A primer in artificial intelligence in cardiovascular medicine.

Driven by recent developments in computational power, algorithms and web-based storage resources, machine learning (ML)-based artificial intelligence (AI) has quickly gained ground as the solution for many technological and societal challenges. AI education has become very popular and is oversubscribed at Dutch universities. Major investments were made in 2018 to develop and build the first AI-driven hospitals to improve patient care and reduce healthcare costs. AI has the potential to greatly enhance traditional statistical analyses in many domains and has been demonstrated to allow the discovery of 'hidden' information in highly complex datasets. As such, AI can also be of significant value in the diagnosis and treatment of cardiovascular disease, and the first applications of AI in the cardiovascular field are promising. However, many professionals in the cardiovascular field involved in patient care, education or science are unaware of the basics behind AI and the existing and expected applications in their field. In this review, we aim to introduce the broad cardiovascular community to the basics of modern ML-based AI and explain several of the commonly used algorithms. We also summarise their initial and future applications relevant to the cardiovascular field.

Non-operative treatment of metacarpal fractures and patient-reported outcomes: a multicentre snapshot study.

PURPOSE: This study aimed to investigate practice variation in non-operative treatment methods and immobilisation duration for metacarpal fractures, and to evaluate patient-reported outcomes. METHODS: Conducted in 12 Dutch hospitals over three months in 2020, this study included adult patients with non-operatively treated solitary metacarpal fractures. Fractures were classified into intra-articular base, extra-articular base, shaft, neck, and intra-articular head fractures. The treatment methods (functional treatment allowing digit mobilisation or immobilisation) and immobilisation duration were assessed. Patient-reported outcomes were evaluated using the Michigan Hand Outcomes Questionnaire (MHQ) at three months post-trauma. RESULTS: Of 389 included patients, shaft fractures were most common (n = 150, 39%), with 93% immobilised, followed by fifth metacarpal neck fractures (n = 93, 24%), with 75% immobilised. Immobilisation rates for fifth metacarpal neck fractures varied between hospitals, ranging from 29% (95% CI 0.10-0.58) to 100% (95% CI 0.78-1.00). The median immobilisation duration for all fractures was 23 days (IQR: 20-28), and hospital setting was independently associated with this duration. Patients with metacarpal shaft fractures immobilised for less than 21 days had higher MHQ scores compared to those immobilised for 21 days or more (median (IQR) 83 (76-100) versus 71 (57-89), p = 0.026). CONCLUSIONS: The results showed practice variation in the treatment of metacarpal fractures, especially in the treatment of fifth MC neck fractures, with some hospitals following the Dutch guideline that advocates functional treatment while others did not. There are suggestions that prolonged immobilisation of metacarpal shaft fractures may lead to a worse MHQ score. These findings underscore the need for adherence to treatment protocols and emphasize functional treatment to potentially improve patient outcomes and cost-effectiveness.

Prevention of postsurgical adhesions using an ultrapure alginate-based gel.

BACKGROUND: Postoperative adhesion formation is a common consequence of abdominal surgery, and constitutes a major source of morbidity and mortality. This study evaluated an ultrapure alginate-based antiadhesive barrier gel. METHODS: Experiments were performed in a rat model with caecal abrasion and peritoneal side wall excision. The primary endpoint was the incidence of adhesions at 14 days after surgery. In experiment 1 (24 rats), animals treated with alginate gel were compared with controls that had no antiadhesive barrier. In experiment 2 (42 rats), alginate gel was compared with sodium hyaluronate carboxymethyl cellulose (HA/CMC) membrane and with no antiadhesive barrier. To check for any remote action of the gel, in experiment 3 (45 rats) application of alginate gel to the ipsilateral versus contralateral side of injury was compared with no antiadhesive barrier. RESULTS: In experiment 1, ultrapure alginate gel reduced the incidence of adhesions from eight of 12 in control animals to one in 12 (P = 0·009). Tissue healing assessed by histology was similar in both groups. In experiment 2, ultrapure alginate gel and HA/CMC membrane showed similar antiadhesive effectiveness, reducing the incidence of adhesions from ten of 14 rats in the control group to three of 14 (P = 0·021) and two of 14 (P = 0·006) respectively. In experiment 3, ultrapure alginate gel reduced the incidence of adhesions at the site of direct application (1 of 15) compared with controls (13 of 15; P = 0·001), but not if applied remotely (9 of 15; P = 0·214). CONCLUSION: Ultrapure alginate gel decreased the incidence of postoperative adhesion formation in this rat model.

