Long-term musculoskeletal function after Open Pelvic ring fractures in Children (OPEC); a multicentre, retrospective case series with follow-up measurement.

Background: The proportion of Open Pelvic fractures in the paediatric population is relatively high. While operative fixation is the primary approach for managing Open Pelvic fractures in adults, there is limited literature on treatment outcomes in Children, particularly regarding long-term musculoskeletal, neurological, and urogenital function. Methods: This multicentre case series included paediatric patients (<18 years old) with Open Pelvic ring fractures treated at one of two major trauma centres in the Netherlands between January 1, 2001 and December 31, 2021. Data collection involved clinical records and long-term assessments, including musculoskeletal function, growth disorders, urogenital function, sexual dysfunction, and sensory motor function. Results: A total of 11 patients were included, primarily females (73 %), with a median age at trauma of 12 years (P25-P75 7-14). Most patients had unstable Pelvic ring fractures resulting from high-energy trauma. Surgical interventions were common, with external fixation as the main initial surgical approach (n = 7, 70 %). Complications were observed in eight (73 %) patients. Musculoskeletal function revealed a range of issues in the lower extremity, daily activities, and mental and emotional domain. Long-term radiologic follow-up showed high rates of Pelvic malunion (n = 7, 64 %). Neurological function assessment showed motor and sensory function impairment in a subset of patients. Urogenital function was moderately affected, and sexual dysfunction was limited with most respondents reporting no issues. Conclusion: Paediatric Open Pelvic fractures are challenging injuries associated with significant short-term complications and long-term musculoskeletal and urogenital issues. Further research is needed to develop tailored treatment strategies and improve outcomes of these patients.

Radiomics approach to distinguish between well differentiated liposarcomas and lipomas on MRI.

BACKGROUND: Well differentiated liposarcoma (WDLPS) can be difficult to distinguish from lipoma. Currently, this distinction is made by testing for MDM2 amplification, which requires a biopsy. The aim of this study was to develop a noninvasive method to predict MDM2 amplification status using radiomics features derived from MRI. METHODS: Patients with an MDM2-negative lipoma or MDM2-positive WDLPS and a pretreatment T1-weighted MRI scan who were referred to Erasmus MC between 2009 and 2018 were included. When available, other MRI sequences were included in the radiomics analysis. Features describing intensity, shape and texture were extracted from the tumour region. Classification was performed using various machine learning approaches. Evaluation was performed through a 100 times random-split cross-validation. The performance of the models was compared with the performance of three expert radiologists. RESULTS: The data set included 116 tumours (58 patients with lipoma, 58 with WDLPS) and originated from 41 different MRI scanners, resulting in wide heterogeneity in imaging hardware and acquisition protocols. The radiomics model based on T1 imaging features alone resulted in a mean area under the curve (AUC) of 0·83, sensitivity of 0·68 and specificity of 0·84. Adding the T2-weighted imaging features in an explorative analysis improved the model to a mean AUC of 0·89, sensitivity of 0·74 and specificity of 0·88. The three radiologists scored an AUC of 0·74 and 0·72 and 0·61 respectively; a sensitivity of 0·74, 0·91 and 0·64; and a specificity of 0·55, 0·36 and 0·59. CONCLUSION: Radiomics is a promising, non-invasive method for differentiating between WDLPS and lipoma, outperforming the scores of the radiologists. Further optimization and validation is needed before introduction into clinical practice.

