Patient-reported outcomes following total shoulder arthroplasty and hemiarthroplasty: an analysis of data from the National Joint Registry.

BACKGROUND: Total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) are used in the management of end-stage glenohumeral arthritis. Improvement in shoulder function and resolution of symptoms are high priorities for patients. The aim of this study was to compare patient-reported outcome measures (PROMs) following TSA and HA. METHODS: Records from the National Joint Registry of England, Wales, Northern Ireland, and the Isle of Man were linked to the PROMs data set. The study included anatomic shoulder arthroplasties performed for osteoarthritis in patients with an intact rotator cuff. Patients with preoperative and postoperative Oxford Shoulder Scores (OSSs) were included. The improvement in OSS at 6 months and 5 years and the trend in scores over time were analyzed for each prosthesis. A cohort of 2002 patients were matched on 10 variables using propensity scores. OSSs at 6 months following TSA vs. HA were compared in the matched sample. RESULTS: There was a significant improvement in the OSS in both groups (P < .001). At 6 months, the OSSs were superior following TSA compared with HA (median 42 vs. 36, P < .001). The median score at 5 years was 44 following TSA and 35 following HA. Score distributions were skewed toward the maximum score. The highest possible score (48) was achieved in 28% (134 of 478) of TSAs and 9% (20 of 235) of HAs at 5 years. The improvement in the preoperative to 6-month OSS reached the minimal clinically important difference of 5.5 in 92% (1653 of 1792) of TSAs and in 80% (416 of 523) of HAs. At 5 years, this improvement was maintained in 91% (339 of 374) of TSAs and 78% (136 of 174) of HAs. CONCLUSION: TSA resulted in superior OSSs at 6 months in patients with osteoarthritis. The median OSS improved from 6 months to 5 years following TSA; however, there was a small decline in scores following HA. A ceiling effect was shown in the OSS following TSA at 5 years.

The risk of revision is higher following shoulder hemiarthroplasty compared with total shoulder arthroplasty for osteoarthritis: a matched cohort study of 11,556 patients from the National Joint Registry, UK.

BACKGROUND AND PURPOSE: Total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) are used in the management of osteoarthritis of the glenohumeral joint. We aimed to determine whether TSA or HA resulted in a lower risk of adverse outcomes in patients of all ages with osteoarthritis and an intact rotator cuff and in a subgroup of patients aged 60 years or younger. PATIENTS AND METHODS: Shoulder arthroplasties recorded in the National Joint Registry, UK, between April 1, 2012 and June 30, 2021, were linked to Hospital Episode Statistics in England. Elective TSAs and HAs were matched on propensity scores based on 11 variables. The primary outcome was all-cause revision. Secondary outcomes were combined revision/non-revision reoperations, 30-day inpatient complications, 1-year mortality, and length of stay. 95% confidence intervals (CI) were reported. RESULTS: 11,556 shoulder arthroplasties were included: 7,641 TSAs, 3,915 HAs. At 8 years 95% (CI 94-96) of TSAs and 91% (CI 90-92) of HAs remained unrevised. The hazard ratio (HR) varied across follow-up: 4-year HR 2.7 (CI 1.9-3.5), 8-year HR 2.0 (CI 0.5-3.5). Rotator cuff insufficiency was the most common revision indication. In patients aged 60 years or younger prosthesis survival at 8 years was 92% (CI 89-94) following TSA and 84% (CI 80-87) following HA. CONCLUSION: The risk of revision was higher following HA in patients with osteoarthritis and an intact rotator cuff. Patients aged 60 years and younger had a higher risk of revision following HA.

Optimization of a Digital Mass Filter for the Isolation of Intact Protein Complexes in Stability Zone 1,1.

Digital mass filters are advantageous for the analysis of large molecules due to the ability to perform ion isolation of high-m/z ions without the generation of very high radio frequency (RF) and DC voltages. Experimentally determined Mathieu stability diagrams of stability zone 1,1 for capacitively coupled digital waveforms show a voltage offset between the quadrupole rod pairs is introduced by the capacitors which is dependent on the voltage magnitude of the waveform and the duty cycle. This changes the ion's a value from a = 0 to a < 0. These effects are illustrated for isolation for single-charge states for various protein complexes up to 800 kDa (GroEL) for stability zone 1,1. Isolation resolving power (m/Δm) of approximately 280 was achieved for an ion of m/z 12,315 (z = 65+ for 800.5 kDa GroEL D398A), which corresponds to an m/z window of 44.

Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.

BACKGROUND: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. METHODS: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. FINDINGS: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. INTERPRETATION: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. FUNDING: The study was funded by the Bill & Melinda Gates Foundation.

Novel robotic technology for the rapid intraoperative manufacture of patient-specific instrumentation allowing for improved glenoid component accuracy in shoulder arthroplasty: a cadaveric study.

BACKGROUND: Accurate prosthesis placement in arthroplasty is an important factor in the long-term success of these interventions. Many types of guidance technology have been described to date often suffering from high costs, complex theater integration, time inefficiency, and problems with day-to-day usability. We present a novel, intraoperative robotics platform, capable of rapid, real-time manufacture of low-cost patient-specific guides while overcoming many of the issues with existing approaches. METHODS: A prototype robotics platform was assessed in a 24-specimen cadaveric trial during sequential simulated shoulder arthroplasty procedures. The platform consisted of a tableside robot with sterile drapes and sterile disposable components. The robot itself comprised a 3D optical scanner, a 3-axis sterile robotic drill, and a 2-axis receptacle into which the disposable consumables were inserted. The consumable was composed of a region of rapidly setting moldable material and a clip allowing it to be reversibly attached to the robot. Computed tomographic (CT) imaging was obtained for all cadaveric specimens, and a surgical plan was created focusing on glenoid component position-specifically, guidewire position to allow for accurate glenoid preparation before implant insertion. Intraoperatively, for every specimen, the relevant osseous anatomy was exposed and humeral and glenoid preparation undertaken in the usual manner. The sterile disposable was used to create a mold of the joint surface. Once set, the mold was inserted into the robot and an optical scan of the surface was undertaken followed by automatic surface registration with the CT data and surgical plan. An automatic guide hole was subsequently drilled into the molded blank, which was removed from the robot and placed back into the patient, with the melded surface ensuring exact replacement. The guidewire was then driven through the guide hole in accordance with the preoperative plan. RESULTS: The novel robotic platform achieved average angular accuracies of 1.9° (standard deviation [SD] 1.3) version and 1.2° (SD 0.7) inclination with positional accuracy of 1.1 mm (SD 0.7) compared to a preoperative plan. DISCUSSION: We have described a novel robotics platform that is able to reliably produce patient-specific intraoperative guides to allow for accurate guidewire placement. Guidance is provided using a portable intraoperative device. The results suggest achieved accuracy levels may be equivalent to those seen in other existing guidance technologies; however, eventual in vivo trials and analysis is required. This technology has potential transferability to improve accuracy in other areas of arthroplasty.

CT-based micromotion analysis method can assess early implant migration and development of radiolucent lines in cemented glenoid components: a clinical feasibility study.

BACKGROUND AND PURPOSE: CT micromotion analysis (CTMA) has been considered as an alternative to radiostereometry (RSA) for assessing early implant migration of orthopedic implants. We investigated the feasibility of CTMA to assess early migration and the progression of radiolucent lines in shoulder arthroplasties over 24 months using sequential low-dose CT scans. PATIENTS AND METHODS: 7 patients were included and underwent 9 primary total shoulder arthroplasties. We made CT scans preoperatively, within 1 week postoperatively, and after 3, 6, 12, and 24 months. At each follow-up, postoperative glenoid migration and any development of radiolucent lines were assessed. Clinical outcomes were recorded at all time points except within 1 week postoperatively. RESULTS: For the glenoid component, the median translation and median rotation were 0.00-0.10 mm and -1.53° to 1.05° at 24 months. Radiolucent lines could be observed around all glenoid components. The radiolucent lines developed from the periphery to the center of the implant for 6 glenoid components during follow-up. The Constant Score improved from a mean of 30 (21-51) preoperatively to 69 (41-88) at 24 months. INTERPRETATION: CTMA can be used to identify early migration and the development of radiolucent lines over time in glenoid components. Clinical trials with a larger sample size and longer follow-up are needed to establish the relationship between migration, radiolucent lines, loosening, and clinical outcome.

Avoiding high-risk rotator cuff loading: Muscle force during three pull-up techniques.

