Secondary Surgery For Removal Research Articles

Assessment of biomechanical strength of titanium versus unsintered-hydroxyapatite/poly-L-lactic acid (u-HA/PLLA) osteosynthesis screws in bilateral sagittal split ramus osteotomy

Titanium osteosynthesis is considered to be stable for the bilateral sagittal split ramus osteotomy (BSSRO) procedure in orthognathic surgery but is disregarded owing to a multitude of complications, the most significant necessitating a secondary surgery for removal. Bioresorbable osteofixation devices, especially third-generation unsintered-hydroxyapatite/poly-L-lactic acid (u-HA/PLLA), are increasingly used in the mandibular region because of their strength and bioactive/osteoconductivity. To date, three titanium bicortical screws has been the standard for the rigid fixation of BSSRO. As data on the use of u-HA/PLLA bicortical screws are limited, we conducted an in vitro biomechanical strength test to evaluate the performance of 12-mm bicortical u-HA/PLLA screws in comparison with titanium screws using mandibular bone models. BSSRO was performed on all specimens, followed by fixation with either three titanium screws or three, four, or five u-HA/PLLA screws, and loading was performed using a clinically presumed occlusal force. Displacement forces (measured in newton ‘N′) of 50 N, 130 N, and 220 N were applied. Our results showed that the use of three u-HA/PLLA screws was unstable, that of four u-HA/PLLA screws was comparable, and that of five u-HA/PLLA screws provided stability equal to that of the three titanium bicortical screws. Although further clinical assessment is needed, our study demonstrated that the five u-HA/PLLA bicortical screws are viable alternatives to titanium in BSSRO osteofixation.

In vitro and in vivo evaluation of effects of high-purity magnesium on tight junction of intestinal epithelial cell.

After anastomosis of sutures or pins, the restoration of intestinal barrier function can avoid several complications, such as tissue damage and inflammation. Our previous studies demonstrated the feasibility of biodegradable magnesium (Mg) pins as novel anastomosing implants to spontaneously absorb in the body, avoiding secondary removal surgery and long-term inflammation. However, the effect of Mg pins on the intestinal tight junction barrier is rarely investigated. In this study, we conducted high-purity Mg pins inserted in the intestine of rats and prepared Mg extracts cultured intestinal epithelial cell line to investigate the biological effect on the intestinal barrier associated with tight junction protein expression. We discovered that the concentration of released Mg ions over 1.7 mM was the critical threshold, above which mRNA expression of intestinal tight junction and cell apoptosis were affected considerably. Results of the immunohistochemical analysis revealed that Mg functions to stimulate ZO-1, caspase-3, occluding, and claudin-3 expressions. We offer new insight into the effectiveness of biodegradable Mg materials as the next generation of intestinal anastomosis pins, which effectively filters toxins as well as bacteria, and reduces inflammation.

Hermetic and Bioresorbable Packaging Materials for MEMS Implantable Pressure Sensors: A Review

Pressure sensors based on microelectromechanical system (MEMS) technology have been employed for measuring the pressure inside the human body due to their small size, lightweight, and low energy consumption. Hermetic packages are necessary to protect the implants from body fluid corrosion. Materials such as metal and glass are usually considered to be hermetic and can ensure several years of lifetime. Materials with low permeability, such as liquid crystal polymers and parylene, are also supposed to be short-term hermetic when the expected lifetime is not too long (less than a year). Water penetration and interface adhesion determine whether the package fails. Helium leakage tests and water concentration tests can be used to predict when the package fails. In addition, for more short-term implantable devices (several days or weeks), bioabsorbable packages can be helpful. The main advantage is that the self-degradation of the packaging material can avoid tissue damage caused by long-term implantation or infection caused by secondary removal surgery.