ANTECEDENTES: Es difícil distinguir los liposarcomas bien diferenciados (well-differentiated liposarcomas, WDLPS) de los lipomas. En la actualidad, esta distinción se realiza mediante la prueba de amplificación del gen MDM2 por biopsia. El objetivo de este estudio fue predecir de forma no invasiva el estado de amplificación del gen MDM2 para diferenciar los lipomas de los WDLPS utilizando características radiómicas a partir de la resonancia magnética. MÉTODOS: Se incluyeron los pacientes remitidos al instituto Erasmus MC entre 2009-2018 por un lipoma MDM2 negativo o WDLPS MDM2 positivo y las resonancias magnéticas potenciadas en T1 correspondientes antes del tratamiento. Cuando estaban disponibles, se incluyeron otras secuencias de MRI en el análisis radiómico. Se describieron la intensidad, forma y textura de la región tumoral. Para la clasificación se utilizaron varios modelos de aprendizaje automático (machine learning). La evaluación se realizó mediante una validación cruzada aleatoria 100x. Se comparó el rendimiento de los modelos con la clasificación realizada por tres radiólogos expertos. RESULTADOS: Se incluyeron 116 pacientes (58 lipomas, 58 WDLPS) y 41 aparatos de MRI, con una gran heterogeneidad en las técnicas y protocolos para la adquisición de imágenes. El modelo radiómico basado únicamente en las características de las imagen en T1 dio como resultado una AUC media de 0,83, con una sensibilidad de 0,68 y una especificidad de 0,84. Un análisis adicional incorporando las imágenes ponderadas en T2 mejoró el modelo con una AUC media de 0,89, una sensibilidad de 0,74 y una especificidad de 0,88. Los tres radiólogos obtuvieron una AUC de 0,74/0,72/0,61, una sensibilidad de 0,74/0,91/0,64 y una especificidad de 0,55/0,36/0,59, respectivamente. CONCLUSIÓN: La radiómica es un método prometedor y no invasivo para diferenciar entre WDLPS y lipomas, superando la valoración de los radiólogos. Sin embargo, se necesita la optimización y validación de esta técnica antes de su introducción en la práctica clínica diaria.

The 30-day mortality of ruptured abdominal aortic aneurysms: influence of gender, age, diameter and comorbidities.

AIM: The aim of this study was to determine the influence of gender, age, the aneurysm diameter and comorbidity on the 30-day mortality after open repair of ruptured abdominal aortic aneurysms (AAA). METHODS: Between January 1, 1993, and December 31, 2006 all consecutive patients who underwent open repair for a ruptured AAA at the tertiary care of Catharina Teaching Hospital were included in this study (N=186). Patients who underwent endovascular repair of their ruptured abdominal aortic aneurysms were excluded from this study. Patient and procedure characteristics were collected and analyzed in relation to 30-day mortality. The association between age, gender, diameter of AAA and comorbidity with 30-day mortality was analyzed with c2 are and logistic regression; a P value <0.05 was considered significant. RESULTS: In this study there were 186 patients with ruptured AAA repair with an 30-day mortality of 36.6% (68/186). Among female patient 30-day mortality was 45.8% (11/24) compared with 35.2% (57/162) among male patients (P=0.31). Patients of 80 years and older had a 61.3% (19/31) 30-day mortality where younger patients had 33% (51/155) 30-day mortality (P=0.02). Thirty-day mortality was 47.2% (17/36) for patients with an AAA less than 65 mm compared with 34% (36/104) for patients with an AAA of 65 mm or larger (P=0.16). Multivariate analysis demonstrated age was a significant predictor of ruptured AAA repair mortality (P=0.017). CONCLUSION: In this study, age was the only significant risk factor of 30-day mortality after open repair in patients with ruptured AAA.

Patient-risk due to negligence by Locum General Practitioners outside of office hours.

In Holland, first tier medical care outside of office hours is provided by regular GP's acting as Locum GP's. On several occasions concerns have been expressed about Locum GP's not visiting the patient when necessary. The number of complaints against Locum GP's submitted to the Medical Boards has been increasing over time and relate in particular to refusals of Locum GP's to visit the patient. In many of these cases the patient died. The paper develops a quantitative estimate of the risk for the patient due to negligence of Locum GP's. The measure of the risk is taken as the number of patients who died unnecessarily due to negligence of Locum GP's as determined by the Medical Boards. The paper estimates that in Holland in the year 2000 about 1500 patients would probably not have died had the Locum GP's working out-of-hours not been negligent by contravening professional standards. In more than half of these cases the Locum GP's did not visit the patient, or did not visit the patient in time, when necessary. This level of patient risk must be regarded as socially unacceptable. One important explanation for these accidents could be that doctors are largely unfamiliar with the professional standards developed by the Medical Boards. Because of the assumptions made and the uncertainty regarding the data used, the actual numbers of these accidents may be higher or lower than estimated here. Although more reliable data will allow the results to be determined more reliably, this is unlikely to change the acceptability of the risk.

