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Background The inclusion of patient-reported outcome measures (PROMs) serves to better quantify aspects of patient outcomes missed with objective measures, including radiographic indices and physical examination findings. We hypothesize that PROMs are inconsistently and heterogeneously captured in the treatment of distal radius fractures. Methods We performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines of all level I and II randomized controlled trials (RCTs) of distal radius fracture treatment of any modality for those older than 50 years of age from January 2008 to January 2018. A total of 23 studies were included in the final analysis. The metrics used by each study to assess outcomes were collected, compared, and described. Results Physical examination findings and radiographic measures were reported in 70% and 74% of studies, respectively. Patient-reported outcomes measures were used to assess outcomes in 74% of studies. Only the Disabilities of the Arm, Shoulder, and Hand was used in greater than half of the studies (57%). Pain scores were assessed in 39% of studies and complications in only 26%. Conclusions There is substantial heterogeneity and lack of standardization in the collection of both objective outcome measures and PROMs in level I and II RCTs for the treatment of distal radius fractures. The ability to compare between studies or aggregate data among studies is therefore limited. Radiographic and physical examination findings remain frequently reported despite known limitations of these metrics. The routine collection of PROMs after the treatment of distal radius fractures can ensure care is directed toward improving what is most important to patients.

Background Respiratory syncytial virus (RSV) is a leading viral respiratory pathogen in infants. The objective of this study was to generate RSV live-attenuated vaccine (LAV) candidates by removing the G-protein mucin domains to attenuate viral replication while retaining immunogenicity through deshielding of surface epitopes. Methods Two LAV candidates were generated from recombinant RSV A2-line19F by deletion of the G-protein mucin domains (A2-line19F-G155) or deletion of the G-protein mucin and transmembrane domains (A2-line19F-G155S). Vaccine attenuation was measured in BALB/c mouse lungs by fluorescent focus unit (FFU) assays and real-time polymerase chain reaction (RT-PCR). Immunogenicity was determined by measuring serum binding and neutralizing antibodies in mice following prime/boost on days 28 and 59. Efficacy was determined by measuring RSV lung viral loads on day 4 postchallenge. Results Both LAVs were undetectable in mouse lungs by FFU assay and elicited similar neutralizing antibody titers compared to A2-line19F on days 28 and 59. Following RSV challenge, vaccinated mice showed no detectable RSV in the lungs by FFU assay and a significant reduction in RSV RNA in the lungs by RT-PCR of 560-fold for A2-line19F-G155 and 604-fold for A2-line19F-G155S compared to RSV-challenged, unvaccinated mice. Conclusions Removal of the G-protein mucin domains produced RSV LAV candidates that were highly attenuated with retained immunogenicity.

Patient satisfaction scores are a popular metric used to evaluate orthopedic care. There is little consistency with how satisfaction is described in the orthopedic literature. Online physician reviews are a growing trend that directly and indirectly affect a surgeon's reputation. There is little correlation of higher satisfaction with improved surgical outcomes, so rating surgical care may be misguided and possibly dangerous. Patient satisfaction is an important part of the patient-centered care model, so rating systems should directly reflect quality. More research is needed to determine the relationship between patient satisfaction and the delivery of quality care. [ Orthopedics . 2022;45(3):e127–e133.]

Background Intra-articular distal radius fractures with small volar lunate facet fragments can be challenging to address with volar plate fixation alone. Volar locked plating with supplementary spring wire fixation has been previously described in a small series but has not been further described in the literature. We hypothesized that this technique can provide adequate fixation for volar lunate facet fragments smaller than 15 mm in length, which are at risk of displacement. Methods We completed a retrospective chart review (2015-2019) of patients who underwent volar locked plating with the addition of supplementary spring wire fixation for intra-articular distal radius fractures with a volar lunate facet fragment (Results Fifteen patients were identified, of which all went on to fracture union. There were no hardware failures or escape of the volar lunate facet fragment at final follow-up. One patient underwent hardware removal for symptoms of flexor tendon irritation. The mean wrist flexion was 59°, wrist extension was 70°, pronation was 81°, and supination was 76°. The mean QuickDASH score was 18.5. The mean postoperative volar tilt was 3.6°. Conclusions Supplementary spring wire fixation with standard volar plating provides stable fixation for lunate facet fragments less than 15 mm. This technique is a safe and reliable alternative to commercially available fragment-specific implants.

