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This review summarizes the current research and outlooks regarding the obstacles to diagnosing and treating early alpha-1-antitrypsin deficiency (AATD). It draws on prior systematic reviews and expert surveys to discover precisely what difficulties exist in early diagnosis and treatment of AATD and elucidate potential solutions to ease these difficulties. The perceived rarity of AATD may translate to a condition poorly understood by primary care physicians, and even many respiratory physicians, which results in opportunities for diagnosis being missed, especially in mild or asymptomatic patients. There are diagnostic techniques involving biomarkers and home testing methods which could improve the rate of early diagnosis. With respect to treatment, AATD involves treating two separate pathologies, lung disease and liver disease. The only specific AATD treatment, augmentation therapy, has proven ability in treating lung disease but not liver disease. Alpha-1-antitrypsin (AAT) synthesized in the liver can form damaging polymers that also result in reduced circulating AAT levels and, whilst liver transplantation is used to effectively treat AATD, it is inappropriate in early disease. Novel therapeutic areas such as gene editing and increasing autophagy are therefore being researched as future treatments. Ultimately, diagnosis and treatment are intrinsically linked in AATD, with earlier diagnosis leading to better treatment options and thus better patient outcomes.

The surgical approach for total hip arthroplasty (THA) has the potential to affect the immediate postoperative recovery; however, there is limited published data comparing the 3 most common surgical approaches. The purpose of the study was to investigate postoperative pain and subsequent opioid consumption between surgical approaches (anterior-AA, lateral-LA, and posterior-PA) in those undergoing primary elective THA.A retrospective cohort study assessed patient demographics (age, sex, and body mass index), American Society of Anesthesiologists grade, opioid naivety, operative details (anesthetic method, fixation method, and local infiltration analgesia), pain scores, and length of stay. Statistical analysis was performed with a 1-way analysis of variance 3 × 1 table with a P value.05.A total of 560 patients were included in the analysis (335 females and 225 males). The cohort consisted of 179 AA, 178 LA, and 203 PA patients. The average postoperative opioid usage was 63.05 (standard deviation [SD] = 42.97), 79.81 (SD = 56.10), and 77.50 (SD = 54.52) oral morphine equivalent daily dose (oMEDD) for the AA, LA, and PA, respectively. The mean difference was 16.8 oMEDD lower in the AA compared with the LA (P.01) and 14.5 oMEDD lower in the AA compared with the PA (P = .02).The direct anterior approach was associated with lower daily opioid usage and pain scores after elective THA in the early postoperative period. This represents a potential 21% reduction in daily opioid dosage when compared with LA patients and 18.7% reduction in PA patients.

Introduction The increasing incidence of acetabular fractures in the elderly and the fracture complexity seen in this cohort represents one of the greatest challenges faced by trauma orthopaedic surgeons today. There are no formal guidelines of best practice in the treatment of these patients. Management options vary from non-operative, acute ORIF, and/or total joint replacement. Although surgical intervention allows for earlier mobilization and avoidance of the complications of prolonged bedrest, the patients ability to tolerate what is often major surgery is always of concern. This is in stark contrast to intracapsular hip fractures, (a fracture within the same joint), where acute surgery is recommended in virtually all cases. Objectives This study was undertaken to evaluate the peri-operative outcomes for geriatric patients undergoing acetabular ORIF and hemiarthroplasty to assess if there is a significant difference in early outcome parameters. Design This is a retrospective case–control study. Setting This study was performed in the National Centre for Pelvic and Acetabular surgery. Patients 42 age- and sex-matched patients with comparable ASA grades were included in each arm of the study. Patient selection in the acetabular ORIF group was consecutive patients managed operatively in the centre during the period 2010–2015. The selection for the hemiarthroplasty group was by random selection of age- and sex-matched patients undergoing hemiarthroplasty during the same period. Main outcome measurements The primary outcomes that were proposed prior to the study being performed was perioperative mortality and post-op complications. Secondary outcomes were operating times, blood loss and need for ICU admission. Results A significant difference between the two cohorts was observed with operative times, blood loss, need for transfusion, and need for ICU admission, all higher in the acetabular ORIF group. There was no significant difference in mortality or post-op infection. Conclusions Our paper supports the concept that acute ORIF of acetabular fractures, with appropriate peri-operative support, can be undertaken safely. There is no difference in the major peri-operative outcomes of mortality or infection when compared with hip fracture patients requiring hemiarthroplasty.