L-glutamate, L-arginine and L-citrulline levels in cerebrospinal fluid of Parkinson's disease, multiple system atrophy, and Alzheimer's disease patients.

Alterations in neuronal nitric oxide (NO) production may play a role in the pathophysiology of Parkinson's disease (PD) Alzheimer's disease (AD), and multiple system atrophy (MSA). The biosynthesis of NO is dependent on the availability of L-arginine, the substrate for NO-synthase (NOS), and on L-glutamate, which stimulates NO synthesis via the NMDA receptor. In this process L-citrulline is formed. We measured the levels of these amino acids in cerebrospinal fluid (CSF) of 108 PD patients, 12 AD patients, 15 MSA patients and 21 healthy subjects. A slight but statistically significant elevation of CSF L-citrulline was found in MSA patients, while CSF L-glutamate was found to be significantly decreased in AD patients. We found no significant changes in L-arginine levels. Although the relation between the CSF levels of these amino acids and neuronal NO production is still unclear, our findings suggest that AD is associated with a decrease in NO synthesis.

Dietary glutamine supplementation reduces plasma nitrate levels in rats.

It was recently shown that L-glutamine inhibits vascular nitric oxide (NO) production in vitro. The present study investigated the effect of glutamine enriched enteral diets on in vivo NO production in the rat. Nitrate, the stable end-product of NO production, was measured in plasma and 24 h urine collections in glutamine supplemented rats (6.25%, 12.5% and 25% w/w) and compared to the effect of isocaloric, nitrogenous control diets. Glutamine supplementation increased plasma levels of glutamine (up to 91%), arginine (up to 17%) and citrulline (up to 54%). After 1 week of glutamine supplementation plasma nitrate levels were significantly reduced by 50% compared to control (P < 0. 0001); irrespective of the amount of supplementation. No further decrease was observed after 2 weeks of feeding. No differences in daily urinary losses were found between the groups. These results point to an in vivo inhibitory effect of glutamine supplemented enteral feeding on NO production.

The use of biliary CEA measurements in the diagnosis of recurrent colorectal cancer.

To assess the usefulness of biliary CEA determinations in the diagnosis of recurrent tumour, gallbladder bile was sampled in patients who underwent laparotomy for proven or suspected recurrent colorectal cancer and in control patients. Biliary CEA concentrations in controls were < 5 ng/ml, whereas significantly elevated CEA concentrations were found in the bile of all patients with tumour recurrence. Serum concentrations in these patients were elevated in 77% only. In a series of 12 patients with (a) suspicious lesion(s) on liver imaging but normal serum CEA concentration during follow-up, biliary CEA determination differentiated clearly between metastases and benign lesions. Biliary CEA determination seems to aid detection of tumour recurrence at an early stage and may preclude unnecessary surgery in patients with undefined liver lesions.

Arginine deficiency in bile duct-ligated rats after surgery: the role of plasma arginase and gut endotoxin restriction.

