Structural basis for selectivity and diversity in angiotensin II receptors.

The angiotensin II receptors AT1R and AT2R serve as key components of the renin-angiotensin-aldosterone system. AT1R has a central role in the regulation of blood pressure, but the function of AT2R is unclear and it has a variety of reported effects. To identify the mechanisms that underlie the differences in function and ligand selectivity between these receptors, here we report crystal structures of human AT2R bound to an AT2R-selective ligand and to an AT1R/AT2R dual ligand, capturing the receptor in an active-like conformation. Unexpectedly, helix VIII was found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G proteins or ß-arrestins, in agreement with the lack of signalling responses in standard cellular assays. Structure-activity relationship, docking and mutagenesis studies revealed the crucial interactions for ligand binding and selectivity. Our results thus provide insights into the structural basis of the distinct functions of the angiotensin receptors, and may guide the design of new selective ligands.

Comparison of 3 Dynamic External Fixation Devices for Proximal Interphalangeal Joint Dorsal Fracture-Dislocations in a Cadaver Model.

PURPOSE: Several improvised dynamic external fixation devices are used for treating unstable dorsal proximal interphalangeal (PIP) joint fracture-dislocations. We compared the effectiveness of 3 constructs for simulated dorsal PIP joint fracture-dislocations in a cadaver model. METHODS: We tested 30 digits from 10 fresh-frozen, thawed cadaver hands. We aimed to remove the palmar 50% of the base of each digit's middle phalanx (P2), simulating an unstable dorsal PIP joint fracture-dislocation. Each PIP joint was then stabilized via external fixation with either a pins-and-rubber-bands construct, pins-only construct, or tuberculin syringe-pins construct. We allocated 10 digits per fixation group. The finger tendons were secured to a computer-controlled stepper motor-driven linear actuator. Via this mechanism, all PIP joints were taken through 1,400 cycles of flexion-extension. With the PIP joint in neutral extension, we measured the P2 dorsal translation at baseline, after fixator stabilization, and after the motion protocol. RESULTS: The actual mean P2 palmar defect created was 48% of the base. All PIP joints were unstable after creating the defect, with a mean initial P2 dorsal displacement of 3.7 mm. After application of the fixators, all PIP joint dislocations were reduced. The median residual P2 dorsal displacements were 0.0 mm for the pins-rubber bands group, 0.1 mm for the pins-only group, and 0.5 mm for the syringe-pins group. There were no cases of PIP joint redislocation after flexion-extension cycling, and the median dorsal P2 displacements were 0.0 mm for the pins-rubber bands group; 0.0 mm for the pins-only group; and 0.5 mm for the syringe-pins group. CONCLUSIONS: All 3 external fixators restored PIP joint stability following simulated dorsal fracture-dislocation, with all reductions maintained after motion testing. The syringe-pins construct had significantly greater median residual P2 dorsal displacement after the initial reduction and motion testing, which is of unclear clinical importance. CLINICAL RELEVANCE: This study informs surgeon decision-making when considering dynamic external fixator options for dorsal PIP joint fracture-dislocations.

Passive Manipulation for Proximal Interphalangeal Joint Extension Contractures.

PURPOSE: We investigated closed passive manipulation as an alternative to surgery for certain proximal interphalangeal (PIP) joint extension contractures. METHODS: We retrospectively reviewed all patients with PIP joint extension contractures treated with passive manipulation at our institution between 2015 and 2019. The included patients were a minimum of 12 weeks from their initial injury/surgery (median 179 days; interquartile range: 130-228 days), had plateaued with therapy, and underwent a 1-time passive manipulation. All included fingers had congruent PIP joints and no indwelling hardware that could have had direct adhesions. Most (80%) patients had a direct injury to the finger ray(s) that led to the contractures. Most (75%) patients had the manipulation performed under local anesthesia in the office. Available measures of passive range of motion (PROM) and active range of motion (AROM) immediately, within 6 weeks, between 6 and 12 weeks, and at >12 weeks after the manipulation were recorded. RESULTS: Twenty-eight patients and 46 digits met the criteria. The median PIP joint PROM improved from 50° to 90° immediately following the manipulation. The median PROM values within 6 weeks, between 6 and 12 weeks, and at >12 weeks following manipulation were 80°, 85°, and 85°, respectively. The median AROM immediately after the manipulation improved from 40° to 90°, and the median AROM values within 6 weeks, between 6 and 12 weeks, and at >12 weeks were 70°, 50°, and 60°, respectively. None of the patients experienced worsening of PIP joint range of motion. One patient who had 4 fingers manipulated had a 45° distal interphalangeal joint extension lag for one of the fingers after the manipulation. Eight fingers underwent later flexor tenolysis or reconstruction to improve AROM after the gains in PROM via manipulation were maintained. CONCLUSIONS: Passive manipulation is an alternative to surgical release for select PIP joint extension contractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Video-Based Assessment of Microsurgical Trainees: An Evaluation of Gender Bias.