Background: Hybrid Russe technique for the treatment of scaphoid nonunion with humpback deformity has been described with a reported 100% union rate. We sought to evaluate the reproducibility of this technique. Methods: We completed a retrospective chart review of patients with a scaphoid waist nonunion and humpback deformity treated with the hybrid Russe technique from 2015 to 2019 with a minimum of 3-month follow-up. Twenty patients with 21 nonunions were included (mean follow-up: 7.0 months). Scapholunate angle was the primary outcome measure. Secondary outcomes included: intrascaphoid angle, radiolunate angle, pain on the visual analog scale (VAS), and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score. Other variables included: time to computed tomography (CT) union, range of motion, and complications. Descriptive statistics were presented. Pre- and postoperative angles, VAS, and QuickDASH scores were evaluated with Wilcoxon signed rank tests. Results: The mean scapholunate angle improved −17.6° ± 6.4°. The mean intrascaphoid angle improved 28.2° ± 6.3°. The mean radiolunate angle improved 12.8° ± 8.8°. Of the 21 scaphoids, 20 (95%) demonstrated union on a CT scan. One patient was diagnosed with a nonunion. In total, 90% of patients noted symmetric range of motion compared with the contralateral side. The mean VAS pain score improved 6 ± 3 points. The mean QuickDASH score improved 10 ± 8 points. Complications (aside from nonunion) included 1 patient with persistent wrist pain that resolved with removal of hardware. Conclusions: The hybrid Russe technique for the treatment of scaphoid nonunions with humpback deformity demonstrates a 95% union rate. This technique is effective, reproducible, and may serve as an alternative to techniques that include structural grafts from distant sites.

The Medicare Access and Children's Health Insurance Program Reauthorization Act established the Quality Payment Program (QPP), which mandates that physicians who meet the threshold in volume of Medicare patients for whom they care participate in this program through either advanced Alternative Payment Models or the Merit-Based Incentive Payment System. Anticipating physicians' concerns regarding the burden of implementing the QPP, feedback from physicians became a critical component of the continued implementation process in 2018. The purpose of this review is to inform hand surgeons regarding the current QPP (early 2019) and for future observation periods.

Background: As medical costs continue to rise, financial distress due to these costs has led to poorer health outcomes and patient cost-coping behavior. Here, we test the null hypothesis that financial distress is not associated with delay of seeking care for hand conditions. Methods: Eighty-seven new patients presenting to the hand clinic for nontraumatic conditions completed our study. Patients completed validated instruments for measuring financial distress, pain catastrophizing, and pain. Questions regarding delay of care were included. The primary outcome was self-reported delay of the current hand clinic visit. Results: Patients who experience high financial distress differed significantly from those who experience low financial distress with respect to age, race, annual household income, and employment status. Those experiencing high financial distress were more likely to report having delayed their visit to the hand clinic (57% vs 30%), higher pain catastrophizing scores (17.7 vs 7.6), and higher average pain in the preceding week (4.5 vs 2.3). After adjusting for age, sex, and pain, high financial distress (adjusted odds ratio [OR] = 4.90) and pain catastrophizing score (adjusted OR = 0.96) were found to be independent predictors of delay. Financial distress was highly associated with annual household income in a multivariable linear regression model. Conclusions: Patients with nontraumatic hand conditions who experience higher financial distress are more likely to delay their visit to the hand clinic. Within health care systems, identification of patients with high financial distress and targeted interventions (eg, social or financial services) may help prevent unnecessary delays in care.

Patients have limited involvement in the development of quality measures that address the experience of undergoing total joint arthroplasty (TJA). Current quality measures may not fully assess the aspects of care that are important to patients. The goal of this study was to understand quality of care in TJA from the patient perspective by exploring patients' knowledge gaps, experiences, and goals. The authors completed a prospective qualitative analysis of patients who had undergone hip or knee TJA. Patients completed an open-ended, structured questionnaire about the surgical and recovery process as it relates to quality of care. The authors used a phenomenologic approach and purposeful sampling to enroll 74 patients 6 to 8 weeks after TJA. Responses underwent thematic analysis. Codes were used to identify themes that were important to patients in quality of care in TJA. The authors identified 3 themes: (1) returning to activity without pain or complication, which included psychological, functional, and complication-related goals; (2) negotiating the physical and psychological challenges of recovery, which encompassed the need for assistance from the caregiver as well as psychological and physical barriers to recovery; and (3) being prepared and informed for the process of surgery, including physical, logistical, and psychological preparation. Both patients and health systems may benefit from efforts to address these patient-centered themes of quality care through quality measures for TJA (eg, improving the psychological challenges of recovery). Future quality measures, such as assessment of patient experience, may be made more patient centered if they measure and improve aspects of care that matter to patients. [ Orthopedics . 2021;44(2):117–122.]

Coronavirus protease nsp5 (M pro , 3CL pro ) remains a primary target for coronavirus therapeutics due to its indispensable and conserved role in the proteolytic processing of the viral replicase polyproteins. In this review, we discuss the diversity of known coronaviruses, the role of nsp5 in coronavirus biology, and the structure and function of this protease across the diversity of known coronaviruses, and evaluate past and present efforts to develop inhibitors to the nsp5 protease with a particular emphasis on new and mostly unexplored potential targets of inhibition. With the recent emergence of pandemic SARS-CoV-2, this review provides novel and potentially innovative strategies and directions to develop effective therapeutics against the coronavirus protease nsp5.

