Red cell distribution width as a predictor of mortality after hip fracture: a systematic review and meta-analysis.

OBJECTIVE: This review examined the association between red cell distribution width (RDW) and mortality after hip fracture. MATERIALS AND METHODS: PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched up to 10th January 2023 for studies comparing mortality after hip fracture based on RDW. All cut-offs of RDW were accepted. Crude and adjusted mortality ratios were pooled separately. RESULTS: Nine studies with 5,274 patients were eligible. Meta-analysis of eight studies reporting crude mortality rates showed that patients with high RDW had a significantly higher risk of mortality than those with low RDW (RR: 2.81 95% CI: 2.05, 3.86 I2=82%). The results did not change in significance on subgroup analyses based on study location, sample size, the cut-off of RDW, and follow-up. Four studies reported adjusted mortality rates. Analysis of the same showed that high RDW was an independent predictor of mortality in hip fracture patients (HR: 3.14 95% CI: 1.38, 7.14 I2=95%). CONCLUSIONS: Within the limitations of the review, RDW was found to be an indicator of mortality in hip fracture patients. High RDW was significantly associated with increased mortality despite different cut-offs among studies. Further research is needed to generate more rigorous evidence.

[Thoughts and practice on the treatment of severe and critical new coronavirus pneumonia].

Severe and critical coronavirus pneumonia 2019 (COVID-19) often occurs in elder patients with multiple comorbidities, and severe hypoxemia events constitute a key factor for the deterioration of some cases. The critical type of COVID-19 could progress into acute respiratory distress syndrome and multi-organ dysfunction, which are the major causes of death. Early non-invasive ventilation (NIV) treatment of possible pathophysiological abnormalities is helpful to improve prognosis. Close monitoring of oxygenation, reducing patients' oxygen consumption, active psychological intervention, and rapid handling of severe hypoxemia events are the key factors for successful NIV treatment. In addition, active adjuvant therapies such as correcting coagulation dysfunction, providing proper nutritional support, accurate volume control, and safe individualized blood glucose monitoring are of great significance.

[Prognostic value of myeloperoxidase concentration in patients with acute coronary syndrome].

Objective: To evaluate the difference of plasma myeloperoxidase (MPO) level in different types of acute coronary syndrome (ACS) patients, and the value of baseline MPO level in predicting short-term and long-term outcomes in patients with ACS. Methods: The study cohort was derived from "the 12th Five-Year" National Science and Technology Support Program Project "Study on Comprehensive Intervention and Prognosis of Acute Coronary Syndrome" . We enrolled all hospitalized ACS patients who were enrolled in "the 12th Five-Year" cohort from January 1, 2011 to December 31, 2013. A total of 630 patients from 20 centers were enrolled. According to the diagnosis, the patients were divided into two groups: ST-segment elevation myocardial infarction (STEMI) group and non-ST-elevation acute coronary syndrome (NSTE-ACS) group. Plasma levels of MPO were measured by ELISA method. Cardiovascular events in the hospital were recorded. All patients were followed-up by telephone, follow-up ended December 31, 2015. The occurrence of major adverse cardiovascular events (MACE, defined as cardiac death, recurrent myocardial infarction, unscheduled coronary revascularization procedure and stroke) and all-cause death were recorded. Logistic regression analysis and Cox regression analysis were used to evaluate the predictive value of baseline MPO levels obtained during hospitalization and the long-term outcomes of ACS patients. Results: A total of 597 ACS patients were enrolled in final analysis. Level of plasma MPO in STEMI patients was significantly higher than that of NSTE-ACS patients (34.02(19.31, 67.87) µg/L vs. 27.25(16.69, 52.92) µg/L, P=0.028) . MPO was not related to the in-hospital cardiovascular events (OR=0.797, 95%CI 0.366-1.737, P=0.569). Follow up was completed in 476 patients, median follow-up time was 796 (32, 1 816) days. There were 23 all-cause deaths and 51 MACE. Plasma MPO level was not an independent predictor for all-cause death (HR=1.434, 95%CI 0.502-4.100, P=0.501) and MACE (HR=1.271, 95%CI 0.662-2.442, P=0.471). Conclusion: In hospitalized ACS patients, level of plasma MPO was significantly higher in STEMI patients than in NSTE-ACS patients, but MPO could not predict the short-term or long-term outcomes in patients with ACS.

