Project NexGen: Developing the Next Generation of COVID-19 Vaccines and Therapeutics to Respond to the Present and Prepare for the Future.

COVID-19 epidemiology and product landscapes have changed considerably since onset of the pandemic. Safe and effective vaccines and therapeutics are available, but the continual emergence of SARS-CoV-2 variants introduce limitations in our ability to prevent and treat disease. Project NextGen is a collaboration between the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR), and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, that is leveraging public-private partnerships to address gaps in the nation's COVID-19 vaccine and therapeutic capabilities. Targeted investments will advance promising next-generation candidates through the most difficult phases of clinical development to encourage further private sector interest for later stage development and commercial availability. New commercial vaccines and therapeutics that are more durable and effective across variants will improve our fight against COVID-19 and transform our response to future threats.

Acute calcium pyrophosphate crystal arthritis is associated with an increased rate of hip and knee joint surgery.

OBJECTIVE: Acute calcium pyrophosphate (CPP) crystal arthritis is a distinct manifestation of calcium pyrophosphate crystal deposition (CPPD). No studies have specifically examined whether acute CPP crystal arthritis is associated with progressive structural joint damage. The objective of this retrospective cohort study was to evaluate the relative rate of hip and knee joint arthroplasties as an estimate of structural joint damage accrual, in a population of patients with acute CPP crystal arthritis. METHODS: Data were collected from Waikato District Health Board (WDHB) to identify an acute CPP crystal arthritis cohort with clinical episodes highly characteristic of acute CPP crystal arthritis. Data on hip and knee joint arthroplasties were collected from the New Zealand Orthopaedic Association's Joint Registry. The rate of arthroplasties in the cohort was compared with the age-ethnicity-matched New Zealand population. Additional analysis was performed for age, obesity (BMI) and ethnicity. RESULTS: The acute CPP crystal arthritis cohort included 99 patients; 63 were male and the median age was 77 years (interquartile range, 71-82). The obesity rate was 36% with a median BMI of 28.4 kg/m2 (interquartile range, 25.8-32.2), comparable to the New Zealand population. The standardized surgical rate ratio in the cohort vs the age-ethnicity-matched New Zealand population was 2.54 (95% CI: 1.39, 4.27). CONCLUSION: Our study identified a considerable increase in the rate of hip and knee joint arthroplasties in patients with episodes of acute CPP crystal arthritis. This suggests CPP crystal arthritis may be a chronic condition, leading to progressive joint damage.

Single-Operator Left atrial appendage Occlusion utilizing Conscious sedation TEE, Lack of Outpatient pre-imaging, and Same-day Expedited discharge (SOLO-CLOSE): A comparison with conventional approach.

BACKGROUND: Left atrial appendage occlusion (LAAO) with WATCHMAN currently requires preprocedural imaging, general anesthesia, and inpatient overnight admission. We sought to facilitate simplification of LAAO. AIMS: We describe and compare SOLO-CLOSE (single-operator LAA occlusion utilizing conscious sedation TEE, lack of outpatient pre-imaging, and same-day expedited discharge) with the conventional approach (CA). METHODS: A single-center retrospective analysis of 163 patients undergoing LAAO between January 2017 and April 2022 was conducted. The SOLO-CLOSE protocol was enacted on December 1, 2020. Before this date, we utilized the CA. The primary efficacy endpoint was defined as successful LAAO with ≤5 mm peri-device leak at time of closure. The primary safety endpoint was the composite incidence of all-cause deaths, any cerebrovascular accident (CVA), device embolization, pericardial effusion, or major postprocedure bleeding within 7 days of the index procedure. Procedure times, 7-day readmission rates, and cost analytics were collected as well. RESULTS: Baseline characteristics were similar in both cohorts. Congestive heart failure (37.5% vs. 11.1%) and malignancy (28.8% vs. 12.5%) were higher in SOLO-CLOSE. Median CHA2D2SVASc score was 5 in both cohorts. The primary efficacy endpoint was met 100% in both cohorts. Primary safety endpoint was similar between cohorts (p = 0.078). Mean procedure time was 30 min shorter in SOLO-CLOSE (p < 0.01). Seven-day readmissions for SOLO-CLOSE was zero. After SOLO-CLOSE implementation, there was a 188% increase in positive contribution margin per case. CONCLUSIONS: The SOLO-CLOSE methodology offers similar efficacy and safety when compared to the CA, while improving clinical efficiency, reducing procedural times, and increasing economic benefit.

