Clinical Applications of 3‐Dimensional Printing Technology in Hip Joint

Three‐dimensional (3D) printing is a digital rapid prototyping technology based on a discrete and heap‐forming principle. We identified 53 articles from PubMed by searching “Hip” and “Printing, Three‐Dimensional”; 52 of the articles were published from 2015 onwards and were, therefore, initially considered and discussed. Clinical application of the 3D printing technique in the hip joint mainly includes three aspects: a 3D‐printed bony 1:1 scale model, a custom prosthesis, and patient‐specific instruments (PSI). Compared with 2‐dimensional image, the shape of bone can be obtained more directly from a 1:1 scale model, which may be beneficial for preoperative evaluation and surgical planning. Custom prostheses can be devised on the basis of radiological images, to not only eliminate the fissure between the prosthesis and the patient's bone but also potentially resulting in the 3D‐printed prosthesis functioning better. As an alternative support to intraoperative computer navigation, PSI can anchor to a specially appointed position on the patient's bone to make accurate bone cuts during surgery following a precise design preoperatively. The 3D printing technique could improve the surgeon's efficiency in the operating room, shorten operative times, and reduce exposure to radiation. Well known for its customization, 3D printing technology presents new potential for treating complex hip joint disease.     

Mixed Reality Combined with Three‐Dimensional Printing Technology in Total Hip Arthroplasty: An Updated Review with a Preliminary Case Presentation

Three‐dimensional (3D) printing technology, virtual reality, and augmented reality technology have been used to help surgeons to complete complex total hip arthroplasty, while their respective shortcomings limit their further application. With the development of technology, mixed reality (MR) technology has been applied to improve the success rate of complicated hip arthroplasty because of its unique advantages. We presented a case of a 59‐year‐old man with an intertrochanteric fracture in the left femur, who had received a prior left hip fusion. After admission to our hospital, a left total hip arthroplasty was performed on the patient using a combination of MR technology and 3D printing technology. Before surgery, 3D reconstruction of a certain bony landmark exposed in the surgical area was first performed. Then a veneer part was designed according to the bony landmark and connected to a reference registration landmark outside the body through a connecting rod. After that, the series of parts were made into a holistic reference registration instrument using 3D printing technology, and the patient's data for bone and surrounding tissue, along with digital 3D information of the reference registration instrument, were imported into the head‐mounted display (HMD). During the operation, the disinfected reference registration instrument was installed on the selected bony landmark, and then the automatic real‐time registration was realized by HMD through recognizing the registration landmark on the reference registration instrument, whereby the patient's virtual bone and other anatomical structures were quickly and accurately superimposed on the real body of the patient. To the best of our knowledge, this is the first report to use MR combined with 3D printing technology in total hip arthroplasty.     

Total Hip Arthroplasty for Crowe Type IV Hip Dysplasia: Surgical Techniques and Postoperative Complications

Total hip arthroplasty (THA) of Crowe type IV developmental dysplasia of the hip (DDH) is challenging. Although traditional (lateral, posterolateral, and posterior) THA approaches have been used with great anatomic success, they damage periarticular muscles, which are already quite weak in type IV DDH. The recently developed direct anterior approach (DAA) can provide an inter‐nerve and inter‐muscle approach for THA of type IV dysplasia hips. However, femur exposure with the DAA could be difficult during surgery and it is hard to apply femoral shortening osteotomy. THA techniques used for type IV DDH include anatomic hip center techniques (true acetabular reconstruction) and high hip center techniques, wherein an acetabulum is reconstructed above the original one. Although anatomic construction of the hip center is considered “the gold standard” treatment, it is impossible if the anatomical acetabular is too small and shallow. Procedures used to support type IV DDH reduction with anatomic hip center techniques include greater trochanter osteotomy, lesser trochanter osteotomy, and subtrochanteric osteotomy. However, these techniques have yet to be standardized, and it is unclear which is best for type IV DDH. One‐state and two‐state non‐osteotomy reduction techniques have also been introduced to treat type IV DDH. Potential complications of THA performed in patients with type IV DDH include leg length discrepancy (LLD), peri‐operative femur fracture, nonunion of the osteotomy site, and nerve injury. It is worth noting that nowadays an increasing number of Crowe type IV DDH patients are more sensitive to postoperative LLD.     