ObjectiveIn people living with HIV (PLHIV), we sought to test the hypothesis that long term anti-retroviral therapy restores the normal T cell repertoire, and investigate the functional relationship of residual repertoire abnormalities to persistent immune system dysregulation.MethodsWe conducted a case-control study in PLHIV and HIV-negative volunteers, of circulating T cell receptor repertoires and whole blood transcriptomes by RNA sequencing, complemented by metadata from routinely collected health care records.ResultsT cell receptor sequencing revealed persistent abnormalities in the clonal T cell repertoire of PLHIV, characterized by reduced repertoire diversity and oligoclonal T cell expansion correlated with elevated CD8 T cell counts. We found no evidence that these expansions were driven by cytomegalovirus or another common antigen. Increased frequency of long CDR3 sequences and reduced frequency of public sequences among the expanded clones implicated abnormal thymic selection as a contributing factor. These abnormalities in the repertoire correlated with systems level evidence of persistent T cell activation in genome-wide blood transcriptomes.ConclusionsThe diversity of T cell receptor repertoires in PLHIV on long term anti-retroviral therapy remains significantly depleted, and skewed by idiosyncratic clones, partly attributable to altered thymic output and associated with T cell mediated chronic immune activation. Further investigation of thymic function and the antigenic drivers of T cell clonal selection in PLHIV are critical to efforts to fully re-establish normal immune function.

Coronavirus protease nsp5 (Mpro, 3CLpro) remains a primary target for coronavirus therapeutics due to its indispensable and conserved role in the proteolytic processing of the viral replicase polyproteins. In this review, we discuss the diversity of known coronaviruses, the role of nsp5 in coronavirus biology, and the structure and function of this protease across the diversity of known coronaviruses, and evaluate past and present efforts to develop inhibitors to the nsp5 protease with a particular emphasis on new and mostly unexplored potential targets of inhibition. With the recent emergence of pandemic SARS-CoV-2, this review provides novel and potentially innovative strategies and directions to develop effective therapeutics against the coronavirus protease nsp5.

Purpose Patient-reported outcome measures (PROMs) have traditionally been used for research purposes, but are now being used to evaluate outcomes from the patient’s perspective and inform ongoing management and quality of care. We used quantitative and qualitative approaches to evaluate the short-version Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and the Patient-Specific Functional Scale (PSFS) with regard to patient preference and measurement of patient goals and their responsiveness after treatment. Methods Patients 18 years or older undergoing elective hand surgery received the QuickDASH and PSFS questionnaires before and at 6 weeks after surgery. Two additional questions intended to elicit patients’ preferences regarding the QuickDASH and PSFS were included. Responsiveness was measured by change in pre- to postoperative score. We analyzed patients’ responses to the 2 additional questions to identify themes in PROM preferences. Results from the quantitative and qualitative analyses were combined into a convergent mixed-methods (eg, quantitative and qualitative) analysis. Results Thirty-eight patients completed preoperative questionnaires; 25 (66%) completed postoperative questionnaires. Seventeen patients (77%) preferred the PSFS, 3 (14%) had no preference, 2 (9%) preferred the QuickDASH. The average change from pre- to postoperative QuickDASH was –10 (SD, 20), and that of the PSFS was –27 (SD, 26). Ten patients (40%) reported QuickDASH score changes above the minimal clinically importance difference (MCID), 17 patients (68%) reported PSFS score changes above the MCID. Content analysis revealed 4 themes in preference for a PROM: instrument simplicity (ease of instrument understanding and completion), personalized assessment (individualization and relevance), goal directed (having measurable aims or objectives), distinct items (concrete or specific instrument items or functions). Conclusions Most patients felt the PSFS better measured their goals because it is a simple, personalized instrument with distinct domains. Clinical relevance Whereas standardized PROMs may better compare across populations, physicians, or conditions, employing PROMs that address patient-specific goals may better assess aspects of care most important to patients. A combination of these 2 types of PROMs can be used to assess outcomes and inform quality of care.

Background There is an urgent need to develop biomarkers that stratify risk of bacterial infection in order to support antimicrobial stewardship in emergency hospital admissions. Methods We used computational machine learning to derive a rule-out blood transcriptomic signature of bacterial infection (SeptiCyte™ TRIAGE) from eight published case-control studies. We then validated this signature by itself in independent case-control data from more than 1500 samples in total, and in combination with our previously published signature for viral infections (SeptiCyte™ VIRUS) using pooled data from a further 1088 samples. Finally, we tested the performance of these signatures in a prospective observational cohort of emergency department (ED) patients with fever, and we used the combined SeptiCyte™ signature in a mixture modelling approach to estimate the prevalence of bacterial and viral infections in febrile ED patients without microbiological diagnoses. Results The combination of SeptiCyte™ TRIAGE with our published signature for viral infections (SeptiCyte™ VIRUS) discriminated bacterial and viral infections in febrile ED patients, with a receiver operating characteristic area under the curve of 0.95 (95% confidence interval 0.90–1), compared to 0.79 (0.68–0.91) for WCC and 0.73 (0.61–0.86) for CRP. At pre-test probabilities 0.35 and 0.72, the combined SeptiCyte™ score achieved a negative predictive value for bacterial infection of 0.97 (0.90–0.99) and 0.86 (0.64–0.96), compared to 0.90 (0.80–0.94) and 0.66 (0.48–0.79) for WCC and 0.88 (0.69–0.95) and 0.60 (0.31–0.72) for CRP. In a mixture modelling approach, the combined SeptiCyte™ score estimated that 24% of febrile ED cases receiving antibacterials without a microbiological diagnosis were due to viral infections. Our analysis also suggested that a proportion of patients with bacterial infection recovered without antibacterials. Conclusions Blood transcriptional biomarkers offer exciting opportunities to support precision antibacterial prescribing in ED and improve diagnostic classification of patients without microbiologically confirmed infections.