Enal-azomethine ylides: application in the synthesis of functionalized pyrroles.

Rhodium-catalyzed [3 + 2] annulation of diazoenals and N-alkyl imines resulted in N-alkyl-pyrrole-3-carbaldehyde derivatives. The reaction involves thermal 6π-electrocyclization and aromatization of a new class of enal-azomethine ylides (EAYs). The EAYs derived from dihydroisoquinoline and 2H-azirine gave fused-pyrrole and pyridine derivatives, respectively. The synthetic importance of pyrrole products has been demonstrated by one-step synthesis of the biologically relevant pyrrolo[3,2-c]quinoline scaffold as well as pyrrolo[2,1-a]isoquinoline which is a core structure of lamellarin alkaloids.

Safety Parameters for the Use of Holmium:YAG Laser in the Treatment of Biliary Calculi: The Ex-Vivo Model.

Background and Objectives: While studies have demonstrated the efficacy of cholangioscopy-guided Holmium-Yttrium aluminum garnet (Ho:YAG) laser lithotripsy for the treatment of refractory bile duct stones, data regarding the safety of the operating parameters for laser lithotripsy are lacking. The aim of this study was to determine safe, yet effective, energy settings for Ho:YAG laser in the ex-vivo model. Materials and Methods: This ex vivo experimental study utilized the Ho:YAG laser on porcine bile duct epithelium and human gallstones. Ho:YAG laser lithotripsy was applied in different power settings from 8 to 15 Watts (W) to six explanted porcine bile ducts. Settings that appeared safe were then utilized to fragment seventy-three human gallstones. Results: The median bile duct perforation times with the Ho:YAG laser between 8-15 W were: >60 s (8 W); 23 s (9 W); 29 s (10 W); 27 s (12 W); 12 s (14 W); and 8 s (15 W). Statistically significant differences in the median perforation times were noted between 8 W vs. 15 W, 9 W vs. 15 W, 10 W vs. 15 W, and 12 W vs. 15 W (p < 0.05). When using a 365 µm Ho:YAG laser probe at 8-12 W, the fragmentation rates on various size stones were: 100% (<1.5 cm); 80-100% (1.6-2.0 cm) and 0-32% (>2.0 cm). Optimal fragmentation was seen utilizing 12 W with high energy (2.4 J) and low frequency (5 Hz) settings. Using a larger 550 µm probe at these settings resulted in 100% fragmentation of stones larger than 2 cm. Conclusions: The Ho:YAG laser appears to be safe and effective in the treatment of large bile duct stones when used between 8-12 W in 5 s bursts in an ex vivo model utilizing porcine bile ducts and human gallstones.

Ankle fractures with Chaput fragment: A new classification system with insights into morphology and relation to surgical treatment.

BACKGROUND: The Chaput fragment, a bony avulsion of the anterolateral margin of the distal tibia, is a less commonly discussed fracture pattern in ankle injuries. Its significance in ankle fractures and the optimal fixation technique remains unclear due to limited literature. This study aims to describe the morphology of ankle fractures with Chaput fragment and introduce a new classification system. MATERIALS AND METHODS: We retrospectively analyzed 33 patients with ankle fractures with associated Chaput fragment treated at our institute over a 3-year period. Data on patient demographics, fracture classification, surgical approach, and fixation method were collected, and a novel classification system for Chaput fragments was proposed. RESULTS: Four distinct morphological types of Chaput fragment were identified (types 1-4), and three newer variants of trimalleolar fractures were identified (anterior, lateral, and medial variants). Type 1 refers to a small avulsion fragment attached to the anterior-inferior tibiofibular ligament; Type 2 is an anterolateral oblique type; Type 3 refers to an anterolateral fragment with extension into the medial malleolus and Type 4 is a comminuted Chaput fragment. Type 1 Chaput fragment was the most prevalent (60.6%), followed by Type 2 (24.3%), Type 4 (9.1%), and Type 3 (6.1%). The fixation methods ranged from screw fixation, plate fixation, and suture fixation to combinations of these techniques or even indirect stabilization with syndesmotic screws. CONCLUSION: Our new classification system based on morphology includes all possible variants of Chaput fracture. This preliminary data needs to be corroborated by more studies and validated by a larger number of observers.

