. Plasma amino acids were normal in both patients. One patient had low 5-hydroxyindoleacetic acid levels, a serotoninergic metabolite. We explored the expression of collectrin in the murine brain and found it to be particularly abundant in the hippocampus, brainstem, and cerebellum. We propose that collectrin deficiency in humans can be associated with aminoaciduria and a clinical picture similar to that seen in Hartnup disease. Further studies are needed to explore the role of collectrin deficiency in the neurological phenotypes.

Short chain enoyl-CoA hydratase (SCEH) deficiency leads to a severe form of autosomal recessive Leigh syndrome with inevitable neurological decline and early mortality. SCEH is most notably involved in valine catabolism, a deficiency of which results in various metabolic alterations, including increased levels of the highly reactive metabolite 2-methacrylyl-CoA. With no proven treatments available to date, it has been speculated that patients may respond to a valine restricted diet and/or N-acetylcysteine supplementation, as suggested by early studies of a very similar inborn error of metabolism, 3-hydroxyisobutyryl-CoA hydrolase deficiency. We describe a patient with typical Leigh syndrome clinical findings and identified compound heterozygous variants in ECSH1. Valine-restricted diet was initiated at 6 months of age and N-acetylcysteine supplementation at 9 months with subsequent improvement in growth and slow progress in developmental milestones. However, at 15 months, the patient aspirated during a breakthrough seizure from which he did not recover and died soon after from related complications. This report highlights some of the challenges that remain in the management and treatment of SCEH deficiency, while demonstrating that a valine restricted diet and N-acetylcysteine can be safely administered with the potential for clinical improvement.

Bernhard von Langenbeck is undeniably one of the world's greatest surgeons and inventors. The influence which he exerted upon the practice of surgery, as apparent by the numerous surgical tools and 21 operations credited to his name, represents the notable contributions of this amazing man. Despite the tools and techniques which bear his name, the establishment of a surgical journal, and his role in co-founding the German Surgical Society, many attest that Bernhard von Langenbeck's greatest contribution to the professional field was the vast knowledge he imparted on his pupils. Commonly credited with training nearly every celebrated surgical operator of his time, von Langenbeck merits posthumous acknowledgement for his vast contributions to the field of medicine and surgery.

Introduction: With rising global antibiotic resistance, stewardship programs aimed at controlling multi-drug resistant (MDR) pathogens have begun to gain acceptance. These programs stress appropriate antibiotic selection, dosage and duration. A growing literature suggests serum procalcitonin (PCT) levels may be useful in guiding antibiotic duration and de-escalation. This report sought to evaluate the evidence-based data available from prospective randomized controlled trials (RCT) on the role of PCT in guiding reductions in antibiotic duration in adult sepsis patients. Methods: A comprehensive search of all published prospective RCT(s) on the use of PCT as a tool for guiding antibiotic therapy in adult sepsis patients was conducted using PubMed, Medline Plus and Google Scholar (2007-2013). Keywords searched included, “procalcitonin”, “sepsis-therapy”, “sepsis biomarker”, “antibiotic duration”, “drug de-escalation”, and “antimicrobial stewardship”. Results: Four RCT(s) involving 826 adult sepsis patients have evaluated the role of serum PCT levels to guide criteria for cessation of antibiotic therapy based either on specific PCT levels or PCT kinetics. Bouadma et al. (N = 621) stopped antibiotics when the PCT concentration was et al. (N = 27) discontinued antibiotics if clinical signs of infection improved and the PCT value decreased to et al. (N = 110) ceased antibiotics when the PCT decreased to 1 ng/mL. The PCT arm showed a 2-day reduction in antibiotics. Finally, Nobre et al. (N = 68) stopped antibiotics when PCT levels decreased by 90% or more from the initial value, but not prior to Day 3 (if baseline PCT measured p

