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.

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.

Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI.

Background: As differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility. Methods: Three study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists. Findings: The validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85). Interpretation: The radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics. Funding: Hanarth fonds.

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.

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.

Decreased cerebrospinal fluid nitrate levels in Parkinson's disease, Alzheimer's disease and multiple system atrophy patients.

Nitric oxide (NO) is a recently discovered endogenous mediator of vasodilatation, neurotransmission, and macrophage cytotoxicity. NO is thought to have a function in memory and in long-term potentiation. At high concentrations NO is neurotoxic and may play a role in neurodegeneration. NO is formed from L-arginine by the enzyme NO synthase (NOS), for which tetrahydrobiopterin (BH4) is a necessary co-factor. Alzheimer's disease (AD) and, to a lesser degree, Parkinson's disease (PD) are thought to be associated with increased microglial activity, suggesting that NO production may be increased. Alternatively, in circumstances of reduced levels of intracellular L-arginine or BH4, NO production is diminished and neurotoxic oxygen radicals may be produced. Since BH4 is decreased in AD and PD brains, these diseases may be associated with decreased NO production. We investigated these two alternatives by measuring the NO degradation products nitrite and nitrate in cerebrospinal fluid (CSF) of PD (n = 103), AD (n = 13), and multiple system atrophy (MSA; n = 14) patients and controls (n = 20). We found for all patient groups, compared with controls, significantly decreased levels of nitrate, but not nitrite. This finding seems to indicate a decreased NO production of the central nervous system (CNS) in these neurodegenerative disorders.

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.

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.

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.

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.

The passive protection of lambs against Clostridium perfringens type D with semi-purified hyperimmune serum.

Weaned lambs, having a detectable level of maternal antibodies (1-2 units/ml) against C. perfringens type D, showed protective antitoxin levels lasting for 29 days after receiving a single parenteral dose of 200 units/kg hyperimmune serum. Lambs, having no maternal antibodies (less than 0,07 units/ml) to C. perfringens type D but receiving the same dose of hyperimmune serum, maintained protective antibody levels for only 21 days. Three weeks after the titres fell below the minimum protective level of 0,15 units/ml, both these groups were treated again in the same manner. The passive immunity conferred in both groups now lasted for 42 days. When the hyperimmune serum was administered to lambs already immunized by vaccination, a slight increase was noted in the antibody titre.

The effect of passive immunization on active immunity against Clostridium perfringens type D in lambs.

Lambs in different stages of development of active immunity against Clostridium perfringens type D were treated with partially purified immunoglobulin in an attempt to superimpose a passive immunity on an existing or developing active immunity. Three different studies were undertaken to determine the impact of partial purified immunoglobulins on these vaccinated animals. In 2 of the 3 studies, active immunity was induced by administering the normal routine enterotoxaemia vaccinations and allowing the basic immunity to become established, for a period ranging from 2 weeks for the animals in study 1 and 4 months for those in study 2, before passive immunization with the partially purified immunoglobulins took place. An increase in the epsilon antibody titre occurred in each of the 2 studies after the animals were passively immunized with immunoglobulin, though this increase was not statistically significant (P greater than 0.05). In the 3rd study, when the animals were given the initial vaccination of the Onderstepoort enterotoxaemia oil adjuvant vaccine together with the immunoglobulin, an immediate increase in the epsilon antitoxin titre occurred that was statistically significant (P less than 0.05) 2-14 days after administration. No negative effects were noted on the development of an initial active immunity or an existing active immunity against Clostridium perfringens type D when they were passively immunized with partially purified immunoglobulin.

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.

Phytohemagglutinin skin testing in critically ill surgical patients.

Phytohemagglutinin (PHA) skin tests were performed in 225 critically ill surgical patients with respiratory failure. The study population was composed of 68 trauma patients who had suffered severe multiple injuries and 157 nontrauma patients who had a variety of surgical complications. The initial skin test response, obtained at the beginning of mechanical ventilation, was negative in 31% of the trauma patients and in 49% of the nontrauma patients. In the group of trauma patients, a higher mortality rate was noted in negative initial skin test responders compared with positive initial responders (38 and 15%, respectively; p less than 0.05). In the group of nontrauma patients, no association could be demonstrated between skin test unresponsiveness and mortality. With sequential testing, most (70%) of the patients were found to show at least one negative skin test reaction while in the intensive care unit. There was no difference in mortality between patients who remained reactive to PHA and patients with one or more negative skin test responses. These findings show that surgical intensive care patients frequently have an impaired cellular immunocompetence as indicated by a failed skin test response to PHA. However, PHA skin testing has little or no value in predicting outcome in these patients.

Effect of selective proximal and truncal vagotomy on canine gallbladder bile composition.

In 6 dogs the influence of consecutively a selective proximal vagotomy (SPV) and a truncal vagotomy (TV) on gallbladder bile composition was studied. Following SPV no significant changes in biliary lipids were observed. On the other hand, after TV an increase of deoxycholic acid (D) and a concomitant decrease of cholic acid (C) occurred, resulting in a marked increase of the D/C ratio. Although a positive correlation was found between the D/C ratio and the lithogenic index of bile, the change in bile acid composition after TV was accompanied with only a slight, statistically not significant increase of the lithogenic index. It is concluded that in the dog neither SPV nor TV is a definitely lithogenic procedure.

Evaluation of the Venom Ex apparatus in the initial treatment of puff adder envenomation. A study in rabbits.

The Venom Ex apparatus has been evaluated for the treatment of puff adder bite. Rabbits were injected with double the lethal dose of puff adder venom, followed by treatment with the Venom Ex cutting and suction apparatus. Controls received no treatment. The percentage of venom extracted as determined by radial immunodiffusion was very low after intramuscular injection and significantly higher after subcutaneous injection. However, all treated and control animals injected subcutaneously, recovered while all animals injected intramuscularly died, irrespective of treatment. Blood venom levels were extremely low in all animals. Venom Ex treatment did not improve survival or affect local necrosis significantly.

Similar hypocholesterolemic effect of ileal bypass and ileal excision in pigs.

We have compared the effect of partial ileal bypass versus ileal excision on the level of serum cholesterol in cholesterol-fed pigs. Both surgical procedures drastically lowered serum cholesterol in spite of continuation of cholesterol feeding. No evidence was obtained for a differential hypocholesterolemic effect of ileal bypass and excision.