Diclofenac causes more leakage than naproxen in anastomoses in the small intestine of the rat.

BACKGROUND: Non-steroid anti-inflammatory drugs such as the cyclooxygenase isoenzyme inhibitors diclofenac and naproxen are increasingly used for perioperative pain relief, while their potential effects on wound healing are scarcely investigated. METHODS: In 104 male Wistar rats, an anastomosis was constructed in both colon and ileum. The rats were divided into groups who received diclofenac (4 mg kg(-1) day(-1)) or naproxen (10 mg kg(-1) day(-1)) daily from the day of surgery or from day 3 after surgery. Animals were killed on day 3 or 7 and analysed for signs of anastomotic dehiscence and wound strength of anastomoses and abdominal fascia. RESULTS: Anastomotic leakage in the ileum (p < 0.0001) and mortality rates (p = 0.001) were significantly increased in the diclofenac group. On day 7, the anastomotic bursting pressure in the ileum remained below that of the controls in the diclofenac- and naproxen-treated rats. When administration of diclofenac was postponed to day 3 after surgery, anastomotic dehiscence was almost absent. The colonic anastomosis and abdominal wall always remained unaffected. CONCLUSIONS: This study implies that immediate postoperative administration of diclofenac and, to a far lesser extent, naproxen can affect healing in the ileal anastomosis in the rat. This negative effect can be prevented by a short postoperative delay in administration. On steroid anti-inflammatory drugs such as the cyclooxygenase isoenzyme inhibitors diclofenac and naproxen are increasingly used for perioperative pain relief, while their potential effects on wound healing are scarcely investigated.

Perioperative pain relief by a COX-2 inhibitor affects ileal repair and provides a model for anastomotic leakage in the intestine.

The authors examined the potential of the cyclooxygenase 2 (COX-2) inhibitor carprofen to reproducibly induce anastomotic leakage. In experiment 1, an anastomosis was constructed in both ileum and colon of 20 rats, and they were given carprofen (5 mg/kg subcutaneously every 24 hours) or buprenorphine (0.02 mg/kg subcutaneously every 12 hours). In another 20 rats an anastomosis was constructed in either ileum or colon, and all received carprofen (experiment 2). Animals were sacrificed after 3 days. In experiment 1, the ileal dehiscence rate was 60% in the carprofen group and 0% in the buprenorphine group (P = .0108). Colonic anastomoses in both groups remained patent. In experiment 2, the anastomotic leakage rate was 80% in ileum and 0% in colon. Thus, COX-2 inhibitors can severely interfere with intestinal healing, particularly in the ileum. Perioperative administration of carprofen yields a unique model for anastomotic leakage, which allows translational research on the effectiveness of perisuture line reinforcement.

The development of burn scar contractures and impact on joint function, disability and quality of life in low- and middle-income countries: A prospective cohort study with one-year follow-up.

OBJECTIVE: The aim of this study was to assess the development of burn scar contractures and their impact on joint function, disability and quality of life in a low-income country. METHODS: Patients with severe burns were eligible. Passive range of motion (ROM) was assessed using lateral goniometry. To assess the development of contractures, the measured ROM was compared to the normal ROM. To determine joint function, the normal ROM was compared to the functional ROM. In addition, disability and quality of life (QoL) were assessed. Assessments were from admission up to 12 months after injury. RESULTS: Thirty-six patients were enrolled, with a total of 124 affected joints. The follow-up rate was 83%. Limited ROM compared to normal ROM values was observed in 26/104 joints (25%) at 12 months. Limited functional ROM was observed in 55/115 joints (48%) at discharge and decreased to 22/98 joints (22%) at 12 months. Patients who had a contracture at 12 months reported more disability and lower QoL, compared to patients without a contracture (median disability 0.28 versus 0.17 (p = 0.01); QoL median 0.60 versus 0.76 (p = 0.001)). Significant predictors of developing joint contractures were patient delay and the percentage of TBSA deep burns. CONCLUSION: The prevalence of burn scar contractures was high in a low-income country. The joints with burn scar contracture were frequently limited in function. Patients who developed a contracture reported significantly more disability and lower QoL. To limit the development of burn scar contractures, timely access to safe burn care should be improved in low-income countries.

