Early line-probe assay using DNA specimens in patients with pulmonary TB.

BACKGROUND: We investigated the feasibility of early line-probe assay (LPA) using remnant DNA of Mycobacterium tuberculosis from polymerase chain reaction (PCR) test.METHODS: M. tuberculosis DNA specimens with cycle threshold (Ct) values reported and collected from patients with known results for both LPA with culture isolates and phenotype drug susceptibility testing (pDST) were selected. The diagnostic performance of DNA-based LPA according to the Ct value was investigated.RESULTS: A total of 143 respiratory specimens were included. For isoniazid resistance, the accuracy in subgroups with Ct value <25, 25-29 and ≥29 was respectively 96.8%, 65.7% and 13.3%. For rifampicin resistance, accuracy in subgroups with Ct values <29 and ≥29 was respectively 87.8% and 13.3%. When compared to the pDST results, sensitivity, specificity, positive predictive value and negative predictive value in specimens with Ct values <25 was respectively 1.00 (95% CI 0.69-1.00), 0.95 (95% CI 0.76-1.00), 0.91 (95% CI 0.59-1.00) and 1.00 (95% CI 0.83-1.00) for isoniazid resistance. For rifampicin resistance, corresponding values in subgroups with Ct values <29 were respectively 0.89 (95% CI 0.52-1.00), 0.98 (95% CI 0.91-1.00), 0.80 (95% CI 0.50-0.94) and 0.99 (95% CI 0.92-1.00).CONCLUSIONS: DNA-based early LPA with remnant DNA from respiratory samples was feasible and accurate when the Ct values were low.

Microcomputed analysis of nerve angioarchitecture after combined stem cell delivery and surgical angiogenesis to nerve allograft.

INTRODUCTION: A detailed three-dimensional (3D) evaluation of microvasculature is evolving to be a powerful tool, providing mechanistic understanding of angiomodulating strategies. The aim of this study was to evaluate the microvascular architecture of nerve allografts after combined stem cell delivery and surgical angiogenesis in a rat sciatic nerve defect model. MATERIALS AND METHODS: In 25 Lewis rats, sciatic nerve gaps were repaired with (i) autografts, (ii) allografts, (iii) allografts wrapped in a pedicled superficial inferior epigastric artery fascia (SIEF) flap to provide surgical angiogenesis, combined with (iv) undifferentiated mesenchymal stem cells (MSC) and (v) MSCs differentiated into Schwann cell-like cells. At two weeks, vascular volume was measured using microcomputed tomography, and percentage and volume of vessels at different diameters were evaluated and compared with controls. RESULTS: The vascular volume was significantly greatest in allografts treated with undifferentiated MSCs and surgical angiogenesis combined as compared to all experimental groups (P<0.01 as compared to autografts, P<0.0001 to allografts, and P<0.05 to SIEF and SIEF combined with differentiated MSCs, respectively). Volume and diameters of vessel segments in nerve allografts were enhanced by surgical angiogenesis. These distributions were further improved when surgical angiogenesis was combined with stem cells, with greatest increase found when combined with undifferentiated MSCs. CONCLUSIONS: The interaction between vascularity and stem cells remains complex, however, this study provides some insight into its synergistic mechanisms. The combination of surgical angiogenesis with undifferentiated MSCs specifically, results in the greatest increase in revascularization, size of vessels, and stimulation of vessels to reach the middle longitudinal third of the nerve allograft.

Reasons why patients with tuberculosis in South Korea stop anti-TB treatment: a cross-sectional study.

BACKGROUND: As there had been no reduction in the TB burden in South Korea since 2000, a public-private mix (PPM) strategy was launched in 2011. The purpose of this study was to investigate the reasons for lost to follow-up (LTFU) among TB patients and their clinical characteristics.METHOD: A multicentre, cross-sectional study based on in-depth interviews with patients and their families by TB specialist nurses was conducted. Patients who were reported with a final outcome of LTFU in 2015-2017 at all PPM hospitals across the country were enrolled. Enrolled patients were classified into six subgroups by age and three major reasons for LTFU (adverse effects, refusal of treatment, marginalisation) and their clinical features were compared.RESULTS: Among 780 patients, those who were lost to follow-up due to adverse effects accounted for the largest proportion (n = 387). LTFU in those aged <65 years who refused treatment (n = 189) and those aged <65 years who were marginalised (n = 108) were related to having smear-positive TB and a previous history of unfavourable outcomes.CONCLUSION: To reduce LTFU in South Korea, comprehensive strategies, including management of adverse effects, systematic counselling and education, should be implemented.

