Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Effects of using the simplified airway risk index vs usual airway assessment on unanticipated difficult tracheal intubation - a cluster randomized trial with 64,273 participants.

BACKGROUND: Unanticipated difficult intubation remains a challenge in anaesthesia. The Simplified Airway Risk Index (SARI) is a multivariable risk model consisting of seven independent risk factors for difficult intubation. Our aim was to compare preoperative airway assessment based on the SARI with usual airway assessment. METHODS: From 01.10.2012 to 31.12.2013, 28 departments were cluster-randomized to apply the SARI model or usual airway assessment. The SARI group implemented the SARI model. The Non-SARI group continued usual airway assessment, thus reflecting a group of anaesthetists' heterogeneous individual airway assessments. Preoperative prediction of difficult intubation and actual intubation difficulties were registered in the Danish Anaesthesia Database for both groups. Patients who were preoperatively scheduled for intubation by advanced techniques (e.g. video laryngoscopy; flexible optic scope) were excluded from the primary analysis. Primary outcomes were the proportions of unanticipated difficult and unanticipated easy intubation. RESULTS: A total of 26 departments (15 SARI and 11 Non-SARI) and 64 273 participants were included. In the primary analyses 29 209 SARI and 30 305 Non-SARI participants were included.In SARI departments 2.4% (696) of the participants had an unanticipated difficult intubation vs 2.4% (723) in Non-SARI departments. Odds ratio (OR) adjusted for design variables was 1.03 (95% CI: 0.77-1.38). The proportion of unanticipated easy intubation was 1.42% (415) in SARI departments vs 1.00% (302) in Non-SARI departments. Adjusted OR was 1.26 (0.68-2.34). CONCLUSIONS: Using the SARI compared with usual airway assessment we detected no statistical significant changes in unanticipated difficult- or easy intubations. CLINICAL TRIAL REGISTRATION: NCT01718561.

Relocation of patients after cardiac surgery: is it worth the effort?

BACKGROUND: Fast-track protocols may facilitate early patient discharge from the site of surgery through the implementation of more expedient pathways. However, costs may merely be shifted towards other parts of the health care system. We aimed to investigate the consequence of patient transfers on overall hospitalisation, follow-up and readmission rate after cardiac surgery. METHODS: A single-centre descriptive cohort study using prospectively entered registry data. The study included 4,515 patients who underwent cardiac surgery at Aarhus University Hospital during the period 1 April 2006 to 31 December 2012. Patients were grouped and analysed based on type of discharge: Directly from site of surgery or after transfer to a regional hospital. The cohort was obtained from the Western Denmark Heart Registry and matched to the Danish National Hospital Register. RESULTS: Median overall length of stay was 9 days (7.0;14.4). Transferred patients had longer length of stay, median difference of 2.0 days, p < 0.001. Time to first outpatient consultation was 41(30;58) days in transferred patients vs. 45(29;74) days, p < 0.001. 18.6% was readmitted within 30 days. Mean time to readmission was 18.4 ± 6.4 days. Median length of readmission was 3(1,6) days. There was no difference in readmissions between groups. Leading cause of readmission was cardiovascular disease with 48%. CONCLUSION: Transfer of patients does not overtly reduce health care costs, but overall LOS and time to first outpatient consultation are substantially longer in patients transferred to secondary hospitals than in patients discharged directly. Readmission rate is high during the month after surgery, but with no difference between groups.

N-terminally and C-terminally truncated forms of glucose-dependent insulinotropic polypeptide are high-affinity competitive antagonists of the human GIP receptor.

