A robust knock-in approach using a minimal promoter and a minicircle.

Knock-in reporter (KI) animals are essential tools in biomedical research to study gene expression impacting diverse biological events. While CRISPR/Cas9-mediated genome editing allows for the successful generation of KI animals, several factors should be considered, such as low expression of the target gene, prevention of bacterial DNA integration, and in-frame editing. To circumvent these challenges, we developed a new strategy that utilizes minicircle technology and introduces a minimal promoter. We demonstrated that minicircles serve as an efficient donor DNA in zebrafish, significantly enhancing KI events compared to plasmids containing bacterial backbones. In an attempt to generate a KI reporter for scn8ab, we precisely integrated a fluorescence gene at the start codon. However, the seamlessly integrated reporter was unable to direct expression that recapitulates endogenous scn8ab expression. To overcome this obstacle, we introduced the hsp70 minimal promoter to provide an ectopic transcription initiation site and succeeded in establishing stable KI transgenic reporters for scn8ab. This strategy also created a fgf20b KI reporter line with a high success rate. Furthermore, our data revealed that an unexpectedly edited genome can inappropriately influence the integrated reporter gene expression, highlighting the importance of selecting a proper KI line. Overall, our approach utilizing a minicircle and an ectopic promoter establishes a robust and efficient strategy for KI generation, expanding our capacity to create KI animals.

Voltage-gated sodium channel scn8a is required for innervation and regeneration of amputated adult zebrafish fins.

Teleost fishes and urodele amphibians can regenerate amputated appendages, whereas this ability is restricted to digit tips in adult mammals. One key component of appendage regeneration is reinnervation of the wound area. However, how innervation is regulated in injured appendages of adult vertebrates has seen limited research attention. From a forward genetics screen for temperature-sensitive defects in zebrafish fin regeneration, we identified a mutation that disrupted regeneration while also inducing paralysis at the restrictive temperature. Genetic mapping and complementation tests identify a mutation in the major neuronal voltage-gated sodium channel (VGSC) gene scn8ab. Conditional disruption of scn8ab impairs early regenerative events, including blastema formation, but does not affect morphogenesis of established regenerates. Whereas scn8ab mutations reduced neural activity as expected, they also disrupted axon regrowth and patterning in fin regenerates, resulting in hypoinnervation. Our findings indicate that the activity of VGSCs plays a proregenerative role by promoting innervation of appendage stumps.

Decoding an organ regeneration switch by dissecting cardiac regeneration enhancers.

Heart regeneration in regeneration-competent organisms can be accomplished through the remodeling of gene expression in response to cardiac injury. This dynamic transcriptional response relies on the activities of tissue regeneration enhancer elements (TREEs); however, the mechanisms underlying TREEs are poorly understood. We dissected a cardiac regeneration enhancer in zebrafish to elucidate the mechanisms governing spatiotemporal gene expression during heart regeneration. Cardiac lepb regeneration enhancer (cLEN) exhibits dynamic, regeneration-dependent activity in the heart. We found that multiple injury-activated regulatory elements are distributed throughout the enhancer region. This analysis also revealed that cardiac regeneration enhancers are not only activated by injury, but surprisingly, they are also actively repressed in the absence of injury. Our data identified a short (22 bp) DNA element containing a key repressive element. Comparative analysis across Danio species indicated that the repressive element is conserved in closely related species. The repression mechanism is not operational during embryogenesis and emerges when the heart begins to mature. Incorporating both activation and repression components into the mechanism of tissue regeneration constitutes a new paradigm that might be extrapolated to other regeneration scenarios.

Work-from-home is here to stay: Call for flexibility in post-pandemic work policies.