BACKGROUND: Gender bias in graduate medical evaluations remains a challenging issue. This study evaluates implicit gender bias in video-based evaluations of microsurgical technique, which has not previously been described in the literature. METHODS: Two videos were recorded of microsurgical anastomosis; the first was performed by a hand/microsurgery fellow and the second by an expert microsurgeon. A total of 150 surgeons with microsurgical experience were recruited to evaluate the videos; they were told these videos depicted a surgical trainee 1 month into fellowship followed by the same trainee 10 months later. The only variable was the name ("Rachel" or "David") that each participant was randomly assigned to evaluate. Participants were asked to score each video for quality, technique, efficiency, as well as overall progression and development after the second video compared with the initial video. To focus on bias, these outcome measures were selected to be purposefully subjective and all ratings were based on a subjective 1to 10 scale (10 = excellent). RESULTS: The analysis included 150 participants (75% male). There were no statistically significant differences in scores between the "female" and "male" trainee. The trainees received the same median initial (1-month video) and final (11th-month video) scores for all criteria except initial technique, in which the female trainee received a 7 and the male trainee received an 8. Notably, 11-month scores were consistently the same or lower than 1-month scores for both study groups (p < 0.001). There were also no differences within either study group based on participant sex. Microsurgery practitioners overall rated both groups lower than those who do not currently practice microsurgery. CONCLUSION: Our study did not identify a gender bias in this evaluation method. Further investigation into how we assess and grade trainees as well as the presence and impact of implicit biases on varying surgical assessment methods is warranted.

The Syringe External Fixator: Short- and Medium-Term Functional Outcomes From This Inexpensive and Customizable Treatment for Comminuted Intra-Articular Fractures of the Hand.

PURPOSE: Comminuted intra-articular fractures and fracture dislocations of the metacarpophalangeal (MCP) and interphalangeal joints are challenging. Dynamic external fixation, permitting early joint motion while still minimizing forces across the healing joint, can result in acceptable postoperative active range of motion (AROM). However, some fractures are not initially stable enough for early dynamic motion; further, many available dynamic external fixation systems are costly and cumbersome. We reviewed our experience using an external fixator made from a 1-mL syringe and K-wires and report outcomes using it as a static fixator, dynamic fixator, or configured as a static fixator and then converted to a dynamic fixator in the clinic. METHODS: Patients with intra-articular fractures and fracture dislocations of the MCP and proximal interphalangeal (PIP) joints treated between 2014 and 2020 using syringe external fixators were retrospectively reviewed. We reviewed demographics, mechanisms, treatment types and durations, and postoperative AROM, as well as complications including infection, pin loosening, nonunion, hardware failure, and need for further surgery. Patients were analyzed by the level of joint injury (MCP versus PIP) and by treatment pattern. RESULTS: After excluding 23 patients with 25 joint injuries who were lost to follow-up or had inadequate outcome data, 27 patients with 29 joint injuries were reviewed. The average follow-up was 171 days after surgery. The postoperative AROM at the MCP level averaged 55° for static fixation and 30° for static-to-dynamic fixation. The postoperative AROM at the PIP level averaged 64° for static fixation, 66° for static-to-dynamic fixation, and 80° for dynamic fixation. Three pin site infections and 2 loose pins were reported. CONCLUSIONS: The syringe external fixator is an inexpensive, effective, and customizable treatment for intra-articular MCP and interphalangeal fractures and fracture dislocations, and results in acceptable postoperative AROM outcomes and complication rates. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The Impact of Dividing the Flexor Tendon Pulleys on Tendon Excursion and Work of Flexion in a Cadaveric Model.