Purpose A question prompt list (QPL) is a tool that lists possible questions a patient may want to ask their surgeon. Its purpose is to improve patient-physician communication and increase patient engagement. Although QPLs have been developed in other specialties, one does not exist for hand conditions. We sought to develop a QPL for use in the hand surgery clinic using a mixed-methods design. Methods We drafted a QPL based on prior work outside of hand surgery and then used an exploratory sequential mixed-methods design (both qualitative and quantitative methods) to finalize the QPL. Qualitative evaluation included both a written questionnaire completed by a patient advisory board, hand therapists, and hand surgeons, as well as cognitive interviews conducted with clinic patients using the tool. Revisions to the QPL were made after each phase of qualitative analysis. The final QPL was then evaluated quantitatively using the system usability score (SUS) questionnaire to assess its usability. Results A patient advisory board consisting of 6 patients, 5 hand therapists, and 6 hand surgeons completed the written questionnaire. Thirteen patients completed a cognitive interview of the QPL. We completed a content analysis of the qualitative data and incorporated the findings into the QPL. Twenty patients then reviewed the final QPL pamphlet and completed the SUS questionnaire. The resulting SUS score of 78.8 indicated above-average usability of the QPL tool. Conclusions The QPL developed in this study, from the perspective of multiple stakeholders, provides a usable tool to engage and prompt patients in asking questions during their visit with their hand surgeon with the potential to improve communication and patient-centered care. Clinical relevance This study provides clinicians with a QPL developed for use in the hand surgery clinic setting, aimed at facilitating more thorough patient-provider discussion.

Carpal tunnel syndrome requires multiple decisions during its management, including regarding preoperative studies, surgical technique, and postoperative wound management. Whether patients have varying preferences for the degree to which they share in decisions during different phases of care has not been explored. The goal of our study was to evaluate the degree to which patients want to be involved along the care pathway in the management of carpal tunnel syndrome.We performed a prospective, multicenter study of patients undergoing carpal tunnel surgery at 5 academic medical centers. Patients received a 27-item questionnaire to rate their preferred level of involvement for decisions made during 3 phases of care for carpal tunnel surgery: preoperative, intraoperative, and postoperative. Preferences for participation were quantified using the Control Preferences Scale. These questions were scored on a scale of 0 to 4, with patient-only decisions scoring 0, semiactive decisions scoring 1, equally collaborative decisions scoring 2, semipassive decisions scoring 3, and physician-only decisions scoring 4. Descriptive statistics were calculated.Seventy-one patients completed the survey between November 2018 and April 2019. Overall, patients preferred semipassive decisions in all phases of care (median score, 3). Patients preferred equally collaborative decisions for preoperative decisions (median score, 2). Patients preferred a semipassive decision-making role for intraoperative and postoperative decisions (median score, 3), suggesting these did not need to be equally shared.Patients with carpal tunnel syndrome prefer varying degrees of involvement in the decision-making process of their care and prefer a semipassive role in intraoperative and postoperative decisions.Strategies to engage patients to varying degrees for all decisions during the management of carpal tunnel syndrome, such as decision aids for preoperative surgical decisions and educational handouts for intraoperative decisions, may facilitate aligning decisions with patient preferences for shared decision-making.

Purpose Hand conditions are common, and often require a discussion of the tradeoffs of different treatment options. Our goal was to evaluate whether providing patients with a Question Prompt List (QPL) for common hand conditions improves their perceived involvement in care compared with providing patients with 3 generic questions. Methods We performed a prospective, single-center, pragmatic randomized controlled trial. We created a QPL pamphlet for patients with common hand conditions. New patients with common hand conditions were enrolled between April 2019 and July 2019 and were randomized into either the QPL group (with 35 hand-specific questions) or the AskShareKnow group (3 generic questions: [1] What are my options? [2] What are the possible benefits and harms of those options? [3] How likely are each of these benefit and harms to happen to me?). Both groups received the questions prior to meeting with their surgeon. We used the Perceived Involvement in Care Scale (PICS), a validated instrument designed to evaluate patient participation in decision-making, as our primary outcome. The maximum PICS score is 13, and a higher score indicates higher perceived involvement. Results One hundred twenty-six patients participated in the study, with 63 patients in the QPL group and 63 patients in the AskShareKnow group. The demographic characteristics were similar in the 2 groups. The mean AskShareKnow group PICS score was 8.3 ± 2.2 and the mean QPL PICS score was 7.5 ± 2.8, which was not deemed clinically significant. Conclusions The QPLs do not increase perceived involvement in care in patients with hand conditions compared with providing patients with 3 generic questions. Clinical relevance Various approaches have been evaluated to help improve patient involvement in their care. In hand surgery, 3 generic questions were no different than a lengthy QPL with respect to patient involvement in their care.