Heavily loaded overhead training tasks, such as pull-ups are an effective strength training and rehabilitation exercise requiring high muscle forces maintained over a large range of motion. This study used experiments and computational modeling to examine loading patterns during three different pull-up variants and highlighted risks to vulnerable musculoskeletal structures. Optical motion tracking and a force platform captured kinematics and kinetics of 11 male subjects with no history of shoulder pathology, during performance of three pull-up variants-pronated front grip, pronated wide grip, and supinated reverse grip. UK National Shoulder model (UKNSM) simulated biomechanics of the shoulder girdle. Muscle forces and activation patterns were analyzed by repeated measures ANOVA with post-hoc comparisons. Motor group recruitment was similar across all pull-up techniques, with upper limb depression occurring secondary to torso elevation. Stress-time profiles show significant differences in individual muscle patterns among the three pull-up variants, with the most marked differences between wide grip and reverse grip. Comparing across techniques, latissimus dorsi was relatively more active in wide pull-ups (P < .01); front pull-ups favored activation of biceps brachii and brachialis (P < .02); reverse pull-ups displayed higher proportional rotator cuff activation (P < .01). Pull-ups promote stability of the shoulder girdle and activation of scapula stabilizers and performing pull-ups over their full range of motion is important as different techniques and phases emphasize different muscles. Shoulder rehabilitation and strength & conditioning programs should encourage incorporation of all three pull-up variants with systematic progression to provide greater global strengthening of the torso and upper limb musculature.

Do preterm bones still break? Incidence of rib fracture and osteopenia of prematurity in very low birth weight infants.

AIM: Extremely premature babies are at risk of osteopenia of prematurity (OOP) as bone mineralisation in utero increases exponentially after 24 weeks gestation. Our aim was to assess the bone health of very low birth weight (VLBW) infants. We wanted to establish the incidences of OOP and rib fracture. We also looked at which biochemical markers best predicted OOP. Bone health in this vulnerable population is an important aspect of management which should not be overlooked. METHODS: This was an observational study which included all VLBW infants, born in a national maternity hospital, over a 5-year period. All X-rays performed on these infants were reviewed. Data were also collected on biochemical markers associated with bone health. The medical records of infants with rib fractures were reviewed looking for causes of bone fragility. RESULTS: Of the 609 VLBW infants included in the study, only two cases of definitive rib fractures were found. This represents a rib fracture incidence of 3 per 1000. Thirty-nine percent of VLBW babies showed radiological evidence suggestive of OOP. CONCLUSION: Our findings show a lower rate of rib fracture in preterm infants compared to previous evidence. We also showed that these fractures were not evident on the final X-ray prior to discharge. This implies that when an ex-preterm infant presents to the emergency department with a rib fracture there should be an even higher suspicion for non-accidental injury than previously thought.

A biomechanical confirmation of the relationship between critical shoulder angle (CSA) and articular joint loading.

BACKGROUND: The critical shoulder angle (CSA) has been shown to be correlated with shoulder disease states. The biomechanical hypothesis to explain this correlation is that the CSA changes the shear and compressive forces on the shoulder. The objective of this study is to test this hypothesis by use of a validated computational shoulder model. Specifically, this study assesses the impact on glenohumeral biomechanics of modifying the CSA. METHODS: An inverse dynamics 3-dimensional musculoskeletal model of the shoulder was used to quantify muscle forces and glenohumeral joint forces. The CSA was changed by altering the attachment point of the middle deltoid into a normal CSA (33°), a reduced CSA of 28°, and an increased CSA of 38°. Subject-specific kinematics of slow and fast speed abduction in the scapular plane and slow and fast forward flexion measured by a 3-dimensional motion capture system were used to quantify joint reaction shear and compressive forces. RESULTS: Increasing the CSA results in increased superior-inferior forces (shearing forces; integrated over the range of motion; P < .05). Reducing CSA results in increased lateromedial (compressive) forces for both the maximum and integrated sum of the forces over the whole motion (P < .01). DISCUSSION/CONCLUSION: Changes in the CSA modify glenohumeral joint biomechanics with increasing CSA producing higher shear forces that could contribute to rotator cuff overuse, whereas reducing the CSA results in higher compressive forces that contribute to joint wear.

Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.

