Reduced adiponectin levels in patients with COVID-19 acute respiratory failure: A case-control study.

Hypoadiponectinemia is speculated to play a key role in the relationship between obesity and COVID-19 respiratory failure. However, only one study has examined adiponectin levels in COVID-19 patients, and none have investigated adiponectin levels strictly in patients with acute respiratory failure. In this study, we performed a retrospective case-control study of adipokine levels in patients with acute respiratory failure caused by either COVID-19 or other viral/bacterial source. All patients with COVID-19 respiratory failure in the University of Virginia Biorepository and Tissue Research database were included. We also selected patients with non-COVID-19 infectious respiratory failure from the same biorepository to serve as a comparison cohort. Plasma adipokine levels were measured on three occasions during the first 72 hours of hospitalization. Twelve patients with COVID-19 respiratory failure and 17 patients with other infectious respiratory failure were studied. Adiponectin levels were significantly lower in patients with COVID-19 respiratory failure, even after adjustment for age, sex, BMI, and other covariates. In conclusion, adiponectin levels appear to be reduced in COVID-19 respiratory failure. Larger studies are needed to confirm this report.

Rotating Hinge Implants for Complex Primary and Revision Total Knee Arthroplasty.

BACKGROUND: Contemporary rotating hinge knee (RHK) prosthesis has shown improved survival rates over earlier generations. However, reports of high complication and mechanical failure rates highlight the need for more clinical outcome data in the complex primary and revision setting. The purpose of this study is to report our results of using a contemporary rotating hinge for complex primary and revision total knee arthroplasty. METHODS: Using a prospectively maintained surgical database, 79 knees in 76 patients who underwent an RHK of a single design for either a complex primary (14 knees) or revision total knee arthroplasty (65 knees) were identified. This included 19% undergoing an RHK for periprosthetic joint infection and 32.9% who had concomitant extensor mechanism repair. The cohort consisted of 60 women and 16 men with a mean age of 66.7 years (range 39-89) at the time of surgery. Patient outcomes were assessed using Knee Society Scores and radiographs were reviewed for signs of wear and loosening. Failure rates were estimated using Kaplan-Meier survival curves. RESULTS: At a minimum of 2 years, 13 patients had died and 4 were lost to follow-up, leaving 62 knees in 59 patients who were followed for a mean of 55.2 months (range 24-146). The mean Knee Society Scores improved from 35.7 to 66.2 points (P < .01). The incidence of complications was 38.7%. The most common complications were periprosthetic fracture, extensor mechanism rupture, and periprosthetic infection. Estimated survival was 70.7% at 5 years. CONCLUSION: Despite improvements in design and biomaterials, there remains a relatively high complication rate associated with the use of a modern RHK implant. While aseptic loosening was rare, periprosthetic fracture, infection, and extensor mechanism failure were substantial emphasizing the complex nature of these cases.

Revision Total Hip Arthroplasty With a Monoblock Splined Tapered Grit-Blasted Titanium Stem.

BACKGROUND: In revision total hip arthroplasty (THA), proximal femoral bone loss creates a challenge of achieving adequate stem fixation. The purpose of this study was to examine the outcomes of a monoblock, splined, tapered femoral stem in revision THA. METHODS: Outcomes of revision THA using a nonmodular, splined, tapered femoral stem from a single surgeon were reviewed. With a minimum of 2-year follow-up, there were 68 cases (67 patients). Paprosky classification was 3A or greater in 85% of the cases. Preoperative and postoperative Harris Hip Scores (HHS), radiographic subsidence and osseointegration, limb length discrepancy, complications, and reoperations were analyzed. RESULTS: The Harris Hip Score improved from 37.4 ± SD 19.4 preoperatively to 64.6 ± SD 21.8 at final follow-up (P < .001). There were 16 revision procedures-8 for septic indications and 8 for aseptic indications. Subsidence occurred at a rate of 3.0% and dislocation at 7.4%. Limb length discrepancy of more than 1 cm after revision was noted in 13.6% of patients. Bone ingrowth was observed in all but 4 patients (94.1%). At 4-year follow-up, Kaplan-Meier estimated survival was 72.9% (95% confidence interval [CI] 57.0-83.8) for all causes of revision, 86.6% (95% CI 72.0-93.9) for all aseptic revision, and 95.5% (95% CI 86.8-98.5) for aseptic femoral revision. CONCLUSION: Although complications were significant, revision for femoral aseptic loosening occurred in only 3 patients. Given the ability of this monoblock splined tapered stem to adequately provide fixation during complex revision THA, it remains a viable option in the setting of substantial femoral bone defects.

Determining the Threshold for HbA1c as a Predictor for Adverse Outcomes After Total Joint Arthroplasty: A Multicenter, Retrospective Study.