Acute burn care in resource-limited settings: A cohort study on treatment and outcomes in a rural regional referral hospital in Tanzania.

BACKGROUND: Only a few papers are published on the safety and effectiveness of acute burn care in low-income countries. A cohort study was therefore carried out to determine such outcomes. METHODS: The study was conducted in a rural Tanzanian hospital in 2017-2018. All patients admitted with burns were eligible. Complications were scored during admission as an indication for safety. Survivors of severe burn injuries were evaluated for time of reepithelialization, graft take, disability (WHODAS2.0) and quality of life (EQ5D-3L) up to 3 months post-injury, as an indication of effectiveness. RESULTS: Patients presented on average at 5 days after injury (SD 11, median 1, IQR 0-4). Three patients died at admission. The remaining 79 were included in the cohort. Their median age was 3 years (IQR 2-9, range 0.5-49), mean TBSA burned 12% (SD10%) and mortality rate 11.4%. No surgery-related mortality or life-threatening complications were observed. Skin grafting was performed on 29 patients at a delayed stage (median 23 days, IQR 15-47). Complications of skin grafts included partial (25% of procedures) and complete graft necrosis (8% of procedures). The mean time to reepithelialization was 52 (SD 42) days after admission. Disability and quality of life improved from admission to 3 months after injury (p<0.001, p<0.001, respectively). CONCLUSION: In this resource-limited setting patients presented after a delay and with multiple complications. The mortality during the first two weeks after admission was high. Surgery was found to be safe and effective. A significant improvement in disability and quality of life was observed.

Experimental study of radioimmunotherapy versus chemotherapy for colorectal cancer.

BACKGROUND: Radioimmunotherapy (RIT) has been shown to reduce the incidence of local recurrence of colorectal cancer in an experimental model. The aim of the present study was to investigate the survival benefit of RIT compared with chemotherapy. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of CC531 tumour cells. The therapeutic efficacy of (177) Lu-labelled MG1 (single intravenous dose of 300 MBq/kg, n = 20) was compared with that of 5-fluorouracil-based chemotherapy (6 weekly cycles administered intraperitoneally, n = 20) and no treatment (n = 20). The primary endpoint was survival. Toxicity was monitored by bodyweight measurement. RESULTS: Both chemotherapy and RIT affected bodyweight, but the weight of animals in the RIT group remained significantly higher than in the chemotherapy group (median slope of bodyweight plot 0·48 versus 0·30 g/day; P < 0·001). Kaplan-Meier analysis showed that overall survival in the RIT and chemotherapy groups was significantly better than that in the control group (50 and 46 per cent versus 25 per cent respectively after 170 days; P = 0·024 and P = 0·029). Survival after treatment with RIT did not differ from that after chemotherapy (P = 0·911). CONCLUSION: RIT is as effective as chemotherapy in experimental colorectal cancer.

Radiological findings in spontaneous cerebrospinal fluid leaks of the temporal bone.

BACKGROUND AND OBJECTIVE: Spontaneous cerebrospinal fluid leak of the temporal bone is an emerging clinical entity for which prompt and accurate diagnosis is difficult given the subtle signs and symptoms that patients present with. This study sought to describe the key temporal bone abnormalities in patients with spontaneous cerebrospinal fluid leak. METHODS: A retrospective cohort study was conducted of adult patients with biochemically confirmed spontaneous cerebrospinal fluid leak. Demographics and radiological features identified on computed tomography imaging of the temporal bones and/or magnetic resonance imaging were analysed. RESULTS: Sixty-one patients with spontaneous cerebrospinal fluid leak were identified. Fifty-four patients (88.5 per cent) underwent both temporal bone computed tomography and magnetic resonance imaging. Despite imaging revealing bilateral defects in over 75 per cent of the cohort, only two patients presented with bilateral spontaneous cerebrospinal fluid leaks. Anterior tegmen mastoideum defects were most common, with an average size of 2.5 mm (range, 1-10 mm). CONCLUSION: Temporal bone computed tomography is sensitive for the identification of defects when suspicion exists. In the setting of an opacified middle ear and/or mastoid, close examination of the skull base is crucial given that this fluid is potentially cerebrospinal fluid.