In early 2020, the Covid-19 pandemic forced employees in tech companies worldwide to abruptly transition from working in offices to working from their homes. During two years of predominantly working from home, employees and managers alike formed expectations about what post-pandemic working life should look like. Many companies are experimenting with new work policies that balance employee- and manager expectations regarding where, when and how work should be done in the future. In this article, we gather experiences of the new trend of remote working based on the synthesis of 22 company-internal surveys of employee preferences for WFH, and 26 post-pandemic work policies from 17 companies and their sites, covering 12 countries in total. Our results are threefold. First, through the new work policies, all companies formally give employees more flexibility regarding working time and location. Second, there is a great variation in how much flexibility the companies are willing to yield to the employees. The paper details the different formulations that companies adopted to document the extent of permitted WFH, exceptions, relocation permits and the authorisation procedures. Third, we document a change in the psychological contract between employees and managers, where the option of working from home is converted from an exclusive perk that managers could choose to give to the few, to a core privilege that all employees feel they are entitled to. Finally, there are indications that as the companies learn and solicit feedback regarding the efficiency of the chosen strategies, we will see further developments and changes in the work policies concerning how much flexibility to work whenever and from wherever they grant. Through these findings, the paper contributes to a growing literature about the new trends emerging from the pandemic in tech companies and spells out practical implications onwards.

Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To describe a case of functional tremor occurring after a successful MR-guided focused ultrasound thalamotomy (MRgFUS) for essential tremor. METHODS: A 71-year-old right-handed man with essential tremor was referred to us for consideration of deep brain stimulation surgery for worsening bilateral upper limb tremor after a successful left MRgFUS for essential tremor. RESULTS: On clinical exam, signs compatible with a functional tremor were noted, including entertainability and suppressibility. Electrophysiological studies were consistent with essential tremor and superimposed tremor fulfilling the laboratory-supported criteria for functional tremor. DISCUSSION: We describe the first reported case of a functional movement disorder occurring after successful MRgFUS procedure for essential tremor. Recognising this entity and its development after such therapeutic interventions is essential to avoid further unnecessary invasive therapies.

A validated outcome categorization of the knee society score for total knee arthroplasty.

PURPOSE: To determine cutoff values for the Knee Society Scores (KSS) indicative of a categorical scale of medium-term outcomes. METHODS: One hundred and fifty-five patients who underwent primary cruciate-retaining TKA with a patellar button for osteoarthritis at a single-centre were assessed prospectively by the KSS and short-form Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) simultaneously at the 3-year follow-up. A validated categorization of the WOMAC score was used as a standard. The area under the curve (AUC) of receiver-operating characteristic (ROC) was used to assess the discriminative analysis accuracy of the, and the Youden index estimated the optimal cutoff point. RESULTS: For the KSS-knee score, the cutoff for an excellent outcome was 90.3 (AUC 0.75, 95% CI 0.71-0.78), 76.6 (AUC 76.6, 95% CI 0.70-076) for good, 64.8 (AUC 0.76, 95% CI 0.72-0.79) for fair, and < 64.8 (AUC 0.69, 95% CI 0.67-0.73) for poor. For the KSS-function score, the cutoff values were 85.2 (AUC 0.71, 95% CI 0.69-0.75), 73.1 (AUC 0.72, 95% CI, 0.70-0.76), 55.7 (AUC 0.70, 95% CI 0.71-0.74), and < 55.7 (AUC 0.68, 95% CI 0.66-0.72), respectively. CONCLUSION: A KSS-knee score ≥ of 90 was considered an excellent outcome, 77 good, 65 fair, and < 65 poor. For the KSS-function, those values are 85, 73, 56 and < 56, respectively. The treatment outcome's judgement may be clearer for the surgeon concerning a particular patient when using cutoff values for the scoring system employed, such as those determined in the present study. LEVEL OF EVIDENCE: II.

Inhibition of Bacterial Adhesion and Biofilm Formation by Seed-Derived Ethanol Extracts from Persea americana Mill.

The increase in antibiotic resistance demands innovative strategies to combat microorganisms. The current study evaluated the antibacterial and antivirulence effects of ethanol extracts from Persea americana seeds obtained by the Soxhlet (SE) and maceration (MaE) methods. The UHPLC-DAD-QTOF analysis showed mainly the presence of polyphenols and neolignan. Ethanol extracts were not cytotoxic to mammalian cells (CC50 > 500 µg/mL) and displayed a moderate antibacterial activity against Pseudomonas aeruginosa (IC50 = 87 and 187 µg/mL) and Staphylococcus aureus (IC50 = 144 and 159 µg/mL). Interestingly, no antibacterial activity was found against Escherichia coli. SE and MaE extracts were also able to significantly reduce the bacterial adhesion to A549 lung epithelial cells. Additionally, both extracts inhibited the biofilm growth at 24 h and facilitated the release of internal cell components in P. aeruginosa, which might be associated with cell membrane destabilization. Real-time PCR and agarose electrophoresis gel analysis indicated that avocado seed ethanol extracts (64 µg/mL) downregulated virulence-related factors such as mexT and lasA genes. Our results support the potential of bioproducts from P. americana seeds as anti-adhesive and anti-biofilm agents.

