Abdominal pain in patients with inflammatory bowel disease in remission: A prospective study on contributing factors.

BACKGROUND: Abdominal pain is highly prevalent in patients with inflammatory bowel disease (IBD) in remission, but the aetiology is incompletely understood. AIM: To investigate the association of clinical, lifestyle and psychosocial factors with abdominal pain in patients with IBD in remission. METHODS: We performed a prospective multicentre study enrolling consecutive patients with IBD. Data were collected between 1 January 2020 and 1 July 2021, using myIBDcoach, an established remote monitoring platform for IBD. Chronic abdominal pain in IBD in remission (IBDremissionPain+) was defined as abdominal pain score ≥3 (0-10 NRS) on ≥1/3 of all assessments, combined with faecal calprotectin <150 µg/g in 90 days around periodic assessments. Disease activity, lifestyle and psychosocial factors were assessed every 1-3 months during 18 months. Using linear mixed models, the association of these factors with abdominal pain over time was analysed. RESULTS: We included 559 patients, of whom 429 (76.7%) remained in biochemical remission. Of these, 198 (46.2%) fulfilled the criteria for chronic abdominal pain. IBDremissionPain+ patients were characterised by female sex, younger age, higher BMI, and shorter disease duration. They reported more often or higher levels of stress, fatigue, depressive and anxiety symptoms, and life events (all p < 0.001). In the multivariable analysis, sex, disease entity, fatigue, depressive symptoms and life events were associated with abdominal pain over time (all p < 0.05). CONCLUSION: In this cohort of patients with IBD in remission, abdominal pain was common and associated with psychosocial factors. A more holistic treatment approach for patients with IBD suffering from abdominal pain may improve quality of care and subjective wellbeing.

Combined transverse thoracis plane and pectoral nerve blocks for breast surgery under sedation.

The pectoral nerves 2 (pecs 2) block is widely used as adjunct to general anaesthesia for breast surgery. There are a few case reports and a single case series that describe regional anaesthesia as a single technique or supplemented by light to moderate sedation. Here we describe the management of a 91-year-old ASA physical status 4 patient who presented with a T4 breast malignancy. She was considered unfit for general anaesthesia due to significant valvular heart disease. A wide local excision was successfully performed under a pecs 2 block and a transverse thoracis plane block, supplemented with light sedation. We consider this technique to be a good option for selected patients who are considered unfit for general anaesthesia.

Continuous erector spinae plane block versus thoracic epidural analgesia in video-assisted thoracic surgery: a study protocol for a prospective randomized open label non-inferiority trial.

BACKGROUND: Thoracic epidural analgesia is considered the gold standard for pain relief in video-assisted thoracoscopic surgery. This neuraxial technique blocks pain sensation by injecting a local anesthetic agent in the epidural space near the spinal cord to block spinal nerve roots. Recently, the erector spinae plane block has been introduced as a practical alternative to the thoracic epidural. This interfascial regional anesthesia technique interrupts pain sensation by injecting a local anesthetic agent in between the muscular layers of the thoracic wall. Several case series and three RCTs described it as an effective pain management technique in video-assisted thoracoscopic surgery (Scimia et al., Reg Anesth Pain Med 42:537, 2017; Adhikary et al., Indian J Anaesth 62:75-8, 2018; Kim, A randomized controlled trial comparing continuous erector spinae plane block with thoracic epidural analgesia for postoperative pain management in video-assisted thoracic surgery, n.d.; Yao et al., J Clin Anesth 63:109783, 2020; Ciftci et al., J Cardiothorac Vasc Anesth 34:444-9, 2020). The objective of this study is to test the hypothesis that a continuous erector spinae plane block incorporated into an opioid-based systemic multimodal analgesia regimen is non-inferior in terms of the quality of postoperative recovery compared to continuous thoracic epidural local anesthetic-opioid analgesia in patients undergoing elective unilateral video-assisted thoracoscopic surgery. METHODS: This is a prospective randomized open label non-inferiority trial. A total of 90 adult patients undergoing video-assisted thoracoscopic surgery will be randomized 1:1 to receive pain treatment with either (1) continuous erector spinae plane block plus intravenous patient-controlled analgesia with piritramide (study group) or (2) continuous thoracic epidural analgesia with a local anesthetic-opioid infusate (control group). All patients will receive additional systemic multimodal analgesia with paracetamol and non-steroidal anti-inflammatory drugs. The primary endpoint is the quality of recovery as measured by the Quality of Recovery-15 score. Secondary endpoints are postoperative pain as Numerical Rating Score scores, length of hospital stay, failure of analgesic technique, postoperative morphine-equivalent consumption, itching, nausea and vomiting, total operative time, complications related to surgery, perioperative hypotension, complications related to pain treatment, duration of bladder catheterization, and time of first assisted mobilization > 20 m and of mobilization to sitting in a chair. DISCUSSION: This randomized controlled trial aims to confirm whether continuous erector spinae plane block plus patient-controlled opioid analgesia can equal the analgesic effect of a thoracic epidural local anesthetic-opioid infusion in patients undergoing video-assisted thoracoscopic surgery. TRIAL REGISTRATION: Netherlands Trial Register NL6433 . Registered on 1 March 2018. This trial was prospectively registered.