Reduced restenosis and enhanced re-endothelialization of functional biodegradable vascular scaffolds by everolimus and magnesium hydroxide

BackgroundCoronary artery disease is a cardiovascular disease with a high mortality and mortality rate in modern society. Vascular stent insertion to restore blood flow is essential to treat this disease. A fully biodegradable vascular scaffold (BVS) is a vascular poly (L-lactic acid) (PLLA) stent that is receiving growing interest as this is biodegradable in the body and does not require secondary removal surgery. However, acidic byproducts composed of PLLA produced during the biodegradation of the BVS can induce an inflammatory response. Magnesium hydroxide, a basic inorganic particle, neutralizes the acidic byproducts of PLLA. MethodsIn this study, we investigated using a BVS coated with everolimus and surface-modified magnesium hydroxide that suppresses smooth muscle cell proliferation and protects endothelial cells, respectively. The various characteristics of the functional stent were evaluated using in vitro and in vivo analyses. ResultsThe BVS was successfully prepared with evenly coated everolimus and surface-modified magnesium hydroxide. A neutral pH value was maintained by magnesium hydroxide during degradation, and everolimus was released for one month. The coated BVS effectively inhibited protein adsorption and platelet adhesion, demonstrating excellent blood compatibility. In vitro analysis showed that BVS protects endothelial cells with magnesium hydroxide and selectively inhibits smooth muscle cell proliferation via everolimus treatment. The functional BVS was inserted into porcine coronary arteries for 28 days, and the results demonstrated that the restenosis and inflammation greatly decreased and re-endothelialization was enhanced as compared to others.ConclusionsThis study provides new insights into the design of drug-incorporated BVS stent for coronary artery disease.Graphical

Novel Mg-Ca-La alloys for guided bone regeneration: Mechanical performance, stress corrosion behavior and biocompatibility

Guided bone regeneration (GBR) is a therapeutic method that is used to augment deficient ridges before dental implantation. The non-absorbable membranes need secondary removal surgery, while absorbable collagen membranes fail while being applied to large bone defects because of their relatively low stiffness. The “ideal” membrane for use in GBR has yet to be developed. This study aims to develop and explore the feasibility of Mg-Ca-La alloys for application in GBR. Mg-0.2Ca-0.2La alloy exhibits fine microstructure and a good combination of tensile strength and ductility. Mg-0.2Ca-0.2La alloy is also capable of supporting the adhesion, proliferation and migration of human gingival fibroblasts, and shows good cytocompatibility on MC3T3-E1 cells. The GBR membranes usually need intraoperative bending or shaping to adapt the alveolar ridge. The additional effect of bending stress on magnesium-based materials must be considered due to a well-known issue, namely stress-corrosion cracking (SCC). The SCC results reveal that the bended Mg-0.2Ca-0.2La presents a uniform corrosion morphology with a corrosion rate of 0.09 mm/yr, which is 61% less than that of unstressed ones. Mg-0.2Ca-0.2La alloy possesses adequate strength and ductility, high biocompatibility and slow degradation under bending stress, contributing to adequate malleability and sustained spatial stability for membrane use.

Shape memory polymer hydrogels with cell-responsive degradation mechanisms for Crohn's fistula closure.

Crohn's disease, a form of inflammatory bowel disease, commonly results in fistulas, tunneling wounds between portions of the urinary, reproductive, and/or digestive systems. These tunneling wounds cause pain, infection, and abscess formation. Of Crohn's patients with fistula formation, 83% undergo surgical intervention to either drain or bypass the fistula openings, and ~23% of these patients ultimately require bowel resections. Current treatment options, such as setons, fibrin glues, and bioprosthetic plugs, are prone to infection, dislodging, and/or require a secondary removal surgery. Thus, there is a need for fistula filling material that can be easily and stably implanted and then degraded during fistula healing to eliminate the need for removal. Here, the development of a shape memory polymer hydrogel foam containing polyvinyl alcohol (PVA) and cornstarch (CS) with a disulfide polyurethane crosslinker is presented. These materials undergo controlled degradation by amylase, which is present in the digestive tract, and by reducing thiol species such as glutathione/dithiothreitol. Increasing CS content and using lower molecular weight PVA can be used to increase the degradation rate of the materials while maintaining shape memory properties that could be utilized for easy implantation. This material platform is based on low-cost and easily accessible components and provides a biomaterial scaffold with cell-responsive degradation mechanisms for future potential use in Crohn's fistula treatment.