Short-chain enoyl-CoA hydratase (SCEH or ECHS1) deficiency is a rare inborn error of metabolism caused by biallelic mutations in the gene ECHS1 (OMIM 602292). Clinical presentation includes infantile-onset severe developmental delay, regression, seizures, elevated lactate, and brain MRI abnormalities consistent with Leigh syndrome (LS). Characteristic abnormal biochemical findings are secondary to dysfunction of valine metabolism. We describe four patients from two consanguineous families (one Pakistani and one Irish Traveler), who presented in infancy with LS. Urine organic acid analysis by GC/MS showed increased levels of erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconate (3-MGC). Increased urine excretion of methacrylyl-CoA and acryloyl-CoA related metabolites analyzed by LC-MS/MS, were suggestive of SCEH deficiency; this was confirmed in patient fibroblasts. Both families were shown to harbor homozygous pathogenic variants in the ECHS1 gene; a c.476A > G (p.Gln159Arg) ECHS1variant in the Pakistani family and a c.538A > G, p.(Thr180Ala) ECHS1 variant in the Irish Traveler family. The c.538A > G, p.(Thr180Ala) ECHS1 variant was postulated to represent a Canadian founder mutation, but we present SNP genotyping data to support Irish ancestry of this variant with a haplotype common to the previously reported Canadian patients and our Irish Traveler family. The presence of detectable erythro-2,3-dihydroxy-2-methylbutyrate is a nonspecific marker on urine organic acid analysis but this finding, together with increased excretion of 3-MGC, elevated plasma lactate, and normal acylcarnitine profile in patients with a Leigh-like presentation should prompt consideration of a diagnosis of SCEH deficiency and genetic analysis of ECHS1. ECHS1 deficiency can be added to the list of conditions with 3-MGA.

The Eden-Hybbinette procedure is one hundred years old! A historical view of the concept and its evolutions.

INTRODUCTION: One hundred years ago, before Bankart, Latarjet or Bristow, Eden and Hybbinette developed a procedure to treat anterior shoulder instability and currently, this eponymous term is known by every shoulder surgeon. The purpose of this review is to summarise the historical "Eden-Hybbinette" procedure and its evolutions during the last century and discuss results. METHOD: On the centenary of the first publication on the "Eden-Hybbinette procedure", a search was conducted on Medline, Google Scholar and in the grey literature, to find its initial concept and description, and the evolutions. RESULTS: The initial procedure was based on the concepts of glenoid bony augmentation (anatomic reconstruction with an autograft from the tibia) and capsulorrhaphy. The main evolutionary themes identified were the origin of the graft (autograft with iliac crest, allograft), graft positioning and fixation (no fixation device, screws), and the surgical approach (split of the subscapularis tendon in open surgery, arthroscopy). Studies with long-term follow-up exhibited good results, considered similar as those with other classic bone-block procedures. Development of osteoarthritis during the following years after the procedure is not usual and not related to the graft unless if there is articular protrusion. CONCLUSION: The Eden-Hybbinette procedure is one of the oldest surgical interventions still commonly used for chronic anterior shoulder instability. The changes to the procedure over the last 100 years allow it to remain a contemporary solution for both primary surgery and revision cases.

Methodology and Characterization of Isolation and Preconcentration in a Gas-Filled Digital Linear Ion Guide.

Digital operation of linear ion guides allows them to operate as traps and mass filters by modulating the duty cycles of the two driving waveforms. A gas-filled (5 mTorr) digitally driven quadrupole ion guide was used to demonstrate ion isolation and preconcentration. These abilities allow ion trapping mass spectrometers to be filled to capacity with only ions in the range of interest at essentially any value of m/z. Due to the unique performance characteristics of digitally operated quadrupoles, isolation with purely duty cycle enhanced waveforms was developed with three increasingly sophisticated isolation methods. First, the guide was used as a gas-filled transmission mass filter using the waveform duty cycle to generate a narrow mass window. The second method used broadband trapping to collect ions and translationally cool along the transmission axis before shifting the duty cycle to filter the trapped ions. A subsequent duty cycle change axially ejected the filtered population for measurement. The third method improved resolution by shifting the operating frequency during isolation. The resolving power was optimized with the shift frequency to yield a device limited resolving power of 400 (m/Δm). It is the temporal control of the duration of the isolation process that sets digital waveform based isolation apart from the current technology and that minimizes ion loss even when the mass is very large. Preconcentration by repeated trapping and isolation of an individual charge state was also demonstrated to saturate the ion guide with that charge state. These digital isolation and preconcentration techniques will permit the same isolation resolution (m/Δm) at any value of mass or m/z without significant ion loss as long as the secular frequencies do not significantly overlap while in the trapping mode. It is therefore ideal for the isolation and preconcentration of single charge states of large proteins and complexes.

Rotator cuff-sparing approaches for glenohumeral joint access: an anatomic feasibility study.

