Hyperglycemic Hyperosmolar State During Induction Chemotherapy for Acute Lymphoblastic Leukemia.

We present the case of a 16-year-old boy who presented with fatigue, polyuria, and polydipsia while on chemotherapy for his relapsed acute lymphoblastic leukemia (ALL). Blood gas examination confirmed the diagnosis of hyperosmolar hyperglycemic state. The etiology for his hyperglycemia was most likely a result of oral glucocorticoid therapy combined with asparaginase therapy-both are a cornerstone of induction chemotherapy for ALL. The patient was aggressively rehydrated with saline, and medications were administered to correct his hyperkalemia. He was then slowly brought to euglycemia with a continuous infusion of insulin. Although hyperosmolar hyperglycemic state is rare during the treatment of ALL, frontline providers should be aware of this diagnosis because of the significant risk of hypovolemic shock and death if correction of hyperglycemia occurs prior to complete fluid resuscitation.

Cognitive reserve is a determinant of health-related quality of life in patients with cirrhosis, independent of covert hepatic encephalopathy and model for end-stage liver disease score.

BACKGROUND & AIMS: Covert hepatic encephalopathy (CHE) is associated with cognitive dysfunction, which affects daily function and health-related quality of life (HRQOL) in patients with cirrhosis. The effects of CHE and liver disease are determined by cognitive reserve­the ability of the brain to cope with increasing damage while continuing to function­and are assessed by composite intelligence quotient (IQ) scores. We examined cognitive reserve as a determinant of HRQOL in patients with cirrhosis. METHODS: We performed a prospective study of 118 outpatients with cirrhosis without overt HE (age, 56 y). We studied cognition using the standard paper-pencil battery; patients with below-normal results for more than 2 tests were considered to have CHE. We also assessed HRQOL (using the sickness impact profile [SIP]), psychosocial and physical scores (a high score indicates reduced HRQOL), model for end-stage liver disease (MELD) scores, and cognitive reserve (using the Barona Index, a validated IQ analysis, based on age, race, education, residence area, and occupation). Cognitive reserve was divided into average and high groups (<109 or >109), and MELD and SIP scores were compared. We performed regression analyses, using total SIP score and psychosocial and physical dimensions as outcomes, with cognitive reserve, CHE, and MELD score as predictors. RESULTS: Study participants had average MELD scores of 9, and 14 years of education; 81% were white, 63% were urban residents, their mean IQ was 108 ± 8, and 54% had average cognitive reserve (the remaining 46% had high reserves). CHE was diagnosed in 49% of patients. Cognitive reserve was lower in patients with CHE (109) than without (105; P = .02). Cognitive reserve correlated with total SIP and psychosocial score (both r = -0.4; P < .001) and physical score (r = -0.3; P = .01), but not MELD score (P = .8). Patients with high cognitive reserve had a better HRQOL, despite similar MELD scores. In regression analyses, cognitive reserve was a significant predictor of total SIP (P < .001), psychosocial (P < .001), and physical scores (P < .03), independent of CHE, MELD, or psychiatric disorders. CONCLUSIONS: A higher cognitive reserve is associated with a better HRQOL in patients with cirrhosis, despite similar disease severity and prevalence. This indicates that patients with good cognitive reserve are better able to withstand the demands of cirrhosis progression and CHE, leading to a better HRQOL. Patients with lower cognitive reserve may need more dedicated and earlier measures to improve HRQOL. Cognitive reserve should be considered when interpreting HRQOL and cognitive tests to evaluate patients with cirrhosis.

Stabilizing bony plate in guided endodontic surgery using an innovative approach.