Transient thyroiditis after parathyroidectomy for tertiary hyperparathyroidism.

Thyrotoxicosis due to thyroiditis is predominantly caused by infection or autoimmune disease of the thyroid. Parathyroid surgery however, is a lesser known cause of thyroiditis, due to thyroid manipulation. We treated a patient who developed transient symptomatic thyroiditis following parathyroid surgery for tertiary hyperparathyroidism. Therefore, the differential diagnosis for patients with symptoms after parathyroid surgery should include transient thyroiditis.

A standardized protocol for perioperative antibiotic prophylaxis is associated with improvement of timing and reduction of costs.

The objectives of this study were to implement a uniform guideline for perioperative antibiotic prophylaxis (PAP) and to measure the impact on timing and costs of PAP. The effects of implementation of the new guideline describing the application of PAP were measured by comparing the choice of agents and their timing in a random sample of procedures before and after implementation. Before the intervention, 153 procedures from different specialties were observed; eight different antibiotics in different dosages were used and in 20% of the procedures, PAP was given after the incision. Two months after the intervention, 147 procedures were observed; three different antibiotics were given and all were used in the correct dosage. There was a significant reduction of administration of PAP after the incision from 20 to 7% (P=0.002). Besides the quality improvements, the modified PAP protocol resulted in a net annual savings of at least 112,000 US dollars. This study shows that the implementation of a uniform, simple and clear protocol for PAP is associated with improved dosing and timing. The costs of PAP were also reduced.

Craniovascular selectivity of eletriptan and sumatriptan in human isolated blood vessels.

BACKGROUND: Eletriptan is a 5-HT(1B/1D) receptor agonist with proven efficacy in the acute treatment of migraine. OBJECTIVE: To assess the craniovascular selectivity of eletriptan and sumatriptan in blood vessels predictive of therapeutic efficacy (human middle meningeal artery) and adverse coronary side effects (human coronary artery and human saphenous vein). METHOD: The authors obtained coronary artery from organ donors (n = 9), middle meningeal artery from patients (n = 11) undergoing craniotomy, and saphenous vein from patients (n = 9) undergoing coronary bypass surgery. Concentration-response curves to eletriptan and sumatriptan were constructed to obtain measurements of efficacy (maximum contraction, E(max)) and potency (concentration eliciting 50% of E(max), EC(50)). The contraction that is likely to be induced at the maximal free plasma concentration (C(max)) was determined by calculating C(max)/EC(50) ratios and by interpolation of the concentration-response curves. RESULTS: Eletriptan and sumatriptan induced concentration-dependent contractions of meningeal artery, coronary artery, and saphenous vein. Eletriptan was less potent than sumatriptan in coronary artery, whereas both compounds had similar potency in meningeal artery and saphenous vein. However, the potency of eletriptan and sumatriptan was higher in meningeal artery than in coronary artery (86-fold for eletriptan and 30-fold for sumatriptan) or saphenous vein (66- and 25-fold). The efficacy of eletriptan and sumatriptan was similar within tissues. The predicted contraction by eletriptan (40 mg and 80 mg) and sumatriptan (100 mg) at free C(max) observed in clinical trials was similar in meningeal artery, whereas in coronary artery and saphenous vein it was lower for 40 mg eletriptan than for sumatriptan. CONCLUSIONS: At therapeutic concentrations both eletriptan and sumatriptan contract middle meningeal artery more than coronary artery. This suggests that in patients with healthy coronary arteries, they have a limited propensity to cause adverse coronary side effects. However, both drugs remain contraindicated in patients with coronary artery disease.

Pharmacological analysis of contractile effects of eletriptan and sumatriptan on human isolated blood vessels.