BACKGROUND: The deltopectoral approach for total shoulder arthroplasty can result in subscapularis dysfunction. In addition, glenoid wear is more prevalent posteriorly, a region difficult to access with this approach. We propose a posterior approach for access in total shoulder arthroplasty that uses the internervous interval between the infraspinatus and teres minor. This study compares this internervous posterior approach with other rotator cuff-sparing techniques, namely, the subscapularis-splitting and rotator interval approaches. METHODS: The 3 approaches were performed on 12 fresh frozen cadavers. The degree of circumferential access to the glenohumeral joint, the force exerted on the rotator cuff, the proximity of neurovascular structures, and the depth of the incisions were measured, and digital photographs of the approaches in different arm positions were analyzed. RESULTS: The posterior approach permits direct linear access to 60% of the humeral and 59% of the glenoid joint circumference compared with 39% and 42% for the subscapularis-splitting approach and 37% and 28% for the rotator interval approach. The mean force of retraction on the rotator cuff was 2.76 (standard deviation [SD], 1.10) N with the posterior approach, 2.72 (SD, 1.22) N with the rotator interval, and 4.75 (SD, 2.56) N with the subscapularis-splitting approach. From the digital photographs and depth measurements, the estimated volumetric access available for instrumentation during surgery was comparable for the 3 approaches. CONCLUSION: The internervous posterior approach provides greater access to the shoulder joint while minimizing damage to the rotator cuff.

Evaluating scrotal masses.

Scrotal complaints can be challenging to diagnose because of overlapping signs and symptoms among various presentations. Failure to properly identify and manage testicular malfunctions such as testicular torsion, testicular cancer, varicocele, and hydrocele may lead to patient infertility, testicle loss, or death. This article describes proper assessment of scrotal masses, recognition of potentially life-threatening testicular conditions, and appropriate diagnostic evaluations for each pathology.

Carbohydrate-binding module tribes.

At present, 69 families of carbohydrate-binding modules (CBMs) have been isolated by statistically significant differences in the amino acid sequences (primary structures) of their members, with most members of different families showing little if any homology. On the other hand, members of the same family have primary and tertiary (three-dimensional) structures that can be computationally aligned, suggesting that they are descended from common protein ancestors. Members of the large majority of CBM families are ß-sandwiches. This raises the question of whether members of different families are descended from distant common ancestors, and therefore are members of the same tribe. We have attacked this problem by attempting to computationally superimpose tertiary structure representatives of each of the 53 CBM families that have members with known tertiary structures. When successful, we have aligned locations of secondary structure elements and determined root mean square deviations and percentages of similarity between adjacent amino acid residues in structures from similar families. Further criteria leading to tribal membership are amino acid chain lengths and bound ligands. These considerations have led us to assign 27 families to nine tribes. Eight of the tribes have members with ß-sandwich structures, while the ninth is composed of structures with ß-trefoils.

Fatty acid synthesis enzyme clans.

Ketoacyl reductases (KRs), hydroxyacyl dehydratases (HDs), and enoyl reductases (ERs) are part of the fatty acid/polyketide synthesis cycle. They are known as acyl dehydrogenases, enoyl hydratases, and hydroxyacyl dehydrogenases, respectively, when catalyzing their reverse reactions. Earlier, we classified these enzymes into four KR, eight HD, and five ER families by statistical criteria. Members of all four KR families and three ER families have Rossmann folds, while five HD family members have HotDog folds. This suggests that those proteins with the same folds in different families may be distantly related, and therefore in clans, even though their amino acid sequences may not be homologous. We have now defined two clans containing three of the four KR families and two of the eight HD families, using manual and statistical tests. One of the ER families is related to the KR clan.

The methodological quality of health economic evaluations for the management of hip fractures: A systematic review of the literature.

BACKGROUND AND OBJECTIVES: Approximately 76,000 people a year sustain a hip fracture in the UK and the estimated cost to the NHS is £1.4 billion a year. Health economic evaluations (HEEs) are one of the methods employed by decision makers to deliver healthcare policy supported by clinical and economic evidence. The objective of this study was to (1) identify and characterize HEEs for the management of patients with hip fractures, and (2) examine their methodological quality. METHODS: A literature search was performed in MEDLINE, EMBASE and the NHS Economic Evaluation Database. Studies that met the specified definition for a HEE and evaluated hip fracture management were included. Methodological quality was assessed using the Consensus on Health Economic Criteria (CHEC). RESULTS: Twenty-seven publications met the inclusion criteria of this study and were included in our descriptive and methodological analysis. Domains of methodology that performed poorly included use of an appropriate time horizon (66.7% of studies), incremental analysis of costs and outcomes (63%), future discounting (44.4%), sensitivity analysis (40.7%), declaration of conflicts of interest (37%) and discussion of ethical considerations (29.6%). CONCLUSIONS: HEEs for patients with hip fractures are increasing in publication in recent years. Most of these studies fail to adopt a societal perspective and key aspects of their methodology are poor. The development of future HEEs in this field must adhere to established principles of methodology, so that better quality research can be used to inform health policy on the management of patients with a hip fracture.