Corrosion behavior of biodegradable metals in two different simulated physiological solutions: Comparison of Mg, Zn and Fe

Bio-absorbable metals have been proposed to overcome the limitations of permanent implant materials, particularly the risk of chronic inflammation and secondary surgery for removal after healing. The most researched bio-absorbable metal is magnesium, followed by iron and zinc, but there is little work comparing the different metals under the same experimental conditions. Herein, degradation performance of Mg/Zn/Fe was investigated via immersion test (28 days) and electrochemical tests under two buffer systems, simulated body fluid solution (SBF) and Dulbecco’s Modified Eagle’s cell culture medium (DMEM). Corrosion rate was initially slower in DMEM for all metals, Mg showed the fastest corrosion rate in both SBF and DMEM. The influence of the electrolyte on the corrosion behaviour was strongest for Mg. Importantly, the ranking of the corrosion rate of the three metals changes with immersion time. Noteworthy is a strong increase of corrosion resistance of Mg with time during the first 24 h of immersion. Corrosion morphology and corrosion products were characterized with SEM, EDS, FTIR, XPS and XRD. In general, the corrosion product layers are much more uniform in DMEM, besides, the insoluble corrosion product/precipitation consisted of metallic oxides/hydroxides, phosphates and carbonates. Slower corrosion rate in DMEM solution can therefore be due to formation of a more protective precipitate layer, adsorbed amino acids, and absence of Tris-HCl that accelerates corrosion in SBF.

Silk reservoir implants for sustained drug delivery.

Biomaterial implants for the sustained delivery of therapeutics can be utilized to deliver drugs at near-constant rates over extended time frames to provide an alternative to daily oral medications. The biomaterials used to construct these systems, however, are often not bioresorbable and thus require a secondary surgery for removal from the body, and fabrication of these systems may require the use of harsh chemical solvents. To address these shortcomings, a fabrication process was developed to generate biodegradable drug reservoir systems from regenerated silk fibroin protein solution (23% w/v). The tubular systems, with an inner diameter of 2.0 mm and wall thickness < 250µm, were developed using an all-aqueous solution-gel-solid phase transition curing process. Two different clinically-relevant therapeutics were released at near-constant rates for 30 days (> 100µg/day). The protein secondary structure of the devices consisted of 40% crystalline beta sheet. Mechanically, radial compression (1mm/min) of unloaded systems demonstrated Young's moduli similar to cancellous (spongy) bone (100 to 250 MPa) and the systems showed good recovery under cyclic compression (to 17.5% strain). The devices could be generated in complex shapes (e.g., hollow cylinders) via an additive molding process, offering the potential for drug delivery but also for broader applications in tissue engineering and diagnostics.

New possibilities: the LockDown device for distal clavicle fractures.

Background and hypothesisThe majority of distal clavicle fractures are displaced fractures and constitute a treatment challenge because they have a 30% chance of delayed union or nonunion. Although several options for surgical reconstruction have been described, in patients with a comminuted and/or small distal fragment, these reconstructive options have proved to be prone to failure. Moreover, secondary surgery for removal is necessary in most cases. We hypothesized that the LockDown device, a braided synthetic ligament device, combined with resection of the distal fracture fragment is a suitable alternative in specified patients with distal clavicle fractures.MethodsEleven patients with distal clavicle fractures were treated with distal fracture resection and the LockDown procedure. All patients underwent regular follow-up with data collection; additionally, 7 were assessed at 1-year follow-up according to the study protocol. On the basis of radiography, these patients had a clear coracoclavicular ligament disruption and subsequent cranial dislocation of the medial fragment. Regular follow-up was performed at 6 weeks, 3 months, and 6 months. Control radiographs were taken at 3 and 6 months. Furthermore, the 7 enrolled patients were assessed at 1 year, when the Disabilities of the Arm, Shoulder and Hand score, Constant shoulder score, Nottingham Clavicle Score, and range of motion were recorded. Residual pain was ascertained by a visual analog scale score.ResultsIn total, 11 patients were treated with distal clavicle resection and the LockDown procedure. Eight patients underwent surgery within 3 weeks after presentation at the emergency department. The other 3 patients were operated on after a trial of conservative treatment (due to persisting pain and delayed union). None of the patients had postoperative complications. At 3 months, 9 of the 11 patients had made a full recovery.DiscussionAll 11 patients had good short-term clinical outcomes. None showed acromioclavicular instability. Furthermore, secondary surgery was avoided, and hardware complications did not occur. In low-demand patients or patients with a high risk of nonunion, this technique may be a favorable alternative to other known techniques.