The anatomy and clinical significance of the sinuvertebral nerve is a topic of considerable interest among anatomists and clinicians, particularly its role in discogenic pain. It has required decades of research to appreciate its role, but not until recently could these studies be compiled to establish a more complete description of its clinical significance. The sinuvertebral nerve is a recurrent nerve that originates from the ventral ramus, re-entering the spinal canal via the intervertebral foramina to innervate multiple meningeal and non-meningeal structures. Its complex anatomy and relationship to discogenic pain have warranted great interest among clinical anatomists owing to its sympathetic contribution to the lumbar spine. Knowledge of the nerve has been used to design a variety of diagnostic and treatment procedures for chronic discogenic pain. This paper reviews the anatomy and clinical aspects of the sinuvertebral nerve.

Abraham Colles is known among the medical community for his detailed description of Colles' fracture, one of the most common occurring skeletal injuries. It is remarkable that something as seemingly simple as the diagnosis of Colles' fracture had not been established until nearly 200 years ago. While that may have been his most well known accomplishment, Colles made several other contributions to medicine across multiple fields of practice. In the field of anatomy, he is also credited for his discovery and description of Colles' fascia and Colles' ligament. Less commonly known, however, are his clinical observations and offered treatment regimens for syphilis, as well as his achievement in performing the first surgery for axillary artery aneurysm. The current paper will review the life and contributions of this early surgeon and anatomist. Clin. Anat. 27:670–674, 2014. © 2013 Wiley Periodicals, Inc.

Benjamin Alcock (1801–?) was a prominent anatomist from Ireland who is remembered most for his description of the pudendal canal. He was privileged to train under the great Irish anatomist, Abraham Colles. Following his training and several early teaching engagements, he was appointed as the first Professor of Anatomy and Physiology at Queen's College, Cork. He became a Fellow of the Royal College of Surgeons in Ireland. After several years of teaching at Queen's College, Alcock was forced to resign after a dispute over the Anatomy Act of 1832, during which he conveyed his disapproval of participation in the procurement of corpses for the school. Several years after his resignation, he left for the United States and removed himself from the view of the profession. His anatomical contributions were published in The Cyclopaedia of Anatomy and Physiology. The description he gave of the sheath enclosing the pudendal nerve and internal pudendal vessels is his most famous contribution to the literature. He is remembered eponymously for Alcock's canal. This article's intent is to clearly and concisely depict the life and contribution of Benjamin Alcock. Clin. Anat. 26:662–666, 2013. © 2012 Wiley Periodicals, Inc.

The complexity of embryological development of the gastrointestinal tract and mesentery provides a platform for the formation of a wide variety of variant veils, folds, and membranes, collectively termed peritoneal bands. These structures, which represent anatomically unabsorbed portions of the omentum and mesentery, although often benign, have the potential to cause clinically significant manifestations in both the neonate and adult. Although these deviant structures may be identified over a broad range of the abdominal cavity, they are most commonly identified in the regions of the duodenum, duodenojejunal flexure, ileocecal junction, and ascending colon. As a result of the diverse location of these variant structures, clinical manifestations are highly variable, ranging from acute presentations of intestinal necrosis as a result of strangulated midgut volvulus to chronic, vague abdominal pain. This article seeks to highlight the importance of a thorough anatomical understanding of the distribution of the various abnormal peritoneal folds, bands, and ligaments, which may result from aberrations in embryonic gastrointestinal development and their respective clinical implications. Moreover, to advance the knowledge of peritoneal bands, this article discusses the appropriate diagnostic studies and treatment interventions required for these variant structures.

