Dyspnoea improves following composite repair of giant paraoesophageal hernia.

INTRODUCTION: Paraoesophageal hernias (PEH) are often symptomatic and can lead to life-threatening complications such as volvulus and ischaemia. Dyspnoea is one of the most prevalent symptoms of giant hiatus herniae. The primary outcome of this study is resolution of dyspnoea following composite repair of giant paraoesophageal hernia. Secondary outcomes include complications of surgery, hernia recurrence rates and effect of recurrence on dyspnoea. METHODS: Data were extracted from a prospectively maintained single-surgeon database containing records of all patients undergoing composite repair of paraoesophageal hernia. Patients presenting with dyspnoea who underwent composite laparoscopic repair of giant (>30% of stomach above diaphragm) paraoesophageal hernia between March 2009 and December 2015 were included. RESULTS: Inclusion criteria were met by 154 patients. The mean age at time of surgery was 71.2 years (range 49-93, SD 9.66) with an average BMI of 28 (range 19-38kg/m2, SD 4.1). On average hernia contained 64% of stomach (range 30-100%, SD 20.2). One procedure was converted to laparotomy. Surgery resulted in near complete resolution of dyspnoea (2.6% postoperatively, p<0.001). Recurrence rate was 24% and was not associated with persistent dyspnoea. There was one death and two significant complications. CONCLUSION: Dyspnoea resolves following laparoscopic repair of giant paraoesophageal hernia. The presence of dyspnoea in patients with known large paraoesophageal hernia should be regarded as an indication for referral to a surgical service with expertise in hiatal hernia management.

High incidence of dyspnoea and pulmonary aspiration in giant hiatus hernia: a previously unrecognised cause of dyspnoea.

INTRODUCTION: Dyspnoea is common in patients with giant paraoesophageal hernia (PEH). Pulmonary aspiration has not previously been recognised as a significant contributory factor. Aspiration pneumonia in association with both gastro-oesophageal reflux disease (GORD) and PEH has a high mortality rate. There is debate about routine anti-reflux measures with surgical repair. Reflux aspiration has been examined in a consecutive cohort using scintigraphic scanning and symptoms. METHODS: Reflux aspiration scintigraphy (RASP) results and symptoms were evaluated in consecutive patients with PEH managed in our service between January 2012 and March 2017. RESULTS: PEH was diagnosed in 96 patients. Preoperative reflux pulmonary scanning was performed in 70 patients: 54 were female (77.1%) and the mean age was 68 years (range 49-85). Dyspnoea was the most common symptom (77.1%), and a symptomatic history of aspiration was seen in 18 patients (25.7%). Clinical aspiration was confirmed by RASP in 13 of these cases. Silent RASP aspiration occurred in a further 27 patients without clinical symptoms. RASP was negative in five patients with clinical symptoms of aspiration. No aspiration by either criterion was present in 27 patients. Dysphagia was negatively related to aspiration on RASP (p<0.01), whereas dyspnoea was not (p=0.857). CONCLUSION: GORD, dyspnoea and silent pulmonary aspiration are frequent occurrences in the presence of giant PEH. Subjective aspiration was the most specific and positive predictor of pulmonary aspiration. Dyspnoea in PEH patients may be caused by pulmonary aspiration, cardiac compression and gas trapping. The high rate of pulmonary aspiration in PEH patients may support anti-reflux repair.

Using machine learning techniques to characterize sleep-deprived driving behavior.