Global prospective case series of ERCPs using a single-use duodenoscope.

BACKGROUND: The first commercialized single-use duodenoscope was cleared by the US Food and Drug Administration in December 2019. Data regarding endoscopic retrograde cholangiopancreatography (ERCP) using a single-use duodenoscope are needed on a broader range of cases conducted by endoscopists with varying levels of experience in a wide range of geographic areas. METHODS: 61 endoscopists at 22 academic centers in 11 countries performed ERCP procedures in adult patients aged ≥ 18. Outcomes included ERCP completion for the intended indication, rate of crossover to a reusable endoscope, device performance ratings, and serious adverse events (SAEs). RESULTS: Among 551 patients, 236 (42.8 %) were aged > 65, 281 (51.0 %) were men, and 256 (46.5 %) had their procedure as an inpatient. ERCPs included 196 (35.6 %) with American Society for Gastrointestinal Endoscopy complexity of grades 3-4. A total of 529 ERCPs (96.0 %) were completed: 503 (91.3 %) using only the single-use duodenoscope, and 26 (4.7 %) with crossover to a reusable endoscope. There were 22 ERCPs (4.0 %) that were not completed, of which 11 (2.0 %) included a crossover and 11 (2.0 %) were aborted cases (no crossover). Median ERCP completion time was 24.0 minutes. Median overall satisfaction with the single-use duodenoscope was 8.0 (scale of 1 to 10 [best]). SAEs were reported in 43 patients (7.8 %), including 17 (3.1 %) who developed post-ERCP pancreatitis. CONCLUSIONS: In academic medical centers over a wide geographic distribution, endoscopists with varying levels of experience using the first marketed single-use duodenoscope had good ERCP procedural success and reported high performance ratings for this device.

Pediatric ERCP: Factors for Success and Complication-A 17-Year, Multisite Experience.

OBJECTIVES: Endoscopic retrograde cholangiopancreatography (ERCP) is an increasingly utilized procedure in pediatric populations. A lack of dedicated pediatric research has led endoscopists to extrapolate adult risk factors and preventative strategies to children. The aim of this multisite, retrospective study was to identify risks for adverse events, procedure failure, and prolonged courses in pediatric patients undergoing ERCP. METHODS: Pediatric patients who had an ERCP at one of our academic centers were identified by query of their electronic medical records. Pre-procedure and post-procedure data were collected with ERCP-related adverse events defined according to the consensus criteria developed by Cotton et al 2010. RESULTS: Between January 2004 and January 2021, 287 children had a total of 716 ERCPs. The procedure success rate was 95.5% with no mortality and an adverse event rate of 12.7%. Younger age was associated with increased case complexity, increased adverse events, and an increased rate of repeat ERCP. Case complexity score correlated with increased procedure time ( P < 0.001) and increased adverse events (tau 0.24, P < 0.01); stent removal and pancreatic stenting were more likely to precede an adverse event. Pancreatitis, pancreatic divisum, and pancreatic stricture/stenosis were associated with increased adverse events and rates of repeat ERCP. CONCLUSIONS: Pediatric ERCP adverse event rates are higher than adults. The complexity grading system proposed by the Cotton et al appears to have applicability to pediatric patients. Young age and interventions affecting the pancreatic duct are associated with adverse ERCP outcomes in pediatrics.

