Time Of Initial Evaluation Research Articles

Prognosis for dogs with stage III osteosarcoma following treatment with amputation and chemotherapy with and without metastasectomy.

OBJECTIVE To determine survival times of selected dogs with metastatic (stage III) osteosarcoma, whether disease-free interval (DFI) was associated with survival time after diagnosis of stage III disease (ie, stage III survival time), and whether a survival benefit of metastasectomy existed. DESIGN Retrospective case series with nested cohort study. ANIMALS 194 client-owned dogs treated for histologically confirmed appendicular osteosarcoma from 1997 through 2009. PROCEDURES Dogs were included if they had stage I or II osteosarcoma at the time of initial evaluation, had amputation of the affected appendage and ≥ 1 dose of chemotherapy afterward, and developed metastasis within the follow-up period or prior to death. Data collected from the medical records included signalment, primary tumor location, clinical and laboratory findings, whether metastasectomy was performed, and outcome. Various factors were examined for associations with outcome. RESULTS Dogs that received no treatment for the metastasis had a median survival time between 49 and 57 days after diagnosis of stage III osteosarcoma. Duration of the preceding DFI had no association with this period. Metastasectomy alone was associated with a longer median stage III survival time (232 days) than no metastasectomy (49 days). Among all dogs identified as qualifying for pulmonary metastasectomy on the basis of < 3 pulmonary nodules visible on thoracic radiographs and a DFI > 275 days (n = 21), a survival advantage was also identified for those that actually received pulmonary metastasectomy (6). CONCLUSIONS AND CLINICAL RELEVANCE Preceding DFI had no influence on survival time of dogs with stage III osteosarcoma. Metastasectomy was associated with an increase in survival time for selected dogs.

Malignant Breast Tumors : Role of MRI in Predicting Histopathological Grading

Introduction: Magnetic Resonance Imaging (MRI) is an established supplemental technique to mammography and ultrasonography for evaluation of breast lesions. Diffusion-weighted MR imaging (DWI) has recently been integrated into the standard breast MRI in addition to images obtained from dynamic contrast enhanced MRI. DWI is quantified using the Apparent Diffusion Coefficient (ADC) value which is the measurement of the mean diffusivity of water in tissues along three orthogonal directions. Aim of the Work: The aim of this study was to investigate the relationship between DWI findings (represented by ADC values) and the dynamic contrast enhanced MRI findings (including functional parameters and morphological criteria) with the histopathological grade of malignant breast tumors. Methodology: 25 Patients (age >30 years) were enrolled in this study. All patients were referred either from the screening clinic or the outpatient clinic of Eldemerdash Hospital with clinically suspicious findings and the abnormality was detected by mammography and/or ultrasound. Included masses are those with BI-RADS 5 category on imaging, with no previous biopsy or treatment. There was no knowledge about the histopathological diagnosis at the time of initial evaluation. Exclusion criteria were breast masses with diagnosed or proved benign features. All patients were scheduled for dynamic MRI with diffusion weighted imaging in addition to the conventional MR imaging. Results: Histopathological analysis revealed all 25 lesions to be invasive ductal carcinomas not otherwise specified. Grading of included carcinomas was as follows: 3 lesions (12.0%) were grade I, 14 lesions (56.0%) were grade II and 8 lesions (32.0%) were grade III. Conclusion: That makes DWI the best non-invasive tool available to predict grades of breast carcinoma. However, further larger and more detailed studies are still needed to fully understand the role MR imaging in distinguishing different histological grades of breast cancer.

Serial Radiographs Do Not Change the Clinical Course of Nonoperative Stable OTA/AO 44-B1 Ankle Fractures