OBJECTIVE: Sleep deprivation is known to affect driving behavior and may lead to serious car accidents similar to the effects from e.g., alcohol. In a previous study, we have demonstrated that the use of machine learning techniques allows adequate characterization of abnormal driving behavior after alprazolam and/or alcohol intake. In the present study, we extend this approach to sleep deprivation and test the model for characterization of new interventions. We aimed to classify abnormal driving behavior after sleep deprivation, and, by using a machine learning model, we tested if this model could also pick up abnormal driving behavior resulting from other interventions. METHODS: Data were collected during a previous study, in which 24 subjects were tested after being sleep-deprived and after a well-rested night. Features were calculated from several driving parameters, such as the lateral position, speed of the car, and steering speed. In the present study, we used a gradient boosting model to classify sleep deprivation. The model was validated using a 5-fold cross validation technique. Next, probability scores were used to identify the overlap of driving behavior after sleep deprivation and driving behavior affected by other interventions. In the current study alprazolam, alcohol, and placebo are used to test/validate the approach. RESULTS: The sleep deprivation model detected abnormal driving behavior in the simulator with an accuracy of 77 ± 9%. Abnormal driving behavior after alprazolam, and to a lesser extent also after alcohol intake, showed remarkably similar characteristics to sleep deprivation. The average probability score for alprazolam and alcohol measurements was 0.79, for alcohol 0.63, and for placebo only 0.27 and 0.30, matching the expected relative drowsiness. CONCLUSION: We developed a model detecting abnormal driving induced by sleep deprivation. The model shows the similarities in driving characteristics between sleep deprivation and other interventions, i.e., alcohol and alprazolam. Consequently, our model for sleep deprivation may serve as a next reference point for a driving test battery of newly developed drugs.

The use of machine learning improves the assessment of drug-induced driving behaviour.

RATIONALE: Car-driving performance is negatively affected by the intake of alcohol, tranquillizers, sedatives and sleep deprivation. Although several studies have shown that the standard deviation of the lateral position on the road (SDLP) is sensitive to drug-induced changes in simulated and real driving performance tests, this parameter alone might not fully assess and quantify deviant or unsafe driving. OBJECTIVE: Using machine learning we investigated if including multiple simulator-derived parameters, rather than the SDLP alone would provide a more accurate assessment of the effect of substances affecting driving performance. We specifically analysed the effects of alcohol and alprazolam. METHODS: The data used in the present study were collected during a previous study on driving effects of alcohol and alprazolam in 24 healthy subjects (12 M, 12 F, mean age 26 years, range 20-43 years). Various driving features, such as speed and steering variations, were quantified and the influence of administration of alcohol or alprazolam was assessed to assist in designing a predictive model for abnormal driving behaviour. RESULTS: Adding additional features besides the SDLP increased the model performance for prediction of drug-induced abnormal driving behaviour (from an accuracy of 65 %-83 % after alprazolam intake and from 50 % to 76 % after alcohol ingestion). Driving behaviour influenced by alcohol and alprazolam was characterised by different feature importance, indicating that the two interventions influenced driving behaviour in a different way. CONCLUSION: Machine learning using multiple driving features in addition to the state-of-the-art SDLP improves the assessment of drug-induced abnormal driving behaviour. The created models may facilitate quantitative description of abnormal driving behaviour in the development and application of psychopharmacological medicines. Our models require further validation using similar and unknown interventions.

Body mass index related electrocardiographic findings in healthy young individuals with a normal body mass index.

INTRODUCTION: An increased body mass index (BMI) (>25 kg/m2) is associated with a wide range of electrocardiographic changes. However, the association between electrocardiographic changes and BMI in healthy young individuals with a normal BMI (18.5-25 kg/m2) is unknown. The aim of this study was to evaluate the association between BMI and electrocardiographic parameters. METHODS: Data from 1,290 volunteers aged 18 to 30 years collected at our centre were analysed. Only subjects considered healthy by a physician after review of collected data with a normal BMI and in sinus rhythm were included in the analysis. Subjects with a normal BMI (18.5-25 kg/m2) were divided into BMI quartiles analysis and a backward multivariate regression analysis with a normal BMI as a continuous variable was performed. RESULTS: Mean age was 22.7 ± 3.0 years, mean BMI was 22.0, and 73.4% were male. There were significant differences between the BMI quartiles in terms of maximum P-wave duration, P-wave balance, total P-wave area in lead V1, PR-interval duration, and heart axis. In the multivariate model maximum P-wave duration (standardised coefficient (SC) = +0.112, P < 0.001), P-wave balance in lead V1 (SC = +0.072, P < 0.001), heart axis (SC = -0.164, P < 0.001), and Sokolow-Lyon voltage (SC = -0.097, P < 0.001) were independently associated with BMI. CONCLUSION: Increased BMI was related with discrete electrocardiographic alterations including an increased P-wave duration, increased P-wave balance, a leftward shift of the heart axis, and decreased Sokolow-Lyon voltage on a standard twelve lead electrocardiogram in healthy young individuals with a normal BMI.