Sputum colour may mark bacterial involvement in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, whether colour vision deficiency (CVD) in COPD patients could impact the use of sputum colour charts as part of a guide to antibiotic use in exacerbations is unknown. This study used an exploratory mixed-method approach to establish the likelihood that COPD patients will be colour blind and whether this would result in the sputum colour chart being unusable in the context of the patients’ self-management of their condition. CVD is under-reported in primary care and comorbidities in COPD patients increase the risk of acquiring CVD. Participants diagnosed with CVD and risk of acquiring CVD were able to use the sputum colour charts. Colour charts are likely to be usable even in the context of undiagnosed CVD in COPD patients.

The seminal observation of severe deficiency of alpha-1-antitrypsin (AAT) with premature emphysema over 50 years ago led to the elastase–antielastase hypothesis of lung disease. Subsequent research identified alpha-1-antitrypsin deficiency (AATD) as an inherited metabolic genetic condition caused by mutations on the SERPINA1 gene, resulting in a reduction in the serum concentration of AAT.1 The role of AAT is to act as an inhibitor to the enzyme neutrophil elastase, and it is crucial in the homeostasis of elastase–antielastase activity, with an imbalance in this activity causing lung disease via a cycle of inflammation and proteolytic damage leading to premature emphysema, disability and death. There are over 100 mutations of SERPINA1 described in the literature, some of which are associated with AATD. The normal genotype is designated PiMM; the most common genotype resulting in severe deficiency is designated PiZZ. AATD is an autosomal codominant condition so heterozygosity can also create in genotypes resulting in mild and intermediate deficiency, such as PiMZ and PiSZ. The prevalence of AATD worldwide is estimated between 0.02% and 0.05%. Normal AAT serum concentration would be in the range 20–53 µmol/L, while deficient genotypes express varying levels, from 55% for PiMZ to 40% for PiSZ and

Background Graves’ disease is the commonest cause of thyrotoxicosis whilst thyrotropin (TSH)-producing pituitary adenomas (thyrotropinomas, TSHomas) are very rare and account for just 1–2% of all pituitary adenomas. Coexistence of a TSHoma and Graves’ disease has been very rarely reported. Here, we report a case of a patient whose initial presentation with primary thyrotoxicosis due to Graves’ disease, was subsequently followed by a relapse of thyrotoxicosis due to a probable TSHoma. Case A sixty-eight year old woman was referred to our department with classical features of thyrotoxicosis. Initial biochemistry confirmed hyperthyroxinaemia [free thyroxine (fT4) 20.4 pmol/L (reference range 7.0–16.0)] and a suppressed TSH [11C-methionine PET/CT scan coregistered with volumetric MRI (Met-PET-MRICR) demonstrated high tracer uptake in the left lateral sella region suggestive of a functioning adenoma. The patient declined surgery and was unable to tolerate cabergoline or octreotide. Thereafter, she has elected to pursue a conservative approach with periodic surveillance. Conclusion This is a very unusual case of thyrotoxicosis caused by two different processes occurring in the same patient. It highlights the importance of considering dual pathology when previously concordant thyroid function tests become discordant. It also highlights a potential role of Met-PET-MRICR in the localisation of functioning pituitary tumours.

Commenting on the use of DNA sequencing in helping to reduce the reported under-diagnosing of alpha-1-antitrypsin deficiencyhttps://bit.ly/2ZPZbjx

Acetabular fractures are associated with damage to the femoral head, acetabular cartilage and labrum and possible disruption of the femoral head blood supply. Treatment aims to provide the best opportunity for restoration of joint function and to prevent long-term complications. Surgical intervention, in the form of open reduction and internal fixation (ORIF), is often required. Where post-traumatic osteoarthritis develops after ORIF, total hip arthroplasty (THA) is often required. Our aim here has been to identify and highlight our experience with the key technical points associated with successful outcomes for THA in this setting. A single-centre retrospective review of patients with acetabular fractures treated with ORIF and subsequent THA over a 4-year period was undertaken. Demographics, mechanism of injury, complications, interval time between surgeries, intra-operative outcomes and post-operative outcomes were recorded. Particular emphasis is made to describe standard pre-operative and intra-operative protocols. Twenty-five patients were identified, with a mean age of 51.1 years at time of first ORIF. 60% presented following RTA. 80% of fractures involved the posterior wall or column. Meantime to eventual THA was 2.3 years. Mean THA duration was 1.52 h, with mean intra-operative blood loss and length of stay of 585 ml and 5 days, respectively. 24% required intra-operative removal of metal, with only one patient suffering a complication post-THA. Acceptable post-operative outcomes were demonstrated throughout the case series. In describing the pre-operative work up, intra-operative findings and intra-operative and post-operative complications encountered, common important technical points associated with a successful surgical strategy are described. Furthermore, potential pitfalls that may be encountered can be anticipated.