Evaluation of two-dimensional ultrasonography and computed tomography in the mapping and measuring of canine urinary bladder tumors.

Determining the dimensions of transitional cell carcinomas (TCCs) of the urinary bladder in dogs is important in assessing tumor progression and the response to treatment. The primary aim of this study was to evaluate the reliability of a standardized two-dimensional (2-D) ultrasound (US) protocol performed by a single experienced operator. Secondary aims were to compare World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and to compare measurements by two operators following these guidelines. These were evaluated by inter-operator and intra-operator reliability using the concordance correlation coefficient (CCC) and Cohen's κ statistics, which demonstrated substantial to better agreement by an experienced operator using either set of guidelines. It was demonstrated that 2-D US provides a reliable means to determine the dimensions of urinary bladder TCC when an experienced operator used a standardized protocol. In a subset of dogs, urinary bladder distension was varied, which resulted in differences in measurement with 2-D US and computed tomography.

Cardiac and Metabolic Variables in Obese Dogs.

BACKGROUND: The etiology of obesity-related cardiac dysfunction (ORCD) is linked to metabolic syndrome in people. Studies have indicated that obese dogs have components of metabolic syndrome, warranting evaluation for ORCD in obese dogs. OBJECTIVES: To evaluate cardiac structure and function and metabolic variables in obese dogs compared to ideal weight dogs. ANIMALS: Forty-six healthy, small-breed (<25 pounds), obese dogs (n = 29) compared to ideal weight dogs (n = 17). METHODS: A cross-sectional study of cardiac structure and function by standard and strain echocardiographic measurements and quantification of serum metabolic variables (insulin:glucose ratios, lipid analysis, adiponectin, inflammatory markers). RESULTS: Compared to the ideal weight controls, obese dogs had cardiac changes characterized by an increased interventricular septal width in diastole to left ventricular internal dimension in diastole ratio, decreased ratios of peak early to peak late left ventricular inflow velocities, and ratios of peak early to peak late mitral annular tissue velocities, and increased fractional shortening and ejection fraction percentages. The left ventricular posterior wall width in diastole to left ventricular internal dimension in diastole ratios were not significantly different between groups. Systolic blood pressure was not significantly different between groups. Obese dogs had metabolic derangements characterized by increased insulin:glucose ratios, dyslipidemias with increased cholesterol, triglyceride, and high-density lipoprotein concentrations, decreased adiponectin concentrations, and increased concentrations of interleukin 8 and keratinocyte-derived chemokine-like inflammatory cytokines. CONCLUSIONS AND CLINICAL IMPORTANCE: Compared to ideal weight controls, obese dogs have alterations in cardiac structure and function as well as insulin resistance, dyslipidemia, hypoadiponectinemia, and increased concentrations of inflammatory markers. These findings warrant additional studies to investigate inflammation, dyslipidemia, and possibly systemic hypertension as potential contributing factors for altered cardiac function.

Skeletal Metastasis of Canine Urothelial Carcinoma: Pathologic and Computed Tomographic Features.