Surgical management of ulnar styloid fractures: comparison of fixation with anchor suture and tension band wire

BackgroundLimited reference is available regarding surgical management in symptomatic ulnar styloid fractures with small bony avulsion. The study goal is to report the surgical outcomes using anchor suture fixation with comparison to traditional tension band wire fixation.MethodsWe retrospectively reviewed the medical records in patients who underwent surgical repair for unilateral ulnar styloid fractures with distal radioulnar instability between 2004 and 2017. A total of 31 patients were enrolled including two kinds of fixation methods. Anchor suture fixation plus distal radioulnar joint pinning was performed in ten patients with tiny avulsion bony fragments (group A); tension band wire fixation was performed in 21 patients with big styloid fracture fragments (group B). Patient characteristics and 2-year treatment outcomes were compared between two groups based on Mayo Modified Wrist Score (MMWS); Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH); visual analog scale (VAS), and surgical complication. Descriptive statistics were used for calculation of key variables; a p value of < 0.05 was considered statistically significant.ResultsBased on Gaulke classification, there were five subtypes in group A and three subtypes in group B. Incidence of concomitant distal radius fractures was significantly higher in group B; other patient characteristics including age, sex, injury side, and time to surgery showed no significant difference. Outcome assessment regarding MMWS, QuickDASH, and VAS was comparable between two groups. Bone-related complications including nonunion, DRUJ subluxation, and styloid resorption were analyzed; the difference was not significant. Incidence of implant-related complications including migration and secondary removal surgery was significantly higher in group B (p = 0.021).ConclusionSurgical fixation in symptomatic ulnar styloid fractures yields comparable treatment outcomes in both fracture patterns. Implant-related complication with secondary removal surgery is more common in tension band wire group. Anchor suture fixation is a feasible option for tiny styloid avulsion fragments with limited surgical complication.

New Resorbable Membrane Materials for Guided Bone Regeneration

Membranes are used for guided bone regeneration (GBR) in bone defects. Resorbable membranes of collagen or aliphatic polyesters that do not require secondary surgery for removal, unlike non-resorbable membranes, have been marketed for GBR. Platelet rich fibrin membrane and silk-based membranes have recently been assessed as membranes for GBR. Studies have been conducted on resorbable membranes with new materials to improve physical properties and bone regeneration without any adverse inflammatory reactions. However, clinical research data remain limited. More studies are needed to commercialize such membranes.

Evaluation of Fronto-Orbital Advancement Using Titanium-Based Internal Fixation for Corrective Pediatric Craniofacial Surgery.

For successful reshaping of the cranial vault in terms of corrective fronto-orbital advancement (FOA) efficient and reliable internal fixation systems for stabilization of bone fragments are indispensable. The rate of complications and feasibility of corrective FOA with the usage of titanium-based rigid fixation systems is rarely analyzed and discussed. The authors retrospectively reviewed the medical records of 42 patients who received corrective FOA with the implementation of titanium internal rigid fixation and consecutive secondary surgery for removal. The reliability of the fixation system was judged by the outcome of the FOA as evaluated by the Whitaker score, esthetic outcome as well as by the complication rate of the secondary intervention, necessary for removal of the fixation system. All patients were categorized as Whitaker I (no further treatment desirable). Esthetic outcome was excellent in all patients as judged by surgeon and parents. Mean age at the time of FOA was 9.3 months. Time to removal, duration of the second hospital stay for removal of the fixation system, and duration of surgical drains were on average 5 months, 2 days, and 1.7 days, respectively. Mean duration of the secondary surgery was 63 min. No complications occurred. Our investigation supports the usage of titanium internal rigid fixation systems in pediatric craniofacial surgery, thereby providing a reliable alternative to avoid the well-documented problems of bio-absorbable plate fixation systems.