A systematic literature review of the human skin microbiome as biomarker for dermatological drug development.

AIMS: To explore the potential of the skin microbiome as biomarker in six dermatological conditions: atopic dermatitis (AD), acne vulgaris (AV), psoriasis vulgaris (PV), hidradenitis suppurativa (HS), seborrhoeic dermatitis/pityriasis capitis (SD/PC) and ulcus cruris (UC). METHODS: A systematic literature review was conducted according to the PRISMA guidelines. Two investigators independently reviewed the included studies and ranked the suitability microbiome implementation for early phase clinical studies in an adapted GRADE method. RESULTS: In total, 841 papers were identified and after screening of titles and abstracts for eligibility we identified 42 manuscripts that could be included in the review. Eleven studies were included for AD, five for AV, 10 for PV, two for HS, four for SD and 10 for UC. For AD and AV, multiple studies report the relationship between the skin microbiome, disease severity and clinical response to treatment. This is currently lacking for the remaining conditions. CONCLUSION: For two indications - AD and AV - there is preliminary evidence to support implementation of the skin microbiome as biomarkers in early phase clinical trials. For PV, UC, SD and HS there is insufficient evidence from the literature. More microbiome-directed prospective studies studying the effect of current treatments on the microbiome with special attention for patient meta-data, sampling methods and analysis methods are needed to draw more substantial conclusions.

A Novel Technique of Paravertebral Thoracic and Preperitoneal Analgesia Enhances Early Recovery After Oesophagectomy.

BACKGROUND: Excellent analgesia following oesophagectomy facilitates patient comfort, early extubation, physiotherapy and mobilisation, reduces post-operative complications and should enhance recovery. Thoracic epidural analgesia (TEA), the gold standard analgesic regimen for this procedure, is often associated with systemic hypotension treated with inotropes or fluid. This may compromise enhanced recovery and be complicated by anastomotic ischaemia or tissue oedema. METHODS: We report a novel analgesic regimen to reduce post-operative inotrope usage. Infusion of ropivicaine via bilateral preperitoneal and right paravertebral catheters was used. Patient-controlled epidural pethidine provided rescue analgesia (WC) (n = 21). A retrospective audit of inotrope requirement, mean pain scores, episodes of respiratory depression and excessive sedation, need for reintubation, reoperation in the first 5 post-operative days, time to mobilisation, time in intensive care, time in hospital and 30-day mortality were measured. These results were compared with those of an earlier patient group who received a thoracic epidural infusion of low-dose local anaesthetic and fentanyl (TEA) (n = 21). RESULTS: Inotrope use was reduced by 29% in the WC group (p = 0.03) and the mean intensive care stay reduced by 2.4 days (p = 0.03), as was reintubation rate (p = 0.01) and early mobilisation (p = 0.03). The pain score was comparable in both groups, and there was no difference in the other outcomes examined. CONCLUSION: The data demonstrated that it was possible to provide excellent post-oesophagectomy analgesia equivalent to thoracic epidural infusions of local anaesthetic with reduction in inotrope requirements, intensive care stay, more rapid mobilisation, facilitating enhanced recovery.

Fundoplication for laryngopharyngeal reflux despite preoperative dysphagia.

INTRODUCTION Fundoplication for laryngopharyngeal disease with oesophageal dysmotility has led to mixed outcomes. In the presence of preoperative dysphagia and oesophageal dysmotility, this procedure has engendered concern in certain regards. METHODS This paper describes a consecutive series of laryngopharyngeal reflux (LPR) patients with a high frequency of dysmotility. Patients were selected for surgery with 24-hour dual channel pH monitoring, oesophageal manometry and standardised reflux scintigraphy. RESULTS Following careful patient selection, 33 patients underwent fundoplication by laparoscopy. Surgery had high efficacy in symptom control and there was no adverse dysphagia. CONCLUSIONS Evidence of proximal reflux can select a group of patients for good results of fundoplication for atypical symptoms.