Decompressive craniectomy in diffuse traumatic brain injury.

BACKGROUND: It is unclear whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure. METHODS: From December 2002 through April 2010, we randomly assigned 155 adults with severe diffuse traumatic brain injury and intracranial hypertension that was refractory to first-tier therapies to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The original primary outcome was an unfavorable outcome (a composite of death, vegetative state, or severe disability), as evaluated on the Extended Glasgow Outcome Scale 6 months after the injury. The final primary outcome was the score on the Extended Glasgow Outcome Scale at 6 months. RESULTS: Patients in the craniectomy group, as compared with those in the standard-care group, had less time with intracranial pressures above the treatment threshold (P<0.001), fewer interventions for increased intracranial pressure (P<0.02 for all comparisons), and fewer days in the intensive care unit (ICU) (P<0.001). However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care (odds ratio for a worse score in the craniectomy group, 1.84; 95% confidence interval [CI], 1.05 to 3.24; P=0.03) and a greater risk of an unfavorable outcome (odds ratio, 2.21; 95% CI, 1.14 to 4.26; P=0.02). Rates of death at 6 months were similar in the craniectomy group (19%) and the standard-care group (18%). CONCLUSIONS: In adults with severe diffuse traumatic brain injury and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and the length of stay in the ICU but was associated with more unfavorable outcomes. (Funded by the National Health and Medical Research Council of Australia and others; DECRA Australian Clinical Trials Registry number, ACTRN012605000009617.).

Development of MS(n) in digitally operated linear ion guides.

This publication demonstrates the use of digital waveform manipulation in linear ion guides to trap isolated ions and fragment them before mass analysis by time-of-flight mass spectrometry (TOF-MS). Ion trapping and collection was performed by waveform duty cycle manipulation to create a negative axial potential between the rods and the end-cap electrodes. Ion isolation can be performed by duty cycle manipulation to narrow the range of stable masses while continuing to axially trap the ions. Further ion isolation can then be performed by jumping the quadrupole frequency to each side of the stability zone to eliminate ions above and below the isolated ion mass. Collision-induced dissociation was demonstrated by duty cycle manipulation to either axially or radially excite the ions. The methods for performing these types of excitations are discussed and demonstrated. These techniques can be combined or used separately for MS(n) analysis. The use of frequency and duty cycle manipulation of the applied waveforms simplifies the hardware while greatly increasing the capabilities of linear ion guides and quadrupole time-of-flight mass spectrometers (Q-TOF-MS). Linear quadrupoles can now be used as high efficiency ion traps for collection, isolation, and tandem mass spectrometry at any value of m/z when operated digitally.

Molecular mechanism of a hotdog-fold acyl-CoA thioesterase.

Thioesterases are enzymes that hydrolyze thioester bonds between a carbonyl group and a sulfur atom. They catalyze key steps in fatty acid biosynthesis and metabolism, as well as polyketide biosynthesis. The reaction molecular mechanism of most hotdog-fold acyl-CoA thioesterases remains unknown, but several hypotheses have been put forward in structural and biochemical investigations. The reaction of a human thioesterase (hTHEM2), representing a thioesterase family with a hotdog fold where a coenzyme A moiety is cleaved, was simulated by quantum mechanics/molecular mechanics metadynamics techniques to elucidate atomic and electronic details of its mechanism, its transition-state conformation, and the free energy landscape of the process. A single-displacement acid-base-like mechanism, in which a nucleophilic water molecule is activated by an aspartate residue acting as a base, was found, confirming previous experimental proposals. The results provide unambiguous evidence of the formation of a tetrahedral-like transition state. They also explain the roles of other conserved active-site residues during the reaction, especially that of a nearby histidine/serine pair that protonates the thioester sulfur atom, the participation of which could not be elucidated from mutation analyses alone.