Exploring the neuroregenerative potential of tacrolimus.

Introduction: The clinical use of tacrolimus is characterized by many side effects which include neurotoxicity. In contrast, tacrolimus has also shown to have neuroregenerative properties. On a molecular level, the mechanisms of action could provide us more insight into understanding the neurobiological effects. The aim of this article is to review current evidence regarding the use of tacrolimus in peripheral nerve injuries.Areas covered: Available data on tacrolimus' indications were summarized and molecular mechanisms were elucidated to possibly understand the conflicting neurotoxic and neuroregenerative effects. The potential clinical applications of tacrolimus, as immunosuppressant and enhancer of nerve regeneration in peripheral nerve injuries, are discussed. Finally, concepts of delivery are explored.Expert opinion: It is unclear what the exact neurobiological effects of tacrolimus are. Besides its known calcineurin inhibiting properties, the mechanism of action of tacrolimus is mediated by its binding to FK506-binding protein-52, resulting in a bimodal dose response. Experimental models found that tacrolimus administration is preferred up to three days prior to or within 10 days post-nerve reconstruction. Moreover, the indication for the use of tacrolimus has been expanding to fields of dermatology, ophthalmology, orthopedic surgery and rheumatology to improve outcomes after various indications.

Intra-luminal gene therapy in the porcine artery using a recombinant adeno-associated virus 9.

The ability to improve or restore blood flow and promote healing in ischemic tissue has many potential clinical applications. Augmentation by direct delivery of growth factors may further enhance results, but requires a method for sustained delivery. In this study, we have tested the ability of adeno-associated virus 9 (AAV9) delivered within the lumen of a porcine artery to transfect the vessel and produce a desired product. The marker chosen was green fluorescent protein (GFP) (Ke et al., 2011). In 4 farm pigs the cranial tibial artery was surgically exposed. The vessel was temporarily clamped proximally, and divided distally. A cannula was placed intraluminally, and the arterial segment was injected with 1×10E13 particles of AAV9.CB7.CI.GFP·WPRE.rBG. At 14days the transfected cranial tibial artery as well as the liver, spleen and kidneys were harvested. ELISA and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) were used to analyze the artery for GFP production. Significant GFP expression was seen in all transfected cranial tibial vessels, as determined by both GFP protein production (ELISA) and mRNA (RT-qPCR). No GFP was identified in liver, spleen or kidney, nor in the no-GFP control animal artery. Adeno-associated virus 9 is an appropriate vector for gene therapy experiments in the porcine artery model. This vector, and the intraluminal deliver method described result in robust gene expression at 2weeks without evident systemic spill of the virus. The ability to limit delivery of the gene to an isolated segment of vessel is desirable for future research applications.

The outcome and complications of vascularised fibular grafts.

AIMS: Free vascularised fibular grafting has been used for the treatment of large bony defects for more than 40 years. However, there is little information about the risk factors for failure and whether newer locking techniques of fixation improve the rates of union. The purpose of this study was to compare the rates of union of free fibular grafts fixed with locking and traditional techniques, and to quantify the risk factors for nonunion and failure. PATIENTS AND METHODS: A retrospective review involved 134 consecutive procedures over a period of 20 years. Of these, 25 were excluded leaving 109 patients in the study. There were 66 men and 43 women, with a mean age of 33 years (5 to 78). Most (62) were performed for oncological indications, and the most common site (52) was the lower limb. Rate of union was estimated using the Kaplan-Meier method and risk factors for nonunion were assessed using Cox regression. All patients were followed up for at least one year. RESULTS: The rate of union was 82% at two years and 97% at five years. Union was achieved after the initial procedure in 76 patients (70%) at a mean of ten months (3 to 19), and overall union was achieved in 99 patients (91%). No surgical factor, including the use of locked fixation or supplementary corticocancellous bone grafts increased the rate of union. A history of smoking was significantly associated with a risk of nonunion. DISCUSSION: Free vascularised fibular grafting is a successful form of treatment for large bony defects. These results suggest that the use of modern techniques of fixation does not affect the risk of nonunion when compared with traditional forms of fixation, and smoking increases the risk of nonunion following this procedure. Cite this article: Bone Joint J 2017;99-B:134-8.

The rate of successful four-corner arthrodesis with a locking, dorsal circular polyether-ether-ketone (PEEK-Optima) plate.