PURPOSE: The A2 and A4 pulleys of the flexor tendon system have traditionally been considered critical components of efficient digital flexion. This dogma has recently been challenged. Using fresh human cadaveric hands and a model to measure force and excursion, we sought to clarify the clinical importance of releasing different pulleys. METHODS: Combinations of A1, A2, and A4 pulleys were released on the index, middle, ring, and little fingers of fresh, cadaveric hands. The excursion was measured as the distance the tendon was pulled by the motor to achieve palm touchdown. The force applied by the motor was constant (25 N); work was derived from the product of force and excursion (distance). The change in excursion and work needed to achieve palm touchdown before and after pulley release was measured. Excursion varies among digits and specimens at baseline; therefore, the percentage change from the intact state was used to compare groups. We compared A2 versus A1, A4 versus A1, A4 versus A2, A1 + A2 versus A2, and A1 + A4 versus A4. RESULTS: Isolated A2 or A4 release had the greatest individual impact on the excursion (4.77% ± 1.52% and 3.88% ± 1.93%, respectively). When A1 was released with A2 (9.90% ± 2.52%), the additional impact on the excursion was significant; however, when A1 was released with A4 (2.63% ± 2.81%), the impact was marginal. No clinically or statistically significant change in the work of flexion was detected. CONCLUSIONS: A1 release was clinically significant when added to A2 release but not when added to A4 release. Sacrifice of the A2 and A4 pulleys resulted in a statistically significant, but clinically negligible, difference in flexor tendon excursion. These data suggest that the A1 pulley should be preserved when other proximal pulley components are likely to be compromised. These data also add further support to the concept that the A2 pulley or the A4 pulley can be released as needed for optimal tenorrhaphy. CLINICAL RELEVANCE: During flexor tendon repair, the length of contiguous pulley release may have more impact on final tendon excursion than which specific pulleys are released.

The Modified Vilkki Procedure: Vascularized Metatarsophalangeal Joint Transfer to Reconstruct a Full-Length Radius in Type III Radial Hypoplasia.

Radial longitudinal deficiency is a spectrum of deformity ranging from thumb hypoplasia to a shortened or absent radius. Traditional treatments are hindered by recurrent deformity and disruption of future forearm growth. These deficiencies can be addressed by a Vilkki procedure in which a free second toe metatarsophalangeal joint is used to restore a radial column and provide viable physes for continued forearm growth. A classic Vilkki procedure positions the proximal toe metacarpal on the native ulna to create a Y-shaped one-bone forearm. We report a case of a modified Vilkki procedure in which a 2-bone forearm is created using the proximal toe metacarpal to reconstruct the entire radius. In patients with type III radial longitudinal deficiency with suitable residual radius length, the modified Vilkki procedure can allow reconstruction of a 2-bone forearm. This affords the patient correction of the pathoanatomy and the potential for balanced growth and pronosupination.

Zone I Flexor Digitorum Profundus Repair: A Surgical Technique.

We present an all-inside technique for zone I flexor tendon repair that combines suture anchor fixation with buried back-up fixation. The back-up fixation uses transosseous tunnels and a dorsal counterincision to allow a suture tied dorsal to the distal phalanx and buried. This technique is strong and permits early active range of motion. The dorsal tie-over does not require a suture button and, therefore, does not imperil the nail matrix. The surgical technique is herein described including the proposed anesthesia (wide awake), the incisions (midlateral), the exposures, and the repair itself.

Reconstruction of digit planer injuries using component transfer of double second toes: A case report.

The purpose of this report is to show that customized component second-toe transfers may improve functional and aesthetic outcomes following bone, soft tissue, and joint destruction of traumatically injured digits. A 22-year-old male sustained a planer injury resulting in loss of the distal volar soft tissues of the middle, ring, and small fingers, along with variable destruction of middle phalanges and distal interphalangeal joints. Simultaneous vascularized second-toe transfers were performed with customized joint and pulp reconstruction of middle and small fingers. The ring finger was salvaged using non-vascularized autologous bone graft and acellular dermal matrix. The patient had an uncomplicated postoperative course. Five-year strength, sensory and patient reported outcomes represent overall satisfactory results. Strength testing revealed the injured hand to perform within 90% strength of the uninjured side. Sensory outcomes showed present but diminished sensory perception in each of the injured digits. The patient's upper extremity function, physical health, quality of life, and foot health were overall acceptable, and he returned to using his hand for typing, writing, weight-lifting, and woodworking.