Eletriptan, a second-generation triptan with high affinity for 5-HT(1B/1D) receptors, is highly effective in migraine, with or without aura. We compared the effects of eletriptan and sumatriptan on the human isolated middle meningeal and coronary arteries and saphenous vein, used as models for therapeutic efficacy and potential side effects, and have investigated the role of 5-HT(1B/1D) receptors in contractions induced by these triptans. Concentration-response curves to eletriptan and sumatriptan were constructed in the absence or presence of a selective 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-4-(4-py rid yl) benzamide (GR125743). All three blood vessels constricted in response to eletriptan and sumatriptan, but the middle meningeal artery relaxed following the highest concentration (100 microM) of eletriptan. In the middle meningeal artery, GR125743 antagonised the contractions induced by both eletriptan (pEC(50): 7.34+/-0.13) and sumatriptan (pEC(50): 6.91+/-0.17) to a similar degree (pA(2): 8. 81+/-0.17 and 8.64+/-0.21, respectively). In the human coronary artery and saphenous vein, sumatriptan-induced contractions (pEC(50): 6.24+/-0.14 and 6.19+/-0.12, respectively) were also potently antagonised by GR125743 (pA(2): 8.18+/-0.27 and 8.34+/-0.12, respectively). The eletriptan-induced contractions of the human saphenous vein (pEC(50): 6.09+/-0.13) were antagonised less effectively by GR125743 (pK(B): 7.73+/-0.18), and those of the human coronary artery (pEC(50): 5.54+/-0.22) remained unaffected by GR125743 up to a concentration of 100 nM. These results suggest that (i) based on the differences in pEC(50) values, the cranioselectivity of eletriptan (63-fold) is higher than that of sumatriptan (5-fold) in coronary artery, (ii) the contractile effects of sumatriptan and eletriptan (lower concentrations) in the three blood vessels are mediated via the 5-HT(1B) receptor, and (iii) additional mechanisms seem to be involved in coronary artery and saphenous vein contractions and middle meningeal artery relaxation following high concentrations of eletriptan.

Biotechnology stock prices before public announcements: evidence of insider trading?

BACKGROUND: Unique financial challenges faced by biotechnology companies developing therapeutics have contributed to the creation of a highly sensitive market, where stock prices are capable of great fluctuation. The potential for significant financial reward and the nature of the scientific review process make this industry susceptible to illegal share trading on nonpublic information. We examined stock prices of biotechnology products before and after announcement of Phase III clinical trial and Food and Drug Administration (FDA) Advisory Panel results for indirect evidence of insider trading. METHODS: Biotechnology stock prices were recorded for 98 products undergoing Phase III clinical trials and 49 products undergoing FDA Advisory Panel review between 1990 and 1998. Prices were recorded for 120 consecutive trading days before and after public announcement of these two events. We compared the average change in stock price of successful products ('winners') with unsuccessful products ('losers') before the public announcement of results for both critical events. RESULTS: The difference between average stock price change from 120 to 3 days before public announcement of results of Phase III clinical trial winners (+27%) and losers (-4%) was highly significant (P = 0.0007). A similar but non-significant difference was observed between the average stock price of winning (+27%) and losing products (+13%) before FDA Advisory Panel review announcements (P = 0.25). CONCLUSIONS: Our results provide indirect evidence that insider trading may be common in the biotechnology industry. Clinical investigators may wish to consider this issue before participating in any equity position in the biotechnology industry, especially if they are going to perform research for those companies.

A new surgical complication related to corticosteroids in a patient with Henoch-Schönlein purpura.

In this case presentation of a 4-year-old boy with histopathologically proven Henoch-Schönlein purpura the authors report a surgical complication that occurred under corticosteroids; this had not been described previously. Relief of abdominal pain was dramatic and the hematemesis disappeared, but an entero-enteral fistula and abscess developed without any sign of peritonitis. Therefore, when corticosteroids are used for symptomatic relief, and intermittent bowel obstruction persists during their use, surgical complications should be suspected. In such cases, intermittent small bowel obstruction might be the only sign of a grave surgical complication.

[Surgical case report: diagnosis of associated abdominal lesions in penetrating injuries of the lower chest]. / Chirurgische casuïstiek: diagnose van de geassocieerde abdominale letsels bij de laagthoracaal penetrerende wonde.

We discuss the way to diagnose intra-abdominal lesions caused by penetrating objects in the lower thorax. Let us call these wounds penetrating wounds. Two kinds of penetrating wounds are considered: 1. shotwounds; 2. knifewounds. 1. In shotwounds of the lower thorax there is not any non-surgical method available to find the associated intra-abdominal lesions. In these cases the results of: 1. physical examination; 2. local wound exploration; 3. echography of the abdomen and 4. peritoneal lavage cannot be trusted. Only laparotomy can show us if any associated lesion in the abdomen exists. 2. For knifewounds we can make almost the same remarks: 1. physical examination; 2. local exploration of the lesion; 3. echography of the abdomen are not to be considered as good diagnostic tools to find the associated intra-abdominal wounds. However in this situation the results of peritoneal lavage are to be trusted. Without omitting a 24 h observation of the patient the most rational criteria for a positive peritoneal lavage are red blood cell greater than 100.000/mm3; white blood cell greater than 500/mm3.