BACKGROUND & AIMS: Arginine deficiency may underlie the cellular immune depression after surgery in obstructive jaundice, which is associated with gut-derived endotoxemia. The aim of this study was to study arginine metabolism in the bile duct-ligated rat (BDL) after laparotomy. METHODS: Treatment with cholestyramine, a known endotoxin binder, was used to evaluate the role of gut-derived endotoxemia. RESULTS: In BDL rats, arginine levels were lower compared with those in sham-operated controls (P < 0.005), despite a three-fold increase in renal arginine release (P < 0.01). Liver and gut arginine handling also could not explain the reduced arginine levels. Higher plasma arginase activity (P < 0.0001) was measured in BDL rats, explaining both the lower arginine levels (r = 0.73, P < 0.01) and the increase in arginase product levels: ornithine (P < 0.005 and r = 0.72; P < 0.01) and urea (P < 0.01). Cholestyramine treatment prevented the decrease in postoperative arginine deficiency by reducing plasma arginase activity by 43% (P < 0.005). In addition, it significantly lowered plasma levels of the other liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and alkaline phosphatase; P < 0.05) in BDL rats. CONCLUSIONS: The study concluded that arginine deficiency in BDL rats after surgery is caused by high plasma liver arginase activity. Cholestyramine prevented the arginine deficiency by reducing plasma arginase activity through the inhibition of additional endotoxin-mediated hepatocellular damage after surgery in BDL rats.

The role of nitric oxide in bacterial meningitis in children.

To investigate the role of nitric oxide (NO) in bacterial meningitis, concentrations in serum, cerebrospinal fluid (CSF), or both of the precursor (L-arginine) and degradation products of NO (nitrate, nitrite) and tumor necrosis factor (TNF)-alpha were measured in 35 patients and 30 controls. CSF nitrate levels were significantly elevated, mainly due to increased blood-brain barrier permeability, and are therefore not a good parameter for gauging endogenous NO production in the CSF compartment. CSF NO/nitrite levels were significantly elevated in patients. NO/nitrite levels decreased over time (26%/6 h; P < .001). CSF levels of NO/nitrite correlated with those of TNF-alpha (r = .55; P = .001) and glucose (r = -.43; P = .02). CSF levels of L-arginine were lower in patients than in controls (P < .001). Dexamethasone did not exert a significant effect on NO metabolism. In conclusion, enhanced NO production may contribute to anaerobic glycolysis and neurologic damage in bacterial meningitis.

Detection of occult liver metastases by measurement of biliary carcinoembryonic antigen concentrations.

OBJECTIVE: To assess whether biliary CEA concentrations can be used as early markers of occult liver metastases in patients with colorectal cancer. DESIGN: Consecutive open study. SETTING: University hospital, The Netherlands. SUBJECTS: 76 patients with a primary colorectal carcinoma (group 1) and 19 patients who had recently undergone a curative resection of a locally advanced carcinoma (group 2). INTERVENTIONS: Bile sampling by transhepatic puncture of the gallbladder. MAIN OUTCOME MEASURE: Recurrence of tumour. RESULTS: Twenty-one of the 76 patients (28%) with primary colorectal carcinoma had liver metastases; all had a raised biliary CEA concentration. Of the remaining 55 patients 39 (71%) also had raised CEA concentrations. At a median follow-up of 30 months, only seven patients had developed liver metastases, indicating a high number of false-positive results. In Group 2 7/19 patients (37%) had a CEA concentration above the cut-off point. Six of them developed recurrent tumour; 2 patients had liver metastases and 4 others had extrahepatic recurrences. None of the 12 patients with biliary CEA concentrations within the reference range has developed recurrent tumour. CONCLUSION: Biliary CEA concentrations do not predict the presence of occult liver metastases if bile samples are taken during resection of the primary tumour. If samples are taken some time afterwards, a raised CEA concentration seems to predict recurrence at an early stage, either in or outside the liver.

Serum nitrate levels in ulcerative colitis and Crohn's disease.