V-Y turndown flap augmentation for acute quadriceps rupture after total knee arthroplasty: a prospective matched cohort study.

PURPOSE: To evaluate the effectiveness of the quadriceps V-Y turndown augmentation for acute quadriceps tendon ruptures in the setting of TKA. METHODS: Prospective cohort of 22 patients with quadriceps rupture after TKA were compared with 44 matched patients underwent TKA without quadriceps rupture. Quadriceps ruptures were treated within three weeks after injury by suture augmented with Scuderi quadriceps V-Y turndown flap. Clinical evaluation was performed by the Knee Society Scores (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and range of motion. Patellar height was assessed by the Blackburne-Peel ratio. RESULTS: The mean follow-up was 3.3 (range, 3-4) years. At the final follow-up, there were significant improvements in mean KSS scores in both groups (p = 0.001). In the quadriceps group, the mean flexion for all patients, but one with arthrodesis for periprosthetic infection, was 100.1° (range, 90-110°) and mean extensor lag was 7.1° (range, 0-20°). There were significant differences between groups in KSS scores (p = 0.001). Active flexion (p = 0.020) and extension (p = 0.001) were significantly better in the control group. However, there was no significant difference in WOMAC scores (p = 0.252) or patient satisfaction (p = 0.352). There were no quadriceps reruptures. One patient with periprosthetic infection was treated with arthrodesis. CONCLUSION: The quadriceps V-Y turndown is an effective and safe procedure for quadriceps ruptures in the setting of TKA. Although the functional outcomes were lower than in TKA patients with no quadriceps rupture, the quality of life and satisfaction were successful in the TKA patients with quadriceps rupture.

Chemical and Pharmacological Potential of Coccoloba cowellii, an Endemic Endangered Plant from Cuba.

Coccoloba cowellii Britton (Polygonaceae) is an endemic and critically endangered plant that only grows in Camagüey, a province of Cuba. In this study, a total of 13 compounds were identified in a methanolic leaf extract, employing a dereplication of the UHPLC-HRMS data by means of feature-based molecular networking (FBMN) analysis in the Global Natural Products Social Molecular Network (GNPS), together with the interpretation of the MS/MS data and comparison with the literature. The major constituents were glucuronides and glycosides of myricetin and quercetin, as well as epichatechin-3-O-gallate, catechin, epicatechin and gallic acid, all of them being reported for the first time in C. cowellii leaves. The leaf extract was also tested against various microorganisms, and it showed a strong antifungal effect against Candida albicans ATCC B59630 (azole-resistant) (IC50 2.1 µg/mL) and Cryptococcus neoformans ATCC B66663 (IC50 4.1 µg/mL) with no cytotoxicity (CC50 > 64.0 µg/mL) on MRC-5 SV2 cells, determined by the resazurin assay. Additionally, the extract strongly inhibited COX-1 and COX-2 enzyme activity using a cell-free experiment in a dose-dependent manner, being significantly more active on COX-1 (IC50 4.9 µg/mL) than on COX-2 (IC50 10.4 µg/mL). The constituents identified as well as the pharmacological activities measured highlight the potential of C. cowellii leaves, increasing the interest in the implementation of conservation strategies for this species.

Competing Substrates for the Bifunctional Diaminopimelic Acid Epimerase/Glutamate Racemase Modulate Peptidoglycan Synthesis in Chlamydia trachomatis.