Burn scar contracture release surgery effectively improves functional range of motion, disability and quality of life: A pre/post cohort study with long-term follow-up in a Low- and Middle-Income Country.

OBJECTIVE: Burn scar contractures limit range of motion (ROM) of joints and have substantial impact on disability and the quality of life (QoL) of patients, particularly in a Low- and Middle-Income Country (LMIC) setting. Studies on the long-term outcome are lacking globally; this study describes the long-term impact of contracture release surgery performed in an LMIC. METHODS: This is a pre-post cohort study, conducted in a referral hospital in Tanzania. Patients who underwent burn scar contracture release surgery in 2017-2018 were eligible. ROM (goniometry), disability (WHODAS 2.0) and QoL (EQ-5D) were assessed. The ROM data were compared to the ROM that is required to perform activities of daily living without compensation, i.e. functional ROM. Assessments were performed preoperatively and at 1, 3, 6 and 12 months postoperatively. RESULTS: In total, 44 patients underwent surgery on 115 affected joints. At 12 months, the follow-up rate was 86%. The mean preoperative ROM was 37.3% of functional ROM (SD 31.2). This improved up to 108.7% at 12 months postoperatively (SD 42.0, p < 0.001). Disability-free survival improved from 55% preoperatively to 97% at 12 months (p < 0.001) postoperatively. QoL improved from 0.69 preoperatively, to 0.93 (max 1.0) at 12 months postoperatively (p < 0.001). Patients who regained functional ROM in all affected joints reported significantly less disability (p < 0.001) and higher QoL (p < 0.001) compared to patients without functional ROM. CONCLUSIONS: Contracture release surgery performed in an LMIC significantly improved functional ROM, disability and QoL. Results showed that regaining a functional joint is associated with less disability and higher QoL.

Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery for peritoneal carcinomatosis in an experimental model.

BACKGROUND: The combination of cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the treatment of choice for selected patients with peritoneal carcinomatosis (PC) of colorectal origin. However, it remains to be proven whether the addition of HIPEC to CS is essential for the reported survival benefit. METHODS: Sixty WAG/Rij rats were inoculated intraperitoneally with the rat colonic carcinoma cell line CC-531. Animals were randomized into three treatment groups: CS alone, CS followed by HIPEC (mitomycin 15 mg/m(2) ) and CS followed by HIPEC (mitomycin 35 mg/m(2) ). Survival was the primary outcome parameter. RESULTS: The median survival of rats treated with CS alone was 43 days. Rats receiving HIPEC 15 mg/m(2) and HIPEC 35 mg/m(2) both had a significantly longer median survival of 75 days (P = 0·003) and 97 days (P < 0·001) respectively. Rats receiving HIPEC showed a significantly lower tumour load at autopsy compared with rats treated with CS alone. CONCLUSION: A combination of CS and HIPEC results in longer survival than CS alone in rats with PC of colorectal origin.

Neoadjuvant radiochemotherapy increases matrix metalloproteinase activity in healthy tissue in esophageal cancer patients.