Introduction The objective of this non-interventional study was to investigate the long-term safety and effectiveness of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) in the UK and Ireland. Methods Patients were prescribed CZP at their physicians’ discretion and followed during routine clinical practice for up to 88 weeks. DAS28(ESR) response (defined as at least a 1.2-point reduction from baseline) was measured in the full analysis set (FAS) at week 12, and patients were categorized by week 12 responder status in all subsequent analyses. The primary outcome was DAS28(ESR) response at week 78. Secondary outcomes included change from baseline in DAS28(ESR), HAQ-DI, and RADAI scores at week 78, and EULAR response at week 78. Adverse drug reactions (ADRs) were recorded for all patients who received at least one dose of CZP. Results A total of 149 patients were enrolled, of whom 111 (74.5%) formed the FAS. At week 12, 80 patients (72.1%) were DAS28(ESR) responders and 31 (27.9%) non-responders. Compared to non-responders, a greater proportion of week 12 responders had a DAS28(ESR) response at week 78 (43.8% versus 22.6%). Improvements in DAS28(ESR), HAQ-DI, and RADAI scores were also greater on average among week 12 responders, as was the proportion of patients meeting EULAR criteria. Overall, 9 patients (6.1%) experienced 13 ADRs during the study. Conclusion These data demonstrate the safety and effectiveness of CZP in adult patients with RA treated during routine clinical practice in the UK and Ireland. Trial Registration ClinicalTrials.gov identifier, NCT01288287. Funding UCB Pharma. Electronic supplementary material The online version of this article (10.1007/s12325-018-0758-1) contains supplementary material, which is available to authorized users.

Traumatic brain injury (TBI) remains a major, global public health concern. Over the last 15 years, a significant body of evidence has emerged demonstrating that post-traumatic hypopituitarism (PTHP) is a common and clinically significant consequence of TBI. Non-specific symptomology and the lack of an agreed approach to screening for PTHP has led to significant under-diagnosis of this debilitating disease. In this review, we will discuss the frequency and clinical significance of acute and chronic PTHP as described in the current literature highlighting the evidence base for screening and hormone replacement in these patients. We will also offer a pragmatic approach to identifying relevant anterior pituitary dysfunction after TBI and a follow-up strategy for those patients. Specific controversies and remaining unanswered questions will be addressed.

\ud \ud Background\ud \ud Current methods for assessing concussion during rugby matches rely on rudimentary behavioural assessment, focusing on balance and gross motor function. Cognitive testing with the Sports Concussion Assessment Tool has recently been included, but there are a paucity of normative and baseline data for this test. This study examined the utility of the Trail Making Test (TMT), which is a neuropsychological test of executive function in two parts (TMT-A and TMT-B), to assist identification of cognitive impairments caused by impacts during rugby games.\ud \ud Methods\ud \ud 27 elite male rugby league players contracted to a professional rugby club were recruited towards the end of the season. Each player was tested on three occasions within a 2 week period with both TMT-A and TMT-B for baseline assessment. Each player was additionally assessed after full contact training on 2 consecutive days and during preseason training. Individual baseline data were calculated from the best of the baseline assessments, and time differences were examined with ANOVA.\ud \ud Findings\ud \ud No instances of concussion occurred during data collection. For TMT-A there was no significant difference (F(3, 24)=2·88, I2=0·27) between baseline (mean 13·79 s [SD 5·32], 95% CI 9·34–18·23), post-training day 1 (11·38 [2·63], 9·18–13·58), post-training day 2 (11·16 [1·94], 9·55–12·79), and preseason (11·79 [2·64], 9·58–13·99). For TMT-B there was no significant difference between baseline (31·50 [5·37], 27·01–35·99), post-training day 1 (28·07 [8·82], 20·70–35·44), post-training day 2 (26·18 [6·16], 21·03–31·33), and preseason (26·98 [4·89], 22·89–31·07).\ud \ud Interpretation\ud \ud These findings indicate that there were no significant differences in performance of these executive tasks from baseline to post-training (end of season and preseason). These data show stability of TMT-A and TMT-B data across a competitive rugby league season. Importantly, use of measures of variation such as CIs for these tasks can provide a metric for calculating minimally important clinical differences within cognition.\ud \ud Funding\ud \ud None.