To assess radiographic markers of ankle stability in stable OTA/AO 44-B1 ankle fractures. Retrospective review. Academic Level-I trauma hospital. One hundred thirty-four patients with stable OTA/AO 44-B1 (Danis-Weber B, Supination-External Rotation-II) ankle fractures. Analysis of mortise view radiographs at the time of initial evaluation and final follow-up. (1) medial clear space; (2) Mueller-Nose Distance. Change in radiographic measurements resulting in conversion to operative intervention. Patients followed up an average of 2.6 visits in our clinics (SD 1.06). Patients received an average of 11.2 individual radiographic images to evaluate their injury (SD 3.9, maximum 29). No patients progressed to surgery in this cohort. Mean medial clear space at the time of injury was 3.4 mm (SD 0.8) and was 3.3 mm (SD 0.7) at the time of final follow-up (P = 0.1). Mean Mueller-Nose measurement at the time of injury was 3.5 mm (SD 1.0) and was 3.5 mm (SD 0.8) at the time of final follow-up (P = 0.47). No patients with stable OTA/AO 44-B1 fractures proceeded to surgery for loss of tibiotalar reduction or any other cause. Radiographic relationships were conserved during the follow-up, and serial radiographs may not be needed when managing these patients. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Is Serial Monitoring of Myeloid Mutations Clinically Relevant in Myelodysplastic Syndromes (MDS): A Report on Behalf of the MDS Clinical Research Consortium (CRC)

▪Introduction:Somatic mutations are common in MDS and mutation profiling is becoming increasingly standard as part of the initial diagnostic evaluation. The value of serial monitoring of mutation profiles in MDS patients at multiple disease course time points is unknown. We evaluated the impact of serial mutation monitoring in a cohort of MDS patients.Methods:MDS patients from participating institutions of the MDS CRC with molecular genetic data by next-generation sequencing available from at least two distinct time points were included in analyses. Mutations present at the first time point were compared to those present at subsequent time points and correlated with age, International Prognostic Scoring System (IPSS) score, and overall survival, measured from diagnosis. Cox proportional hazards model of time from diagnosis to death or loss of follow up with time varying number of mutated genes, gained genes and lost genes adjusted for sex, age at diagnosis, and IPSS category at/near diagnosis was applied.Results:Of 737 MDS patients with molecular genetic data available from 1994 to 2016, 94 had information on the 18 genes presented in Table 1 from at least two distinct time points. Patients had a median of 2 (range 2-9) myeloid mutation panel assessments, with a median interval of 3.3 months (range 0.1-39) between studies. Mutation testing was repeated at the investigator's discretion either at time of suspected disease progression or change of therapy.Clinical characteristics of the patients are summarized in Table 2. Almost half (46%) had an initial mutation profile performed within 1 month of diagnosis, 23 patients (24%) within 1-12 months, and 28 patients (30%) more than 12 months after diagnosis. At the time of initial evaluation, patients had a median of 1.5 mutations (range 0-4), with the most common being TP53 (28%), RUNX1 (20%) TET2 (18%), DNMT3A (17%), and ASXL1 (17%). Independent of age or IPSS score at baseline, the number of mutations initially present in a gene set consisting of ASXL1, EZH2, ETV6, RUNX1, TP53 was associated with poor overall survival (HR 2.19, p=0.003, 95% CI, 1.30-3.69). Overall, 32 patients (34%) acquired at least one additional mutation at subsequent testing, including ASXL1 (10%), RUNX1 (7%), TP53 (5%), SETBP1 (5%), and DNMT3A (4%).The acquisition of additional mutations in any gene in subsequent testing was associated with worse overall survival (HR 1.93, p=0.0002, Cl, 1.36-2.75), irrespective of age, IPSS score, and the number of mutations initially identified among the core group of five prognostically significant mutations. Of note, treatment was similar for patients who were found to have acquired additional mutations compared to those who did not: hypomethylation agents (93% vs 80%, p=0.11), lenalidomide (10% vs 11%, p=0.94), and chemotherapy (38% vs 49%, p=0.33). Patients who acquired at least one additional mutation beyond those identified at diagnosis had a higher rate of acute myeloid leukemia transformation (62% vs 37%, p=0.02). Additional acquired mutations were more likely to be observed in serial testing after AML transformation, compared to patients without AML transformation (36% vs 17%, p=0.01). In this model, acquisition of a mutation in DNMT3A, IDH1, IDH2, SETBP1, or TET2 was associated with poor overall survival (HR 3.88, p=0.006, CI, 1.46-10.3). Gain of mutations in CBL, MPL, NPM1, or PHF6 was also associated with poor survival (HR 8.15, p=0.0008, CI, 2.38-27.86). Loss of mutation in serial testing was observed in 33% of patients was and did not correlate with overall survival (HR 0.66, p=0.25, CI, 0.32-1.36). A small subset of patients who underwent allogeneic stem cell transplantation were found to lose their diagnostic mutation(s) at the time of transplant.Conclusions:The acquisition of new mutations in MDS patients undergoing serial monitoring is associated with poor overall survival independent of age, sex, and IPSS, in some part related to the indication for testing. Serial mutation profiling identified a small number of patients who acquired "actionable" mutations for which clinical trials were potentially available, but did not substantively alter treatment choices. Further investigation of the relationships between disease biology, treatment effects, and acquisition/loss of mutations should be conducted in the context of clinical trials. The role of serial mutation profiling in MDS warrants further investigation. [Display omitted] [Display omitted] DisclosuresLee:Boehringer Ingelheim: Consultancy; Baxalta: Consultancy; Amgen: Consultancy; Alexion Pharmaceuticals: Consultancy; Pfizer Inc: Consultancy. Steensma:Genoptix: Consultancy; Janssen: Consultancy; Millenium/Takeda: Consultancy; Ariad: Equity Ownership; Celgene: Consultancy; Amgen: Consultancy. Ritchie:Arian: Speakers Bureau; Novartis: Honoraria; Incyte: Speakers Bureau; Pfizer: Honoraria; Celgene: Speakers Bureau. Desai:Boehringer Ingelheim: Consultancy. Komrokji:Boehringer-Ingelheim: Research Funding; Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy.

