Tourniquetless Total Knee Arthroplasty With Modern Perioperative Protocols Decreases Pain and Opioid Consumption in Women.

BACKGROUND: This study examined whether a modern total knee arthroplasty (TKA) protocol without a tourniquet results in less patient-reported pain and in-hospital opioid consumption compared to TKA with a tourniquet. METHODS: A retrospective study of 203 primary unilateral cemented TKAs consecutively performed with or without tourniquet was performed. Identical perioperative pain and blood loss protocols were used in all cases. In tourniquetless TKAs, the tourniquet was not inflated at any time, and sterile CO2 gas compression maximized cement interdigitation. RESULTS: After exclusions for scientific confounds, 184 TKAs (93 with tourniquet; 91 tourniquetless) were analyzed. Controlling for multiple covariates, females with a tourniquet reported significantly more pain (P = .002) and opioid consumption (P < .001) the first 24 hours after surgery compared to females without a tourniquet. There were no differences in pain (P = .192) or amount of opioids consumed (P = .203) among males with and without a tourniquet. Tourniquet use resulted in a significant reduction in blood loss for both females (P ≤ .040) and males (P ≤ .020), although the total blood savings of approximately 200 mL is of unknown clinical significance. CONCLUSION: Avoiding tourniquet use during TKA for females may be a relatively risk-free adjunct to minimize opioid consumption during hospitalization. Further study is warranted to elucidate the factors accounting for different outcomes in females and males.

Tranexamic Acid and Computer-Assisted Surgery in Cemented and Cementless Total Knee Arthroplasty: Are the Effects Additive for Blood Conservation?

INTRODUCTION: Efforts continue to minimize blood loss associated with total knee arthroplasty (TKA). The primary objective of this study was to determine whether computer-assisted surgery (CAS) and tranexamic acid (TXA) were additive in minimizing blood loss in cemented TKA. The secondary objective was to assess the combined effectiveness of CAS and TXA in cementless TKA. MATERIALS AND METHODS: A retrospective study of 393 consecutive primary TKAs with cemented and cementless fixation was performed. Cemented and cementless fixation TKA cohorts were divided into three subgroups: (1) neither CAS nor TXA was used, (2) CAS alone was used, or (3) CAS plus TXA was used. Three blood loss metrics were calculated: (1) postoperative change in hemoglobin, (2) total drain output, and (3) calculated total blood loss. RESULTS: After exclusions, 267 cemented TKAs and 35 cementless or hybrid TKAs were available for analysis. In cemented TKAs, the mean postoperative hemoglobin decrease was 2.9 g/dL in patients without CAS or TXA, 2.5 g/dL in the CAS only group, and 2.1 g/dL in the CAS and TXA group (p = 0.001). Median total drain output was lower in the CAS plus TXA group (230 ml) compared to the CAS alone (442.5 ml), and the neither CAS nor TXA group (620 ml) (p = 0.001). Mean calculated total blood loss was 1258.7 ml in the group with neither CAS nor TXA, 1023.8 ml in CAS alone, and 869.1 ml for both the CAS and TXA group (p = 0.001). In cementless TKA, the postoperative hemoglobin drop decreased from 3.3 g/dL in the neither CAS nor TXA group to 2.5 g/dL with CAS alone and 1.9 g/dL in the CAS plus TXA (p = 0.024). Mean total drain output progressively declined with CAS alone and for those with CAS plus TXA compared to those without CAS or TXA (p = 0.004). CONCLUSIONS: An encouraging additive decrease in blood loss after TKA can occur with utilization of both CAS and TXA. The additive effect of both modalities appears to exist in cemented and cementless fixation techniques. Whether this blood conservation will result in improved patient outcomes remains unknown and should be the topic of further study.

Functional impairment of bone formation in the pathogenesis of osteoporosis: the bone marrow regenerative competence.

The skeleton is a high-renewal organ that undergoes ongoing cycles of remodeling. The regenerative bone formation arm ultimately declines in the aging, postmenopausal skeleton, but current therapies do not adequately address this deficit. Bone marrow is the primary source of the skeletal anabolic response and the mesenchymal stem cells (MSCs), which give rise to bone matrix-producing osteoblasts. The identity of these stem cells is emerging, but it now appears that the term 'MSC' has often been misapplied to the bone marrow stromal cell (BMSC), a progeny of the MSC. Nevertheless, the changes in BMSC phenotype associated with age and estrogen depletion likely contribute to the attenuated regenerative competence of the marrow and may reflect alterations in MSC phenotype. Here we summarize current concepts in bone marrow MSC identity, and within this context, review recent observations on changes in bone marrow population dynamics associated with aging and menopause.

Arthrotomy Dehiscence After Total Knee Arthroplasty With a Barbed Suture.

INTRODUCTION: Meticulous arthrotomy closure during total knee arthroplasty (TKA) is essential to preserve quadriceps strength and maintain proper patellar tracking. We recently encountered a subset of patients referred with anterior knee pain, a palpable retinaculum defect, and quadriceps weakness. Each patient was found to have an arthrotomy dehiscence. This study highlights arthrotomy dehiscence as a failure mechanism after TKA. METHODS: A retrospective case series of patients who underwent primary TKA followed by subsequent capsular dehiscence was reviewed. We investigated whether the dehiscence was related to trauma, the presence of a palpable arthrotomy defect, patellar tracking, quadriceps strength, and the type of closure technique. RESULTS: All patients had an atraumatic disruption and presented with anterior knee pain and quadriceps weakness. Fourteen of 18 patients (78%) had a palpable defect along the medial retinaculum. Nine of 18 patients (50%) had patellar subluxation or tilting. Barbed sutures were used in 13 of 18 (72%) patients. A simple arthrotomy repair (44%) or a vastus medialis obliquus advancement (56%) was used successfully in all patients. DISCUSSION: Atraumatic arthrotomy dehiscence as a cause of TKA failure historically has been a rare event. Recently, we have noticed a disturbing number of patients presenting with this failure mechanism. With this study, we call attention to this unique atraumatic failure mechanism in patients presenting with anterior knee pain after TKA. Surgeons should be aware of this risk when using barbed sutures alone and should consider routinely reinforcing the arthrotomy with interrupted sutures. LEVEL OF EVIDENCE: Level IV, Retrospective Case Series.