The purpose of this study is to evaluate the rate of union after four-corner arthrodesis with a locking, dorsal circular plate comprised of polyether-ether-ketone. A retrospective review was conducted of all patients who underwent four-corner arthrodesis with a locking, dorsal circular plate at our institution from January 2005 to May 2009. The primary outcome measure was radiographic and clinical union. During the study period, 26 consecutive wrists underwent four-corner arthrodesis with a locking, dorsal circular plate. Twenty-three wrists were included. The mean clinical follow-up was 16 months (range 3-37). Union was achieved in 22 of 23 wrists at a mean time of 3 months (range 1-12). There was one partial union that underwent successful revision arthrodesis. In summary, four-corner fusion with a polyether-ether-ketone locking, dorsal circular plate results in high union rates. The use of a radiolucent plate allows for more accurate assessment of union with the biomechanical advantages of a fixed angle construct.

Survey of hand surgeons regarding their perceived needs for an expanded upper extremity fellowship.

PURPOSE: To survey practicing hand surgeons regarding their perceived need for an expanded upper extremity fellowship. METHODS: Electronic surveys were sent to 248 surgeons who had completed a hand surgery fellowship between 2008 and 2010. The survey was structured to ascertain whether there was a need for expanded education encompassing the entire upper extremity. Four separate mailings were made. Of the 248 surgeons who were sent the survey, 131 (53%) responded. Of the respondents, 74% (97) were trained in orthopedics, 16% (21) in plastic surgery, and 10% (13) in general surgery. RESULTS: Of the 131 respondents, 7% (9) felt that 1 year of specialty training was insufficient, 48% (63) had sought shoulder and elbow training in their fellowship, and 52% (68) did not have dedicated plastic surgery rotations. Microsurgical experience was variable: 8% (10) of respondents had not been exposed to replantation, 23% (30) had not been exposed to free flap surgery, 32% (42) had not participated in brachial plexus surgery, and 17% (22) had not done a vascularized bone graft. Fifty-six percent (73) of respondents had not had dedicated time for research during their fellowship. Eleven percent (15) had obtained additional training after their fellowship, including shoulder and elbow, microsurgery, pediatrics, and peripheral nerve surgery. When asked if they would have applied to a 2-year hand and upper extremity fellowship, 60% (79) of respondents would have applied. CONCLUSIONS: Based on the results of this survey, 1 year of hand fellowship training has been perceived as inadequate by 7% (9) of respondents, with exposure insufficient in shoulder and elbow, microsurgery, pediatrics, and clinical research. Further critical review of hand fellowship education should be considered, with the availability of extended fellowship tracks for those requesting an increased breadth of upper extremity surgical training.

Vascularized bone grafts for scaphoid nonunions.

Scaphoid fractures that fail to unite are at risk of developing avascular necrosis and progressive structural collapse, thereby complicating attempts at revision surgical treatment. Vascularized bone grafts have demonstrated utility in promoting consolidation in the treatment of scaphoid nonunions complicated by avascular necrosis. Numerous pedicled and free vascularized grafts have been described with variable, but generally favorable, outcomes. Understanding the indications for different grafts is critical to the successful application of these techniques and grafts in the treatment of challenging scaphoid nonunions.

Biomechanical comparison of three fixation techniques used for four-corner arthrodesis.

Clinical results following four-corner arthrodesis vary and suggest that nonunion may be related to certain fixation techniques. The purpose of our study was to examine the displacement between the lunate and capitate following a simulated four-corner arthrodesis with the hypothesis that three types of fixation (Kirschner wires, dorsal circular plate, and a locked dorsal circular plate) would allow different amounts of displacement during simulated wrist flexion and extension. Cadaver wrists with simulated four-corner arthrodeses were loaded cyclically either to implant failure or until the lunocapitate displacement exceeded 1 mm. The locked dorsal circular plate group was significantly more stable than the dorsal circular plate and K-wire groups (p = 0.018 and p = 0.006). While these locked dorsal circular plates appear to be very stable our results are limited only to the biomechanical behavior of these fixation techniques within a cadaver model.

Vascularized medial femoral condyle corticoperiosteal flaps for the treatment of recalcitrant humeral nonunions.