BACKGROUND AND PURPOSE: Glucose-dependent insulinotropic polypeptide (GIP) affects lipid, bone and glucose homeostasis. High-affinity ligands for the GIP receptor are needed to elucidate the physiological functions and pharmacological potential of GIP in vivo. GIP(1-30)NH2 is a naturally occurring truncation of GIP(1-42). Here, we have characterized eight N-terminal truncations of human GIP(1-30)NH2 . EXPERIMENTAL APPROACH: COS-7 cells were transiently transfected with human GIP receptors and assessed for cAMP accumulation upon ligand stimulation or competition binding with (125) I-labelled GIP(1-42), GIP(1-30)NH2 , GIP(2-30)NH2 or GIP(3-30)NH2 . KEY RESULTS: GIP(1-30)NH2 displaced (125) I-GIP(1-42) as effectively as GIP(1-42) (Ki 0.75 nM), whereas the eight truncations displayed lower affinities (Ki 2.3-347 nM) with highest affinities for GIP(3-30)NH2 and GIP(5-30)NH2 (5-30)NH2 . Only GIP(1-30)NH2 (Emax 100% of GIP(1-42)) and GIP(2-30)NH2 (Emax 20%) were agonists. GIP(2- to 9-30)NH2 displayed antagonism (IC50 12-450 nM) and Schild plot analyses identified GIP(3-30)NH2 and GIP(5-30)NH2 as competitive antagonists (Ki 15 nM). GIP(3-30) NH2 was a 26-fold more potent antagonist than GIP(3-42). Binding studies with agonist ((125) I-GIP(1-30)NH2 ), partial agonist ((125) I-GIP(2-30)NH2 ) and competitive antagonist ((125) I-GIP(3-30)NH2 ) revealed distinct receptor conformations for these three ligand classes. CONCLUSIONS AND IMPLICATIONS: The N-terminus is crucial for GIP agonist activity. Removal of the C-terminus of the endogenous GIP(3-42) creates another naturally occurring, more potent, antagonist GIP(3-30)NH2 , which like GIP(5-30)NH2 , was a high-affinity competitive antagonist. These peptides may be suitable tools for basic GIP research and future pharmacological interventions.

Species-specific action of (Pro3)GIP - a full agonist at human GIP receptors, but a partial agonist and competitive antagonist at rat and mouse GIP receptors.

BACKGROUND AND PURPOSE: Specific, high potency receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent, insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist, (Pro3)GIP, and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system. EXPERIMENTAL APPROACH: Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation and assayed in competition binding using (125) I-human GIP. Using isolated perfused pancreata both from wild type and GIP receptor-deficient rodents, insulin-releasing, glucagon-releasing and somatostatin-releasing properties in response to species-specific GIP and (Pro3)GIP analogues were evaluated. KEY RESULTS: Human (Pro3)GIP is a full agonist at human GIP receptors with similar efficacy (Emax ) for cAMP production as human GIP, while both rat and mouse(Pro3)GIP were partial agonists on their corresponding receptors. Rodent GIPs are more potent and efficacious at their receptors than human GIP. In perfused pancreata in the presence of 7 mM glucose, both rodent (Pro3)GIP analogues induced modest insulin, glucagon and somatostatin secretion, corresponding to the partial agonist activities observed in cAMP production. CONCLUSIONS AND IMPLICATIONS: When evaluating new compounds, it is important to consider interspecies differences both at the receptor and ligand level. Thus, in rodent models, human GIP is a comparatively weak partial agonist. Human (Pro3)GIP was not an antagonist at human GIP receptors, so there is still a need for a potent antagonist in order to elucidate the physiology of human GIP.

Physical activity enhances metabolic fitness independently of cardiorespiratory fitness in marathon runners.

High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI). Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg) (similar-VO2max). The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max). Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy), improved exercise metabolism (lactate threshold), and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases.

Point-of-Care Clinical Ultrasound for Medical Students.