Medium-term durability of giant hiatus hernia repair without mesh.

Introduction This is the second report on objective review of 100 patients who underwent composite fundoplication-cardiopexy for repair of giant hiatus hernia (GHH) at a median of 24 months following surgery. Outcomes were objective follow-up by endoscopy and quality of life (QoL) by Gastrointestinal Quality of Life Index (GIQLI), modified Visick scores and dysphagia scores. The initial report for this cohort suggested a low objective recurrence rate (9%) and substantial improvements in QoL indices. Methods The rate of hernia recurrence was assessed with Kaplan-Meier analysis and covariates were analysed with the Cox proportional hazards model. Paired t-tests and related samples Wilcoxon signed-rank tests were used to compare QoL scores. Unpaired data were compared with the independent samples t-test and Mann-Whitney U test. Results Objective review was obtained in 97% of the patients. There were five recurrences of hernias that had a vertical height of >2cm from the diaphragmatic hiatus, with three patients requiring reoperation for severe dysphagia. Small recurrences (<2cm) occurred in 20 patients. The median time to recurrence was 40 months (95% confidence interval: 34-46 months). At two years, recurrence of any size had occurred in 24% of cases. At follow-up review (median: 27 months), the mean GIQLI score was 109 (p=0.279), the median modified Visick score was 2 (p=0.954) and the median dysphagia score was 41 (p=0.623). There was no evidence that the GIQLI score (p=0.089), the modified Visick score (p=0.339) or the dysphagia score (p=0.445) changed significantly after recurrence. Conclusions There was a sustained improvement in overall QoL and reflux scores after GHH repair. QoL scores showed persistent improvement in reflux and overall health, even in the subgroup with recurrence. The majority (80%) of recurrences were small and recurrent herniation did not appear to significantly change QoL. The rates of recurrence and QoL are comparable with those for other methods of repair.

Durability of giant hiatus hernia repair in 455 patients over 20 years.

INTRODUCTION: The surgical management of symptomatic giant hiatus hernia (GHH) aims to improve quality of life (QoL) and reduce the risk of life threatening complications. Previous reports are predominantly those with small sample sizes and short follow-up periods. The present study sought to assess a large cohort of patients for recurrence and QoL over a longer time period. METHODS: This was a follow-up study of a prospectively collected database of 455 consecutive patients. Primary repair of GHH was evaluated by endoscopy/barium meal for recurrence and a standardised symptom questionnaire for QoL. Recurrence was assessed for size, elapsed time, oesophagitis and symptoms. RESULTS: Objective and subjective review was achieved in 91.9% and 68.6% of patients. The median age was 69 years (range: 15-93 years) and 64% were female. Laparoscopic repair was completed in 95% (mesh in 6% and Collis gastroplasty in 7%). The 30-day mortality rate was 0.9%. The proportion of patients alive at five and ten years were 90% and 75% respectively. Postoperative QoL scores improved from a mean of 95 to 111 (p<0.01) and were stable over time (112 at 10 years). The overall recurrence rate was 35.6% (149/418) at 42 months; this was 11.5% (48/418) for hernias >2cm and 24.2% (101/418) for <2cm. The rate of new recurrence at 0-1 years was 13.7% (>2cm = 3.4%, <2cm = 10.3%), at 1-5 years it was 30.8% (>2cm = 9.5%, <2cm = 21.3%), at 5-10 years it was 40.1% (>2cm = 13.8%, <2cm = 26.3%) and at over 10 years it was 50.0% (>2cm = 25.0%, <2cm = 25.0%). Recurrence was associated with oesophagitis but not decreased QoL. Revision surgery was required in 4.8% of cases (14.8% with recurrence). There were no interval major GHH complications. CONCLUSIONS: Surgery has provided sustained QoL improvements irrespective of recurrence. Recurrence occurred progressively over ten years and may predispose to oesophagitis.