BACKGROUND: Several methods have been used in the management of humeral nonunions. With the advent of modern microsurgical techniques, vascularized bone grafting is becoming increasingly used to improve local biology. We report our experience in the use of a vascularized corticoperiosteal bone flap from the medial femoral supracondylar region in the treatment of recalcitrant humeral nonunions. METHODS: A retrospective review was performed of all patients treated with this technique over a 4-year period within our institution. Patient demographics, nonunion characteristics, complications, and long-term outcomes were analyzed. RESULTS: Six patients underwent vascularized periosteal graft reconstruction. Prior to this, all had failed an average of three procedures with the length of nonunion ranging from 6 to 68 months. All six nonunions healed by an average of 6.8 months (range 2-12 months). Two patients required additional secondary procedures. Functional outcome improved in all patients as adjudged by disabilities of the arm, shoulder, and hand, Mayo elbow performance, and Constant Murley scores. CONCLUSIONS: The vascularized medial femoral condyle corticoperiosteal flap provides an additional treatment option for the management of humeral nonunions.

Medial femoral condyle vascularized bone grafts for scaphoid nonunions.

Free vascularized bone grafts from the medial femoral condyle provide both structural support and blood supply to promote union in the difficult subset of scaphoid nonunions complicated by humpback deformity and proximal pole avascular necrosis. These nonunions have not consistently achieved union when treated with grafts which fail to restore scaphoid geometry or vascularity. The rationale, indications, contraindications, technique and results of bone grafting scaphoid nonunions with grafts harvested from the medial femoral condyle are presented.

Vascularized bone grafting from the dorsal distal radius for Kienböck's disease: technique, indications and review of the literature.

The goals of surgical procedures in Kienböck's disease are to preserve wrist function, revascularize the necrotic lunate and maintain normal wrist kinematics when possible. Of the various treatment options, pedicled vascularized bone grafts from the dorsal distal radius permit the transfer of vascularized osseous tissue to the necrotic lunate in order to revascularize it. Vascularized bone grafting is an attractive alternative to conventional bone grafting by improving the local biological environment and thereby promoting revascularization. Recent advances in the anatomy and physiology of vascularized pedicled bone grafts have increased our ability to apply them to the treatment of Kienböck's disease. The purpose of this article is to describe the detailed vascular anatomy of the dorsal distal radius, the surgical technique, indications as well as contraindications of our preferred method of pedicled vascularized bone grafts of Kienböck's disease.

The arterial anatomy of the medial femoral condyle and its clinical implications.

The success of vascularized bone grafts from the medial femoral condyle in various clinical applications has sparked renewed interest in the microvascular anatomy of this region. This study describes the arterial supply of the distal medial femoral condyle and its implications in harvesting vascularized bone grafts. The location, branching pattern, internal diameter, and distribution of perforators of the descending genicular artery and superior medial genicular artery in 19 fresh cadaveric lower limbs were recorded. The descending genicular artery was present in 89% and the superior medial genicular artery was present in 100% of specimens with average distances proximal to the articular surface of 13.7 cm and 5.2 cm, respectively. The average number of perforating vessels was greatest in the posterior distal quadrant of the condyle. The blood supply of the medial femoral condyle is plentiful and consistent making it a useful source for free vascularized bone grafts.

Wrist instability.

The topic of wrist or carpal instability has been a source of confusion and miscommunication for decades. The terminology can often be difficult to understand and one surgeon's concept of instability may be completely different from another's. This is by no means a comprehensive review of carpal instability, which has often been the focus of numerous multi-volume textbooks. The purpose of this paper is to detail the basics of carpal instability, the anatomy, pathomechanics, terminology and basic principles of treatment.

Acetabular stress fractures in military endurance athletes and recruits: incidence and MRI and scintigraphic findings.

OBJECTIVE: To evaluate the incidence and the MRI and scintigraphic appearance of acetabular stress (fatigue) fractures in military endurance athletes and recruits. DESIGN AND PATIENTS: One hundred and seventy-eight active duty military endurance trainees with a history of activity-related hip pain were evaluated by both MRI and bone scan over a 2-year period. Patients in the study ranged in age from 17 to 45 years. They had hip pain related to activity and had plain radiographs of the hip and pelvis that were interpreted as normal or equivocal. The study was originally designed to evaluate the MRI and scintigraphic appearance of femoral neck stress fractures. Patients had scintigraphy and a limited MRI examination (coronal imaging only) within 48 h of the bone scan. Twelve patients demonstrated imaging findings compatible with acetabular stress fractures. RESULTS: Stress fractures are common in endurance athletes and in military populations; however, stress fracture of the acetabulum is uncommon. Twelve of 178 patients (6.7%) in our study had imaging findings consistent with acetabular stress fractures. Two patterns were identified. Seven of the 12 (58%) patients had acetabular roof stress fractures. In this group, two cases of bilateral acetabular roof stress fractures were identified, one with a synchronous tensile sided femoral neck stress fracture. The remaining five of 12 (42%) patients had anterior column stress fractures, rarely occurring in isolation, and almost always occurring with inferior pubic ramus stress fracture (4 of 5, or 80%). One case of bilateral anterior column stress fractures was identified without additional sites of injury. CONCLUSIONS: Stress fractures are commonplace in military populations, especially endurance trainees. Acetabular stress fractures are rare and therefore unrecognized, but do occur and may be a cause for activity-related hip pain in a small percentage of military endurance athletes and recruits.