STUDY DESIGN A retrospective cohort study. OBJECTIVE To compare the complications between posterior cervical fusions with and without recombinant human bone morphogenetic protein 2 (rhBMP2). SUMMARY OF BACKGROUND DATA Use of rhBMP2 in anterior cervical spinal fusion procedures can lead to potential complications such as neck edema, resulting in airway complications or neurological compression. However, there are no data on the complications associated with the "off-label" use of rhBMP2 in upper and lower posterior cervical fusion approaches. MATERIALS AND METHODS Patients from the PearlDiver database who had a posterior cervical fusion between 2005 and 2011 were identified. We evaluated complications within 90 days after fusion and data was divided in 2 groups: (1) posterior cervical fusion including upper cervical spine O-C2 (upper group) and (2) posterior cervical fusion including lower cervical spine C3-C7 (lower group). Complications were divided into: any complication, neck-related complications, wound-related complications, and other complications. RESULTS Of the 352 patients in the upper group, 73 patients (20.7%) received rhBMP2, and 279 patients (79.3%) did not. Likewise, in the lower group of 2372 patients, 378 patients (15.9%) had surgery with rhBMP2 and 1994 patients (84.1%) without. In the upper group, complications were observed in 7 patients (9.6%) with and 34 patients (12%) without rhBMP2. In the lower group, complications were observed in 42 patients (11%) with and 276 patients (14%) without rhBMP2. Furthermore, in the lower group the wound-related complications were significantly higher in the rhBMP2 group (23 patients, 6.1%) compared with the non-rhBMP2 group (75 patients, 3.8%). CONCLUSIONS Our data showed that the use of rhBMP2 does not increase the risk of complications in upper cervical spine fusion procedures. However, in the lower cervical spine, rhBMP2 may elevate the risk of wound-related complications. Overall, there were no major complications associated with the use of rhBMP2 for posterior cervical fusion approaches. LEVEL OF EVIDENCE Level III.

Study Design: A multicenter, retrospective review of C5 palsy after cervical spine surgery. Objective: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. Methods: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ2 tests or Fisher exact tests for categorical variables. Results: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). Conclusion: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date.

Study Design: A multicentered retrospective case series. Objective: To determine the incidence and circumstances surrounding the development of a symptomatic postoperative epidural hematoma in the cervical spine. Methods: Patients who underwent cervical spine surgery between January 1, 2005, and December 31, 2011, at 23 institutions were reviewed, and all patients who developed an epidural hematoma were identified. Results: A total of 16 582 cervical spine surgeries were identified, and 15 patients developed a postoperative epidural hematoma, for a total incidence of 0.090%. Substantial variation between institutions was noted, with 11 sites reporting no epidural hematomas, and 1 site reporting an incidence of 0.76%. All patients initially presented with a neurologic deficit. Nine patients had complete resolution of the neurologic deficit after hematoma evacuation; however 2 of the 3 patients (66%) who had a delay in the diagnosis of the epidural hematoma had residual neurologic deficits compared to only 4 of the 12 patients (33%) who had no delay in the diagnosis or treatment (P = .53). Additionally, the patients who experienced a postoperative epidural hematoma did not experience any significant improvement in health-related quality-of-life metrics as a result of the index procedure at final follow-up evaluation. Conclusion: This is the largest series to date to analyze the incidence of an epidural hematoma following cervical spine surgery, and this study suggest that an epidural hematoma occurs in approximately 1 out of 1000 cervical spine surgeries. Prompt diagnosis and treatment may improve the chance of making a complete neurologic recovery, but patients who develop this complication do not show improvements in the health-related quality-of-life measurements.

Study Design: A retrospective multicenter study. Objective: Routine cervical spine surgeries are typically associated with low complication rates, but serious complications can occur. Intraoperative death is a very rare complication and there is no literature on its incidence. The purpose of this study was to determine the intraoperative mortality rates and associated risk factors in patients undergoing cervical spine surgery. Methods: Twenty-one surgical centers from the AOSpine North America Clinical Research Network participated in the study. Medical records of patients who received cervical spine surgery from January 1, 2005, to December 31, 2011, were reviewed to identify occurrence of intraoperative death. Results: A total of 258 patients across 21 centers met the inclusion criteria. Most of the surgeries were done using the anterior approach (53.9%), followed by posterior (39.1%) and circumferential (7%). Average patient age was 57.1 ± 13.2 years, and there were more male patients (54.7% male and 45.3% female). There was no case of intraoperative death. Conclusions: Death during cervical spine surgery is a very rare complication. In our multicenter study, there was a 0% mortality rate. Using an adequate surgical approach for patient diagnosis and comorbidities may be the reason how the occurrence of this catastrophic adverse event was prevented in our patient population.