Does robotic-assisted surgery improve outcomes of total hip arthroplasty compared to manual technique? A systematic review and meta-analysis.

BACKGROUND: Robot-assisted total hip arthroplasty (THA) is an emerging technology that claims to position implants with very high accuracy. However, there is currently limited data in literature on whether this improved accuracy leads to better long-term clinical outcomes. This systematic review compares the outcomes of THA done with the help of robotic assistance (RA) to those done with conventional manual techniques (MTs). METHODS: Four electronic databases were searched for eligible articles that directly compared robot-assisted THA to manual THA and had data on the radiological or clinical outcomes of both. Data on various outcome parameters were collected. Meta-analysis was conducted using a random-effects model with 95% CIs. RESULTS: A total of 17 articles were found eligible for inclusion, and 3600 cases were analysed. Mean operating time in the RA group was significantly longer than in the MT group. RA resulted in significantly more acetabular cups being placed inside Lewinnek's and Callanan's safe zones (p<0.001) and had significantly reduced limb length discrepancy compared with MT. There were no statistically significant differences in the two groups in terms of incidence of perioperative complications, need for revision surgery and long-term functional outcome. CONCLUSION: RA leads to highly accurate implant placement and leads to significantly reduced limb length discrepancies. However, the authors do not recommend robot-assisted techniques for routine THAs due to lack of adequate long-term follow-up data, prolonged surgical times and no significant differences in the rate of complications and implant survivorship compared with conventional MTs.

The use of the femoral neck system (FNS) leads to better outcomes in the surgical management of femoral neck fractures in adults compared to fixation with cannulated screws: A systematic review and meta-analysis.

BACKGROUND: Intracapsular femoral neck fractures are challenging to treat, with outcomes depending on the quality of reduction, and the stability of fixation. Cannulated cancellous screws (CCS) are the most commonly used implants to fix these fractures, but failure rates are significant. The recently introduced femoral neck system (FNS) may be a better option than CCS fixation and this review attempts to compare the results. METHODS: Four electronic databases were searched for eligible articles that had comparative data on the outcomes of fixation of adult femoral neck fractures with FNS and CCS. Data on various outcome parameters were collected. Meta-analysis was conducted using a random-effects model with 95% confidence intervals. RESULTS: Eight studies with 509 cases having a mean age of 50.8 years were included for final analysis. FNS was found to be associated with significantly reduced complication rates (p < 0.001), decreased incidence of postoperative femoral neck shortening (p < 0.001), quicker time to fracture union (p = 0.002), and better functional outcome scores (p < 0.001) compared to cannulated screws. FNS was also associated with a shorter operating time (mean difference 6.65 min) although not statistically significant (p = 0.24). CCS group had significantly reduced mean blood loss (p < 0.001). CONCLUSION: The available literature supports FNS as a better option for adult femoral neck fractures, with a lower complication rate, quicker union, and better clinical outcomes. LEVEL OF EVIDENCE: Level 3.

Complications and mid to long term outcomes for hip resurfacing versus total hip replacement: a systematic review and meta-analysis.

INTRODUCTION: The long-term results of total hip replacement (THR) are excellent; however, it has higher failure rates in young and active patients. Hip resurfacing arthroplasty (HRA) is an alternative in such patients and gaining popularity. This review was done to compare complications and outcomes between HRA and THA by assessing the latest level 1 studies comparing the two from the past 10 years. METHOD: A systematic review and meta-analysis was conducted using three databases (PubMed, EMBASE and SCOPUS) to compare the complications between THR and HRA in medium to long term follow up. The primary outcome of interest included the complication and revision rate between the two techniques. Functional outcomes and ionic levels at follow up were also compared as secondary outcomes. Risk of bias assessment was done using the Cochrane risk of bias tool. RESULT: The present review included 6 level 1 studies. These included 308 THR and 304 HRA. On meta-analysis, overall complications rates were significantly lower in HRA compared to the THA group with an Odds ratio (OR) of 2.17 (95% CI 1.21, 3.88; p = 0.009). No difference was seen between the two groups in terms of revision rate (OR 1.06 95% CI 0.57, 1.99; p = 0.85). Functional outcomes in both the groups were satisfactory but the Harris Hip Score was found to be significantly better in the resurfacing group (MD 2.99 95% CI - 4.01, - 1.96, p < 0.00001). There were increased cobalt and chromium ions in the resurfacing group but no detrimental effect was seen in terms of reported poisoning. CONCLUSION: Despite similar function and revision rates, HRA was seen to have lesser associated complications and ionic levels may not be a detrimental issue. Hip resurfacing provides relative ease during revisions, especially in younger patients and it may be an alternative to THR in the younger population.