Phase I Study of Ruxolitinib for Patients (Pts) with Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) Who Failed at Least One Line of Therapy

Phase I Study of Ruxolitinib for Patients (Pts) with Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) Who Failed at Least One Line of Therapy

CTG18.1 Expansion in TCF4 Increases Likelihood of Transplantation in Fuchs Corneal Dystrophy.

Fuchs dystrophy is the leading indication of corneal transplantation in the United States. A CTG18.1 trinucleotide repeat in TCF4 correlates with increased severity in Fuchs dystrophy; however, quantitative estimates of increased transplantation risk, including effects of age and sex, are unclear. In a tertiary institution clinical practice, 574 participants were enrolled in a longitudinal study of Fuchs dystrophy after slit-lamp biomicroscopy confirmed significant central guttae and/or corneal transplantation in both eyes. We documented clinical history, examination findings, and demographic information. We acquired blood samples, extracted DNA, and sequenced the CTG18.1 trinucleotide repeat in TCF4. In this retrospective case-control study, the number of participants with triplet expansion, defined as greater than 40 CTG repeats, and transplantation status were assessed. Kaplan-Meier estimates of timing and transplantation events were produced. The Cox proportional hazard regression model was used to assess the relationship between age, sex, triplet expansion, and surgery. A total of 106 participants (18.5%) previously underwent corneal transplantation in at least 1 eye at the time of initial evaluation. A higher proportion of individuals harboring allele expansion had undergone transplantation (78/357, 21.8%) compared with those without the expanded allele (28/217, 12.9%), a significant association (P = 0.007). The log-rank test demonstrates a significant difference in survival function over time (P = 0.027), with a hazard ratio of 1.64 (95% confidence interval, 1.05-2.55). Expansion of the TCF4 CTG trinucleotide repeat was associated with 1.64 times higher likelihood of corneal transplantation at a given age in patients with Fuchs dystrophy.

Diagnostic performance of a biomarker panel as a negative predictor for acute appendicitis in adult ED patients with abdominal pain

ObjectivesEvaluate the diagnostic accuracy of the APPY1TM biomarker panel, previously described for use in pediatric patients, for identifying adult ED patients with abdominal pain who are at low risk of acute appendicitis. MethodsThis study prospectively enrolled subjects >18years of age presenting to seven U.S. emergency departments with <72hours of abdominal pain suggesting possible acute appendicitis. The APPY1 panel was performed on blood samples drawn from each patient at the time of initial evaluation and results were correlated with the final diagnosis either positive or negative for acute appendicitis. Results431 patients were enrolled with 422 completing all aspects of the study. The APPY1 biomarker panel exhibited a sensitivity of 97.5% (95% CI, 91.3–99.3%), a negative predictive value of 98.4% (95% CI, 94.4–99.6%), a negative likelihood ratio of 0.07 (95% CI, 0.02–0.27), with a specificity of 36.5% (95% CI, 31.6–41.8%) for acute appendicitis. The panel correctly identified 125 of 342 (36.6%) patients who did not have appendicitis with 2 (2.5%) false negatives. The CT utilization rate in this population was 72.7% (307/422). Of 307 CT scans, 232 were done for patients who did not have appendicitis and 79 (34%) of these patients were correctly identified as negative with "low risk" biomarker panel results, representing 26% (79/307) of all CT scans performed. ConclusionThis biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this prospective adult cohort, thereby potentially reducing the dependence on CT for the evaluation of possible acute appendicitis.