Invasive urothelial (transitional cell) carcinoma (UC) is the most common cancer in the canine urinary tract. Prolonged survival of dogs with UC due to better management of the primary tumor and prevention of urethral obstruction might have contributed to an apparent increase in distant metastasis. Metastasis to bone is particularly concerning because the ensuing pain often leads to euthanasia; however, little is known of the frequency, site, or nature of UC skeletal metastasis. In a retrospective analysis, 17 (9%) of 188 canine UC cases had histologically confirmed skeletal metastasis, mainly to the vertebrae. In a prospective analysis of 21 dogs with UC that underwent total body computed tomography (CT) at euthanasia followed by a standardized pathologic examination, skeletal lesions detected on CT were suspected to be metastatic in 4 dogs and were confirmed as metastatic UC histologically in 3 (14%) dogs. In all 3 cases, skeletal metastasis had been suspected based on history and physical examination; however, 1 dog had additional CT-detected skeletal metastases in a clinically unsuspected location, and 2 dogs had histologically confirmed skeletal metastases that corresponded to nonspecific osseous lesions on CT. These findings suggest that total body CT could be helpful in detecting skeletal metastasis as a cause of bone pain in dogs with UC as well as in identifying clinically "silent" sites of skeletal metastasis.

Retrospective comparison of three doses of metronomic chlorambucil for tolerability and efficacy in dogs with spontaneous cancer.

The study hypothesis is that higher doses of metronomic (low-dose) chlorambucil will improve outcome without significantly worsening adverse events (AE). Retrospectively, 88 dogs were screened to assess for tolerability and response to chlorambucil utilizing retrospective and prospective data sets, comparing metronomic oral daily doses 4, 6 and 8 mg m2 . There were 78 and 70 dogs in the tolerability and efficacy portions, respectively. The severity of gastrointestinal (GI) AE was significantly worse, and time to development of GI events was significantly shorter at 6 mg m2 than at 4 mg m2 (both P < 0.001). Chlorambucil was discontinued earlier in the dogs treated at the 6 mg m2 doses than in the dogs treated at 4 mg m2 (P = 0.015). Thrombocytopenia occurred significantly earlier at 8 mg m2 than at 4 mg m2 (P = 0.017). Higher doses of metronomic (low-dose) chlorambucil did not provide improved responses and were associated with more AE.

Modelling the time at which overcrowding and feed interruption emerge on the swine premises under movement restrictions during a classical swine fever outbreak.

A stochastic risk model was developed to estimate the time elapsed before overcrowding (TOC) or feed interruption (TFI) emerged on the swine premises under movement restrictions during a classical swine fever (CSF) outbreak in Indiana, USA. Nursery (19 to 65 days of age) and grow-to-finish (40 to 165 days of age) pork production operations were modelled separately. Overcrowding was defined as the total weight of pigs on premises exceeding 100% to 115% of the maximum capacity of the premises, which was computed as the total weight of the pigs at harvest/transition age. Algorithms were developed to estimate age-specific weight of the pigs on premises and to compare the daily total weight of the pigs with the threshold weight defining overcrowding to flag the time when the total weight exceeded the threshold (i.e. when overcrowding occurred). To estimate TFI, an algorithm was constructed to model a swine producer's decision to discontinue feed supply by incorporating the assumptions that a longer estimated epidemic duration, a longer time interval between the age of pigs at the onset of the outbreak and the harvest/transition age, or a longer progression of an ongoing outbreak would increase the probability of a producer's decision to discontinue the feed supply. Adverse animal welfare conditions were modelled to emerge shortly after an interruption of feed supply. Simulations were run with 100 000 iterations each for a 365-day period. Overcrowding occurred in all simulated iterations, and feed interruption occurred in 30% of the iterations. The median (5th and 95th percentiles) TOC was 24 days (10, 43) in nursery operations and 78 days (26, 134) in grow-to-finish operations. Most feed interruptions, if they emerged, occurred within 15 days of an outbreak. The median (5th and 95th percentiles) time at which either overcrowding or feed interruption emerged was 19 days (4, 42) in nursery and 57 days (4, 130) in grow-to-finish operations. The study findings suggest that overcrowding and feed interruption could emerge early during a CSF outbreak among swine premises under movement restrictions. The outputs derived from the risk model could be used to estimate and evaluate associated mitigation strategies for alleviating adverse animal welfare conditions resulting from movement restrictions.