Nmp4/CIZ closes the parathyroid hormone anabolic window.

Chronic degenerative diseases are increasing with the aging U.S. population. One consequence of this phenomenon is the need for long-term osteoporosis therapies. Parathyroid hormone (PTH), the only FDA-approved treatment that adds bone to the aged skeleton, loses its potency within two years of initial treatment but the mechanism regulating its limited "anabolic window" is unknown. We have discovered that disabling the nucleocytoplasmic shuttling transcription factor nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) in mice extends the PTH bone-forming capacity. Nmp4 was discovered during our search for nuclear matrix transcription factors that couple this hormone's impact on osteoblast cytoskeletal and nuclear organization with its anabolic capacity. CIZ was independently discovered as a protein that associates with the focal adhesion-associated mechanosensor p130Cas. The Nmp4/CIZ-knockout (KO) skeletal phenotype exhibits a modestly enhanced bone mineral density but manifests an exaggerated response to both PTH and to BMP2 and is resistant to disuse-induced bone loss. The cellular basis of the global Nmp4/CIZ-KO skeletal phenotype remains to be elucidated but may involve an expansion of the bone marrow osteoprogenitor population along with modestly enhanced osteoblast and osteoclast activities supporting anabolic bone turnover. As a shuttling Cys(2)His(2) zinc finger protein, Nmp4/CIZ acts as a repressive transcription factor perhaps associated with epigenetic remodeling complexes, but the functional significance of its interaction with p130Cas is not known. Despite numerous remaining questions, Nmp4/CIZ provides insights into how the anabolic window is regulated, and itself may provide an adjuvant therapy target for the treatment of osteoporosis by extending PTH anabolic efficacy.

Greater Blood Loss in Contemporary Cementless Total Knee Arthroplasty than Cemented Total Knee Arthroplasty despite Tranexamic Acid Use: A Match-Controlled Retrospective Study.

The purpose of this retrospective study was to assess whether tranexamic acid (TXA) reduces blood loss in cementless total knee arthroplasty (TKA) comparable to levels observed with cemented fixation. After exclusions from 109 consecutive TKAs, 76 cementless knees were matched to 78 cemented knees of identical implant and surgeon. Blood loss with and without TXA was compared. There was no difference between cohorts in sex, age, body mass index, American Society of Anesthesiologists Physical Status classification, or preoperative hemoglobin (p ≥ 0.119). Use of TXA reduced median drain output by only 205 mL in cementless knees compared to 470 mL in cemented knees (p < 0.001). Median drain output per hour was highest in cementless knees without TXA (39.5 mL) followed by cemented knees without TXA (38.2 mL), cementless knees with TXA (28.5 mL), and cemented knees with TXA (12.7 mL; p < 0.001). Hemoglobin drop and total blood loss did not differ between cohorts regardless of TXA use. Cementless fixation in TKA resulted in greater intra-articular blood loss as measured by drain output, despite the use of TXA. Further research is warranted to examine whether a higher TXA dose, TXA delivery method, or the application of bone wax sealant would mitigate blood loss in cementless TKA, and subsequently whether intra-articular blood accumulation resulting in postoperative hemarthrosis affects recovery, function, and clinical outcomes.

Nmp4/CIZ suppresses the parathyroid hormone anabolic window by restricting mesenchymal stem cell and osteoprogenitor frequency.

Parathyroid hormone (PTH) anabolic osteoporosis therapy is intrinsically limited by unknown mechanisms. We previously showed that disabling the transcription factor Nmp4/CIZ in mice expanded this anabolic window while modestly elevating bone resorption. This enhanced bone formation requires a lag period to materialize. Wild-type (WT) and Nmp4-knockout (KO) mice exhibited equivalent PTH-induced increases in bone at 2 weeks of treatment, but by 7 weeks, the null mice showed more new bone. At 3-week treatment, serum osteocalcin, a bone formation marker, peaked in WT mice, but continued to increase in null mice. To determine if 3 weeks is the time when the addition of new bone diverges and to investigate its cellular basis, we treated 10-week-old null and WT animals with human PTH (1-34) (30 µg/kg/day) or vehicle before analyzing femoral trabecular architecture and bone marrow (BM) and peripheral blood phenotypic cell profiles. PTH-treated Nmp4-KO mice gained over 2-fold more femoral trabecular bone than WT by 3 weeks. There was no difference between genotypes in BM cellularity or profiles of several blood elements. However, the KO mice exhibited a significant elevation in CFU-F cells, CFU-F(Alk)(Phos+) cells (osteoprogenitors), and a higher percentage of CFU-F(Alk)(Phos+) cells/CFU-F cells consistent with an increase in CD45-/CD146+/CD105+/nestin+ mesenchymal stem cell frequency. Null BM exhibited a 2-fold enhancement in CD8+ T cells known to support osteoprogenitor differentiation and a 1.6-fold increase in CFU-GM colonies (osteoclast progenitors). We propose that Nmp4/CIZ limits the PTH anabolic window by restricting the number of BM stem, progenitor, and blood cells that support anabolic bone remodeling.