Impact of insurance status on ability to return for outpatient management of pediatric supracondylar humerus fractures.

PurposeOutcomes are excellent following surgical management of displaced supracondylar humerus fractures. Short delays until surgical fixation have been shown to be equivalent to immediate fixation with regards to complications. We hypothesized that insurance coverage may impact access to care and the patient’s ability to return to the operating room for outpatient surgery.MethodsA retrospective review of supracondylar humerus fractures treated at a large urban pediatric hospital from 2008 to 2012 was performed. Fractures were classified by the modified Gartland classification and baseline demographics were collected. Time from discharge to office visits and subsequent surgical fixation was calculated for all type II fractures discharged from the emergency department. Insurance status and primary carrier were collected for all patients.Results2584 supracondylar humerus fractures were reviewed, of which 584 were type II fractures. Of the 577 type II fractures with complete records, 383 patients (61 %) were admitted for surgery and the remaining 194 were discharged with plans for outpatient follow-up. There was no difference in insurance status between patients admitted for immediate surgery. Of the 194 patients who were discharged with type 2 fractures after gentle reduction, 59 patients (30.4 %) ultimately underwent surgical fixation. Of these, 42 patients were privately insured (58.3 % of patients with private insurance), 16 had governmental insurance (15.1 %), and 1 was uninsured (6.3 %). Patients with private insurance were 2.46 times more likely to have surgery than patients with public or no insurance (p = 0.005). Of the 135 patients who did not eventually have surgery, 92 (68.1 %) were seen in the clinic. Patients with private insurance were 2.78 times more likely to be seen back in the clinic when compared to publicly insured or uninsured patients (p = 0.0152).ConclusionsDespite an equivalent number of privately insured and publicly insured patients undergoing immediate surgery for type II fractures, those with public or no insurance who were discharged were 2.46 times less likely to obtain outpatient surgery when compared to privately insured patients. Patient insurance status and the ability to follow up in a timely manner should be assessed at the time of initial evaluation in the emergency department.Level of evidence Level 3

Defining and predicting 'intrauterine fetal renal failure' in congenital lower urinary tract obstruction.

The aim of this study was to identify predictors of 'intrauterine fetal renal failure' in fetuses with severe congenital lower urinary tract obstruction (LUTO). We undertook a retrospective study of 31 consecutive fetuses with a diagnosis of LUTO in a tertiary Fetal Center between April 2013 and April 2015. Predictors of 'intrauterine fetal renal failure' were evaluated in those infants with severe LUTO who had either a primary composite outcome measure of neonatal death in the first 24h of life due to severe pulmonary hypoplasia or a need for renal replacement therapy within 7 days of life. The following variables were analyzed: fetal bladder re-expansion 48h after vesicocentesis, fetal renal ultrasound characteristics, fetal urinary indices, and amniotic fluid volume. Of the 31 fetuses included in the study, eight met the criteria for 'intrauterine fetal renal failure'. All of the latter had composite poor postnatal outcomes based on death within 24h of life (n = 6) or need for dialysis within 1week of life (n = 2). The percentage of fetal bladder refilling after vesicocentesis at time of initial evaluation was the only predictor of 'intrauterine fetal renal failure' (cut-off <27%, area under the time-concentration curve 0.86, 95 % confidence interval 0.68-0.99; p = 0.009). We propose the concept of 'intrauterine fetal renal failure' in fetuses with the most severe forms of LUTO. Fetal bladder refilling can be used to reliably predict 'intrauterine fetal renal failure', which is associated with severe pulmonary hypoplasia or the need for dialysis within a few days of life.

Usefulness of whole blood, plasma, peritoneal fluid, and peritoneal fluid supernatant glucose concentrations obtained by a veterinary point-of-care glucometer to identify septic peritonitis in dogs with peritoneal effusion.