Commercially Available Enzyme-Linked Immunosorbent Assay and Polymerase Chain Reaction Tests for Detection of Feline Immunodeficiency Virus Infection.

BACKGROUND: Feline immunodeficiency virus (FIV) infection is an important cause of disease of cats worldwide. Initial screening is commonly performed by commercially available point-of-care (POC) ELISA tests. Confirmatory testing for positive POC test results is recommended. Polymerase chain reaction (PCR) tests for FIV are commonly used additional testing methods; however, reported measures of diagnostic accuracy vary widely between PCR tests, making interpretation of results difficult. HYPOTHESIS/OBJECTIVE: There is very good agreement between results of a commercially available PCR test and a POC ELISA test for FIV for specimens collected from owned and shelter-housed cats. ANIMALS: Blood samples from 168 cats from 2 adoption guarantee shelters, an FIV Sanctuary, and 64 private homes were used. METHODS: This was a prospective study. Whole blood samples were collected in K2 -EDTA, divided, and submitted for PCR and ELISA testing. Follow-up whole blood samples were collected in lithium heparin from cats with discordant results and submitted for virus isolation (VI). RESULTS: There was very good agreement between ELISA and PCR (kappa 0.87; P < .001; 95% CI 0.79, 0.95). Of 168 cats, eleven had discordant ELISA/PCR results: 7 ELISA+/PCR- and 4 ELISA-/PCR+. Using VI as a reference standard, there were 4 false-positive PCR results, 5 false-positive ELISA results, and 1 false-negative PCR result (1 cat lost to follow-up). CONCLUSIONS AND CLINICAL IMPORTANCE: While there was good agreement between the POC ELISA and PCR tests, the discordant results highlight the importance of cautious interpretation of test results and the necessity of confirmatory testing.

Clinical data, clinicopathologic findings and outcome in dogs with amegakaryocytic thrombocytopenia and primary immune-mediated thrombocytopenia.

OBJECTIVES: The aim of this study was to identify distinguishing characteristics between dogs diagnosed with amegakaryocytic thrombocytopenia and those diagnosed with presumed primary peripheral immune-mediated thrombocytopenia. Presenting clinical and clinicopathologic data and outcomes were compared between the two groups. METHODS: Retrospective study performed on seven client-owned dogs diagnosed with amegakaryocytic thrombocytopenia and 34 client-owned dogs with primary peripheral immune-mediated thrombocytopenia. RESULTS: All dogs in the amegakaryocytic thrombocytopenia group were anaemic on presentation with a median haematocrit of 23% (range 9·4 to 36), while the primary peripheral immune-mediated thrombocytopoenia group had a median presenting haematocrit of 35% (range 10 to 53). Dogs with amegakaryocytic thrombocytopenia had a median of five (range 4 to 7) clinical signs of bleeding compared to a median of three (range 0 to 6) in the primary peripheral immune-mediated thrombocytopenia group with 86% (6 of 7) of amegakaryocytic thrombocytopenia dogs requiring a blood transfusion compared to 41% (14 of 34) of primary peripheral immune-mediated thrombocytopenia dogs. Six of the seven amegakaryocytic thrombocytopenia dogs did not survive to discharge, while only five of the 34 primary peripheral immune-mediated thrombocytopenia dogs did not survive to discharge. CLINICAL SIGNIFICANCE: The clinical presentation of dogs with amegakaryocytic thrombocytopenia and primary peripheral immune-mediated thrombocytopenia is similar, but dogs with amegakaryocytic thrombocytopenia had a more severe clinical course compared to primary peripheral immune-mediated thrombocytopenia dogs. The prognosis for dogs with amegakaryocytic thrombocytopenia is poor.

Inter- and intra-rater reliability of calliper-based lymph node measurement in dogs with peripheral nodal lymphomas.