Summary Background Blood transcriptional signatures are candidates for non-sputum triage or confirmatory tests of tuberculosis. Prospective head-to-head comparisons of their diagnostic accuracy in real-world settings are necessary to assess their clinical use. We aimed to compare the diagnostic accuracy of candidate transcriptional signatures identified by systematic review, in a setting with a high burden of tuberculosis and HIV. Methods We did a prospective observational study nested within a diagnostic accuracy study of sputum Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) tests for pulmonary tuberculosis. We recruited consecutive symptomatic adults aged 18 years or older self-presenting to a tuberculosis clinic in Cape Town, South Africa. Participants provided blood for RNA sequencing, and sputum samples for liquid culture and molecular testing using Xpert and Ultra. We assessed the diagnostic accuracy of candidate blood transcriptional signatures for active tuberculosis (including those intended to distinguish active tuberculosis from other diseases) identified by systematic review, compared with culture or Xpert MTB/RIF positivity as the standard reference. In our primary analysis, patients with tuberculosis were defined as those with either a positive liquid culture or Xpert result. Patients with missing blood RNA or sputum results were excluded. Our primary objective was to benchmark the diagnostic accuracy of candidate transcriptional signatures against the WHO target product profile (TPP) for a tuberculosis triage test. Findings Between Feb 12, 2016, and July 18, 2017, we obtained paired sputum and RNA sequencing data from 181 participants, 54 (30%) of whom had confirmed pulmonary tuberculosis. Of 27 eligible signatures identified by systematic review, four achieved the highest diagnostic accuracy with similar area under the receiver operating characteristic curves (Sweeney3: 90·6% [95% CI 85·6–95·6]; Kaforou25: 86·9% [80·9–92·9]; Roe3: 86·9% [80·3–93·5]; and BATF2: 86·8% [80·6–93·1]), independent of age, sex, HIV status, previous tuberculosis, or sputum smear result. At test thresholds that gave 70% specificity (the minimum WHO TPP specificity for a triage test), these four signatures achieved sensitivities between 83·3% (95% CI 71·3–91·0) and 90·7% (80·1–96·0). No signature met the optimum criteria, of 95% sensitivity and 80% specificity proposed by WHO for a triage test, or the minimum criteria (of 65% sensitivity and 98% specificity) for a confirmatory test, but all four correctly identified Ultra-positive, culture-negative patients. Interpretation Selected blood transcriptional signatures met the minimum WHO benchmarks for a tuberculosis triage test but not for a confirmatory test. Further development of the signatures is warranted to investigate their possible effects on clinical and health economic outcomes as part of a triage strategy, or when used as add-on confirmatory test in conjunction with the highly sensitive Ultra test for Mycobacterium tuberculosis DNA. Funding Royal Society Newton Advanced Fellowship, Wellcome Trust, National Institute of Health Research, and UK Medical Research Council.

Mycobacterium tuberculosis (Mtb) is a highly efficient facultative intracellular pathogen circumventing attempts by the immune system to eradicate it. Alveolar macrophages are the primary target for intracellular invasion, and central to its pathogenesis is Mtb’s remarkable capacity to survive and proliferate within the hostile environment of these professional phagocytic cells. Despite its status as an intracellular pathogen, numerous extracellular bacteria can be found in caseating granulomas, the histopathological hallmark of TB disease. Mycobacterium marinum, the closest genetic relative to Mtb, thrives extracellularly in the absence of macrophages in zebrafish. Extracellular Mtb seen in histopathological lesions are likely to arise, at least in part, from macrophage necrosis which is associated with outer membrane damage and release of nuclear and cytoplasmic contents into the extracellular space. But several organisms, including other mycobacteria, have versatile strategies for escape into the extracellular environment, both by triggering cell lysis and leaving the host cell intact. The exit of intracellular organisms is a crucial stage of pathogenesis since cellular escape facilitates spread of infection to neighbouring cell, tissue invasion and onward transmission to new hosts. However, our understanding of the exit of Mtb from human macrophages is limited. Because studies examining mycobacterial control in various in vitro and in vivo models have not sought to quantify extracellular Mtb, the relative ratio and clinical relevance of this population to overall bacterial burden remains a matter of debate. In this study we use a novel high throughput flow cytometric assay based on quantitation of fluorescent Mtb to show that bacteria do not solely remain intracellular upon infection of macrophages, but a significant amount are located extracellularly. Our mathematical model to describe intracellular and extracellular bacillary accumulation predicts that bacteria must be accumulating in the extracellular space by means of a cytolysis independent strategy. We demonstrate the never previously described exit of Mtb from human macrophages by non-lytic egress and experimentally determine the rate at which this occurs. Non-lytic egress may be associated with virulence since we find that Mycobacterium Bovis bacillus Calmette-Guerin (BCG) does not exhibit the same behaviour.