The Effect of Skin Pigmentation on Determination of Limb Ischemia.

PURPOSE: Timely identification of tissue ischemia is critical, both in the traumatized limb and following free tissue transfer. The purpose of this study was to determine if skin pigmentation affects the ability to detect limb ischemia. METHODS: We conducted a study of healthy controls exposed to limb ischemia. The subjects were classified based on skin pigmentation using a defined skin type assessment tool, a visual color scale, and self-description of race. Participants were randomized by limb and tourniquet status; surgeons were blinded to both. Ischemia was induced by tourniquet insufflations, and board-certified orthopedic and plastic surgeons who had completed an accredited hand surgery fellowship conducted physical examinations. The surgeons monitored the forearms at 2, 6, and 10 minutes based on appearance of ischemia, capillary refill, and color in 3 locations on the limbs (posterior interosseous artery flap skin territory, radial forearm flap skin territory, and the digits). RESULTS: We found a significant decrease in the ability to detect ischemia in participants with increased skin pigmentation, as documented by all metrics, when evaluating the posterior interosseous artery and radial forearm flap skin territories at all time points. For example, when monitoring the posterior interosseous artery flap with the tourniquet insufflated at time 10 minutes, 92.9% of Caucasians were correctly identified as being ischemic whereas only 23.3% of African Americans were correctly identified. CONCLUSIONS: Skin pigmentation significantly affects the identification of an ischemic limb/skin flaps on physical examination. Whereas the standard treatment for monitoring of free tissue transfer is clinical examination, that may not be sufficient for patients with increased skin pigmentation. Surgeons should exercise particular vigilance during physical examination of a potentially ischemic limb/skin flaps with greater skin pigmentation. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Proximalization of the Vascularized Toe Joint in Finger Proximal Interphalangeal Joint Reconstruction: A Technique to Derive Optimal Flexion From a Joint With Expected Limited Motion.

When used to reconstruct a finger proximal interphalangeal joint, a free toe interphalangeal joint, without modification, cannot meet the motion demands of the finger to allow palm touchdown. This limitation is the direct result of the toe interphalangeal joint having an intrinsic arc of motion that delivers less flexion than that of a normal functioning finger proximal interphalangeal joint. By modifying the inset of the transferred joint to an extra-anatomical more proximal position, this limitation can be overcome. With a mathematical justification highlighted by a clinical illustration, we demonstrate the feasibility and utility of this "proximalization" technique.

Changes in Wrist Motion After Simulated Scapholunate Arthrodesis: A Cadaveric Study.

PURPOSE: A high incidence of nonunion and relatively poor outcomes with prior fixation techniques has precluded scapholunate (SL) arthrodesis as a standard treatment for SL instability. Our purpose was to determine the impact on range of motion (ROM) of simulated SL arthrodesis via headless screw fixation. METHODS: We performed baseline wrist ROM for 10 cadaveric wrists using a standardized mounting-and-weights system. Extension, flexion, radial deviation, ulnar deviation, dart-thrower's extension, and dart-thrower's flexion were assessed. Two 3.0-mm headless compression screws were inserted across the SL joint to simulate SL arthrodesis. Goniometric measurements and fluoroscopic imaging were repeated to assess ROM differences after simulated SL arthrodesis. We assessed SL angle and gap during testing to ensure there was no significant motion between the scaphoid and lunate, thus confirming stable simulated fusion. Differences in ROM were compared between baseline and simulated SL arthrodesis using paired t tests. RESULTS: Mean SL angle remained constant between pre- and post-arthrodesis imaging (47° ± 6° vs 46° ± 4°) and did not change during post-arthrodesis ROM testing, indicating a stable simulated fusion. Compared with baseline, SL arthrodesis had a statistically significant reduction in maximum flexion of 6° and 9° based on fluoroscopy and goniometry, respectively, in dart-thrower's extension of 5° and 9° based on fluoroscopy and goniometry, respectively, and in dart-thrower's flexion of 6° for both fluoroscopy and goniometry. No other ROMs after simulated SL arthrodesis were significantly different compared with baseline. CONCLUSIONS: The effects of simulated SL arthrodesis on radiocarpal and midcarpal motion compare favorably with motion after SL soft tissue repair and other reconstructive techniques that have been previously reported. The statistically significant decreases in wrist flexion and dart-thrower's extension-flexion after simulated SL arthrodesis are of questionable clinical importance. CLINICAL RELEVANCE: These results may support reconsidering SL arthrodesis as a viable treatment option for acute or chronic SL instability with regard to apparent minimal adverse effects on functional wrist ROM.