The purpose of this study was to assess reliability of lymph node measurements between and within raters in dogs with nodal lymphomas. Three raters measured lymph nodes from 20 dogs twice prior to and once after administering chemotherapy. Sum tumour volume (TV) and sum longest diameter (LD) of all lymph nodes at each time point, and the percent change in measurements following chemotherapy, were calculated for each dog. Inter- and intra-rater reliability were assessed with the intraclass correlation coefficient (ICC). ICC for inter-rater sum TV and sum LD prior to chemotherapy were 0.86 and 0.80, respectively. ICC for inter-rater sum TV and sum LD after chemotherapy were 0.95 and 0.91, respectively. ICC for percent change in sum TV and sum LD were 0.96 and 0.94, respectively. ICC for intra-rater reliability ranged from 0.90 to 0.98 for each rater. Inter- and intra-rater reliability in measurements among the three raters was good to excellent.

Effect of a Limited Iodine Diet on Iodine Uptake by Thyroid Glands in Hyperthyroid Cats.

BACKGROUND: The effect of feeding a limited iodine diet on radioactive iodine uptake in the thyroid glands of hyperthyroid cats is unknown. OBJECTIVES: To determine how feeding limited dietary iodine affects radioactive iodine uptake by the thyroid glands of hyperthyroid cats. ANIMALS: Eight geriatric cats with spontaneous hyperthyroidism. METHODS: Prospective study of eight client owned hyperthyroid cats fed a commercially available iodine limited diet for 6 months. Clinical signs were evaluated and TT4 and fT4 were measured during consumption of the diet. Uptake of (123)I was determined before and 8-16 weeks after exclusive consumption of the diet. RESULTS: Clinical signs of hyperthyroidism resolved in all cats, but there was no significant increase in body weight. TT4 and fT4 decreased into the reference range by 8-16 weeks in all cats. Mean TT4 before consumption of the diet was 9.7 µg/dL (SD 5.2) and after consumption of the diet was 3.1 µg/dL (SD 0.9). Scintigraphy revealed unilateral uptake of isotope in 5 cats and bilateral uptake in 3 cats. Mean percentage uptake of (123)I by the thyroid gland at 8 hours after isotope administration was 16.2 (SD 11.8) before diet consumption and 34.6 (SD 11.7) 8-16 weeks after exclusive consumption of the diet. The percentage increase was variable between cats (38-639%). CONCLUSIONS AND CLINICAL IMPORTANCE: Limited iodine diets increase iodine uptake in the autonomous thyroid glands of hyperthyroid cats. Further studies are necessary to determine if consumption of a limited iodine diet changes sensitivity of the thyroid gland to (131)I treatment.

In vitro comparison of output fluid temperatures for room temperature and prewarmed fluids.

OBJECTIVE: To determine if prewarmed intravenous fluids produce superior fluid output temperatures compared with room temperature fluids at common anaesthetic fluid rates for small animal patients. METHODS: A prospective, randomised, in vitro fluid line test-vein study was performed. Nine flow rates were analysed (10, 20, 60, 100, 140, 180, 220, 260 and 300 mL/hour) for room temperature fluids (21°C) and for five prewarmed fluids (40, 45, 50, 55 and 60°C). RESULTS: For each flow rate tested, room temperature fluids never exceeded 25°C at any time point for each trial (range 18 to 25°C). For each flow rate tested, prewarmed fluids never exceeded 25 · 5°C at any time point for each trial (range 18 to 25 · 5°C). The mean output fluid temperature of prewarmed fluids was significantly warmer than room temperature fluids only at 300 mL/hour for 40°C (P = 0 · 0012), 45°C (P = 0 · 004), 50°C (P = 0 · 0002), 55°C (P = 0 · 0001) and 60°C (P < 0 · 0001). CLINICAL SIGNIFICANCE: There was no thermodynamic benefit to utilising prewarmed intravenous fluids (up to 60°C) compared with room temperature intravenous fluids at common anaesthetic fluid rates for small animals.