BACKGROUND: Although HbA1c is commonly used for assessing glycemic control before surgery, there is no consensus regarding its role and the appropriate threshold in predicting adverse outcomes. This study was designed to evaluate the potential link between HbA1c and subsequent periprosthetic joint infection (PJI), with the intention of determining the optimal threshold for HbA1c. METHODS: This is a multicenter retrospective study, which identified 1645 diabetic patients who underwent primary total joint arthroplasty (1004 knees and 641 hips) between 2001 and 2015. All patients had an HbA1c measured within 3 months of surgery. The primary outcome of interest was a PJI at 1 year based on the Musculoskeletal Infection Society criteria. Secondary outcomes included orthopedic (wound and mechanical complications) and nonorthopedic complications (sepsis, thromboembolism, genitourinary, and cardiovascular complications). A regression analysis was performed to determine the independent influence of HbA1c for predicting PJI. RESULTS: Overall 22 cases of PJI occurred at 1 year (1.3%). HbA1c at a threshold of 7.7 was distinct for predicting PJI (area under the curve, 0.65; 95% confidence interval, 0.51-0.78). Using this threshold, PJI rates increased from 0.8% (11 of 1441) to 5.4% (11 of 204). In the stepwise logistic regression analysis, PJI remained the only variable associated with higher HbA1c (odds ratio, 1.5; confidence interval, 1.2-2.0; P = .0001). There was no association between high HbA1c levels and other complications assessed. CONCLUSION: High HbA1c levels are associated with an increased risk for PJI. A threshold of 7.7% seems to be more indicative of infection than the commonly used 7% and should perhaps be the goal in preoperative patient optimization.

An Aprotinin Containing Fibrin Sealant Does Not Reduce Blood Loss in Total Hip Arthroplasty.

BACKGROUND: Fibrin sealants are topical agents used to reduce perioperative blood loss; however, their efficacy in total hip arthroplasty (THA) remains uncertain. The purpose of this study was to determine if a fibrin sealant containing aprotinin as an antifibrinolytic agent, TISSEEL (Baxter, Deerfield, IL), reduces postoperative blood loss and transfusion during THA when compared with intravenous (IV) tranexamic acid (TXA) and control groups. METHODS: Three retrospective uniform cohorts of primary THA procedures were identified, from a prospectively maintained database: 1 group who received TISSEEL, 1 group who received 1 g IV TXA, and 1 group who received neither (control). There were 80 patients in each group. Outcome measures included the lowest measured hemoglobin during postoperative hospitalization, greatest decrease in hemoglobin from preoperative to postoperative values, and blood transfusion rates. RESULTS: The minimum postoperative hemoglobin level was significantly lower for TISSEEL patients compared with that of IV TXA patients (P = .021) and no different when compared with that of control patients (P = .134). Patients receiving fibrin sealant had a greater hemoglobin level decrease compared with that of IV TXA (P = .029) and control (P = .036). Postoperative transfusion rates were no different for the group receiving TISSEEL compared with those of control (P = .375) and were statistically greater when compared with those of IV TXA (P = .002). CONCLUSION: TISSEEL fibrin sealant does not reduce postoperative blood loss or transfusions; however, IV TXA reduced postoperative transfusions compared with TISSEEL and control. Therefore, TXA is recommended to reduce perioperative blood loss, while, utilization of a fibrin sealant requires further refinements before being adopted for routine use in THA.

Prospective Assessment of Sleep Quality Before and After Primary Total Joint Replacement.

Sleep disruption is a common, yet rarely addressed, complaint among patients who have undergone total joint arthroplasty (TJA). This study assessed sleep quality before and after primary TJA. A total of 105 patients who underwent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) prospectively completed questionnaires during the preoperative, early postoperative, and late postoperative periods. The survey included the Epworth Sleepiness Scale, current sleeping habits, and patient perspectives of sleep quality and duration. In the early postoperative period (4.7±2.0 weeks), patients reported significant increases in sleep disturbance as denoted by increased length of time to fall asleep (P=.006) and mean nightly awakenings (P=.002) compared with the preoperative baseline. At late postoperative follow-up (40.8±19.5 weeks), patients' sleep quality subsequently improved above the preoperative baseline. Approximately 40% of patients tried a new sleeping method postoperatively, the most common being new pillow placement. No significant differences in pre- or postoperative sleeping trends were noted between THA and TKA patients. These findings suggest transient sleep disturbance is common in the early postoperative period, with subsequent improvement by 10-month follow-up after a primary TJA. Given the growing importance of patient satisfaction in health care systems, orthopedic surgeons must manage patients' expectations while working with them to optimize sleep quality after TJA. A multimodal approach with preoperative counseling, early postoperative sleep modifications, and possibly preemptive use of medications may improve transient sleep disturbance among TJA patients. [Orthopedics. 2017; 40(4):e636-e640.].

Intra-Articular Knee Injections Before Total Knee Arthroplasty: Outcomes and Complication Rates.