Looking beyond low bone mineral density: multiple insufficiency fractures in a woman with post-menopausal osteoporosis on alendronate therapy.

Insufficiency fractures occur most commonly in the pelvic girdle and in the sacrum, followed by the tibia and the femoral neck. Insufficiency fractures of the femoral diaphyses are rare, with only few reported cases in the literature. The strongest associations exist with untreated osteoporosis. We describe an unusual case of multiple insufficiency fractures in a 73-yr-old Chinese woman who presented with a 10-month history of bilateral groin pain and difficulty with walking in the absence of trauma, diagnosed 18 months following the commencement of anti-resorptive therapy with alendronate. The pathogenesis of such insufficiency fractures is poorly understood, but next to low bone mineral density and micro-architectural damage likely involves other components such as changes in bone turnover and patient-related factors (e.g. non-compliance). This case report and review of the literature draws attention to some of the challenges in the diagnosis and management of such rare insufficiency fractures.

Lateral hip pain: does imaging predict response to localized injection?

Lateral hip pain is a common complaint in patients with a history of lower back pain from spinal disease. These patients often are diagnosed and treated for trochanteric bursitis because of localized pain and tenderness in the lateral hip. We presumed numerous scintigraphic features could provide diagnostic criteria for diagnosing gluteus medius tendinitis and trochanteric bursitis. A study was designed to assess the scintigraphic criteria for diagnosis of trochanteric bursitis and to evaluate the relationship of trochanteric bursitis to gluteus medius tendinitis and lumbar degenerative disease in predicting relapse after injection. We evaluated 97 patients with greater trochanteric pain syndrome to find a correlation between trochanteric bursitis, gluteus medius tendinitis, and spinal degenerative disease using scintigraphy and magnetic resonance imaging. We also evaluated predictors for responding to trochanteric injection of local anesthetic/glucocorticoid injection. We found a correlation between lumbar degenerative disease, gluteus medius tendinopathy, and trochanteric bursitis. Of these, 30 of 48 patients (63%) responded to injection of local anesthetic and glucocorticoids. The major predictor of relapse of pain after injection in 18 patients was the presence of moderate to severe lumbar degenerative disease seen on scintigraphic imaging. We propose a mechanistic model of the greater trochanteric pain syndrome to explain the interrelationship and response to therapy. Scintigraphy can provide sensitive and specific diagnoses of gluteus medius tendinitis and trochanteric bursitis.

Degenerative spondylolysis: a concise report of scintigraphic observations.

OBJECTIVES: Spondylolysis is traditionally thought to be a diagnosis of adolescence and childhood, and is ascribed to mechanical stress through the immature pars interarticularis. Over the last 4 yr we have noted a presentation of spondylolysis in association with hypertrophic zygapophyseal joint disease in the lumbar spine in an older age group. METHODS: Records of 94 patients presenting with low back pain were examined. A pattern of intense zygapophyseal joint uptake in association with extended uptake in the pars interarticularis was ascribed as degenerative spondylolysis. RESULTS: The ages of the 94 cases ranged from 33 to 80 yr (mean 64 yr). There were 53 males and 41 females. In the group with degenerative spondylolysis the mean age was 72 yr, with four females and two males. None of these six patients gave a history of childhood spinal disease or back pain and all were relatively inactive in terms of current participation in sport. All cases of spondylolysis were confirmed by computed tomography scanning. CONCLUSION: The finding of hypertrophic zygapophyseal joint disease in association with spondylolysis is easily recognized by scintigraphic tomographic imaging.

Scintigraphic measurement of tracheal mucus velocity in vivo.