[Truncal vagotomy with pyloroplasty as a routine procedure in perforated duodenal ulcer]. / Trunculaire vagotomie met pyloroplastie als routine ingreep voor het geperforeerd ulcus bulbi.

Truncal vagotomy and pyloroplasty for perforated duodenal ulcer. A retrospective study of 220 patients operated upon between 1959 and 1982 for perforated duodenal ulcer by truncal vagotomy and pyloroplasty shows that this operation can be performed as safely as suture plication, even in the critically ill patient. The advantages of this procedure as the routine treatment of perforated duodenal ulcer are discussed.

A 28-year-old pregnant woman with a very rare cause of jugular vein thrombosis.

During pregnancy, venous thrombosis of the distal extremities is not uncommon. However, thrombosis in the upper part of the body, such as jugular vein thrombosis, is rare. If underlying causes such as ovarian hyperstimulation syndrome (OHSS) or septic thrombophlebitis (Lemierre's syndrome) are excluded, a serous borderline ovary tumour (BOT) must be considered and MR imaging of the abdomen could be performed to find a primary tumour mass.

The amino acid sequence of crystalline sheets: a proteolytic fragment of the major head protein (gP23) of bacteriophage T4.

A peptide, obtained from T4 phage major capsid protein gP23 by chymotryptic digestion, has been shown to form two types of crystalline sheets, hexagonal and rectangular. The sheet peptide was subjected to conventional sequencing work. Together with the DNA sequence of gene 23, the results showed that the peptide consisted of 155 amino acids, located from 295 to 449 in the nascent gP23 and from 230 to 384 in the matured gP23.

Further studies on a rapid protein hydrolysis method.

Proteins may be hydrolysed for amino-acid analysis by a trifluoroacetic acid/HCl mixture at 166 degrees C for 25 or 50 min. A number of uncommon amino acids and certain amino-acid derivatives were subjected to this procedure and their decomposition rates were determined.

A new polyacrylamide gel electrophoresis system. Separation of small peptides and proteins in a volatile buffer system after modification with a strongly acidic fluorescent NH2 reagent.

Polyacrylamide gel electrophoresis is one of the most efficient methods for separation and identification of proteins. A new gel electrophoresis system has been developed in order to facilitate both separation and extraction of peptides and proteins ranging in molecular weight from approximately 200 up to 100 000. This system involves the use of a volatile buffer, triethylamine/formic acid pH 11.7, and a reaction with a covalently binding NH2 reagent, 1,3,6-trisulfonylpyrene 8-isothiocyanate. Under these conditions, the addition of strongly negative charges to proteins is achieved which allows migration according to molecular weight. The modified proteins being fluorescent require neither fixation nor staining for their detection. This is an absolute requirement especially when dealing with small peptides. An additional advantage of such a modification is the increased solubility of the proteins which makes their extraction easier and more efficient. THe extracted proteins are easily freed from salts and other small molecules simply by evaporation and they are readily available for sequencing analysis using Edman degradation, carboxypeptidase digestion or amino acid analysis.

The potential anti-migraine compound SB-220453 does not contract human isolated blood vessels or myocardium; a comparison with sumatriptan.

The mechanistically novel benzopyran derivative SB-220453, which is undergoing clinical evaluation in migraine, exhibits a high affinity for a selective, but not yet characterized, binding site in the human brain. It inhibits nitric oxide release and cerebral vasodilatation following cortical spreading depression as well as carotid vasodilatation induced by trigeminal nerve stimulation in the cat. The aim of our study was to investigate the contractile properties of SB-220453 on a number of human isolated blood vessels (coronary artery, saphenous vein and middle meningeal artery) as well as atrial and ventricular cardiac trabeculae. While sumatriptan induced marked contractions in three blood vessels investigated, SB-220453 was devoid of any effect. In atrial and ventricular cardiac trabeculae, neither SB-220453 nor sumatriptan displayed a positive or negative inotropic effect. Since SB-220453 did not contract the middle meningeal artery, we conclude that potential anti-migraine effects are not mediated via a direct cerebral vasoconstriction. The lack of activity of SB-220453 in coronary artery, saphenous vein and cardiac trabeculae demonstrates that the compound is unlikely to cause adverse cardiac side-effects.