High-risk prognostic factors for adults with well-differentiated thyroid cancer (WDTC) have been well established, but the same is not true for pediatric patients. This study sought to determine whether validated adult prognostic systems are applicable to pediatric patients and to develop a novel prognostic scale that may better reflect outcomes in pediatric subgroups.We queried 62,007 cases of WDTC from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2009) to identify 895 patients20 years of age with WDTC. Data abstracted included age, gender, race, histology type, primary tumor size, cancer stage, and mortality. Odds ratio and 95% confidence intervals were set and data were analyzed with SAS version 9.2.Among 895 pediatric WDTC patients, the overall cause-specific mortality was 0.8%. The presence of distant metastasis was associated with the worst prognosis (P = .0045) followed by larger primary tumor size (P = .0135) and male gender (P = .0162). When classified into low-, moderate-, and high-risk categories according to the distant metastasis (Me), larger primary tumor size (S), and male sex (S) (MeSS) algorithm, mortality rates were 0%, 2.7%, and 23%, respectively.Commonly used prognostic indices for WDTC in adults do not reliably predict poor outcomes among pediatric patients. Rather, a system based on MeSS is more applicable to pediatric patients. Patients who exhibit a high MeSS score have a significantly worse overall survival than those who do not express any MeSS characteristics.

The complexity of embryological development of the gastrointestinal tract and mesentery provides a platform for the formation of a wide variety of variant veils, folds, and membranes, collectively termed peritoneal bands. These structures, which represent anatomically unabsorbed portions of the omentum and mesentery, although often benign, have the potential to cause clinically significant manifestations in both the neonate and adult. Although these deviant structures may be identified over a broad range of the abdominal cavity, they are most commonly identified in the regions of the duodenum, duodenojejunal flexure, ileocecal junction, and ascending colon. As a result of the diverse location of these variant structures, clinical manifestations are highly variable, ranging from acute presentations of intestinal necrosis as a result of strangulated midgut volvulus to chronic, vague abdominal pain. This article seeks to highlight the importance of a thorough anatomical understanding of the distribution of the various abnormal peritoneal folds, bands, and ligaments, which may result from aberrations in embryonic gastrointestinal development and their respective clinical implications. Moreover, to advance the knowledge of peritoneal bands, this article discusses the appropriate diagnostic studies and treatment interventions required for these variant structures.

Bernhard von Langenbeck is undeniably one of the world's greatest surgeons and inventors. The influence which he exerted upon the practice of surgery, as apparent by the numerous surgical tools and 21 operations credited to his name, represents the notable contributions of this amazing man. Despite the tools and techniques which bear his name, the establishment of a surgical journal, and his role in co-founding the German Surgical Society, many attest that Bernhard von Langenbeck's greatest contribution to the professional field was the vast knowledge he imparted on his pupils. Commonly credited with training nearly every celebrated surgical operator of his time, von Langenbeck merits posthumous acknowledgement for his vast contributions to the field of medicine and surgery.

A single pathophysiological mechanism of Chiari Type I malformations (CM-I) has been a topic of debate. To help better understand CM-I, the authors review disorders known to be associated with CM-I. The primary methodology found among most of them is deformation of the posterior cranial fossa, usually with subsequent decrease in volume. Other mechanisms exist as well, which can be categorized as either congenital or acquired. In understanding the relationship of such disorders with CM-I, we may gain further insight into the process by which cerebellar tonsillar herniation occurs. Some of these pathologies appear to be true associations, but many appear to be spurious.

Benjamin Alcock (1801-?) was a prominent anatomist from Ireland who is remembered most for his description of the pudendal canal. He was privileged to train under the great Irish anatomist, Abraham Colles. Following his training and several early teaching engagements, he was appointed as the first Professor of Anatomy and Physiology at Queen's College, Cork. He became a Fellow of the Royal College of Surgeons in Ireland. After several years of teaching at Queen's College, Alcock was forced to resign after a dispute over the Anatomy Act of 1832, during which he conveyed his disapproval of participation in the procurement of corpses for the school. Several years after his resignation, he left for the United States and removed himself from the view of the profession. His anatomical contributions were published in The Cyclopaedia of Anatomy and Physiology. The description he gave of the sheath enclosing the pudendal nerve and internal pudendal vessels is his most famous contribution to the literature. He is remembered eponymously for Alcock's canal. This article's intent is to clearly and concisely depict the life and contribution of Benjamin Alcock.