Treatment of isolated injuries of the lunotriquetral ligament. A comparison of arthrodesis, ligament reconstruction and ligament repair.

We studied 57 patients with isolated lunotriquetral injuries treated by arthrodesis, direct ligament repair, or ligament reconstruction. The outcomes were compared by using written questionnaires, the Disabilities of the Arm, Shoulder and Hand (DASH) score, range of movement, strength, morbidity and rates of reoperation. Isolated lunotriquetral injury was confirmed by arthroscopy or arthrotomy. The mean age of the patients was 30.7 years (15.4 to 53.7) and the injuries were subacute or chronic in 98.2%. Eight patients underwent lunotriquetral reconstruction using a distally-based strip of the tendon of extensor carpi ulnaris, 27 had lunotriquetral repair and 22 had lunotriquetral arthrodesis. The mean follow-up was 9.5 years (2 to 22). The probability of remaining free from complications at five years was 68.6% for reconstruction, 13.5% for repair, and less than 1% for arthrodesis. Of the lunotriquetral arthrodeses, 40.9% developed nonunion and 22.7% developed ulnocarpal impaction. The probability of not requiring further surgery at five years was 68.6% for reconstruction, 23.3% for repair and 21.8% for arthrodesis. The DASH scores for each group were not significantly different. Objective improvements in strength and movement, subjective indicators of pain relief and satisfaction were significantly higher in the lunotriquetral repair and reconstruction groups than in those undergoing arthrodesis.

Chondrolysis and joint destruction secondary to snake envenomation.

Although snakebite injuries to the hand are common, intra-articular envenomation has rarely been reported. In this article, we describe a patient who was bitten by a rattlesnake and whose left-index-finger distal interphalangeal joint sustained intra-articular envenomation that resulted in aseptic chondrolysis and severe joint destruction 1.5 years later. Multiple cultures and biopsies were negative, and histology was consistent with nonspecific degenerative changes secondary to necrosis of the articular cartilage from retained toxins. The patient chose arthrodesis; 24 months postoperatively, he was pain-free and had returned to work.

Volar A1 pulley approach for fixation of avulsion fractures of the base of the proximal phalanx.

Avulsion fractures of the base of the proximal phalanx associated with collateral ligament instability, excluding the thumb, are relatively rare. While the indications for surgical intervention vary, dorsal approaches have been advocated despite the volar location of the fracture fragment and orientation of the collateral ligaments. Ten patients with 11 avulsion fractures at the base of the proximal phalanx associated with collateral ligament instability were treated with open reduction and internal fixation using a volar A1 pulley approach. Anatomic restoration of the articular surface and collateral ligament stability were obtained in all patients. All fractures healed between 5 and 9 weeks (average, 6 weeks). After an average 19.4-month follow-up period all patients had full range of motion of the metacarpophalangeal joint, collateral ligament stability, and grip strength of at least 90% of the uninjured hand. No perioperative complications occurred. The average DASH score at last follow-up examination was 1.8 (range, 0-6). All patients were satisfied with the outcome of surgery. The volar A1 pulley approach is a direct and effective approach for reduction and fixation of avulsion fractures of the base of the proximal phalanx associated with collateral ligament instability.

Synostosis of the ring-small finger metacarpal in Apert acrosyndactyly hands: incidence and treatment.

SUMMARY: This study reports on the incidence of a synostosis between the ring-small metacarpal bases in patients with Apert syndrome and describes a technique to resect the synostosis and insert silicone sheets to improve hand function. Records of 9 patients (18 hands) were evaluated. Average age at follow-up was 9.5 years. Three relationships between the ring-small metacarpals were observed. Type I hands (22%) had no abnormal interconnections; type II hands (33%) possessed a synostosis since birth; type III hands (44%) did not possess a synostosis at birth, but one later developed at average age of 79 months. Total incidence of synostosis was 77%. Five patients underwent excision of the synostosis. At an average of 16 postoperative months, 4 of these patients experienced improvement in hand prehension. In patients with Apert syndrome, resection of abnormal interconnections between the ring-small metacarpals is highly recommended to improve hand prehension based on the high incidence of a synostosis in this region.