To evaluate the usefulness of a veterinary point-of-care glucometer for identification of septic peritonitis in dogs with peritoneal effusion (PE). Prospective clinical evaluation. 39 dogs with PE. Blood and peritoneal fluid convenience samples were collected concurrently in all dogs at the time of initial evaluation. A veterinary point-of-care glucometer was used to measure glucose concentration in heparinized whole blood, plasma, peritoneal fluid, and peritoneal fluid supernatant samples. Seventeen dogs had confirmed septic peritonitis, and 22 dogs had nonseptic PE. Sensitivity, specificity, positive and negative predictive values, and accuracy of identification of dogs with septic peritonitis were calculated for glucose concentration differences for whole blood versus peritoneal fluid (WB-PF), plasma versus peritoneal fluid (P-PF), and plasma versus peritoneal fluid supernatant (P-PFS). With a cutoff of > 20 mg/dL, the glucose concentration difference for WB-PF was an insensitive indicator of septic peritonitis (sensitivity, 41.2%; specificity, 100%). In comparison, the glucose concentration differences for P-PF and P-PFS had a higher sensitivity for septic peritonitis (88.2% and 82.4%, respectively) but a lower specificity (80% and 77.8%, respectively). With a glucose concentration difference cutoff of ≥ 38 mg/dL, specificity, positive predictive value, and accuracy of P-PF and P-PFS improved. Determination of the glucose concentration difference for WB-PF with the veterinary point-of-care glucometer was not useful in identifying all dogs with septic peritonitis. A glucose concentration difference of ≥ 38 mg/dL for P-PF or P-PFS, however, supported an accurate diagnosis of septic peritonitis in dogs with PE.

Functional outcomes in Rett syndrome

AimTo relate functional outcomes to mutation type and age at evaluation in patients with Rett syndrome (RTT). MethodWe identified 96 RTT patients with mutations in the MECP2 (methyl-CpG-binding protein 2) gene. Chart analysis, clinical evaluation, and functional measures were completed. ResultsAmong 11 mutation groups, a statistically significant group effect of mutation type was observed for self-care, upper extremity function, and mobility, on standardized measures administered by occupational and physical therapists. Patients with R133C and uncommon mutations tended to perform best on upper extremity and self-care items, whereas patients with R133C, R306C and R294X had the highest scores on the mobility items. The worst performers on upper extremity and self-care items were patients with large deletions, R255X, R168X, and T158M mutations. The lowest scores for mobility were found in patients with T158M, R255X, R168X, and R270X mutations. On categorical variables as reported by parents at the time of initial evaluation, patients with R133C and R294X were most likely to have hand use, those with R133C, R294X, R306C and small deletions were most likely to be ambulatory, and those with R133C were most likely to be verbal. InterpretationFunctional performance in RTT patients may relate to the type of mutation. Knowledge of these relationships is useful for developing appropriate rehabilitation strategies and prognosis.

A Comparison of Non-Operative and Operative Treatment of Complete Proximal Hamstring Ruptures