BACKGROUND: Neoadjuvant radiochemotherapy (RCT) is thought to result in a favorable oncological outcome in esophageal cancer patients. Unfortunately, it also implies that adjacent healthy tissue is preoperatively exposed to the potential damaging influence of RCT. Here, the impact of preoperative RCT on matrix metalloproteinase (MMP) expression in healthy esophageal tissue aligned with the tumor at the time of surgery is examined. PATIENTS AND METHODS: 23 patients participating in a clinical trial were randomized to either the control (n = 12) or the neoadjuvant RCT group (n = 11). In the latter group, surgery was performed 5 weeks after the last course of RCT. Full-thickness biopsies were taken from healthy esophageal tissue at the proximal border of the resection specimen and more distally next to the tumor. MMP-2 and MMP-9 activity in the samples was assessed by quantitative gelatin zymography and immunohistochemistry. RESULTS: In the proximal segment, the activities of the MMP-9-dimer (135 kDa) and proMMP-9 (92 kDa) were significantly increased in the RCT group as compared with the control group: 28.5 versus 3.0 (p = 0.025) and 87.7 versus 13.0 (p = 0.015) arbitrary units for 135 kDa and 92 kDa, respectively. In the distal part, RCT resulted in a significant increase of proMMP-2 (72 kDa: 35.8 versus 17.8, p = 0.005) and proMMP-9 (81.2 versus 23.3, p = 0.03). CONCLUSION: In esophageal cancer patients, neoadjuvant RCT results in increased MMP expression in healthy esophageal tissue as measured at the time of surgery. Since increased levels of MMPs are associated with severe postoperative complications including anastomotic leakage this finding necessitates further clinical research.

Radioimmunotherapy prevents local recurrence of colonic cancer in an experimental model.

BACKGROUND: Radioimmunotherapy (RIT) is suitable for the treatment of microscopic residual disease and might therefore have an adjuvant role after colonic cancer surgery. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of 2 x 10(6) CC531 tumour cells. The biodistribution of (111)In-labelled MG1 monoclonal antibody was assessed after intraperitoneal administration. The therapeutic efficacy of (177)Lu-labelled MG1 (74 MBq per rat), administered on the day of surgery (D0, n = 13) or 5 days later (D5, n = 13), was compared with that of carrier only (n = 13). The primary endpoint was perianastomotic tumour growth 28 days after surgery. RESULTS: (111)In-labelled MG1 preferentially accumulated in perianastomotic CC531 tumours. RIT resulted in a transient reduction in bodyweight in both treatment groups compared with controls, but there were no other signs of clinical discomfort. No macroscopic or microscopic perianastomotic tumour growth was found in eight of 11 animals in the D0 group and 11 of 13 in the D5 group, whereas 11 of 13 controls had macroscopic tumour (P = 0.011 and P = 0.001 respectively). CONCLUSION: This study suggests that RIT may be an effective adjuvant treatment for preventing local recurrence after resection of colonic cancer.

Recombinant human deoxyribonuclease for the treatment of acute asthma in children.

BACKGROUND: Airway obstruction in acute asthma is the result of airway smooth muscle contraction, inflammation and mucus plugging. Case reports suggest that mucolytic therapy might be beneficial in acute asthma. The aim of this study was to determine the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) in addition to standard treatment at the emergency department in children with an asthma exacerbation. METHODS: In a multicentre randomised double-blind controlled clinical trial, 121 children brought to the emergency room for a moderate to severe asthma exacerbation were randomly assigned to receive either a single dose of 5 mg nebulised rhDNase or placebo following the second dose of bronchodilators. An asthma score (scale 5-15) was assessed at baseline and at 1, 2, 6, 12 and 24 h. The primary outcome variable was the asthma score 1 h after the study medication. RESULTS: One hour after the study medication the asthma score in the rhDNase group showed an adjusted mean decrease from baseline of 1.0 (95% CI 0.5 to 1.6) points compared with 0.7 (95% CI 0.3 to 1.2) points in the placebo group (mean difference 0.4 (95% CI -0.2 to 1.0) points; p = 0.23). The asthma score over the study period of 24 h also did not differ significantly between the rhDNase and placebo group (mean difference 0.2 (95% CI -0.3 to 0.7) points, p = 0.40). The duration of oxygen supplementation and number of bronchodilator treatments in the first 24 h were similar in both groups. CONCLUSION: Adding a single dose of nebulised rhDNase to standard treatment in the emergency room has no beneficial effects in children with moderate to severe acute asthma.

The effects of adjuvant experimental radioimmunotherapy and hyperthermic intraperitoneal chemotherapy on intestinal and abdominal healing after cytoreductive surgery for peritoneal carcinomatosis in the rat.