Endodontic microsurgery in tandem with advanced radiographic techniques has led to the emergence of guided surgeries. Preservation of the cortical bone to enhance the healing and stabilization of tissues surrounding the tooth of concern can now be facilitated by bone cement used in the field of orthopedics. This case report details a guided endodontic surgery technique in 17 years old where a traumatic infliction leads to a phoenix abscess. The technique elaborated emphasizes on the three-dimensional printing of a surgical template with the help of cone-beam computed tomography, followed using a medical-grade bone cement in the most minimal manner to reposition the buccal cortical bone. A 12-month-old follow-up revealed the patient to be asymptomatic with a flawless periapical region radiographically. This case testifies that the optimum use of available biomedical material in surgical endodontics can assure a predictable prognosis.

Differential expression of cytochrome P450 omega-hydroxylase isoforms and their association with clinicopathological features in pancreatic ductal adenocarcinoma.

BACKGROUND: The cytochrome P450 (CYP) superfamily consists of enzymes that catalyze the oxidation of lipids, steroids, and drugs. In particular, the CYP4 family plays an essential role in lipid metabolism by the ω-hydroxylation of terminal ends of fatty acids. Disturbance of this system has been associated with increased angiogenesis, proliferation, and metastasis of several cancers. This study aimed to detect the expression of CYP4 isoforms (CYP4A11, CYP4F2, CYP4F3) in pancreatic ductal adenocarcinoma (PDA) and their association with clinicopathological features. METHODS: Pancreatic specimens were collected from 73 patients who underwent surgical resection at the Thomas Jefferson University Hospital. Quantitative polymerase chain reaction was used to examine the cytochrome P450 isoforms in PDA (n = 62), adjacent-normal (n = 30), and benign tissues (n = 11). Logistic regression models were used to analyze gene expression among tissue types. Spearman rank correlations were calculated for isoform expression and for age. Differences in expression by gender were assessed via t test. Other clinicopathological variables (diabetes, smoking, obesity, T stage, perineural invasion, nodal status) were analyzed by Wilcoxon rank sum. RESULTS: CYP4 expression for isoforms was significantly higher in PDA tissues versus matched-adjacent tissues (p < 0.01). PDA tumors expressed significantly higher levels of CYP4F2 and CYP4F3 when compared to benign lesions (p < 0.01). Significant associations were found between low levels of CYP4F2 and CYP4F3 and increased age of PDA patients. Interestingly, all isoforms were expressed at higher levels in male patients. CONCLUSIONS: Transcriptional upregulation of cytochrome P450 ω-hydroxylase suggests that these enzymes have the potential to be used as distinguishing markers in pancreatic pathology.

Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech.

Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 subjects with a neurodegenerative speech and language disorder were prospectively recruited and underwent detailed speech and language, neurological, neuropsychological and neuroimaging testing. The neuroimaging battery included 3.0 tesla volumetric head magnetic resonance imaging, [(18)F]-fluorodeoxyglucose and [(11)C] Pittsburg compound B positron emission tomography scanning. Twelve subjects were identified as having apraxia of speech without any signs of aphasia based on a comprehensive battery of language tests; hence, none met criteria for primary progressive aphasia. These subjects with primary progressive apraxia of speech included eight females and four males, with a mean age of onset of 73 years (range: 49-82). There were no specific additional shared patterns of neurological or neuropsychological impairment in the subjects with primary progressive apraxia of speech, but there was individual variability. Some subjects, for example, had mild features of behavioural change, executive dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter revealed focal atrophy of superior lateral premotor cortex and supplementary motor area. Voxel-based morphometry of white matter showed volume loss in these same regions but with extension of loss involving the inferior premotor cortex and body of the corpus callosum. These same areas of white matter loss were observed with diffusion tensor imaging analysis, which also demonstrated reduced fractional anisotropy and increased mean diffusivity of the superior longitudinal fasciculus, particularly the premotor components. Statistical parametric mapping of the [(18)F]-fluorodeoxyglucose positron emission tomography scans revealed focal hypometabolism of superior lateral premotor cortex and supplementary motor area, although there was some variability across subjects noted with CortexID analysis. [(11)C]-Pittsburg compound B positron emission tomography binding was increased in only one of the 12 subjects, although it was unclear whether the increase was actually related to the primary progressive apraxia of speech. A syndrome characterized by progressive pure apraxia of speech clearly exists, with a neuroanatomic correlate of superior lateral premotor and supplementary motor atrophy, making this syndrome distinct from primary progressive aphasia.