Per-oral pancreatoscopy-guided lithotripsy vs. extracorporeal shock wave lithotripsy for treating refractory main pancreatic duct stones in chronic pancreatitis: Protocol for an open-label multi-center randomized clinical trial.

BACKGROUNDS/OBJECTIVES: Patients with chronic pancreatitis may develop pancreatic duct stones that can obstruct outflow leading to ductal hypertension and pain. Both endoscopic retrograde pancreatography (ERP) with per-oral pancreatoscopy (POP) and intraductal lithotripsy and extracorporeal shock wave lithotripsy (ESWL) are feasible options to attempt ductal stone clearance. This study aims to compare POP-guided lithotripsy with ESWL in the management of refractory symptomatic main pancreatic duct stones. METHODS: This is an open-label, multi-center, parallel, randomized clinical trial. Patients with chronic pancreatitis and main pancreatic duct stones ≥5 mm who fail standard ERP methods for stone removal will be eligible for this study. In total, 150 subjects will be randomized 1:1 to either ESWL or POP. A maximum of 4 sessions of either ESWL or POP will be allowed in each arm, with crossover permitted thereafter. The primary outcome is complete stone clearance and secondary outcomes include quality of life, pain scores, number of interventions, and daily opiate requirements. CONCLUSIONS: This study aims to answer the question of which lithotripsy method is superior in removing refractory pancreatic duct stones while addressing the effects of lithotripsy on quality of life and pain in patients with chronic calcific pancreatitis (ClinicalTrials.gov NCT04115826).

Endoscopy versus early surgery for the management of chronic pancreatitis: a systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic stone removal and stenting of pancreatic strictures are the initial treatment for treating chronic pancreatitis-related pain. Surgery is considered when endoscopic interventions fail to improve symptoms. In this meta-analysis, we have compared early surgery versus endoscopic interventions. METHODS: The study was performed as per the PRISMA statement. The literature search was conducted on online databases to identify studies that compared endoscopy and surgery for the management of chronic pancreatitis symptoms. Primary outcomes of interest were pain relief, complications, and exocrine/endocrine insufficiency. Secondary outcomes were mean length of stay and mean number of procedures. Pooled odds ratio (OR) was calculated using random-effects model with 95% confidence interval (CI). RESULTS: Of a total of 9880 articles that were screened, three randomized controlled trials and two retrospective studies with 602 patients (71.4% males) were found to be eligible. Endoscopic interventions were performed in 317 patients and 285 patients underwent early surgery. Early surgery provided significantly better pain relief compared to endoscopy (OR 0.46; 95%CI 0.27-0.80; p = 0.01; I2 = 17.65%) and required less number of procedures (Mean difference 1.66; 95%CI 0.9-2.43; p = 0.00; I2 = 96.46%). There was no significant difference in procedure-related complication (OR 0.91; 95%CI 0.51-1.61; p = 0.74; I2 = 38.8%), endocrine (OR 1.18; 95%CI 0.63-2.20; p = 0.61; I2 = 28.24%), or exocrine insufficiency (OR 1.78; 95%CI 0.66-4.79; p = 0.25; I2 = 30.97%) or the length of stay (Mean difference 1.21; 95%CI -7.12 to 4.70; p = 0.69). CONCLUSION: Compared to endoscopy, early surgery appears to be better in controlling chronic pancreatitis-related pain, with no significant difference in procedure-related complications. However, larger randomized controlled trials are needed to ascertain their efficacy.