Mucociliary clearance (MCC) is an important mechanism for removing inhaled particles, secretions and cellular debris from the respiratory tract. Here, a direct measurement of tracheal mucus velocity (TMV) for assessment of MCC, suitable for clinical and research use, is reported, and a comparison is made of TMV in normal subjects and patients with chronic obstructive pulmonary disease (COPD). A 0.1-mL bolus of radiolabelled (2-5 MBq), technetium-labelled macroaggregated human albumin (99mTc MAA) was injected through the cricothyroid membrane into the trachea of 20 young (< 50 yrs) and 12 older (> 50 yrs) normal subjects and 34 patients with COPD. Repeat studies were carried out in 13 normal subjects and 16 COPD patients. Movement of the bolus in the trachea was recorded (15 min) using a gamma camera interfaced to a computer. Data were analysed using specifically designed software. The test was well tolerated by subjects and patients, and no significant adverse events were reported. No significant differences were observed between data recorded from different regions of the bolus (leading edge, peak, trailing edge) by analysis of variance (ANOVA). Bland-Altman plots of the repeat studies indicated that data were more variable in normal subjects (coefficient of repeatability (COR) 10.3 mm.min-1) than in COPD patients (COR 5.5 mm.min-1). TMV (mean +/- SD) in young normal subjects (n = 20) was 10.7 +/- 3.5 mm.min-1. TMV was reduced in older normal subjects (n = 12; 6.5 +/- 2.6 mm.min-1) and further reduced in COPD (n = 34; 2.1 +/- 2.7 mm.min-1). In conclusion, this technique can be used to measure tracheal mucus velocity rapidly and safely in healthy subjects and patients with respiratory tract disease. This study has confirmed that tracheal mucus velocity declines with age and is further impaired in patients with chronic obstructive pulmonary disease.

Synovial osteochondromatosis presenting as a mass in the buttock.

A 42-year-old woman, who had received a radiologic diagnosis of synovial osteochondromatosis many years before, was examined for a painful right hip and a large immobile mass in the right buttock. Findings of radiologic and scintigraphic imaging were consistent with synovial osteochondromatosis. The patient underwent arthrotomy and excision of the large mass and several smaller masses to control pain and to identify possible malignant change.

Prognostic value of 99m Tc leukocyte scintigraphy in diabetic pedal osteomyelitis.

While leukocyte scintigraphy is accurate in detection of pedal osteomyelitis, there has been little data relating the technique to outcomes. We designed a trial to examine the prognostic value of sequential 99m Tc labeled leukocyte scans to establish the diagnosis of osteomyelitis and after three to four weeks of culture-guided antibiotic therapy. Twenty-three diabetic patients with proven pedal osteomyelitis (21/23) or persistent uptake (2/23) on the sequence of scans were studied. Five additional episodes of osteomyelitis developed in the group over the period of the study. Eleven patients demonstrated persistent uptake in the sequential scans. Nine progressed to amputation. The remaining two patients were biopsy-negative for infection, did not have cutaneous ulceration and were thought to have rapidly progressive arthropathy. Sequential leukocyte scintigraphy accurately predicts the need for amputation and can circumvent ineffective prolonged antibiotic therapy.

Occurrence of pulmonary thromboembolism immediately after arthroplasty.

INTRODUCTION: Respiratory complications are common after arthroplasty, with pulmonary thromboembolic disease (PTE) and fat emboli being the most serious. A scintigraphic study was designed to assess the occurrence of both diseases. A prospective tomographic study of perfusion was performed within 24 h of arthroplasty. Details of the detection of fat embolism will be presented elsewhere. METHODS: Patients with previous PTE were excluded. Tomographic lung studies were acquired after 99mTc-macroaggregated albumin injection. Pre- and post-operative arterial blood gases (ABGs) and relevant chest radiography/computed tomography scans were obtained. ABGs were analysed as the difference in alveolar-arterial oxygen gradients, pre- and post-operatively (DA-a). RESULTS: Forty patients were studied (16F, 24M) with a mean age of 71 years (range 36-88 years). Of these, 16 were hip and 24 knee arthroplasties. PTE was detected in 25 of 38 (66%) patients evaluated. The value of DA-a was significantly different between patients with PTE and without PTE (P>0.05). Administration of prophylactic pre-operative low molecular weight heparin makes no difference to the early onset of PTE. CONCLUSION: There is a high incidence of PTE immediately after arthroplasty.