Exercises in canine physical rehabilitation: range of motion of the forelimb during stair and ramp ascent.

OBJECTIVES: To evaluate overall joint range of motion of the forelimb in healthy dogs ascending stairs compared with incline slope walking. METHODS: Normal canine forelimb kinematics (range of motion, flexion and extension) were compared during ascent of stairs or a ramp, and compared to unimpeded trotting on a flat surface. Eight adult dogs with no evidence of orthopaedic or neurological lameness were assessed using a 2-dimensional kinematic system as they walked up a custom built ramp and stairs. RESULTS: In healthy dogs, ramp and stair ascent consistently had greater range of motion compared to trotting on a flat surface, and ramp ascent had significantly greater range of motion compared to stair ascent (P<0·05). Shoulder flexion and extension, elbow extension and carpal flexion were all significantly greater while ascending the ramp compared to stairs. Shoulder extension on the flat was significantly greater than while ascending stairs. CLINICAL SIGNIFICANCE: When planning physical rehabilitation exercises following injury to the forelimb, stair and ramp ascent may be considered, as both augment range of motion of joints. Ramp ascent provides the greatest increase in range of motion of forelimb joints.

Randomized masked controlled clinical trial to compare 7-day and 14-day course length of doxycycline in the treatment of Mycoplasma felis infection in shelter cats.

The aim of this study was to compare the clinical and microbial efficacy of a 7-day or a 14-day course of doxycycline for the treatment of Mycoplasma felis-infected cats with clinical signs of upper respiratory tract disease (URTD) assessed using clinical scoring criteria. Cats were randomly allocated to either the Doxy-7 group (N=20; 7-day course of oral doxycyline liquid followed by 7-days placebo); or the Doxy-14 group (N=20; 14-day course of oral doxycycline). There were no significant differences in Mycoplasma load between groups at Day 1 or Day 7 (P>0.05), but at Day 14 mean Mycoplasma load was lower in the Doxy-14 group (P=0.01). Mycoplasma load reduced over Days 1-7 in each group (P<0.01), but only the Doxy-14 group had a significantly reduced Mycoplasma load at Day 14 compared to Day 1 (P<0.01). On Day 14, 11 (55%) cats in the Doxy-7 group and 5 (25%) cats in the Doxy-14 group had positive PCR results for M. felis. There was a statistically significant reduction within each group across the Day 1-7 period for ocular discharge, nasal discharge, demeanor, and food intake scores (P<0.01 for each score category). Nasal discharge scores and sneezing scores were statistically lower in the Doxy-14 group than in the Doxy-7 group on individual days during the Day 8-14 period (P<0.05). We conclude that in M. felis-infected cats with clinical signs of URTD, a 14-day course of oral doxycycline produced superior microbial but not clinical results compared to a 7-day course of treatment.

The incretin effect in cats: comparison between oral glucose, lipids, and amino acids.

Incretin hormones are secreted from the intestines in response to specific nutrients. They potentiate insulin secretion and have other beneficial effects in glucose homeostasis. We aimed to study the incretin effect in cats and to compare the effect of oral glucose, lipids, or amino acids on serum concentrations of insulin, total glucose-dependent insulinotropic peptide (GIP) and total glucagon-like peptide 1 (GLP-1). Ten healthy cats were used in a repeated measures design. Glucose, lipid, or amino acids were administered through nasoesophageal tubes on separate days. Blood glucose (BG) concentrations were matched between experiments by measuring BG every 5 min and infusing glucose intravenously at a changing rate. Intravenous glucose infusion with no prior treatment served as control. The incretin effect was estimated as the difference in insulin area under the curve (AUC) after oral compared with intravenous glucose. Temporal changes and total amount of hormone secretions were compared between treatment groups with the use of mixed models. Total glucose infused (TGI) at a mean dose of 0.49 g/kg resulted in slightly higher BG compared with 1 g/kg oral glucose (P = 0.038), but insulin concentrations were not significantly different (P = 0.367). BG and the TGI were not significantly different after the 3 oral challenges. Total GIP AUC was larger after lipids compared with amino acids (P = 0.0012) but GIP concentrations did not increase after oral glucose. Insulin and GIP concentrations were positively correlated after lipid (P < 0.001) and amino acids (P < 0.001) stimulations, respectively, but not after oral glucose stimulation. Total GLP-1 AUC was similar after all three oral stimulations. Insulin and GLP-1 concentrations were positively correlated after glucose (P = 0.001), amino acids (P < 0.001), or lipids (P = 0.001) stimulations. Our data indirectly support an insulinotropic effect of GIP and GLP-1. Potentiation of insulin secretion after oral glucose is minimal in cats and is mediated by GLP-1 but not GIP.