Primary angiosarcoma of aorta: A systematic review.

PURPOSE: To elucidate the epidemiology, anatomical, presentation, classification, pathology, investigative modalities, management and prognosis of primary angiosarcoma of the aorta. MATERIAL AND METHODS: A systematic review of literature from the database inception to January 2021 in PubMed and Embase, CINAHL and Cochrane Library in accordance to PRISMA was conducted. Retrieval and extraction was performed by two independent reviewers. The hierarchy of the evidence was assessed through the National Institute for Health and Care Excellence Checklist. Data were subjected to pooled prevalence analysis, Kaplan-Meier survival and test of probability using log-rank analysis. This review is registered with International Prospective Register of Systematic Reviews: RD42021231314. RESULTS: 82 studies with n = 123 cases met the inclusion criterion. Abdominal (45%) aorta was the commonest anatomical site with female predominance in ascending aorta (4:1) and aortic arch (2:1). The longest survival was in the ascending aorta and the shortest in the abdominal aorta [540 (interquartile range [IQR], 7-1560 days vs. 180 (IQR, 1-5730 days)], respectively. The overall median survival was 210 days (IQR, 1-5730 days) or 7 months. Lack of metastasis (47%) was a marker of longer survival (p < 0.03) irrespective of other attributes. CONCLUSION: The pathophysiology appears to be a trend of increasing fatigue, fever and weight loss associated with segmental dysfunction of the aorta projecting occlusive or destructive phenotypes. Computed tomography angiography features of volume-occupying, bulky, polypoid (intraluminal), protrusive vegetation, hyper vascular without atherosclerotic lesions are extremely suggestive of PA of the aorta at 5th and 6th decades of life.

Outcomes and complications of the INFIX technique for unstable pelvic ring injuries with high-velocity trauma: a systematic review and meta-analysis.

BACKGROUND: The pelvic INFIX technique has been proposed as a useful alternative to symphyseal plating for management of unstable pelvic ring injuries. The minimally invasive nature of the procedure, shorter operative time and less perioperative blood loss have been purported as potential advantages. QUESTIONS/PURPOSES: This systematic review and meta-analysis were conducted to determine the outcomes and complications of the INFIX technique for unstable pelvic ring injuries. METHODS: A systematic review of literature was performed on the PubMed, EMBASE and Scopus databases. Prospective and retrospective studies in all languages, whether comparative or non-comparative, pertaining to the use of INFIX in pelvic fractures were included. Studies which did not evaluate INFIX, case reports, conference abstracts and those with less than 10 cases were excluded. Cadaveric studies, technique papers and studies that did not describe the prespecified outcome measures were also excluded. Meta-analysis consisted of two different arms: a comparative arm, to compare INFIX to symphyseal plating, and a non-comparative meta-analysis arm, to determine pooled rates of outcomes and complications. Risk of bias was determined by the Methodological Index for Non-Randomised Studies (MINORS) tool. RESULTS: A total of 22 studies were included in the systematic review, of which 7 were comparative and 15 were non-comparative. 746 patients were included for qualitative analysis and pooled analysis done for 589 patients. The average follow-up of these studies ranged from a minimum of 5.4 months to a maximum of 54 months. Comparative meta-analysis (n = 3 studies) of plating and INFIX showed significantly lesser blood loss (mean difference = 176.46 mL; 95% CI - 207.54 to - 145.38) and shorter operative time (mean difference = 26.43 min, 95% CI - 31.79 to - 21.07) with INFIX, but no significant difference in the overall complication rates (OR 1.59, 95% CI 0.83-3.05) and functional outcome scores (mean difference = - 2.51, 95% CI - 5.73 to 0.71). Pooled analysis showed overall good radiological (mean percentage of excellent to good reduction = 91.4%, 95% CI 0.860-0.969) and functional outcomes (mean Majeed score = 86.48, 95% CI 83.34-89.61) with INFIX. The most common complications were lateral femoral cutaneous nerve (LFCN) injury (overall rate 28%, 95% CI 15.1-41%) and heterotopic ossification (HO) (overall rate 9.4%, 95% CI 5.5-13.3%); rates of other complications were low. Significant heterogeneity was noted in the pooled analysis of blood loss, operative time, functional outcome, HO and LFCN injury. The overall strength of evidence was found to be weak. CONCLUSION: The INFIX technique can be considered as a viable alternative to symphyseal plating for unstable pelvic ring injuries. It has the advantages of shorter operative times and less blood loss, along with comparable functional outcomes, when compared to plating. Overall, good functional outcomes can be expected. However, well-designed, multi-center randomized controlled trials are needed to conclusively prove the benefit of this technique.