Objectives:Early repair of acute proximal hamstring ruptures provides better clinical results than delayed repairs. However, it is unclear how the non-operative treatment compares to the operative treatment of these injuries. We compare the clinical results of non-operative and operative treatment of acute proximal hamstring ruptures.Methods:A retrospective case-control study of patients with a complete, retracted, proximal hamstring rupture was performed from 2007 to 2013. All patients were given the option of a proximal hamstring repair at the time of initial evaluation. Patients at least 12 months from the time of surgery or injury were included for evaluation. Acute proximal hamstring injuries were included; and partial proximal hamstring tears and chronic injuries repaired were excluded. The primary outcome measure was the lower extremity functional score (LEFS). Secondary outcome measures included the SF-12 physical and mental component scores, a single leg hop (average of three jumps), the patient's perception of strength (0-100%), and ability to return to activity.Results:A total of 25 patients were enrolled. The 14 patients treated surgically sustained injuries at 46.98 ± 9.73 years of age, were repaired at 28.14 ± 14.06 days, and evaluated at 50.62 ± 10.11 years of age. The 11 patients treated non-operatively sustained injuries at 55.6 ± 10.45 years of age (p = 0.05), attempted therapy an average of 4.6 ± 3.22 months, and were evaluated at 58.4 ± 8.31 years of age (p= 0.06). The LEFS for the surgical and non-surgical groups was 74.71 ± 5.38 and 68.5 ± 7.92 (p = 0.04), respectively. SF-12 mental and physical components scores were similar between groups. The average single leg hop of the injured extremity in the surgical and non-surgical groups was 119.1 ± 27.68 cm and 56.1 ± 31.2 cm (p = 0.0001), respectively. When compared to the uninjured leg, the average single leg hop in the injured leg was 5.1 ± 12.1 cm and 1.2 ± 17.2 cm (p = 0.51) shorter in both the surgical and non-surgical groups, respectively. The LEFS had a weak correlation with the average single leg hop and age in the surgical (R2 = 0.2478 and 0.0664, respectively) and non-surgical (R2 = 0.0023 and 0.052, respectively) groups. The patient's perception of strength was similar between the surgical and non-surgical groups (86.07 ± 12.12% and 83.6 ± 14.15%, p = 0.64). All patients in the operative group were able to return to pre-injury activities whereas three were unable to in the non-operative group (chi-square stat = 4.33, p = 0.03).Conclusion:Patients with acute proximal hamstring ruptures treated surgically have better lower extremity function and a higher likelihood of returning to pre-injury activities than patients treated non-surgically.

Frontotemporal Dementia and Psychiatric Illness: Emerging Clinical and Biological Links in Gene Carriers

To describe psychiatric presentations in individuals with genetic mutations causing frontotemporal dementia (FTD). Case descriptions from five carriers of FTD-related gene mutations with symptoms associated with non-neurodegenerative psychiatric disease. A comprehensive research program investigating genetic and non-genetic FTD at the University of California, San Francisco Memory and Aging Center. Three proband and two non-proband gene carriers. Medical history and neurological examination, neuropsychological testing, magnetic resonance and/or positron emission tomography imaging, and a genetic analysis to screen for dementia-related mutations. Genetic status was unknown at the time of initial evaluation. The chosen cases are illustrative of the variety of presentations of psychiatric symptoms in FTD gene carriers. In some cases, a non-neurodegenerative psychiatric illness was diagnosed based on specific symptoms, but the diagnosis may have been inappropriate based on the overall syndrome. In other cases, symptoms closely resembling those seen in non-neurodegenerative psychiatric illness did occur, in some cases immediately preceding the development of dementia, and in other cases developing a decade prior to dementia symptoms. Psychiatric symptoms in FTD gene carriers can be very similar to those seen in non-neurodegenerative psychiatric illness. Psychiatric symptoms with atypical features (e.g., late-life onset, insidiously worsening course) should prompt careful assessment for neurodegenerative disease. Guidelines for such an assessment should be established.

Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous mast cell tumors: 386 cases (2009-2014).

To compare the Kiupel (2 categories) and Patnaik (3 categories) histologic grading systems for predicting the presence of metastasis at the time of initial examination in dogs with cutaneous mast cell tumors (MCTs). Retrospective case series. 386 client-owned dogs with cutaneous MCTs. Medical records of dogs with newly diagnosed, histologically confirmed cutaneous MCTs that had undergone complete clinical staging were reviewed for clinical and histopathologic data. All Patnaik grade 1 MCTs (n = 52) were classified as Kiupel low-grade MCTs, and all Patnaik grade 3 MCTs (43) were classified as Kiupel high-grade MCTs. Of the 291 Patnaik grade 2 MCTs, 243 (83.5%) were classified as Kiupel low-grade tumors, and 48 (16.5%) were classified as Kiupel high-grade MCTs. Dogs with Patnaik grade 3 MCTs were significantly more likely to have metastases at the time of initial examination than were dogs with grade 1 or 2 MCTs (OR, 5.46), and dogs with Kiupel high-grade MCTs were significantly more likely to have metastases than were dogs with Kiupel low-grade MCTs (OR, 2.54). However, 3 of 52 (5.8%) dogs with Patnaik grade 1 tumors, 48 of 291 (16.5%) dogs with Patnaik grade 2 tumors, and 44 of 295 (14.9%) dogs with Kiupel low-grade tumors had metastatic disease. Findings indicated that in dogs with cutaneous MCTs, prognostication should not rely on histologic grade alone, regardless of grading system used, but should take into account results of clinical staging.