Effect of parvoviral enteritis on plasma citrulline concentration in dogs.

BACKGROUND: Plasma citrulline concentration is a reliable marker of global enterocyte mass in humans and is markedly decreased in diffuse small intestinal diseases. However, the relationship between acute intestinal damage and plasma citrulline concentration in dogs has never been documented. HYPOTHESIS: That dogs with parvoviral enteritis have a lower plasma citrulline concentration than healthy dogs and that plasma citrulline concentration is a predictor of death in puppies with parvoviral enteritis. ANIMALS: Sixty-one dogs with spontaneous parvoviral enteritis and 14 healthy age-matched control dogs. METHODS: Observational cohort study. Plasma citrulline concentration was measured by liquid chromatography and tandem mass spectrometry in blood samples collected at admission and each day until death or discharge from the hospital. Parvovirus enteritis was confirmed by electron microscopy on a fecal sample. RESULTS: Median (interquartile range) plasma citrulline concentrations at admission were 2.8 µmol/L (range: 0.3, 49.0; P < .001 versus controls) in survivors (n = 49), 2.1 µmol/L (range: 0.5, 6.4, P < .001 versus controls) in nonsurvivors (n = 12) and 38.6 µmol/L (range: 11.4, 96.1) in controls (n = 14), respectively. There was no significant difference in plasma citrulline concentration between survivors and nonsurvivors within the parvovirus-infected puppies, and plasma citrulline concentration was not significantly associated with outcome in parvoviral enteritis. There were no significant changes in plasma citrulline concentration over the 8-day follow-up period. CONCLUSION AND CLINICAL IMPORTANCE: Parvovirus enteritis is associated with a severe decrease in plasma citrulline concentration that does not appear to have any significant prognostic value.

Bone resorption in syndromes of the Ras/MAPK pathway.

Disorders of the Ras/mitogen-activated protein kinase (MAPK) pathway have an overlapping skeletal phenotype (e.g. scoliosis, osteopenia). The Ras proteins regulate cell proliferation and differentiation and neurofibromatosis type 1 (NF1) individuals have osteoclast hyperactivity and increased bone resorption as measured by urine pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Pyd and Dpd are hydroxylysine-derived crosslinks of collagen found in bone and cartilage and excreted in the urine. Dpd is most abundant in bone. The aim of this study was to evaluate if other syndromes of the Ras/MAPK pathway have increased bone resorption, which may impact the skeletal phenotype. Participants were individuals with Noonan syndrome (n = 14), Costello syndrome (n = 21), and cardiofaciocutaneous (CFC) syndrome (n = 14). Pyridinium crosslinks from two consecutive first morning urines were extracted after acid hydrolysis and analyzed by high performance liquid chromatography. Three separate analyses of covariance were performed to compare Pyd, Dpd, and Dpd/Pyd ratio of each group to controls after controlling for age. Data were compared to 99 healthy controls. The Dpd and the Dpd/Pyd ratio were elevated (p < 0.0001) in all three conditions compared to controls suggesting that collagen degradation was predominantly from bone. The data suggest that the Ras/MAPK signal transduction pathway is important in bone homeostasis.