Do multiple physiological OCT biomarkers indicate age-related decline in rod mitochondrial function in C57BL/6J mice?

Purpose: To test the hypothesis that rod photoreceptor mitochondria function in vivo progressively declines over time. Methods: 2, 12, and 24 month-old dark- and light-adapted C57BL/6J (B6J) mice were examined by OCT. We measured (i) an index of mitochondrial configuration within photoreceptors measured from the profile shape aspect ratio (MCP/AR) of the hyperreflective band posterior to the external limiting membrane (ELM), (ii) a proxy for energy-dependent pH-triggered water removal, the thickness of the ELM-retinal pigment epithelium (ELM-RPE), and its correlate (iii) the hyporeflective band (HB) signal intensity at the photoreceptor tips. Visual performance was assessed by optokinetic tracking. Results: In 2 and 24 month-old mice, MCP/AR in both inferior and superior retina was smaller in light than in dark; no dark-light differences were noted in 12 month-old mice. Dark-adapted inferior and superior, and light-adapted superior, ELM-RPE thickness increased with age. The dark-light difference in ELM-RPE thickness remained constant across all ages. All ages showed a decreased HB signal intensity magnitude in dark relative to light. In 12 month-old mice, the dark-light difference in HB magnitude was greater than in younger and older mice. Anatomically, outer nuclear layer thickness decreased with age. Visual performance indices were reduced at 24 month-old compared to 2 month-old mice. Conclusion: While the working hypothesis was not supported herein, the results raise the possibility of a mid-life adaptation in rod mitochondrial function during healthy aging in B6J mice based on OCT biomarkers, a plasticity that occurred prior to declines in visual performance.

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.

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.

Transducin-Deficient Rod Photoreceptors Evaluated With Optical Coherence Tomography and Oxygen Consumption Rate Energy Biomarkers.

Purpose: To test the hypothesis that rod energy biomarkers in light and dark are similar in mice without functional rod transducin (Gnat1rd17). Methods: Gnat1rd17 and wildtype (WT) mice were studied in canonically low energy demand (light) and high energy demand (dark) conditions. We measured rod inner segment ellipsoid zone (ISez) profile shape, external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness, and magnitude of a hyporeflective band (HB) intensity dip located between photoreceptor tips and apical RPE; antioxidants were given in a subset of mice. Oxygen consumption rate (OCR) and visual performance indexes were also measured. Results: The lower energy demand expected in light-adapted wildtype retinas was associated with an elongated ISez, thicker ELM-RPE, and higher HB magnitude, and lower OCR compared to high energy demand conditions in the dark. Gnat1rd17 mice showed a wildtype-like ISez profile shape at 20 minutes of light that became rounder at 60 minutes; at both times, ELM-RPE was smaller than wildtype values, and the HB magnitude was unmeasurable. OCR was higher than in the dark. Light-adapted Gnat1rd17 mice biomarkers were unaffected by anti-oxidants. Gnat1rd17 mice showed modest outer nuclear layer thinning and no reduction in visual performance indexes. Conclusions: Light-stimulated changes in all biomarkers in WT mice are consistent with the established light-induced decrease in net energy demand. In contrast, biomarker changes in Gnat1rd17 mice raise the possibility that light increases net energy demand in the absence of rod phototransduction.

Functional Changes Within the Rod Inner Segment Ellipsoid in Wildtype Mice: An Optical Coherence Tomography and Electron Microscopy Study.