Inadvertent Intra-Arterial Drug Injections in the Upper Extremity: Systematic Review.

PURPOSE: To review the literature pertaining to inadvertent intra-arterial drug injection in the upper extremity, explore the various treatment options and their outcomes, and identify risk factors for limb amputation following intra-arterial injection. METHODS: A systematic review of Medline, EMBASE, and Cochrane databases (inception to March 2013) was completed for patients presenting with intra-arterial drug injection of the upper extremity. Details on intervention and outcome were extracted and subjected to pooled analysis with amputation as the primary outcome. RESULTS: A total of 25 articles (209 patients) were included for review. Mean patient age was 31 ± 8 years (male, 71%; female, 29%). Prescription opioids (33%) were the most commonly injected substance, and the brachial artery (39%) was the most common site. The overall weighted mean amputation incidence was 29%. Anticoagulants were the most common treatment used (77%). From pooled analysis, conditions requiring antibiotic use were significantly associated with a higher incidence of amputation; whereas use of steroids was associated with a lower incidence of amputation. Patients presenting 14 hours or more after injection and those injecting crushed pills rather than pure substances had significantly higher incidences of amputation. CONCLUSIONS: Intra-arterial drug injection of the upper extremity carries an amputation incidence of nearly 30%. Conditions requiring adjunctive antibiotic use and delay in receiving care were both significantly associated with higher incidences of amputation. No single treatment protocol to date has established superiority. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Functional reconstruction of subtotal thumb metacarpal defect with a vascularized medial femoral condyle flap: case report.

Devastating hand injuries require customized reconstructive strategies to maximize functional outcomes. We report a case of thumb metacarpal reconstruction using a vascularized medial femoral condyle osteocutaneous flap in the setting of nearly complete metacarpal loss. In addition to achieving the traditional goals of reconstructing thumb length and providing stability, the medial femoral condyle flap allowed motion at the carpometacarpal joint. The patient's hand function was further optimized by a component transfer of a proximally injured but distally preserved index finger to the amputated middle finger position. The patient regained satisfactory grip and thumb function with minimal donor site morbidity. This case highlights the role of both creative and established approaches to reconstruct composite tissues following devastating hand injury.

Forearm transplantation osteosynthesis using modified ulnar shortening osteotomy technique.

One of the challenges of forearm-level hand transplantation surgery is the achievement of osseous union of the ulna given the substantial soft tissue dissection, the use of immune modulating medications, and the diaphyseal level of osseous coaptation. Modification of the conventional surgical technique for an elective ulnar shortening osteotomy provides the advantages of precise osteotomy alignment, a large contact surface oblique osteotomy, and lag screw and compression plating technique. A step-by-step description of the developed modification is provided with a case example.

The anterograde homodigital neurovascular island flap.

The value of the human fingertip is incalculable. More than just aesthetic, the fingertip is an instrument through which we navigate our environment and acquire information. All too often, fingertip reconstruction is either not attempted or attempted without adhering to the fundamental principle of "replacing like with like." Through detailed description and case examples, this article highlights the power and utility of the anterograde homodigital neurovascular island flap in fingertip reconstruction. This single-stage flap can reliably resurface large soft tissue defects with sensate glabrous skin.

Histological evaluation of a free medial femoral condyle flap at 21 months.