The Chlamydia trachomatis genome encodes multiple bifunctional enzymes, such as DapF, which is capable of both diaminopimelic acid (DAP) epimerase and glutamate racemase activity. Our previous work demonstrated the bifunctional activity of chlamydial DapF in vitro and in a heterologous system (Escherichia coli). In the present study, we employed a substrate competition strategy to demonstrate DapF Ct function in vivo in C. trachomatis We reasoned that, because DapF Ct utilizes a shared substrate-binding site for both racemase and epimerase activities, only one activity can occur at a time. Therefore, an excess of one substrate relative to another must determine which activity is favored. We show that the addition of excess l-glutamate or meso-DAP (mDAP) to C. trachomatis resulted in 90% reduction in bacterial titers, compared to untreated controls. Excess l-glutamate reduced in vivo synthesis of mDAP by C. trachomatis to undetectable levels, thus confirming that excess racemase substrate led to inhibition of DapF Ct DAP epimerase activity. We previously showed that expression of dapFCt in a murI (racemase) ΔdapF (epimerase) double mutant of E. coli rescues the d-glutamate auxotrophic defect. Addition of excess mDAP inhibited growth of this strain, but overexpression of dapFCt allowed the mutant to overcome growth inhibition. These results confirm that DapF Ct is the primary target of these mDAP and l-glutamate treatments. Our findings demonstrate that suppression of either the glutamate racemase or epimerase activity of DapF compromises the growth of C. trachomatis Thus, a substrate competition strategy can be a useful tool for in vivo validation of an essential bifunctional enzyme.

Minimal clinically important differences and substantial clinical benefits for Knee Society Scores.

PURPOSE: There is a paucity of literature defining the minimal clinically important difference (MCID) for the Knee Society Scores (KSS) after total knee arthroplasty (TKA), and no data on the substantial clinical benefit (SCB) for KSS have been reported. The purpose of this study was to determine MCID and SCB for the KSS in patients with primary TKA. METHODS: The median age of patients was 71.6 (range 50-88) years, and 60.3% were females 507 patients with TKA were prospectively enrolled. Patients completed the KSS before surgery and at second postoperative year. The MCID values of the KSS were estimated using anchor-based method, distribution-based method and receiver operating characteristic (ROC) curve analysis with calculation of the area under curve (AUC). SCB was estimated using ROC. RESULTS: The MCID for KSS-knee score was 7.2 points by the anchor-based method, 7.2 by the distribution-based method, and using a ROC analysis the cutoff point was 8.9 points with an AUC of 0.75. For KSS-function score, the MCID values were 9.7, 6.3, and 10.3 (AUC 0.71), respectively. SCB values were 39.7 points (AUC 0.74) for the KSS-knee score, and 38.6 (AUC 0.76) for the KSS-function score. Logistic regression showed age and Charlson index to negatively affect the changes in KSS. CONCLUSION: Different methods for MCID calculation lead to different results. With the use of ROC curve analysis, patients with an improvement of at least 9 points for KSS-knee and 10 points for KSS-function scores experience a clinically important change, whereas those who have at least an improvement of 40 points for KSS-knee and 39 points for KSS-function scores experience a substantial clinical benefit. These findings can ensure clinical improvement from the patient's perspective and also aid in interpreting results from clinical studies. LEVEL OF EVIDENCE: III.

Outcomes of Total Hip Arthroplasty for Healed Intertrochanteric Hip Fractures. A Matched Retrospective Cohort Study.

BACKGROUND: Many studies have analyzed the outcomes of total hip arthroplasty (THA) after failed intertrochanteric fracture fixation, but not after healed fracture. The objective is to investigate the influence of a prior healed intertrochanteric fracture fixation on the outcomes of a subsequent THA for osteoarthritis. METHODS: This is a matched retrospective cohort study of THA between 43 patients who suffered a prior intertrochanteric fracture successfully managed with internal fixation and 43 patients without prior hip fracture. Mean age was 73.6 vs 74.2 years. A conventional cementless THA was used in both groups. Functional outcome was assessed by the Harris hip score (HHS) and reduced Western Ontario and McMaster Universities Osteoarthritis Index questionnaire. Radiological assessment was also performed. RESULTS: Mean follow-up was 6.6 (range, 5-8) years. The mean operative time and blood transfusion rate were significantly higher in the fracture group (P = .001), but there was no significant difference in the length of stay. HHS significantly improved in both groups. At final follow-up, HHS was significantly higher in nonfracture group (P = .008), but the rate of patients with excellent and good outcomes was similar (P = .616). Western Ontario and McMaster Universities Osteoarthritis Index score at the final follow-up was not different between groups (P = .058). Complication rate was similar between groups. There were no revisions, dislocations, or loose implants in the study group. CONCLUSION: Cementless THA provided successful functional outcomes and implant durability at medium term in patients treated for osteoarthritis following healed intertrochanteric fracture fixation, comparable to those without prior fracture who underwent primary THA. Surgical complexity and complication rate were low.