Purpose: To test the hypothesis that changing energy needs alter mitochondria distribution within the rod inner segment ellipsoid. Methods: In mice with relatively smaller (C57BL/6J [B6J]) or greater (129S6/ev [S6]) retina mitochondria maximum reserve capacity, the profile shape of the rod inner segment ellipsoid zone (ISez) was measured with optical coherence tomography (OCT) under higher (dark) or lower (light) energy demand conditions. ISez profile shape was characterized using an unbiased ellipse descriptor (minor/major aspect ratio). Other bioenergy indexes evaluated include the external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness and the magnitude of the signal intensity of a hyporeflective band located between the photoreceptor tips and apical RPE. The spatial distribution of rod ellipsoid mitochondria were also examined with electron microscopy. Results: In B6J mice, darkness produced a greater ISez aspect ratio, thinner ELM-RPE, and a smaller hyporeflective band intensity than in light. In S6 mice, dark and light ISez aspect ratio values were not different and were greater than in light-adapted B6J mice; dark-adapted S6 mice showed smaller ELM-RPE thinning versus light, and negligible hyporeflective band intensity in the light. In B6J mice, mitochondria number in light increased in the distal inner segment ellipsoid and decreased proximally. In S6 mice, mitochondria number in the inner segment ellipsoid were not different between light and dark, and were greater than in B6J mice. Conclusions: These data raise the possibility that rod mitochondria activity in mice can be noninvasively evaluated based on the ISez profile shape, a new OCT index that complements OCT energy biomarkers measured outside of the ISez region.

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.

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.

Long-Term Patency and Fluid Dynamics of Recipient Artery after End-to-Side Anastomosis for Free Tissue Transfer.

BACKGROUND: End-to-end microvascular anastomoses sacrifice downstream inline perfusion of the recipient vessels. End-to-side anastomoses, in theory, maintain distal inline flow of the recipient vessel. The proposed benefit of the end-to-side technique depends on patency of the distal vessels and subsequent flow parameters, but maintenance of distal perfusion has not been conclusively demonstrated. METHODS: Fifteen patients who underwent a successful extremity free flap procedure via end-to-side anastomoses to a noncritical vessel between 2003 and 2017 were enrolled. Recipient artery patency distal to the anastomosis was assessed using pulse volume recordings and duplex ultrasound imaging. Resistance indices, flow velocities, vessel diameters, volumetric flow, and turbulent flow dimensionless number (Reynolds number) were measured. Comparisons were made to the ipsilateral collateral vessel as well as to the vessels on the nonoperative contralateral limb using paired t tests. RESULTS: Downstream flow was identified in 14 of 15 patients (93 percent patency). There was no statistical difference in resistive indices comparing the anastomotic vessel (0.859 ± 0.300) and the collateral vessel (0.853 ± 0.179) of the ipsilateral extremity. Ultrasound flows were similar; the anastomotic vessel demonstrated downstream volumetric flows of 139 ± 92.0 cm3/min versus 137 ± 41.6 cm3/min within the same vessel of the nonoperative contralateral limb. The anastomotic vessel had Reynolds numbers well below the turbulent threshold (448 ± 202 and 493 ± 127 for the anastomotic and nonoperative contralateral limb, respectively). CONCLUSION: End-to-side anastomosis to noncritical vessels resulted in a 93 percent long-term recipient vessel patency rate, with no statistically significant changes in volumetric flows, resistive indices, or fluid dynamics in the vessels that remained patent.

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.

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.

Syringe External Fixator: An Inexpensive Static-to-Dynamic Treatment for Comminuted Intra-Articular Phalangeal Fractures.

Comminuted intra-articular phalanx fractures are complicated injuries often treated with external fixation. The ideal external fixation system should be affordable, readily available, adaptable, and easy to use. The use of dynamic external fixation has advanced the care of these injuries but can be difficult to implement. The authors present a case example of a patient with a comminuted intra-articular phalangeal fracture of the left small finger treated using a syringe as a static uniplanar fixator that was converted to a dynamic fixator during postoperative recovery.

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.

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.

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.

Microvascular Toe Joint for Proximal Interphalangeal Joint Replacement: Indications, Technique, and Outcomes.

Microvascular toe interphalangeal joint transfer can serve as a means of autogenous digit proximal interphalangeal joint (PIPJ) arthroplasty. Among surgical options for treating dysfunctional, absent, or destroyed PIPJs, free toe joint transfer is the most technically challenging and carries the greatest donor site cost to patients. Despite drawbacks, free toe joint transfer is a valuable tool with considerable advantages over conventional arthroplasty in the appropriate clinical setting. Particular advantages include lifelong durability, coronal plane stability, low infection risk, and growth potential in skeletally immature patients. This technique requires a balanced assessment of the risk-to-benefit ratio for each patient.

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.

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.

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.