Recalcitrant nonunions typically require vascularized bone for reconstruction. In this report, we present a case of an index finger middle phalanx nonunion that was successfully treated with a free medial femoral condyle corticocancellous flap. Nearly 2 years after the free tissue transfer, the patient underwent debulking of the bone flap. This gave us the unique opportunity to examine the histology of the vascularized bone.

The axial stability of the femur after harvest of the medial femoral condyle corticocancellous flap: a biomechanical study of composite femur models.

PURPOSE: Free bone or periosteal flaps from the medial femoral condyle are being employed for treatment of recalcitrant nonunions. When harvested in a corticocancellous fashion, these flaps have the potential to compromise the stability of the femur. This study is designed to test the axial stability of the femur after harvest of corticocancellous flaps using a standardized composite femur model. METHODS: Corticocancellous defects of standardized width and depth (2 cm × 1 cm) were designed with increasing length (3-cm intervals extending from 3 to 24 cm) over the medial femoral condyle of five composite femur models. After harvest of each corticocancellous block, the femur was subjected to an axial force of 9100 N loaded and unloaded over one second using a Mini-Bionix load frame. During the application of force, load and deformation data were collected from the load cell and linear variable differential transducer. To determine changes in stiffness or deformation with increasing flap sizes, analysis of variance with repeated measures was used. If the main effect was found to be significant, a Tukey's test was used to determine differences between specific flap sizes. RESULTS: There were no femur fractures in any femurs for any flap size. Deformation during load increased as the size of the flap increased (2.19 mm ± 0.062 mm for the 3-cm flap defect) to (2.33 mm ± 0.113 mm for the 24-cm flap defect). Post-hoc testing of deformation shows a statistically significant difference only between the 3-cm flap defect and the 15-cm flap defect (2.19 vs. 2.30 mm) (P = 0.002). The range of stiffness is between 4,339 and 4,697 N mm(-1) . Stiffness tends to decrease significantly (P < 0.001) with increasing flap size. Harvest of flap sizes greater or equal than 9 cm results in significantly lower stiffness compared to the 3-cm flap. CONCLUSIONS: In this composite femur model, when stressed with supraphysiologic forces, the femur retains its axial stability even after harvest of large corticocancellous flaps from its medial aspect. Statistical significance detected in deformation and stiffness may not be clinically relevant if the femur does not fracture after flap harvest. Such was the case in this experiment. The possibility exists of safely harvesting large flaps from this donor site. Corticocancellous flaps from the medial aspect of the femur may serve as an alternative to standard flaps used in medium and large osseous reconstructions. The size of flap that can be safely raised without compromising the stability of the femur has not yet been delineated.

Achieving Functional Outcomes after Surgical Management of Catastrophic Vasopressor-induced Limb Ischemia.

Vasopressor-induced limb ischemia is an unfortunate complication that can occur in patients treated for septic shock. Current literature lacks surgical treatment recommendations for this condition, besides amputation. We describe various reconstructive surgeries and functional outcomes in patients treated surgically for vasopressor-induced limb ischemia. Methods: We retrospectively reviewed patients who were treated for septic shock and developed vasopressor-induced limb ischemia at our tertiary referral academic medical center. We reviewed presentation, treatment, surgical outcomes, and long-term functional outcomes. Results: We present three previously healthy patients who developed gangrene of multiple limbs following the use of vasopressors to treat septic shock. Each patient underwent amputations or limb salvage procedures. Conclusions: Limb ischemia is a devastating complication that can occur after prolonged vasopressor use. The decision to proceed with limb salvage versus amputation of ischemic extremities should be tailored to the individual patient. The main objective should be for the patient to obtain optimal function and quality of life, regardless of the type of surgery.

Locoregional Options for Acute Volar Pulp Fingertip Defects.

The volar fingertip is a unique anatomic structure, delicate yet durable, that allows us to navigate the world, acquire information from our surroundings, and express ourselves. Injuries to the volar finger can cause permanent dysfunction and should be taken seriously. In treating injuries of the volar fingertip, the surgeon has an opportunity to choose from a host of reconstructive options and provide the patient with an outcome suitable to their needs. In doing so, the hand surgeon is well-positioned to aim for the reconstructive ideal of restoring both structure and function.