Background We describe drug-induced liver injury (DILI) secondary to antituberculous treatment (ATT) in a large tuberculosis (TB) centre in London; we identify the proportion who had risk factors for DILI and the timing and outcome of DILI. Methods We identified consecutive patients who developed DILI whilst on treatment for active TB; patients with active TB without DILI were selected as controls. Comprehensive demographic and clinical data, management and outcome were recorded. Results There were 105 (6.9%) cases of ATT-associated DILI amongst 1529 patients diagnosed with active TB between April 2010 and May 2014. Risk factors for DILI were: low patient weight, HIV-1 co-infection, higher baseline ALP, and alcohol intake. Only 25.7% of patients had British or American Thoracic Society defined criteria for liver test (LT) monitoring. Half (53%) of the cases occurred within 2 weeks of starting ATT and 87.6% occurred within 8 weeks. Five (4.8%) of seven deaths were attributable to DILI. Conclusions Only a quarter of patients who developed DILI had British or American Thoracic Society defined criteria for pre-emptive LT monitoring, suggesting that all patients on ATT should be considered for universal liver monitoring particularly during the first 8 weeks of treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2330-z) contains supplementary material, which is available to authorized users.

The Compress implant is used to achieve compliant fixation for endoprosthetic reconstruction during limb salvage. Failures, when they occur, are typically at the bone-implant interface. We describe a case of implant failure at a modular junction near a cold-welded taper adapter, blocking access to the spindle nut. Salvage of the anchor plug was performed in this case to avoid re-cutting the remaining bone.

BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1–negative individuals, and 0.85 in HIV-1–infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR., Blood BATF2 transcripts provide a single biomarker for active tuberculosis and a novel four-gene transcriptional signature differentiates active TB from other infectious diseases with fever.

The purpose of this study was to examine the movement of the spinal cord and its relationship to the spinal canal in patients with mild spondylosis using kinetic magnetic resonance imaging (kMRI).Weight-bearing, multiposition kMRI was performed on symptomatic patients through a full range of flexion-extension. A total of 52 study patients were selected based on the C2-C7 Cobb angle of sagittal alignment: lordotic (from 30 to 45 degrees). We evaluated dynamic changes in different parameters from flexion-extension: spinal canal diameter (CD), spinal cord diameter (SCD), space available for the cord, anterior space available for the cord (ASAC), posterior space available for the cord (PSAC), average distance between the anterior canal and the cord (d-value), and global angle for the spinal canal and cord.The CD tended to decrease from flexion to extension from C3/C4 to C6/C7, however, there were no significant differences at the proximal and distal levels, C2/C3 and C7/T1. There were no significant differences of SCD between different postures. The SCD tended to decrease from C2/C3 to C7/T1. The ASAC followed the same pattern as CD-values. The ASAC was narrowest at C4/C5 and C5/C6. The PSAC tended to increase from C2/C3 to C7/T1. The spinal cord shifted anteriorly with extension and posteriorly with flexion. In addition, the spinal cord maintained its curve with the movement.The kinematics of spinal cord motion may be associated with the pathogenesis of cervical spondylotic myelopathy. However, the spinal cord maintains its curve with position changes. Consequently, different motions of the cervical spine may affect spinal cord migration and cause changes in ASAC and PSAC.

The decision to treat active tuberculosis (TB) is dependent on microbiological tests for the organism or evidence of disease compatible with TB in people with a high demographic risk of exposure. The tuberculin skin test and peripheral blood interferon-γ release assays do not distinguish active TB from a cleared or latent infection. Microbiological culture of mycobacteria is slow. Moreover, the sensitivities of culture and microscopy for acid-fast bacilli and nucleic acid detection by PCR are often compromised by difficulty in obtaining samples from the site of disease. Consequently, we need sensitive and rapid tests for easily obtained clinical samples, which can be deployed to assess patients exposed to TB, discriminate TB from other infectious, inflammatory or autoimmune diseases, and to identify subclinical TB in HIV-1 infected patients prior to commencing antiretroviral therapy. We discuss the evaluation of peripheral blood transcriptomics, proteomics and metabolomics to develop the next generation of rapid diagnostics for active TB. We catalogue the studies published to date seeking to discriminate active TB from healthy volunteers, patients with latent infection and those with other diseases. We identify the limitations of these studies and the barriers to their adoption in clinical practice. In so doing, we aim to develop a framework to guide our approach to discovery and development of diagnostic biomarkers for active TB.