Early Correction of Distal Radius Partial Articular Malunion Leads to Good Long-term Functional Recovery at Mean Follow-up of 4 Years

Background: Distal radius articular step-off or deformity may cause posttraumatic arthritis and poor functional outcome. The purpose of this study was to evaluate pain and functional outcomes in patients with malunited partial articular distal radius fractures who underwent corrective osteotomy. We hypothesized that anatomic restoration of distal radius articular surface after a malunited partial articular distal radius fracture results in improvement in pain and functional measures and delays the development of posttraumatic arthritis. Methods: Seven consecutive patients with mean age of 38 years underwent corrective osteotomy via either a standard dorsal approach or combined dorsal and volar approach. Mean time from injury to corrective osteotomy was 10 weeks. Patients were assessed with respect to Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), forearm and wrist range of motion, pain, and grip strength. Results: At mean follow-up of 44 months, significant improvements in pain scores (7.1-0.9, P < .001), QuickDASH (38.7-11.6, P < .001), grip strength (21.4-30.0 kg, P = .01) were achieved. All range of motion measurements demonstrated significant improvements except forearm pronation. One patient demonstrated radiographic evidence of osteoarthritis but had no pain at final follow-up. No patients required secondary surgery for removal of symptomatic hardware. Conclusions: Based on these findings, we recommend that early corrective osteotomies should be considered in young patients with intra-articular distal radius malunions before considering salvage procedures such as partial or complete wrist arthrodesis.

New fixation approach for transverse metacarpal neck fracture: a biomechanical study

BackgroundFifth metacarpal neck fracture, also known as boxer’s fracture, is the most common metacarpal fracture. Percutaneous Kirschner-wire (K-wire) pinning has been shown to produce favorable clinical results. However, the fixation power of K-wires is a major concern. Plate fixation is also a surgical option, but it has the disadvantages of tendon adhesion, requirement of secondary surgery for removal of the implant, and postoperative joint stiffness. A fixation method that causes little soft tissue damage and provides high biomechanical stability is required for patients with fifth metacarpal neck fracture for whom surgical intervention is indicated. The present study proposed fixation using K-wires and a cerclage wire to treat fifth metacarpal neck fracture. The fixation power of this new method was compared with that of K-wires alone and plates.MethodsWe used a saw blade to create transverse metacarpal neck fractures in 16 artificial metacarpal bone specimens, which were then treated with four types of fixation as follows: (1) locking plate with five locking bicortical screws (LP group), (2) regular plate with five bicortical screws (RP group), (3) two K-wires (K group), and (4) two K-wires and a figure-of-eight cerclage wire (KW group). The specimens were tested by using cantilever bending testing on a material testing system. The stiffness of the four fixation types was determined by observing force–displacement curves. Finally, the Kruskal–Wallis test was adopted to process the data, and the Mann–Whitney exact test was performed to conduct paired comparison between the fixation types.ResultsThe fixation strength levels of the four fixation approaches for treating fifth metacarpal neck fracture were ranked in a descending order of LP group (24.6 ± 5.1 N/mm, median ± interquartile range) > RP group (22.2 ± 5.8 N/mm) ≅ KW group (20.1 ± 3.2 N/mm) > K group (16.9 ± 3.0 N/mm).ConclusionThe fixation strength of two K-wires was significantly higher when reinforcement was provided using a figure-of-eight cerclage wire. The strength of the proposed approach is similar to that of a regular plate with five bicortical screws but weaker than that of a locking plate with the same amount of bicortical screws. Cerclage wire-integrated K-wires can be an alternative method that avoids the excessive soft tissue dissection required for plating in open reduction internal fixation for fifth metacarpal neck fracture.

Progress in bioabsorbable screws used in treatment of injury to distal tibiofibular syndesmosis

As injury to distal tibiofibular syndesmosis is commonly associated with ankle fractures, it calls for timely and correct diagnosis and treatment because it might result in chronic pain and ankle instability. Its severe cases can lead to traumatic arthritis. Stable injury to distal tibiofibular syndesmosis can be treated conservatively, but internal fixation is mostly recommended for severe cases of the injury. Internal fixation with metal screws usually requires a secondary surgery for removal of the implants but application of bioabsorbable screws overcomes this trouble and avoids a secondary surgery and its related complications. This article reviews the advantages of bio-absorbable screws, choice of bioabsorbable materials and screws, therapeutic outcomes and adverse reactions in the treatment of distal tibiofibular syndesmotic injury. Key words: Ankle; Bone screws; Fracture fixation, internal; Distal tibiofibular