BACKGROUND: Nitric oxide is an important mediator in inflammatory and autoimmune-mediated tissue destruction and may be of pathophysiologic importance in inflammatory bowel disease. We studied whether serum levels of nitrate, the stable end-product of nitric oxide, are increased in active Crohn's disease or ulcerative colitis, in comparison with quiescent disease and healthy controls. The setting was the gastroenterology unit of the Free University Hospital, Amsterdam. METHODS: In 146 patients--75 with ulcerative colitis and 71 with Crohn's disease--and 33 controls serum nitrate was measured by the Griess reaction after enzymatic conversion of nitrate to nitrite with nitrate reductase. RESULTS: Median serum nitrate concentrations did not differ statistically significantly between ulcerative colitis (median, 34.2 mumol/l; range, 15.6-229.4 mumol/l), Crohn's disease (median 32.3 mumol; range 13.2-143.2 mumol/l), and healthy controls (median, 28.7 mumol/l; range, 13.0-108.4 mumol/l). However, when active ulcerative colitis patients (median, 44 mumol/l; range, 29.1-229.4 mumol/l were compared with inactive ulcerative colitis patients (median, 31.2 mumol/l; range, 15.6-59.7 mumol/l), a significant difference in nitrate concentration was found (p < 0.0001). A significant positive correlation was found between serum nitrate levels in ulcerative colitis and erythrocyte sedimentation rate (ESR) (r = 0.30, p - 0.01), leucocyte count (r = 0.27, p = 0.02), and thrombocyte count (r = 0.24, p = 0.04). Comparing active Crohn's disease patients (median, 37.5 mumol/l; range, 13.2-143.2 mumol/l) with inactive Crohn's disease patients (median, 31.3 mumol/l; range, 14.5-92.3 mumol/l) also showed a significant difference in serum nitrate concentration (p < 0.009). Serum nitrate levels correlated with the ESR (r = 0.26, p = 0.028) and serum albumin (r = 0.38, p = 0.004) as well. CONCLUSION: Nitric oxide production is increased in both active ulcerative colitis and Crohn's disease and may be implicated in the pathogenesis of inflammatory bowel disease.

Local colonic blood pressure degree through aortic reconstruction procedures: a porcine model.

Sigmoideal ischemia after aortic grafting is a severe complication with high morbidity and mortality. To investigate the basics of this circulatory problem an animal model was created with sigmoideal ischemia that could be quantified. For this purpose a new pig model was developed with stable general circulatory and ventilatory parameters for several hours, while at the same time controlled sigmoideal ischemia was induced. In five pigs a left retroperitoneal approach to the aorta was performed to isolate the caudal mesenteric artery (CMA). Sigmoideal ischemia was achieved by ligating the collateral circulation and constricting the distal aorta. A flow probe was applied to the CMA. An intravascular saturation probe was introduced in the caudal mesenteric vein (CMV) and a pulse oximeter was applied to the serosal surface of the sigmoid. Every hour, blood gas analyses from the carotic artery, CMA, and CMV were completed. Registrations of all circulatory and ventilatory parameters were performed with the help of a computer. The mean flow in the CMA was 29 mL/min (13-45) and decreased to 5 mL/min (3-7) after aortic constriction. Parameters reflecting the stability of the model, such as the cardiac index (mean 89 mL/min kg-1), the mixed venous oxygen saturation (mean 67%), and the total body oxygen consumption (mean 3.3 mL/min kg-1), did not change with statistical significance during 4 h of partial aortic constriction. The conclusion is that a new model has been developed of quantitative sigmoideal ischemia in the pig that was stable for several hours.

Endoluminal pulse oximetry in ischemic colon in a swine model.

BACKGROUND: Postoperative sigmoidal ischemia after aortic grafting is a severe complication. No simple methods are available to detect this entity at an early stage. This study was done to monitor for sigmoidal ischemia with a new endoluminal probe based on pulse oximetry (SmO2). STUDY DESIGN: A prospective controlled animal study was done. Five pigs with low flow in the caudal mesenteric artery (20 percent of the basal flow) and four pigs in a control group were included. General and local circulatory parameters were monitored in the carotid and pulmonary artery and in the caudal mesenteric vein (CMV). Mucosal biopsy specimens were taken for histologic examination. Statistical analysis was done with the Wilcoxon and Mann-Whitney rank sum test and with analysis of variance. RESULTS: During the first two hours of ischemia, no sigmoidal pulse was detected. During the third hour, in three pigs the pulse curve reappeared with a SmO2 of 48 to 88 percent. After two hours, the mean oxygen saturation in the CMV of the ischemic group was 64 percent (compared with the control group, 77 percent, p < 0.05). After one hour, the mean lactate concentrations were 2.0 and 1.3 mmol per L, respectively (p < 0.05). Significant histologic changes occurred with neutrophilic infiltration in the crypts, in the lamina propria, and in the submucosa. CONCLUSIONS: Low-flow sigmoidal ischemia can be detected and monitored with endoluminal pulse oximetry in this model of early sigmoidal ischemia.