Efficacy of oral midazolam for minimal and moderate sedation in pediatric patients: A systematic review

One of the most widely used options for minimal/moderate sedation in pediatric patients is oral midazolam, as it presents an alternative to less well‐accepted routes of administration (eg, intravenous or intranasal) of this well‐known efficacious and well‐tolerated short‐acting benzodiazepine. A systematic review of the literature was conducted in order to identify clinical studies evaluating the effectiveness of oral midazolam for sedation in pediatric patients in the context of premedication before anesthesia or during diagnostic/treatment procedures. The percentage of responders (response rate) after single administration of oral midazolam was evaluated and compared versus placebo in a subset of placebo‐controlled studies. The range of oral midazolam doses providing effective sedation in the different pediatric age subsets was analyzed in order to assess optimum dosing strategies. A total of 25 pediatric clinical studies, utilizing a variety of measures of sedation effectiveness, were selected. These studies included a total of 1472 patients (aged 4 months‐18 years) treated with midazolam (0.25‐1.5 mg/kg) and 138 patients treated with placebo. The response rates [95% confidence interval] with oral midazolam ranged from 36.7% [21.6%, 54.9%] to 97.8% [86.1%, 99.7%], while with placebo response rates ranged from 4.0% [0.6%, 23.5%] to 41.0% [29.4%, 53.6%]. When considering the 4 placebo‐controlled studies, the odds ratios [95% confidence interval] for the comparison of midazolam vs. placebo ranged from 13.4 [5.0, 36.0] to 25.9 [6.7, 100.6]. The analysis of subgroups by context of sedation showed response rates [95% confidence interval] with oral midazolam ranging from 36.7% [21.6%, 54.9%] to 97.0% [94.8%, 98.3%] for anesthetic premedication and from 56.1% [43.1%, 68.4] to 97.8% [86.1%, 99.7%] for medical procedures. The efficacy of midazolam for pediatric minimal/moderate sedation from a dose of 0.25 mg/kg and above was demonstrated. The probability of occurrence of adverse events and over‐sedation increases with increasing doses.     

Factors at de novo donor‐specific antibody initial detection associated with allograft loss: a multicenter study

We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor‐specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death‐censored allograft loss were assessed by Cox proportional modeling. Death‐censored allograft survival was 77.0% (87/113) during a median follow‐up of 2.2 (IQR 1.2–3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6–15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1–13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post‐transplant (years) until donor‐specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody‐mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.     

Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single‐center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r‐ATG/EVR, n = 88), or mycophenolate (r‐ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy‐proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06–0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r‐ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r‐ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).     

Efficacy and safety of prolonged‐release tacrolimus in stable pediatric allograft recipients converted from immediate‐release tacrolimus – a Phase 2, open‐label,single‐arm,one‐way crossover study

There are limited clinical data regarding prolonged‐release tacrolimus (PR‐T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR‐T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate‐release tacrolimus (IR‐T), on a 1:1 mg total‐daily‐dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy‐confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole‐blood trough levels (target 3.5–15 ng/ml) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6–17.7% of patients across follow‐up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug‐related treatment‐emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR‐T to PR‐T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.     

Application of standardized platelet‐rich plasma in elderly patients with complex wounds

In recent years, autologous platelet‐rich plasma (PRP) derivatives have been used widely in the regeneration and repair of tissue, but a standard definition and preparation method for PRP are lacking. We developed a standardized method using platelet indices as quality‐control indicators for PRP preparation. Twenty‐one elderly patients (9 males, 12 females) with complex wounds were treated with standardized platelet‐rich plasma (S‐PRP). The platelet count in PRP after the second centrifugation was 1,069–1,436 × 10⁹/L. We adjusted the platelet concentration in PRP after a second centrifugation to 1,000 × 10⁹/L according to a formula using platelet‐poor plasma (PPP). The standardized preparation method that we developed gave S‐PRP with a relatively uniform platelet concentration. The wounds of 21 patients showed accelerated healing after S‐PRP treatment, and there were no obvious side effects during treatment. These data suggest that our preparation method of S‐PRP, using platelet indices as quality‐control indicators with platelet count of 1,000 × 10⁹/L could be used for the treatment of complex wounds in the elderly. The preparation method of S‐PRP proposed in the present study may be a simple and effective method of PRP quality control.