Locked Intramedullary Total Wrist Arthrodesis

Total wrist arthrodesis is commonly performed using fixation plates, which can produce soft tissue irritation, often require removal, and limit the ability to position the hand in space. The Skeletal Dynamics IMPLATE is an intramedullary total wrist fusion device designed to provide stable fixation while avoiding the problems associated with plates. Radial and metacarpal locked intramedullary nails are inserted and joined by a connector. Desired hand placement is achieved by selecting the proper connector length and angle, then orienting it appropriately. Fusion mass compression is obtained by virtue of longitudinal threads on the radial nail that allow for length adjustment. Seven wrists in three men and four women were treated with this device and followed for a minimum of 24 weeks. In all cases, local cancellous bone graft was used and the third carpometacarpal (CMC) joint incorporated into the fusion. The median age was 49 (range, 28-71) years. Indications for fusion were two posttraumatic arthritides, three rheumatoid arthritides, one spastic deformity, and one infection. Patients were evaluated before surgery and at final follow-up using the Fernandez pain score and grip strength measurements using a hand-held dynamometer. All patients improved their grip strength and decreased their pain scores. All fusions united, and none of the patients presented dorsal soft tissue problems or required implant removal. One rheumatoid patient required secondary surgery for removal of a retained palmar osteophyte. This device delivers stable fixation, facilitates hand placement, and does not require removal.

Silver-doped calcium phosphate cements with antimicrobial activity

There is a current need for the localised delivery of antibiotics in order to treat implant-based bacterial infections. Existing treatments use non-resorbable materials such as poly(methyl methacrylate) beads loaded with antibiotics; unfortunately, as they are not resorbable, these beads require secondary surgery for removal. Calcium phosphate cements have considerable potential for the localised delivery of drugs since they can be resorbed to some extent within the body, eliminating the need for a secondary surgical procedure. Therefore, in this study, the efficacy of both hydroxyapatite and brushite cements in the delivery of silver ions has been investigated. The activity of the Ag + released from the cements was assessed against the growth of both Staphylococcus aureus and Staphylococcus epidermidis; the brushite cement exhibited excellent antibacterial properties and also showed an increase in compressive strength of over 30%. In this study we have found that with a few changes in Ag + concentration it should be possible to produce a fully resorbable bone replacement material that is combined with an antibacterial scaffold with controlled release over a period of time, which is likely to inhibit bacterial infections associated with implantation procedures.

Fabrication and Characterization of Surface Texture for Bone Ingrowth by Sequential Laser Peening Biodegradable Orthopedic Magnesium-Calcium Implants

Biodegradable magnesium-calcium (Mg–Ca) implants have the ability to gradually dissolve and absorb into the human body after implantation. The similar mechanical properties to bone indicate that Mg–Ca is an ideal implant material to minimize the negative effects of stress shielding. Furthermore, using a biodegradable Mg–Ca implant prevents the need for a secondary removal surgery that commonly occurs with permanent metallic implants. The critical issue that hinders the application of Mg–Ca implants is the poor corrosion resistance to human body fluids. The corrosion process adversely affects bone ingrowth that is critical for recovery. Therefore, sequential laser shock peening (LSP) of a biodegradable Mg–Ca alloy was initiated to create a superior surface topography for improving implant performance. LSP is an innovative treatment to fabricate functional patterns on the surface of an implant. A patterned surface promotes bone ingrowth by providing a rough surface texture. Also, LSP imparts deep compressive residual stresses below the surface, which could potentially slow corrosion rates. Unique surface topographies were fabricated by changing the laser power and peening overlap ratio. The resultant effects on surface topography were investigated. Sequential peening at higher overlap ratios (75%) was found to reduce the tensile pileup region by over 40% as well as compress the overall surface by as much as 35 μm.

Spontaneous Autoinflation and Deflation of Double-Lumen Breast Implants

A rare late complication of textured, double-lumen breast implants developed 15 years after routine augmentation mammaplasty. The patient required secondary surgery for removal of the implants in both breasts because of their spontaneous autoinflation and deflation. Mammography showed autoexpansion of the right breast implant and deflation of left breast implant in the outer lumen without evidence of silicone leakage 15 years after implantation. The spherical shape of the right implant was filling with red-brown fluid. The deflated left implant had a thick capsule. Both implants were characterized during surgery and removed. Few reports have described spontaneous autoinflation of breast implants. Several causes of implant autoinflation have been proposed, such as valve defects, osmotic swelling, and inorganic salts produced by the texturization process or injection of saline with nonstandard salt concentrations. However, the exact mechanism remains unknown.