BACKGROUND: Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) results in limited survival benefit and high morbidity and mortality rates in patients with peritoneal carcinomatosis (PC). Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound healing after CS need to be determined. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to CS and anastomotic construction only or followed by RIT or HIPEC. RIT consisted of 74 MBq (177)lutetium-labeled anti-CC531 antibody MG1. HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C during 60 minutes. Anastomotic and abdominal wall strength measurements were performed 3 and 5 days after surgery. RESULTS: At day 5, bursting pressure in ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT group, was lower (P < .01) than in the CS group. In the CS group, the colonic bursting site was more often outside the true anastomotic area (8 of 12 animals) than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall strength in the CS + HIPEC group was significantly (P < .01) lower, at both measuring points, than that in both the CS group and the CS + RIT group. There was no difference between the latter. CONCLUSION: As adjuvant to CS, HIPEC showed a decrease in anastomotic and abdominal wall wound strength in a model of PC of CRC, whereas RIT did not.

Plasminogen activator, but not systemic antibiotic therapy, prevents abscess formation in an experimental model of secondary peritonitis.

BACKGROUND: Intra-abdominal abscesses are sources of recurrent or ongoing abdominal sepsis. They are an important target for prevention and treatment during or after surgical treatment of peritonitis. Experimental data suggest that fibrinolytic therapy may be effective when antibiotics are not. METHODS: Peritonitis was induced via intra-abdominal injection of a faeces and bacteria mixture in male Wistar rats. Surgical debridement was performed after 1 h. Next to untreated controls, animals were treated with antibiotics (ceftriaxone plus metronidazole), recombinant tissue plasminogen activator (rtPA) or both. Abdominal fluid samples were taken at 24, 72 and 120 h for interleukin 6, interleukin 10 and tumour necrosis factor alpha measurements and cell counts. After 5 days the abdomen was inspected for the presence of abscesses. RESULTS: Antibiotics did not significantly affect abscess formation. However, giving rtPA significantly reduced the number of rats with abscesses and the abscess load per rat, both in the absence and presence of concomitant antibiotic therapy. No adverse side-effects were observed and no meaningful differences in the local inflammatory response were found. CONCLUSION: In this rat model, rtPA consistently reduced abscess formation after surgical treatment of secondary peritonitis. It therefore represents a promising adjuvant to conventional therapy.

Mechanical dyssynchrony by 3D echo correlates with acute haemodynamic response to biventricular pacing in heart failure patients.

AIMS: One-third of dilated cardiomyopathy patients receiving a biventricular pacing-device do not respond to this form of therapy. Therefore, the utility of mechanical dyssynchrony by real-time 3D echocardiography (RT3DE) for predicting systolic response to biventricular pacing, of which maximal rate of pressure rise (dP/dt(max)) served as the gold-standard, was evaluated. METHODS AND RESULTS: Seventeen consecutive heart failure patients (aged 64 +/- 10 years, 8 male, 6 ischaemic cardiomyopathy, mean QRS duration 136 +/- 32 ms) underwent RT3DE and biventricular pacing. Post-processing software provided data of global left ventricular (LV) function and the systolic dyssynchrony index of 17 LV segments (SDI(17), %) for mechanical dyssynchrony. During biventricular pacing, percentual change in dP/dt(max) compared to the non-pacing mode, DeltadP/dt(max) was measured invasively with conductance catheters. LV ejection fraction was 31 +/- 10%, SDI(17) was 10.2 +/- 4.2% and percentual DeltadP/dt(max) during biventricular pacing was 14.5 +/- 12.4. A significant correlation (r = 0.729, P = 0.001) was found between SDI(17) and percentual DeltadP/dt(max), and between QRS duration and percentual DeltadP/dt(max) (r = 0.721, P = 0.001). CONCLUSION: The present study suggests that mechanical dyssynchrony measured by RT3DE shows a good correlation with invasively determined acute haemodynamic response to biventricular pacing in patients with symptomatic dilated cardiomyopathy. Future studies are needed to further define the clinical utility of RT3DE in identifying patients who are most likely to respond to cardiac resynchronization therapy.