Arginine supplementation in the prevention and treatment of osteoporosis.

Oral administration of L-arginine in pharmacological doses induces growth hormone and insulin-like growth factor-I responses and stimulates nitric oxide synthesis. Growth hormone and insulin-like growth factor-I are important mediators of bone turnover and osteoblastic bone formation, while nitric oxide is a potent inhibitor of osteoclastic bone resorption. Because of this dual effect on physiological regulators of bone remodeling, L-arginine could potentially increase bone formation over bone resorption, and, consequently, increase bone mass. It is, therefore, hypothesized that oral supplementation of L-arginine may be a novel strategy in the prevention and treatment of osteoporosis. Studies of this simple, safe, and inexpensive therapy seem warranted.

Prevention of primary transfusion-associated cytomegalovirus infection in bone marrow transplant recipients by the removal of white cells from blood components with high-affinity filters.

A prospective study was carried out to determine whether use of cytomegalovirus (CMV) unscreened red blood cells and platelet concentrates, white blood cell (WBC) depleted with high-efficiency filters, would prevent transfusion-associated (TA) CMV infection in CMV seronegative bone marrow transplant recipients. Blood components were filtered in the bloodcentre under quality control and after filtration residual WBC counts were always below 5 x 10(6) cells/U. Since 1990, 23 consecutive allogeneic and 37 autologous CMV seronegative marrow transplant recipients, have been transfused with filtered blood components and followed for 6 months for evidence of CMV infection by monitoring culture and CMV serology. None of the patients showed clinical symptoms of CMV infection, and CMV cultures during episodes of fever were always negative. IgM anti-CMV antibodies were negative during the study in all patients. Low titres of IgG anti-CMV antibodies (5-12 relative ELISA units) were found in 24/60 patients during the first month after bone marrow transplantation (BMT), probably due to passive transfer of IgG administered with the platelet transfusions. 3 and 6 months after BMT, 56 and 48 patients respectively were still alive; and CMV serology was negative in all patients. The results show that TA-CMV infection is preventable by filtration of blood through high-efficiency filters in patients undergoing autologous and allogeneic BMT.

Protective role of NO in the regional hemodynamic changes during acute endotoxemia in rats.

The role of NO during the first hour of endotoxemia is still controversial. To evaluate whether NO is protective or detrimental to the regulation of systemic blood pressure, cardiac output (CO), and organ perfusion in rats during acute endotoxemia, we have studied the effects of inhibition of NO synthesis. Thirty minutes after 0.1 mg NG-nitro-L-arginine (L-NNA; group L, n = 7, partial inhibition), 1 mg L-NNA (group H, n = 6, complete inhibition), or saline (group E, n = 7) intravenous infusion, anesthetized volume-loaded rats were infused with endotoxin Escherichia coli O127:B8 (8 mg.kg-1 x h-1) from time (t) = 0 to 60 min. Organ blood flow was measured with radioactive microspheres. In group H, at time 0, CO was lower than in group E (by -29%; P < 0.05), and systemic vascular resistance (SVR) was higher than in groups E and L (by 72 and 51%, respectively; P < 0.05). Perfusion of the pancreas, stomach, intestines, and kidney was lower (P < 0.05) and corresponding organ vascular resistance (OVR) higher (P < 0.05) in group H than in groups E and L (except kidney in group L). At t = 60 min, in groups H and L, CO was lower (by -45 and -26%, respectively; P < 0.05) and SVR was higher (by 112 and 54%, respectively; P < 0.05) than in group E. In group L only blood flow to the heart, pancreas, intestines, and kidney was significantly lower than in group E, and corresponding OVR was higher.(ABSTRACT TRUNCATED AT 250 WORDS)