PURPOSE: Our institution has recently implemented a point-of-care (POC) ultrasound training program, consisting of an e-learning course and systematic practical hands-on training. The aim of this prospective study was to evaluate the learning outcome of this curriculum. MATERIALS AND METHODS: 16 medical students with no previous ultrasound experience comprised the study group. The program covered a combination of 4 well-described point-of-care (POC) ultrasound protocols (focus assessed transthoracic echocardiography, focused assessment with sonography in trauma, lung ultrasound, and dynamic needle tip positioning for ultrasound-guided vascular access) and it consisted of an e-learning course followed by 4 h of practical hands-on training. Practical skills and image quality were tested 3 times during the study: at baseline, after e-learning, and after hands-on training. RESULTS: Practical skills improved for all 4 protocols; after e-learning as well as after hands-on training. The number of students who were able to perform at least one interpretable image of the heart increased from 7 at baseline to 12 after e-learning, p<0.01, and to all 16 students after hands-on-training, p<0.01. The number of students able to cannulate an artificial vessel increased from 3 to 8 after e-learning and to 15 after hands-on training. CONCLUSION: Medical students with no previous ultrasound experience demonstrated a considerable improvement in practical skill after interactive e-learning and 4 h of hands-on training.

Insulin analogues and severe hypoglycaemia in type 1 diabetes.

INTRODUCTION: The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed regimens. METHODS: A questionnaire was posted from six Danish diabetes clinics to 6112 unselected patients with type 1 diabetes and filled in by 3861 patients (63.2%). Primary endpoint was number of episodes of severe hypoglycaemia in the preceding year. Mild hypoglycaemia was also reported. RESULTS: The frequency of severe hypoglycaemic episodes per patient-year in patients receiving long-acting insulin analogues was 1.47±0.18 versus 1.09±0.10 in patients on long-acting human insulin (p=0.01). The frequency of severe hypoglycaemic episodes per patient-year was 1.09±0.11 in patients on short-acting insulin analogues versus 1.26±0.13 in patients on short-acting human insulin (p=0.15), which was statistically significant in an adjusted analysis. CONCLUSIONS: Severe hypoglycaemia is more frequent in patients with type 1 diabetes treated with long-acting insulin analogues. Confounding by indication may be involved. Clinical intervention trials using insulin analogues in patients prone to severe hypoglycaemia are highly needed.

Treatment of acute severe asthma and chronic obstructive pulmonary disease in Danish hospitals. Do national recommendations improve on the quality of the treatment?

Studies have demonstrated suboptimal treatment of acute severe asthma and chronic obstructive pulmonary disease (COPD). We examined the quality of treatment in Denmark and the effect of intervention, by publication of recommendations for standardised treatment. All 70 hospitals in Denmark with emergency facilities participated in a telephone questionnaire, examining treatment behaviours among house officers. The survey was repeated 3 years later, after publication of national recommendations for treatment of acute exacerbations of asthma and COPD. The response rate in both surveys was 100%. An insufficient handling of nebulisers, a huge variation in the delivered dose of bronchodilators and a suboptimal use of corticosteroids was found. A significant trend towards more liberate use of oxygen was seen in both asthma (3.2 l min(-1) versus 4.8 l min(-1), P<0.001) and COPD (1.5 l min(-1) versus 1.9 l min(-1), P = 0.047). Further, a huge difference in treatment behaviours was revealed from this survey The knowledge among house officers of basic principles of treatment was insufficient. Treatment behaviour was only moderately affected by national publication of detailed recommendations for treatment. This study indicates a need for implementing tools for quality control.

A proposal for a practical treatment guideline designed for the initial two-hours of the management of patients with acute severe asthma and COPD using the principles of evidence-based medicine.

We have proposed a clinical treatment guideline for the management of acute, severe asthma and chronic obstructive pulmonarydisease (COPD) using the principles of evidence-based medicine. The content is based upon practical clinical issues in need of consensus. A previous study has shown that this particular area is in serious need of quality control. Based on a strict 2 h time schedule with a unified treatment plan for both asthma and COPD, it is possible to secure for the patients a well-documented medical therapy promoting decision-making and clarification of the patient within this time limit. A summary of the statements is presented in a one-page, user-friendly format in order to cope with the clinician's need of having access to published evidence quickly and easily. A website (www.phanareth.dk or a website provided by Respiratory Medicine) has been established providing regular updates. A strategy for the implementation and the evaluation process has been planned after the publication of this paper. We believe this approach to be an important step towards an increase in the quality of guidelines and also a tool to make "guideline writers" aware of the responsibility of making their recommendations work.