Internal root resorption: A rare complication of vital pulp therapy using platelet-rich fibrin.

Internal root resorption (IRR) is a specific type of pulp disease categorized by the loss of dentin as a consequence of the action of clastic cells stimulated by pulpal inflammation. It is one of the rare complications following a vital pulp therapy (VPT) procedure. Reported here is a case of IRR as a complication of VPT platelet-rich fibrin pulpotomy procedure in a mature permanent tooth. Diagnosed using cone-beam computed tomography and management of the resorptive defect using biodentin with a follow-up of 1 year.

Direct tests of the energetic basis of abortive cycling in transcription.

Although the synthesis of RNA from a DNA template is (and must be) a generally very stable process to enable transcription of kilobase transcripts, it has long been known that during initial transcription of the first 8-10 bases of RNA complexes are relatively unstable, leading to the release of short abortive RNA transcripts. A wealth of structural data in the past decade has led to specific mechanistic models elaborating an earlier "stressed intermediate" model for initial transcription. In this study, we test fundamental predictions of each of these models in the simple model enzyme T7 RNA polymerase. Nicking or gapping the nontranscribed template DNA immediately upstream of the growing hybrid yields no systematic reduction in abortive falloff, demonstrating clearly that compaction or "scrunching" of this DNA is not a source of functional instability. Similarly, transcription on DNA in which the nontemplate strand in the initially transcribed region is either mismatched or removed altogether leads to at most modest reductions in abortive falloff, indicating that expansion or "scrunching" of the bubble is not the primary driving force for abortive cycling. Finally, energetic stress derived from the observed steric clash of the growing hybrid against the N-terminal domain contributes at most mildly to abortive cycling, as the addition of steric bulk (additional RNA bases) at the upstream end of the hybrid does not lead to predicted positional shifts in observed abortive patterns. We conclude that while structural changes (scrunching) clearly occur in initial transcription, stress from these changes is not the primary force driving abortive cycling.

Injuries in Cricket.

CONTEXT: Cricket is a popular global sport that requires a combination of physical fitness, skill, and strategy. Although a noncontact sport, overuse and impact injuries are common since players engage in a wide range of physical activities, including running, throwing, batting, bowling, catching, and diving. Significant or match time-loss injuries are defined as those that either prevent a player from being fully available for selection in a major match, or during a major match, cause a player to be unable to bat, bowl, or keep wicket when required by either the rules or the team's captain. This review describes the various region-wise injuries sustained in cricket along with their epidemiology, biomechanics, treatment, and prevention. EVIDENCE ACQUISITION: Data were collected from peer-reviewed articles (obtained via PubMed search) published through November 2016 that involved the medical, biomechanical, and epidemiological aspects of cricket injuries. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Cricket was one of the first sports to publish recommended methods for injury surveillance in 2005 from England, South Africa, Australia, the West Indies, and India. While the incidence of injuries is about the same, the prevalence of injuries has increased due to game format changes, increasing number of matches played, and decreased rest between matches. Bowling (41.3%), fielding, and wicket keeping (28.6%) account for most injuries. Acute injuries are most common (64%-76%), followed by acute-on-chronic (16%-22.8%) and chronic ones (8%-22%). The most common modern-day cricket injury is hamstring strain, and the most severe is lumbar stress fracture in young fast bowlers. CONCLUSION: With improved understanding of the scientific and medical aspects of cricket, along with advances in surgical and nonsurgical treatment techniques, the time to return to play has shortened considerably. While the prevalence of cricket injuries has increased, their severity has decreased over the past decades.

Accessory branch of canalis sinuosus mimicking external root resorption: A diagnostic dilemma.