Headache in traumatic brain injuries from blunt head trauma.

To determine the risk of traumatic brain injuries (TBIs) in children with headaches after minor blunt head trauma, particularly when the headaches occur without other findings suggestive of TBIs (ie, isolated headaches). This was a secondary analysis of a prospective observational study of children 2 to 18 years with minor blunt head trauma (ie, Glasgow Coma Scale scores of 14-15). Clinicians assessed the history and characteristics of headaches at the time of initial evaluation, and documented findings onto case report forms. Our outcome measures were (1) clinically important TBI (ciTBI) and (2) TBI visible on computed tomography (CT). Of 27 495 eligible patients, 12 675 (46.1%) had headaches. Of the 12 567 patients who had complete data, 2462 (19.6%) had isolated headaches. ciTBIs occurred in 0 of 2462 patients (0%; 95% confidence interval [CI]: 0%-0.1%) in the isolated headache group versus 162 of 10 105 patients (1.6%; 95% CI: 1.4%-1.9%) in the nonisolated headache group (risk difference, 1.6%; 95% CI: 1.3%-1.9%). TBIs on CT occurred in 3 of 456 patients (0.7%; 95% CI: 0.1%-1.9%) in the isolated headache group versus 271 of 6089 patients (4.5%; 95% CI: 3.9%-5.0%) in the nonisolated headache group (risk difference, 3.8%; 95% CI: 2.3%-4.5%). We found no significant independent associations between the risk of ciTBI or TBI on CT with either headache severity or location. ciTBIs are rare and TBIs on CT are very uncommon in children with minor blunt head trauma when headaches are their only sign or symptom.

An empirically based alternative to DSM-5's disruptive mood dysregulation disorder for ICD-11.

The World Health Organization (WHO)'s priorities for the development of the classification of mental and behavioural disorders in the ICD-11 include increasing its clinical utility in global mental health settings (1) and improving the identification and diagnosis of mental disorders among children and adolescents (2). An issue that has been hotly debated in the area of childhood psychopathology is the assessment, diagnosis and treatment of children with severe irritability and anger (3,4). Although virtually all children display irritable and angry behaviours at times, some children exhibit them more frequently and more intensely, to the extent that they become an impairing form of emotional dysregulation. Recent findings indicate that these children with chronic and severe irritability/anger have not been adequately identified through existing classification systems, are at an increased risk for particular negative outcomes, and have not received appropriate treatment. To the extent that ICD-11 can help clarify the clinical picture of irritability/anger, children and families will benefit from more accurate diagnoses, more useful prognoses, and more effective interventions. This paper provides a brief overview of the issue, followed by several possible options and the current proposal for the classification of childhood irritability/anger in ICD-11. This proposal represents a markedly different – but we believe more scientifically justifiable – solution to the problems in this area than that selected for DSM-5 (5).

Internal obturator muscle transposition for treatment of perineal hernia in dogs: 34 cases (1998–2012)

To evaluate the outcome of dogs with perineal hernia treated with transposition of the internal obturator muscle. Retrospective case series. 34 dogs. Medical records of dogs with perineal hernia surgically treated from 1998 to 2012 were reviewed. Diagnostic methods and surgical techniques were recorded. Dogs were assigned preoperative and postoperative clinical sign scores. Complication and recurrence rates were evaluated over time. Risk factors were determined. Median follow-up time was 345 days (range, 22 to 1,423 days). Complications were observed in 10 dogs. Tenesmus (n = 9), dyschezia (7), fecal impaction (3), stranguria (4), hematochezia (2), urinary incontinence (2), diarrhea (1), urinary tract infection (1), and megacolon (1) occurred following surgery. Bladder retroflexion at the time of initial evaluation or surgery was not a risk factor for complication (hazard ratio, 1.72). One year after surgery, 51.2% dogs were free of complications. Three dogs developed a perineal hernia on the contralateral side between 35 and 95 days after surgery. The 1-year recurrence rate was 27.4%. Median time for recurrence was 28 days after surgery (range, 2 to 364 days). Postoperative tenesmus was a risk factor for the development of recurrence (hazard ratio, 2.29). Internal obturator muscle transposition was used for primary repair of perineal hernia in dogs. Recurrence was recorded as long as 1 year after surgery. Tenesmus was a risk factor for the development of recurrence after treatment of perineal hernia with internal obturator muscle transposition.