Effect of temperature on parasitism and host-feeding of Trichogramma turkestanica (Hymenoptera: Trichogrammatidae) on Ephestia kuehniella (Lepidoptera: Pyralidae).

The egg parasitoid Trichogramma turkestanica Meyer is being evaluated as a biological control agent against the Mediterranean flour moth, Ephestia kuehniella Zeller, in flour mills. The longevity, parasitism and host-feeding of the parasitoid at four constant temperatures (15-30 degrees C) has been determined in the laboratory. The highest fecundity occurred at intermediate temperatures. The number of host eggs killed by host-feeding per female was highest at the two lower temperatures. A very conservative estimate of host-feeding showed that it accounts for approximately half of the mortality of host eggs at 20 and 25 degrees C and thus could constitute a major mortality factor for the flour moth population.

Neonatal cocaine exposure, activity, and responsivity to cocaine in a rodent model.

This study examined the effects of neonatal cocaine exposure on running wheel activity and subsequent responsivity to cocaine using a rodent model. Subjects were artificially reared from postnatal (PND) days 4-10 via an intragastric cannula. The four treatment groups included two cocaine doses (20 mg/kg/day and 40 mg/kg/day), an artificially reared control and a normally reared suckled control. Subjects were tested at either PND 21 through PND 24 (Experiment 1) or PND 60 through PND 70 (Experiment 2) for 2 consecutive days. Testing consisted of a 30-min habituation period followed by injection of either saline (Day 1) or cocaine (Day 2) and an additional 60-min test session. Neonatal treatment had little effect on baseline activity or activity following saline injection at either age. All subjects showed an activation with cocaine injections, however, the activation was more pronounced in juveniles. Again, neonatal treatment did not interact with response to cocaine. These findings suggest that neonatal cocaine exposure does not alter activity or long-term responsivity to 20 mg/kg cocaine as measured in the running wheel apparatus.

Histopathology of smokeless tobacco lesions in professional baseball players. Associations with different types of tobacco.

We examined 142 biopsy specimens of smokeless tobacco-associated oral mucosal lesions from 133 professional baseball players. Four types of epithelial change were observed in the specimens: hyperparakeratosis, hyperorthokeratosis, pale surface staining, and basal cell hyperplasia. These types of epithelial change were associated with the type of smokeless tobacco used (snuff or chewing tobacco) but not with the duration (years) or amount (hours per day) of use. The thickness of hyperkeratosis in a specimen correlated directly with the amount of smokeless tobacco use. The use of snuff was more frequently associated with development of oral mucosal lesions than was the use of chewing tobacco, and snuff appeared to cause a greater variety and severity of epithelial change than did chewing tobacco.

Choristomas of the oral cavity: a review.

The choristoma is a tumorlike mass of normal cells in an abnormal location. Intraoral choristomas have been reported under a wide variety of names. This comprehensive review of the English-language literature on oral choristomas offers a classification of these lesions, analyzes their clinical and histologic features, and discusses possible pathogeneses and treatment.

Peripheral (extraosseous) calcifying odontogenic cyst. A review of forty-five cases.

The peripheral calcifying odontogenic cyst (PCOC) is a rare lesion. The number of well-documented cases reported in the English-language literature until now is 38. The purpose of the present study is twofold: (1) to report seven new cases of PCOC and (2) to review and analyze the clinical and histomorphologic features of the previously reported cases of PCOC together with those of the present study. Most of the lesions were located in the maxillary and mandibular gingiva or alveolar mucosa anterior to the region of the first molar. Histologically, 66% of the lesions were of the cystic variant and 34% of the solid (neoplastic) variant. The terminology of the lesion and its histogenesis are discussed.

Assessing the influence of reversible disease indicators on survival.