Crossed Screw Fixation Versus Dorsal Plating for First Metatarsophalangeal Joint Arthrodesis: A Retrospective Cohort Study.

Multiple fixation techniques for first metatarsophalangeal joint arthrodesis have been described with an average fusion rate of 93.5%. This retrospective cohort study assesses the association between crossed screws (vs dorsal plating) and medical comorbidities and the outcome radiographic union. Bivariate tests of association and multivariable logistic regression were employed to assess differences across fixation type and outcomes. We identified 305 patients who underwent a first metatarsophalangeal joint arthrodesis during the study period. Crossed screw fixation was used in 158 (51.8%) patients while dorsal plating (tubular or anatomic locking plate) was used in 147 (48.2%) patients. Dorsal plating was utilized more often in patients with rheumatoid arthritis (p = .019) and history of smoking (p = .044). At 12 weeks post-operatively there were no significant differences in fusion rates between the two groups (crossed screw group = 95.3% vs dorsal plate group (referent) = 93.5%, Adjusted odds ratio (AOR) 1.39, 95% confidence interval [CI] 0.45-4.26). Not smoking was associated with a greater odds of fusion at 12 weeks (96.2% for nonsmokers vs 75.0% for smokers (referent), AOR 0.07, 95% CI 0.02-0.28). Lower body mass index was associated with a greater odds of fusion at 12 weeks (AOR 0.90, 95% CI 0.82-0.99). Surgeons allowed weightbearing earlier with dorsal plate fixation (2 weeks (interquartile range [IQR] 2.6) versus 5 weeks (IQR 2.6) for crossed screw fixation, p = .001). Patients with multiple medical comorbidities were more likely to require revision surgery than patients having 0-1 comorbidities (p < .05). Crossed screws can provide an inexpensive yet effective option for first metatarsophalangeal joint arthrodesis.

Addressing Transverse Plane Instability in the Modified Lapidus Arthrodesis: A Comparative Study of Screw Versus Suture and Button Fixation Device Technique.

The Lapidus arthrodesis is a powerful procedure for the correction of hallux valgus with metatarsus primus varus. Yet, first ray instability may persist despite correction of the primary deformity with 2 crossed screw fixation. A third screw is often utilized as the additional point of fixation for noteworthy residual transverse plane motion, but it is not without potential complications. The suture and button fixation device may be an appropriate alternative to the third screw construct. This retrospective cohort study identified clinical / radiographic outcomes and complication rates following a third point of fixation with either a screw or suture and button fixation device in patients undergoing a modified Lapidus arthrodesis. One surgeon performed all of the Lapidus procedure with a third screw while the other surgeon performed all with a suture and button fixation device. Of 136 consecutive patients who underwent a modified Lapidus arthrodesis, 83 (61%) patients required a third point of fixation for satisfactory stabilization of the first ray. Surgical technique was similar between the 2 surgeons; however, one utilized the suture and button fixation device method (n = 36), while the other used a third screw for fixation (n = 47). Many of the clinical outcomes, radiographic results, and the union rate were similar between the 2 methods. Nineteen (40%) complications occurred in the third screw group compared to 6 (17%) in the suture and button fixation device group. However, the third screw group demonstrated 100% maintenance of deformity correction at 1 year versus 95% in the suture and button fixation device group. Although fixation with a suture and button fixation device was associated with fewer complications, a larger study is necessary to determine if these variations are statistically significant.