Microbial productivity at hydrothermal vents is among the highest found anywhere in the deep ocean, but constraints on microbial growth and metabolism at vents are lacking. We used a combination of cultivation, molecular, and geochemical tools to verify pure culture H 2 threshold measurements for hyperthermophilic methanogenesis in low-temperature hydrothermal fluids from Axial Volcano and Endeavour Segment in the northeastern Pacific Ocean. Two Methanocaldococcus strains from Axial and Methanocaldococcus jannaschii showed similar Monod growth kinetics when grown in a bioreactor at varying H 2 concentrations. Their H 2 half-saturation value was 66 μM, and growth ceased below 17–23 μM H 2 , 10-fold lower than previously predicted. By comparison, measured H 2 and CH 4 concentrations in fluids suggest that there was generally sufficient H 2 for Methanocaldococcus growth at Axial but not at Endeavour. Fluids from one vent at Axial (Marker 113) had anomalously high CH 4 concentrations and contained various thermal classes of methanogens based on cultivation and mcrA / mrtA analyses. At Endeavour, methanogens were largely undetectable in fluid samples based on cultivation and molecular screens, although abundances of hyperthermophilic heterotrophs were relatively high. Where present, Methanocaldococcus genes were the predominant mcrA / mrtA sequences recovered and comprised ∼0.2–6% of the total archaeal community. Field and coculture data suggest that H 2 limitation may be partly ameliorated by H 2 syntrophy with hyperthermophilic heterotrophs. These data support our estimated H 2 threshold for hyperthermophilic methanogenesis at vents and highlight the need for coupled laboratory and field measurements to constrain microbial distribution and biogeochemical impacts in the deep sea.

Strombolian-style volcanic activity has persisted for six years at the NW Rota-1 submarine volcano in the southern Mariana Arc, allowing direct observation and sampling of gas-rich fluids produced by actively degassing lavas, and permitting study of the magma-hydrothermal transition zone. Fluids sampled centimeters above erupting lava and percolating through volcaniclastic sediments around an active vent have dissolved sulfite >100 mmol/kg, total dissolved sulfide 1 mmol/kg. If NW Rota is representative of submarine arc eruptions, then volcanic vent fluids from seawater-lava interaction on submarine arcs have a significant impact on the global hydrothermal flux of sulfur and Al to the oceans, but a minimal impact on Mg removal. Gas ratios (SO 2 , CO 2 , H 2 , and He) are variable on small spatial and temporal scales, indicative of solubility fractionation and gas scrubbing. Elemental sulfur (S e ) is abundant in solid and molten form, produced primarily by disproportionation of magmatic SO 2 injected into seawater. S e accumulates within the porous rock surrounding the lava conduit connecting the magma source to the seafloor. Accumulated S e can be heated, melted, and pushed upward by rising magma to produce molten S e flows and lavas saturated with S e . Molten S e near the top of the lava conduit may be ejected up into the water column by escaping gases or boiling water. This mechanism of S e accumulation and refluxing may underlie the relatively widespread occurrence of S e deposits of many sizes found on submarine arc volcanoes.

The Laser Inertial Fusion Energy (LIFE) concept is being designed to operate as either a pure fusion or hybrid fusion-fission system. The present work focuses on the pure fusion option. A key component of a LIFE engine is the fusion chamber subsystem. It must absorb the fusion energy, produce fusion fuel to replace that burned in previous targets, and enable both target and laser beam transport to the ignition point. The chamber system also must mitigate target emissions, including ions, x-rays and neutrons and reset itself to enable operation at 10-15 Hz. Finally, the chamber must offer a high level of availability, which implies both a reasonable lifetime and the ability to rapidly replace damaged components. An integrated design that meets all of these requirements is described herein.

In 2009, the Consortium of Academic and Research Libraries in Illinois (CARLI) charged a task force to update and revise recommendations that address cataloging practice and catalog access to electronic resources for libraries participating in the I-Share union catalog. This article presents the results of a survey and recommendations developed by the 2009 Task Force that cover all types of e-resources. Issues covered include: single or separate records for electronic and print versions of a title; the use of aggregator-neutral and provider neutral records; the construction and placement of the Uniform Resource Locator (URL) and notes; and the use of vendor records.

The current study evaluated the structure of a revised (shortened) version of the Creativity Domain Questionnaire (CDQ), examined its relationship with five personality factors, and analyzed potential differences in creativity domains based upon gender and occupational status. One hundred eighty-two students and 60 warehouse employees completed the Revised Creativity Domain Questionnaire (CDQ-R) and the Big Five Factor Markers. Consistent with an exploratory factor analysis of pilot data, a subsequent confirmatory factor analysis of these data supported a four-factor structure for the CDQ-R. Correlations between these four creativity domains and the Big Five personality factors generally were consistent with theoretical expectations. Effects for gender also were consistent with theory. Women perceived themselves as more creative in the Arts general domain while men perceived themselves significantly more creative in Math/Science. There were no effects for occupational status. Creativity takes place in diverse contexts, and we cannot expect the personalities of people who create in different domains to be the same, or to differ in the same ways from comparison subjects. (Helson, 1996, p. 303)

Since 1950, the Human Relations Area Files, Inc. has produced what is currently known as the eHRAF Collection of Ethnography. This article explores the reasons why it was created and describes the structure of this complex collection of ethnographic works. Over time, this resource has been produced in four different formats: paper slips, microfiche, CD-ROM, and online. The similarities among and differences between these are discussed. An attempt to locate any remaining paper sets is described, and a list of current locations of the file in this, its original form, is included.

SUMMARY The authors review the contents of Cataloging & Classification Quarterly and provide an examination of the contributors, article types, and changes in emphasis in topics.