Blocking ADAM17 Function with a Monoclonal Antibody Improves Sepsis Survival in a Murine Model of Polymicrobial Sepsis.

Sepsis is the culmination of hyperinflammation and immune suppression in response to severe infection. Neutrophils are critical early responders to bacterial infection but can become highly dysfunctional during sepsis and other inflammatory disorders. The transmembrane protease ADAM17 (a disintegrin and metalloproteinase 17) is expressed by leukocytes and most other cells and has many substrates that regulate inflammation. We have reported that conditional knockout mice lacking ADAM17 in all leukocytes had a survival advantage during sepsis, which was associated with improved neutrophil effector functions. These and other findings indicate aberrant ADAM17 activity during sepsis. For this study, we evaluated for the first time the effects of an ADAM17 function blocking monoclonal antibody (mAb) on the pathogenesis of polymicrobial sepsis. Mice treated with the ADAM17 mAb MEDI3622 prior to sepsis induction exhibited significantly decreased mortality. When the ADAM17 mAb was combined with antibiotic administration, sepsis survival was markedly enhanced compared to either intervention alone, which was associated with a significant reduction in plasma levels of various inflammation-related factors. MEDI3622 and antibiotic administration after sepsis induction also significantly improved survival. Our results indicate that the combination of blocking ADAM17 as an immune modulator and appropriate antibiotics may provide a new therapeutic avenue for sepsis treatment.

[Analysis of health care demand subsidies and the role of private health care corporations]. / Análisis del subsidio a la demanda para atención de salud y su relación con los holdings de empresas en Chile. Modalidad libre elección en prestadores privados (2000-2018).

This work analyzes the demand subsidies to access health care and their relationship with large private corporations in Chile, through the transfer of public funds through the modality of freedom of choice (MLE) from 2000 to 2018. Therefore, we analyzed the expansion of the health market and the strengthening of health care corporations, identifying the distribution of resources according to type of health provider. We reviewed the annual reports of private health care corporations. We also analyzed billing data according to the provider through the freedom of choice modality from the year 2000 to the year 2018. We identified an increasing transformation of medical work from free exercise to become dependent on private health corporations, and an increase in public dependence on private providers to meet health demands. There is a growing capture of public funds by these holdings, using the strategy of increasing provider property concentration and a trans nationalization of the health market in Chile.

Total Knee Arthroplasty in Patients With Prior Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Few studies have analyzed the outcomes of total knee arthroplasty (TKA) in patients with prior anterior cruciate ligament (ACL) reconstruction, and the reported outcomes are controversial. The purpose of this study is to assess if prior ACL reconstruction had any impact on the outcome of subsequent TKA. METHODS: A matched case-control study was conducted in patients who underwent TKA, including 37 with prior ACL reconstruction and 37 patients without ACL reconstruction. Preoperative and postoperative clinical and radiological data were collected from a prospective arthroplasty database with a minimum follow-up of 5 years. The mean age was 69.6 years, and 59.4% were men. The Knee Society scores, Short Form-12, and Western Ontario and McMaster Universities questionnaires were used for functional evaluations. Visual analogue scale 0-10 was used for patient satisfaction. RESULTS: The mean follow-up after TKA was 6.1 (range 5-7.3) years. Two patients in the ACL group developed knee stiffness requiring manipulation under anesthesia, while 1 patient in the control group suffered superficial wound infection. At last follow-up, no significant differences in functional or radiologic outcomes were found between both groups. The performance of TKA in ACL patients had increased technical difficulty and significantly longer time of surgery, but this had no influence on the outcomes. In the ACL group, 24 knees had technical difficulty in surgery. The main difficulty in most ACL patients was due to varus deformity and increased retraction of the medial soft structures which required progressive medial release. Other 2 knees had difficult knee exposure. One was an unexpected partial patellar tendon avulsion and the other required planned quadriceps snip. CONCLUSION: TKA was an effective procedure for patients with prior ACL reconstruction. The surgeon should be warned of the possible difficulties in the knee exposure and possible need of medial release to obtain an appropriate ligament balance. However, these additional procedures had no negative effect on the outcomes of TKA.