In a randomized clinical trial of the effect of prednisone versus placebo on survival in patients with liver cirrhosis, follow-up visits were scheduled after 3, 6 and 12 months of treatment and thereafter once a year. At each follow-up the prothrombin index, a measure of liver function, was recorded and scored as either low or normal. The interaction between treatment and prothrombin index was analysed using a three-state illness-death model with recovery. The continuous-time Markov process model with constant or piecewise constant intensities suggested by Kay allows inference to proceed even though the status of the disease indicator, here the prothrombin index, is only known at the time of each visit and not between visits. We compare the analysis with the theoretically incorrect, but practically rather common approximation, where the status of the disease indicator is assumed to remain constant from one visit until just before the next. Under this approximation both standard parametric methods and non-parametric approaches developed by Aalen and Johansen are available.

Melanocytic hyperplasia of the oral mucosa.

Lesions that exhibit melanocytic hyperplasia are uncommon in the oral mucosa. They are even more rare than the various morphologic types of nevomelanocytic lesions. This article reports the clinicopathologic features of oral lesions diagnosed as lentigo simplex, junctional lentigo ("jentigo"), atypical melanocytic hyperplasia (melanoma in situ), and melanocanthoma. The proper terminology for these lesions is also discussed.

Oral focal mucinosis.

Oral focal mucinosis (OFM) is an uncommon clinicopathological entity which is considered to be the oral counterpart of cutaneous focal mucinosis and/or cutaneous myxoid cyst. It is comprised of a clinically elevated mass with a histological picture of localized areas of myxomatous connective tissue. The present study adds 15 new cases of OFM to the literature and analyzes their clinical, histological and histochemical features. Most of the lesions were located in the gingiva and alveolar mucosa. The nature of the lesion is unclear and it is suggested that the mucinous accumulation is the result of fibroblastic overproduction of hyaluronic acid.

The retrocuspid papilla of the mandibular lingual gingiva.

The retrocuspid papilla (RCP) is a circumscribed nodule that lies lingual to the mandibular cuspid on the gingival tissue. RCP is observed more frequently in young children and seems to regress or disappear with age. Little information is available in the literature on this entity and there are contradictory reports regarding its histologic features. Histomorphologic analysis of 30 specimens diagnosed as RCP revealed that in most cases (80%) it is composed of loosely-arranged delicate fibrous connective tissue with stellate and multinucleated fibroblasts. Elongation of the rete ridges and/or increased vascularity are also present in a significant number of cases. Stellate and multinucleated fibroblasts are not unique to RCP and they have been described as prominent histologic features in other lesions of skin and mucous membrane. RCP is considered to be a "normal anatomical structure" or an "anatomic variation" of the gingiva. The clinical significance of RCP is that it may simulate pathological gingival conditions from which it must be differentiated.

Hyaline ring granuloma: a distinct oral entity.

Hyaline ring granuloma (HRG) is a distinct oral entity. In this study, 64 cases from the literature are analyzed and two new cases are reported. The lesions could be classified by location as central hyaline ring granuloma (42%) and peripheral hyaline ring granuloma (53%). Radiographically, a radiolucent area irregularly outlined by well-formed trabeculae of bone was found in central HRG, and a poorly defined erosion at the crest of the alveolar ridge was often found in peripheral HRG. Occasionally, the lesion occurred in the connective tissue wall of cysts (5%). The etiology of this condition is controversial, but most lesions were in edentulous areas and most patients had a history of tooth extraction or other trauma. The majority of cases (83%) occurred in the mandible, usually posterior to the premolar. The mean age of patients at diagnosis was 43 years, and the male/female ratio was 1.9:1. Pain was not a symptom, although local discomfort, such as recurrent swelling and tenderness, was noted in many cases. Hyaline rings with giant cell inclusions are the significant features for histopathologic diagnosis. HRG is treated by curettage or surgical excision, care being taken to remove the entire lesion. The removal of a peripheral HRG in an edentulous jaw should be followed by careful smoothing of the bone surface, since the lesion tends to infiltrate and is not well demarcated. Recurrence, probably due to incomplete excision, is uncommon.