[Auto-injection with epinephrine in the finger of a 5-year-old child]. / Auto-injectie met epinefrine in de vinger bij een 5-jarig kind.

A 5-year-old boy with food allergies complicated by anaphylactic reactions with dyspnoea and angioedema had been prescribed an autoinjector with epinephrine (0.15 mg) so that his parents could treat him at home if necessary. The patient accidentally injected himself in a finger, which likely makes him the youngest patient to receive an epinephrine auto-injection reported to date. Treatment consisted of phentolamine (0.15 mg in 0.5 ml normal saline) injected subcutaneously at the site of accidental injection; the dose and volume were not adapted according to the age and body weight of the patient as only a local effect was intended. Finger circulation was restored within 20 minutes. Headache, nausea and vomiting were observed after 30 minutes and were most likely a systemic side effect of phentolamine. No other complications occurred. The patient recovered fully and was discharged the following morning. Intramuscular epinephrine autoinjection is standard therapy for severe anaphylactic reactions. The epinephrine autoinjector was introduced in 1980. As allergy and anaphylaxis become more common, increasing numbers of autoinjectors are prescribed, and it is likely that the number of accidental digital autoinjections will also increase. These digits are then at risk of ischaemic necrosis. There is no consensus on therapeutic strategies in such cases. Phentolamine administration appears to be an effective intervention. However, several recent studies have shown that epinephrine may be used safely in hand surgery, which suggests that accidental digital epinephrine autoinjection may not always require immediate treatment.

A comparison between radioimmunotherapy and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis of colonic origin in rats.

BACKGROUND: Cytoreductive surgery (CS) followed by heated intraperitoneal chemotherapy (HIPEC) is considered the standard of care for the treatment of patients with peritoneal carcinomatosis (PC) of colorectal cancer (CRC). These surgical procedures result in a median survival of 2 years at the cost of considerable morbidity and mortality. In preclinical studies, radioimmunotherapy (RIT) improved survival after CS in a model of induced PC of colonic origin. In the present studies we aimed to compare the efficacy and toxicity of CS followed by adjuvant RIT in experimental PC to the standard of care, HIPEC. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in three groups of Wag/Rij rats. Treatment comprised CS only, CS + RIT or CS + HIPEC, immediately after surgery. RIT consisted of intraperitoneal administration of 74 MBq Lutetium-177 labeled MG1. HIPEC was performed by a closed abdomen perfusion technique using mitomycin C (16 mg/L during 60 minutes). The primary endpoint was survival. RESULTS: CS only or combined with RIT was well tolerated. Rats receiving CS + HIPEC were lethargic, suffered from diarrhea, and lost significantly more weight in the first postoperative week. Median survival of rats treated with CS + RIT was significantly longer than after CS alone (97 and 57 days, respectively, P < .004), whereas survival after CS + HIPEC or CS alone were not significantly different (76 and 57 days, respectively, P = .17). CONCLUSION: Survival after CS was significantly improved by RIT with Lutetium-177-MG1 in rats with PC of colorectal origin. Adjuvant HIPEC did not improve survival and was more toxic than adjuvant RIT.

Rhizobium Lipooligosaccharides Rescue a Carrot Somatic Embryo Mutant.

At a nonpermissive temperature, somatic embryos of the temperature-sensitive (ts) carrot cell mutant ts11 only proceed beyond the globular embryo stage in the presence of medium conditioned by wild-type embryos. The causative component in the conditioned medium has previously been identified as a 32-kD acidic endochitinase. In search of a function for this enzyme in plant embryogenesis, several compounds that contain oligomers of N-acetylglucosamine were tested for their ability to promote ts11 embryo formation. Of these compounds, only the Rhizobium lipooligosaccharides or nodulation (Nod) factors were found to be effective in rescuing the formation of ts11 embryos. These results suggest that N-acetylglucosamine-containing lipooligosaccharides from bacterial origin can mimic the effect of the carrot endochitinase. This endochitinase may therefore be involved in the generation of plant analogs of the Rhizobium Nod factors.