Comparison of Functional Outcomes Between the First and Second Knee in Staged Bilateral Total Knee Arthroplasty With Diverse Intervals Between Stages.

BACKGROUND: The objective of the study was to analyze if the length of interval time between stages influenced functional and quality of life outcomes in patients with staged bilateral primary total knee arthroplasty (TKA). METHODS: This is a retrospective comparative study between 93 patients with an interval between stages of 6-8 months (6-month group), 112 of 12-14 months (1-year group), and 108 of 24-26 months (2-year group). Outcome variables were Knee Society scores, Western Ontario and McMaster Universities, Short Form, and patient satisfaction. RESULTS: Overall, the mean follow-up for the first TKA was 8.2 (range, 7-10) years, and for the second TKA, 6.7 (range, 5-10) years. At last follow-up, functional and patient-related outcomes were similar for both knees, regardless of the interval. However, mental score and patient satisfaction were significantly better for the second than for the first TKA in the 2-year group. Age did not correlate significantly with the functional scores but was significantly correlated with the mental score. CONCLUSION: The performing staged bilateral TKA with a wide interval between surgeries provided equivalent functional outcomes and quality of life for both knees. Postoperative outcomes were not affected by the length of the time interval between procedures or age. Our results can help the surgeon to inform the patients reliably about what they can expect in the delay of a second knee replaced. Thus, patients could make an informed decision.

Prospective study of comminuted articular distal radius fractures stabilized by volar plating in the elderly.

PURPOSE: The objective was to assess the ability of the volar locking plate to maintain the radiographic parameters over the time in elderly patients with complex intra-articular distal radius fractures. METHODS: Prospective cohort of 66 consecutive patients with mean age of 68 (range 60-81) years and AO type C fractures treated with volar locking plate. Radiographic measurements were performed pre and post-operatively at each follow-up. Clinical assessment was made by Patient-Rated Wrist Evaluation scores, Disabilities of the Arm, Shoulder and Hand score, range of motion, and grip strength. RESULTS: The mean post-operative follow-up was 31 (range, 24-47) months. The most difficult parameters to restore intra-operatively were volar tilt and radial height, while radial inclination and ulnar variance were restored in a high rate of patients. There was significant loss of reduction within four post-operative months in volar tilt (p = 0.001) and radial height (p = 0.029). Mean radiographic parameters had no changes from four months to final evaluation. At final follow-up, 50.1% of the patients had all radiographic parameters restored in comparison with the noninvolved wrist, but 83.3% had all radiographic parameters within a functional range (p = 0.001). No significant relationship between radiographic and functional outcomes was found (p = 0.474). CONCLUSIONS: This study found that volar locking plate fixation for displaced intra-articular distal radius fractures in elderly patients was an effective procedure to obtain success functional outcomes. Although reduction loss in volar tilt and radial height occurred within four first months, volar plate was able to maintain fracture stabilization with radiographic parameters within functional range over the time in most patients of these elderly patients.

Comparable outcomes after total knee arthroplasty in patients under 55 years than in older patients: a matched prospective study with minimum follow-up of 10 years.