The aim of this study was to recognize the importance of canalis sinuosus in Endodontics. A 60-year-old male patient reported with the chief complaint of pain and swelling in upper front tooth region for 2 weeks with a history of trauma 21 years back. Clinical examination revealed fractured tooth 21 (maxillary left central incisor) with an associated sinus tract. Radiographic examination revealed diffuse periapical radiolucency in relation to tooth 21 and external resorptive defect in apical third of the root of tooth 11 (maxillary right central incisor). Cone-beam computed tomography advised to plan surgical treatment for the same disclosed the presence of an anatomic variation of canalis sinuosus. The location and course of this canal illuded as a resorptive defect, which is a very rare occurrence. This led to a change in diagnosis with relation to tooth 11 and treatment plan was formulated accordingly.

The Effect of Mineral Trioxide Aggregate on the Periapical Tissues after Unintentional Extrusion beyond the Apical Foramen.

Introduction. Single-step apexification procedures using mineral trioxide aggregate (MTA) have been reported as favorable treatment options for teeth with an open apex, posing greater benefits compared to the other available medicaments. However, controlled apical placement of MTA is a challenging procedure to perform using orthograde approach. This case series describes the outcome of the unintentional extrusion of MTA into periradicular tissues during apexification, in three separate cases. Methods. Three adult patients reported to the Department of Conservative Dentistry and Endodontics for the management of maxillary incisors with open apices. After isolation, conventional access, and cleaning and shaping procedures, one-step MTA apexification was performed. On subsequent radiographs, a considerable amount of MTA was seen to be extruded in all the three cases. Results. During follow-up examination the teeth were seen to be asymptomatic in all cases and radiographically demonstrated repair of the periapical lesion. Conclusion. The results of these cases suggest that extrusion of MTA into the periapical tissues does not cause any detrimental effect, which could be attributed to the biologic properties of MTA.

Conserved Metabolic Changes in Nondiabetic and Type 2 Diabetic Bariatric Surgery Patients: Global Metabolomic Pilot Study.

The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery.

Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion-Preliminary Observations.

According to the epidemiological studies, about 4.4% of American general elderly population has a pronounced hypothyroidism and relies on thyroid hormone supplements daily. The prevalence of hypothyroidism in our patients with pancreatic cancer was much higher, 14.1%. A retrospective analysis was performed on patients who underwent pancreaticoduodenectomy (Whipple procedure) or distal pancreatectomy and splenectomy (DPS) at Thomas Jefferson University Hospital, Philadelphia, from 2005 to 2012. The diagnosis of hypothyroidism was correlated with clinicopathologic parameters including tumor stage, grade, and survival. To further understand how thyroid hormone affects pancreatic cancer behavior, functional studies including wound-induced cell migration, proliferation, and invasion were performed on pancreatic cancer cell lines, MiaPaCa-2 and AsPC-1. We found that hypothyroid patients taking exogenous thyroid hormone were more than three times likely to have perineural invasion, and about twice as likely to have higher T stage, nodal spread, and overall poorer prognostic stage (P < 0.05). Pancreatic cancer cell line studies demonstrated that exogenous thyroid hormone treatment increased cell proliferation, migration, and invasion (P < 0.05). We conclude that exogenous thyroid hormone may contribute to the progression of pancreatic cancer.

Osteopontin (OPN) isoforms, diabetes, obesity, and cancer; what is one got to do with the other? A new role for OPN.