Evaluation of serum biochemical marker concentrations and survival time in dogs with protein-losing enteropathy.

To evaluate serum concentrations of biochemical markers and survival time in dogs with protein-losing enteropathy (PLE). Prospective study. 29 dogs with PLE and 18 dogs with food-responsive diarrhea (FRD). Data regarding serum concentrations of various biochemical markers at the initial evaluation were available for 18 of the 29 dogs with PLE and compared with findings for dogs with FRD. Correlations between biochemical marker concentrations and survival time (interval between time of initial evaluation and death or euthanasia) for dogs with PLE were evaluated. Serum C-reactive protein concentration was high in 13 of 18 dogs with PLE and in 2 of 18 dogs with FRD. Serum concentration of canine pancreatic lipase immunoreactivity was high in 3 dogs with PLE but within the reference interval in all dogs with FRD. Serum α1-proteinase inhibitor concentration was less than the lower reference limit in 9 dogs with PLE and 1 dog with FRD. Compared with findings in dogs with FRD, values of those 3 variables in dogs with PLE were significantly different. Serum calprotectin (measured by radioimmunoassay and ELISA) and S100A12 concentrations were high but did not differ significantly between groups. Seventeen of the 29 dogs with PLE were euthanized owing to this disease; median survival time was 67 days (range, 2 to 2,551 days). Serum C-reactive protein, canine pancreatic lipase immunoreactivity, and α1-proteinase inhibitor concentrations differed significantly between dogs with PLE and FRD. Most initial biomarker concentrations were not predictive of survival time in dogs with PLE.

Recovery from concussion

The professional and lay media have been filled with discussions about concussion, especially among young and adult athletes. The practitioner may have difficulty keeping track of all these new developments and understanding the important points that should become incorporated into practice. This issue of The Journal contains an interesting and important article that certainly will inform practice. Corwin et al from Philadelphia studied a cohort of children in their institution with concussion, asking the question whether there were ways in which the children who had a prolonged recovery (over 4 weeks of symptoms) could be recognized early. These children had fairly significant disability, and recognizing them early in their course could be very helpful in working with children, their families, and schools. Corwin et al present a number of simple historical and physical examination findings, which, when present at the time of initial evaluation, identify children at risk for prolonged symptoms. This is not a battery of high-tech diagnostic interventions, but some easily identifiable markers that can quickly become incorporated into practice. Article page 1207▶ Characteristics of Prolonged Concussion Recovery in a Pediatric Subspecialty Referral PopulationThe Journal of PediatricsVol. 165Issue 6PreviewTo identify pre-existing characteristics associated with prolonged recovery from concussion in a sample of patients referred to a pediatric sports medicine clinic. Full-Text PDF

The Relative Importance of Family History, Gender, Mode of Onset, and Age at Onsetin Predicting Clinical Features of First-Episode Psychotic Disorders.

Family history of psychosis, gender, mode of onset, and age at onset are considered prognostic factors important to clinicians evaluating first-episode psychosis; yet, clinicians have little guidance as to how these four factors differentially predict early-course substance abuse, symptomatology, and functioning. We conducted a "head-to-head comparison" of these four factors regarding their associations with key clinical features at initial hospitalization. We also assessed potential interactions between gender and family history with regard to age at onset of psychosis and symptom severity. Consecutively admitted first-episode patients (n=334) were evaluated in two studies that rigorously assessed a number of early-course variables. Associations among variables of interest were examined using Pearson correlations, χ2 tests, Student's t-tests, and 2×2 factorial analyses of variance. Substance (nicotine, alcohol, and cannabis) abuse and positive symptom severity were predicted only by male gender. Negative symptom severity and global functioning impairments were predicted by earlier age at onset of psychosis. General psychopathology symptom severity was predicted by both mode of onset and age at onset. Interaction effects were not observed with regard to gender and family history in predicting age at onset or symptom severity. The four prognostic features have differential associations with substance abuse, domains of symptom severity, and global functioning. Gender and age at onset of psychosis appear to be more predictive of clinical features at the time of initial evaluation (and thus presumably longer term outcomes) than the presence of a family history of psychosis and a more gradual mode of onset.