Influence of posterior malleolar fragment morphology on the outcomes of trimalleolar fractures: A systematic review and meta-analysis.

BACKGROUND: Trimalleolar fractures are generally considered to have inferior outcomes among ankle injuries. Historically, emphasis was placed on the size of the posterior malleolar fracture (PMF) to guide surgical decision-making and predict outcomes. Recent studies have suggested that the morphology of the PMF fragment is more important than its size. The aim of this systematic review was to determine if the outcomes of trimalleolar fractures depend on the morphology of the PMF as per the Haraguchi classification system after surgical fixation. METHODS: A systematic literature search was conducted in the electronic databases of PubMed, Embase, Scopus, and Ovid. Title and abstracts were screened, and data from eligible studies were extracted. Meta-regression and pooled analysis was performed using appropriate computer software. RESULTS: 11 studies with 597 patients were included in the final analysis. Pooled mean AOFAS score was 87.43 (95% CI 84.24-90.62) after a mean follow-up of 31.6 months. Univariate and multivariate meta-regression analysis demonstrated that as the percentage of Haraguchi type 1 patients increased, there was a statistically significant improvement in outcome scores. A similar trend was noted for Haraguchi type 3 fractures, and a reverse trend was observed for Haraguchi type 2 injuries, although neither were statistically significant. CONCLUSION: Our review suggests that the outcomes of trimalleolar fractures after surgical fixation may depend on the morphology of the PMF, with Haraguchi type 1 fractures having overall superior functional outcomes than Haraguchi type 2 and 3 injuries. Future studies need to done to conclusively prove or refute these findings.

Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. METHODS: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score-matched cohort. RESULTS: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63-0.98]; P=0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site-related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). CONCLUSIONS: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

Sepsis Among Medicare Beneficiaries: 4. Precoronavirus Disease 2019 Update January 2012-February 2020.

OBJECTIVES: To provide updated information on the burdens of sepsis during acute inpatient admissions for Medicare beneficiaries. DESIGN: Analysis of paid Medicare claims via the Centers for Medicare and Medicaid Services DataLink Project. SETTING: All U.S. acute-care hospitals, excluding federally operated hospitals (Veterans Administration and Defense Health Agency). PATIENTS: All Medicare beneficiaries, January 2012-February 2020, with an explicit sepsis diagnostic code assigned during an inpatient admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The count of Medicare Part A/B (fee-for-service) plus Medicare Advantage inpatient sepsis admissions rose from 981,027 (CY2012) to 1,700,433 (CY 2019). The proportion of total admissions with sepsis in the Medicare Advantage population rose from 21.43% to 35.39%, reflecting the increasing beneficiary proportion enrolled in Medicare Advantage. In CY2019, 6-month mortality rates in Medicare fee-for-service beneficiaries for sepsis continued to decline, but remained high: 59.9% for septic shock, 35.5% for severe sepsis, 30.8% for sepsis attributed to a specific organism, and 26.5% for unspecified sepsis. Total fee-for-service-only inpatient hospital costs rose from $17.79B (CY2012) to $22.98B (CY2019). We estimated that the aggregate cost of sepsis hospital care for the entire U.S. population was at least $57.47B in 2019. Inclusion of 14 months' (January 2019-February 2020) newer data exposed new trends: the cost per patient, number of admissions, and fraction of patients with sepsis labeled as present on admission inflected around November 2015, coincident with the change to International Classification of Diseases, 10th Edition, and introduction of the Severe Sepsis and Septic Shock Management Bundle (SEP-1) metric. CONCLUSIONS: Sepsis among Medicare beneficiaries precoronavirus disease 2019 imposed immense burdens upon patients, their families, and the taxpayers.