Alternative splicing of osteopontin (OPN) produces three isoforms: OPNa, OPNb, and OPNc. The aims of this study were to examine the expression profile of OPN isoforms in sera from patients with pancreatic lesions and to determine their correlation with the presence of comorbid systemic inflammatory conditions, such as diabetes and/or obesity. Sera from 90 patients undergoing pancreatic surgery and 29 healthy volunteers were analyzed. Seventeen patients were diabetics, 17 were obese, and 6 had both diabetes and obesity. In patients with pancreatic lesions, OPNb was expressed in 48% of the patients' sera, OPNc in 34%, and both in 5%. The presence of diabetes and/or obesity was associated with complete disappearance of OPNb and expression of only OPNc. OPNc presence was significantly associated with diabetes and obesity (OR = 7.06 [95% CI 1.97-23.3]; p = 0.003). No OPNb or OPNc was detected in the normal sera. Overexpression of OPNb and OPNc isoforms in PDA cells significantly (p < 0.05) increased their activity in soft-agar colony formation and wound healing assays, induced the transcription of interleukin (IL)-6, and reduced tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and IL-10. Our data show for the first time the significant association between serum OPNc and diabetes and/or obesity. Unraveling the functional role of OPN isoforms in systemic inflammation is essential to understanding their significance as therapeutic targets in diabetes and obesity, and during metastasis development in PDA.

Multitasking behaviors of osteopathic medical students.

CONTEXT: To the authors' knowledge, few studies have investigated the relationship between electronic media multitasking by undergraduate and graduate students during lecture and their academic performance, and reports that have looked into this behavior have neglected to investigate factors that may influence students' multitasking during lecture. OBJECTIVE: To determine the extent to which medical students multitask during lecture; the types of multitasking; the frequency of multitasking and factors that influence frequency; and the correlation between multitasking and knowledge acquisition as assessed by a postlecture quiz. METHODS: A 1-page survey assessing students' multitasking behavior was administered to 125 second-year students at Edward Via College of Osteopathic Medicine and collected at the onset of a standard 50-minute lecture. On completion of the 50-minute lecture, an unannounced 10-question multiple-choice quiz was given to assess knowledge acquisition during those lectures. On a separate date, after a standard 50-minute lecture, a second quiz was administered. RESULTS: The 1-page survey revealed that 98% of students check e-mail, 81% use social media, and 74% study for another class. Students spent the most time studying for another class (23 minutes) followed by using social media (13 minutes) and checking e-mail (7 minutes). The most influential factors behind multitasking were examination schedule (91%), lecturer (90%), and the number of lectures in the day (65%). The mean score for quiz 1 (the day after an examination) was 75%, and the mean score for quiz 2 (the day before an examination) was 60%. CONCLUSION: Multitasking during lecture is prominent among medical students, and examination schedule is the most influential factor. Although a robust drop in mean score on a lecture-based, unannounced quiz was identified 1 day before a scheduled examination, the effect from multitasking on this process remains unclear.

Clinical correlates of white matter tract degeneration in progressive supranuclear palsy.

OBJECTIVES: To use diffusion tensor imaging to assess white matter tract degeneration in progressive supranuclear palsy (PSP) and to investigate correlates between tract integrity and clinical measures. DESIGN: Case-control study. SETTING: Tertiary care medical center. PATIENTS/PARTICIPANTS: Twenty patients with probable PSP and 20 age- and sex-matched healthy controls were enrolled. All patients with PSP underwent standardized clinical testing, including the Frontal Behavioral Inventory and Frontal Assessment Battery to assess behavioral change, the PSP Rating Scale to measure disease severity, the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (parts II and III) to measure motor function, and the PSP Saccadic Impairment Scale to measure eye movement abnormalities. METHODS: Fractional anisotropy and mean diffusivity were measured using region of interest analysis and tract-based spatial statistics. RESULTS: Compared with controls, abnormal diffusivity was observed predominantly in the superior cerebellar peduncles, body of the corpus callosum, inferior longitudinal fasciculus, and superior longitudinal fasciculus in patients with PSP. Fractional anisotropy values in the superior cerebellar peduncles correlated with disease severity (r = -0.59, P = .006), inferior longitudinal fasciculus correlated with motor function (r = -0.51, P = .02), and superior longitudinal fasciculus correlated with severity of saccadic impairments (r = -0.45, P = .047). CONCLUSIONS: The results of this study demonstrate that PSP is associated with degeneration of the brainstem, association, and commissural fibers and that this degeneration likely plays an important role in clinical dysfunction.