PURPOSE: To compare outcomes after TKA for osteoarthritis between patients younger than 55 years and older patients. METHODS: A cohort of 61 patients aged 55 years or younger was prospectively matched for gender, body mass index and knee function with patients with median age of 66 (range 60-70) years. Clinical evaluation was performed by the Knee Society scores (KSS), reduced Western Ontario and McMasters Universities (WOMAC) and Short-Form 12 (SF12) questionnaires. Radiological evaluation was also performed. RESULTS: The median follow-up was 12 (range 10-14) years. Survival at 14 years was 96.7% (95% CI 92-100%) in the younger group and 98.2% (95% CI 95-100%) in the older group (n.s.). There was no deep infection or loosening of femoral or patellar component in either group. In the younger group, 2 patients required revision (aseptic tibial loosening at 8 years, and polyethylene wear at 10 years). In the older group, there was 1 revision (aseptic tibial loosening). Revision rate was not significantly different (n.s.). Multivariate analysis showed no significant relationship between revision and age, gender or BMI. At 5-year follow-up, there were no significant differences between groups in KSS knee or function, WOMAC pain or function, or SF12 physical or mental, but in the last evaluation there were better results in younger patients for KSS-function (p = 0.018), WOMAC-function (p = 0.028), SF12-physical (p = 0.001) and SF12-mental (p = 0.035), although these differences were not clinically relevant. A significant decline was noted for KSS-function in either group from 5-year to at last follow-up. CONCLUSIONS: The TKA survival in younger patients was comparable to older active patients, without increased complications or revisions at a minimum follow-up of 10 years. Primary hybrid TKA can provide successful pain relief, function and quality of life in younger patients than 55 years with osteoarthritis. TKA is a suitable option for these young patients with appropriate surgical indications. LEVEL OF EVIDENCE: II.

Risk-Benefit on Quality of Life After Total Knee Arthroplasty in Octogenarians.

BACKGROUND: Clinical outcomes of total knee arthroplasty (TKA) in very older patients have been widely studied, but the available evidence on quality of life (QOL) is limited. The objective was to evaluate the impact of TKA on the QOL in octogenarian patients and assess whether the risk-benefit justified surgery. METHODS: Prospective study comparing 143 octogenarian and 149 septuagenarian patients. QOL was assessed with the Short Form-12 (SF-12) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaires and functional outcomes with the Knee Society score (KSS). Comorbidity, complications, pain, and satisfaction were also assessed. RESULTS: Mean postoperative follow-up was 3.2 years (range, 2-5 years). Comorbidities, medical complications, transfusion rate, and length stay were not different between groups (P < .05). Comorbidities and complications had no influence on the outcomes. There were no significant differences in preoperative knee KSS, WOMAC, or SF-12 mental scores, but octogenarians had significantly lower functional KSS (P = .003) and SF-12 physical scores (P = .005). At the last follow-up, there were no significant differences in KSS, WOMAC, and SF-12 physical scores (P < .05), but octogenarians had higher SF-12 mental (P = .030) and satisfaction (P = .031) scores. CONCLUSION: TKA provided pain relief, satisfaction, and improvement in QOL for octogenarian patients to the level of the septuagenarian patients. TKA was a suitable option for octogenarian patients with appropriate surgical indications and manageable risk.

Isolated human islets require hyperoxia to maintain islet mass, metabolism, and function.

Pancreatic islet transplantation has been recognized as an effective treatment for Type 1 diabetes; however, there is still plenty of room to improve transplantation efficiency. Because islets are metabolically active they require high oxygen to survive; thus hypoxia after transplant is one of the major causes of graft failure. Knowing the optimal oxygen tension for isolated islets would allow a transplant team to provide the best oxygen environment during pre- and post-transplant periods. To address this issue and begin to establish empirically determined guidelines for islet maintenance, we exposed in vitro cultured islets to different partial oxygen pressures (pO2) and assessed changes in islet volume, viability, metabolism, and function. Human islets were cultured for 7 days in different pO2 media corresponding to hypoxia (90 mmHg), normoxia (160 mmHg), and hyerpoxia (270 or 350 mmHg). Compared to normoxia and hypoxia, hyperoxia alleviated the loss of islet volume, maintaining higher islet viability and metabolism as measured by oxygen consumption and glucose-stimulated insulin secretion responses. We predict that maintaining pre- and post-transplanted islets in a hyperoxic environment will alleviate islet volume loss and maintain islet quality thereby improving transplant outcomes.