BACKGROUND: The relationship between intra-articular injections and complication rates after total knee arthroplasty (TKA) remains controversial. This study's purpose was to determine the relationship between the number and timing of intra-articular injections with complications and outcomes after TKA from a single surgeon's database. METHODS: We retrospectively reviewed a series of 442 patients who underwent primary TKA from 2008-2015. Patient demographics, comorbidities, number and timing of ipsilateral intra-articular injections, and preoperative and postoperative functional outcome scores were recorded. Complications and infection rates at a minimum of 12-month follow-up were compared between patients who received 3 or less preoperative injections and those who received 4 or greater before TKA. Multivariate logistic regression analysis was performed to identify independent risk factors for complications and poor short-term outcomes after TKA. RESULTS: Of the 442 patients enrolled in the study, 390 patients (90%) received an ipsilateral injection before TKA. Patients receiving 4 or more injections (175 patients, 40%) did not have a difference in complication rate (14% vs 17%, P = .346), poor functional outcomes (6% vs 9%, P = .299), or infection rate (2% vs 4%, P = .286). When controlling for confounding variables, intra-articular corticosteroid, viscosupplementation, and any injection within 90 days were not associated with an increase in complications, infection, or poor functional outcomes after TKA (all P > .05). CONCLUSION: Our data suggest that there is no relationship between timing and number of intra-articular injections with complication rate, infection, or poor short-term functional outcomes. Further larger studies are needed to confirm these findings.

Cementless vs Cemented Tibial Fixation in Primary Total Knee Arthroplasty.

BACKGROUND: The ideal fixation for modern tibial components in total knee arthroplasty (TKA) remains controversial with uncertainty on whether cementless implants can yield equivalent outcomes to cemented fixation in early follow-up. METHODS: A series of 70 consecutive cases with reverse hybrid cementless fixation were matched to 70 cemented cases from 2008 to 2015 based on implant design and patient demographics. RESULTS: Cementless TKA demonstrated greater aseptic loosening (7 vs 0, P = .013) and revision surgery (10 vs 0, P = .001) than cemented fixation within 5 years of follow-up, but with no clinically significant differences in outcome scores. CONCLUSION: It remains unclear whether early aseptic loosening in cementless TKA can be reduced with enhanced adjunct fixation and what proportion of early failure justifies the potential lifelong fixation through biologic ingrowth of cementless tibial components.

Microglia instruct subventricular zone neurogenesis.

Microglia are increasingly implicated as a source of non-neural regulation of postnatal neurogenesis and neuronal development. To evaluate better the contributions of microglia to neural stem cells (NSCs) of the subventricular neuraxis, we employed an adherent culture system that models the continuing proliferation and differentiation of the dissociated neuropoietic subventricular tissues. In this model, neuropoietic cells retain the ability to self-renew and form multipotent neurospheres, but progressively lose the ability to generate committed neuroblasts with continued culture. Neurogenesis in highly expanded NSCs can be rescued by coculture with microglial cells or microglia-conditioned medium, indicating that microglia provide secreted factor(s) essential for neurogenesis, but not NSC maintenance, self-renewal, or propagation. Our findings suggest an instructive role for microglial cells in contributing to postnatal neurogenesis in the largest neurogenic niche of the mammalian brain.

A method for a more complete in vitro Parkinson's model: slice culture bioassay for modeling maintenance and repair of the nigrostriatal circuit.

Slice culture model systems provide a unique opportunity to monitor and lesion brain circuits in a dish. Using a novel approach, we have generated parasagittal slices from mouse brains that preserve, throughout the culture process, the nigrostriatal circuit. These slices can be cultured for approximately 4 weeks with maintenance of normal neuronal cytoarchitecture. Application of the dopamine specific toxin 6-hydroxy dopamine (6-OHDA) induces a significant decline in tyrosine hydroxylase positive cell bodies and fibers. Using a transgenic mouse with green fluorescent protein (GFP) under the control of the tyrosine hydroxylase promoter, we have been able to visualize in real time the loss of GFP expression in the striatum of slices as a result of 6-OHDA exposure. Using these cultures we have demonstrated the feasibility of modeling cellular replacement strategies. GFP-positive embryonic stem cell-derived neuronal precursors can be tracked in real time throughout the experiment and are amenable to patch clamp recording within the slice environment. In addition, cell differentiation can be observed within these slices and the effects of morphogenetic proteins, like the extracellular matrix molecule laminin, drugs or small molecules can be observed. This unique culture system presents a new approach for modeling Parkinson's disease in vitro, and provides a potentially useful new method for screening cell and molecular therapies for neurodegenerative diseases.

Neuron-to-astrocyte transition: phenotypic fluidity and the formation of hybrid asterons in differentiating neurospheres.

To the extent that their fate choice and differentiation processes can be understood and manipulated, neural stem cells represent a promising therapeutic tool for a variety of neuropathologies. We have previously shown that mature astrocytes possess neural stem cell attributes, and can give rise to neurons through the formation of multipotent neurosphere clones. Here we show that relatively mature neurons generated from neurospheres derived from postnatal subependymal zone or cerebellar cortex undergo a phenotypic transformation into astrocytes that coincides with the appearance of a nonfused, hybrid cell type that shares the morphology, antigenicity, and physiology of both neurons and astrocytes. We refer to this astrocyte/neuron hybrid as an "asteron," and hypothesize that it represents an intermediate step in the trans- or dedifferentiation of neurons into astrocytes. The present finding suggests that seemingly terminally differentiated neural cells may in fact represent points along a bidirectionally fluid continuum of differentiation, with intermediate points represented by "hybrid" cells coexpressing phenotypic markers of more than one lineage.