Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.

Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.

Community-developed checklists for publishing images and image analyses.

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However, for scientists wishing to publish obtained images and image-analysis results, there are currently no unified guidelines for best practices. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here, we present community-developed checklists for preparing light microscopy images and describing image analyses for publications. These checklists offer authors, readers and publishers key recommendations for image formatting and annotation, color selection, data availability and reporting image-analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby to heighten the quality and explanatory power of microscopy data.

A comparison of foot fractures relative to other fragility fractures: a review and analysis of the American Orthopaedic Association's Own the Bone Database.

Evidence regarding the risk factors and characteristics of those with foot fragility fractures compared to non-foot fragility fractures is limited. Foot fragility fracture patients are more likely to be younger female with a higher BMI. A foot fragility fracture is strongly predictive of a subsequent foot fragility fracture. PURPOSE: Osteoporosis can clinically result in fragility fractures. Evidence regarding the risk factors and characteristics of foot fragility fractures compared to non-foot fragility fractures is limited. The American Orthopaedic Association's Own the Bone (OTB) is a bone health initiative with a substantial dataset. The purpose of this study was to examine and compare characteristics of patients presenting with isolated foot fragility fracture to those with a non-foot fragility fracture. METHODS: Between January 2009 and March of 2022, 58,001 fragility fractures occurred that were included in this cohort. A total of 750 patients had foot fragility fracture(s) and 57,251 patients had a non-foot fragility fracture that included shoulder, arm, elbow, forearm, wrist, spine, ribs, pelvis, hip, thigh, knee, tibia/fibula, and ankle. Demographics, fracture history, bone health factors, medication history, and medication use for each patient were reported in the OTB database. This data was utilized in our secondary cohort comparative analysis of characteristics and the risk of future fractures between foot fragility fracture and non-foot fragility fracture groups. RESULTS: Foot fragility fracture patients have a significantly higher probability to be younger (66.9 years old), female (91.5%), and have a higher BMI (28.3 kg/m2) compared to non-foot fragility fracture (p < 0.0001) patients. Patients with a foot fragility fracture are nine times (OR = 9.119, CI = 7.44-11.18, p < 0.001) more likely to have had a prior foot fragility fracture. Young, female patients with a prior foot fragility fracture are at higher risk of a future foot fragility fracture, and this risk increased as BMI increased. CONCLUSIONS: Foot fragility fracture patients are more likely to be female and younger compared to patients with a non-foot fragility fracture. A foot fragility fracture is a sentinel event considering that a prior foot fragility fracture is strongly predictive of a subsequent foot fragility fracture. LEVEL OF EVIDENCE: 3 (retrospective cohort).

Postoperative Infection Rates After Total Ankle Arthroplasty: A Comparison With and Without the Use of a Surgical Helmet System.

Following total joint arthroplasty, surgical site infections (SSI) and periprosthetic joint infections (PJI) are associated with increased patient morbidity and healthcare utilization. Current positive-pressure surgical sterile helmet system (SHS) were developed as a feasible, useful version of the body exhaust system.The use of SHS has not yet been proven to decrease infection rates in the orthopedic literature. The primary purpose of this study is to compare the infection rates between patients who underwent total ankle arthroplasty (TAA) with a surgical team wearing SHS versus without SHS.A retrospective chart review in patients undergoing primary TAA with the surgeon wearing SHS (Group 1) or standard surgical attire (Group 2) was conducted. The primary outcome was postoperative SSI and PJI. The rate of wound complications, revision rates, and associated procedures were also analyzed. We identified 109 patients in Group 1 and 151 patients in Group 2. The rate of SSI was 12.8% in Group 1 and 14.6% in Group 2 (p = .411). The rate of PJI was 0.92% in Group 1 and 2.6% in Group 2 (p = .411). There was no difference in revision rates between the two groups. This study suggests that SHS does not appear to protect against postoperative SSI or PJI after TAA. Conversely, we did not find a higher infection rate compared to standard surgical attire despite recent in-vitro studies suggesting SHS as a source of wound contamination. The utility of SHS does not appear to influence the prevalence of postoperative SSI or PJI.

A Comparison of Outcomes of Revision Surgical Options for the Treatment of Failed Bulk Talar Allograft Transfer: A Systematic Review.

Talar bulk osteochondral allograft transplantation is a useful treatment strategy for large, uncontained osteochondral lesions of talus. Complications and high revision rates from osteochondral talar allograft transfer can be common. Talar graft failure is a devastating complication that results from failure of allograft incorporation within the host bone and subsequent resorption and sometimes subsidence can occur. Treatment options and outcomes for graft failure have rarely been reported. The purpose of this study is to evaluate treatment options and their outcomes for treating talar allograft failure. A systematic review was completed to find all reports of salvage treatments for talar graft failure and outcomes of these reports were analyzed. Eleven studies involving a total of 522 ankles, in 520 patients, met the inclusion criteria. The allograft failure rate was 11.5% in these studies with a reoperation rate of 18.9%. With limited reports, satisfactory outcomes for treatment of graft failure with ankle arthrodesis were 77.3%, 50% for revision allograft procedures, and 50% for total ankle arthroplasty. Considering the large failure rate and reoperation rate for bulk talar allograft transplantations, superior revision, and salvage options are needed. More prospective cohort studies focusing on consistent and standard outcome measures are needed to further assess revision options for failed talar allograft procedures.

Complications of En Bloc Osteochondral Talar Allografts and Treatment of Failures: Literature Review and Case Report.

Reoperation rates and complication rates can be high for patients receiving an osteochondral talar allograft transplant. Complications can include graft failure, delamination of the graft, arthrofibrosis, advancing osteoarthritis, nonunion of malleolar osteotomies, and partial or complete osteonecrosis of the talus. Graft failure refers to failure of graft incorporation with subsequent necrosis and subsidence. Treatment options for talar graft failure are limited, and outcomes for these treatments have rarely been reported. We present a review of the published data on the complications and treatments for failed talar allograft transplantation. A case report is presented on a young woman who experienced graft failure and osteonecrosis of her talar allograft transplant. Because of the size of the present osteonecrosis, an ankle arthrodesis was performed as the initial revision procedure. Talar necrosis was removed and revascularized from the ankle fusion with solid fusion was confirmed with computed tomography. Symptomatic adjacent joint pain quickly developed in the hindfoot after the ankle fusion, and 12 months later an ankle fusion conversion to total ankle arthroplasty was performed. The patient has returned to normal activity with significant reduction in pain at most recent follow-up visit. This patient was followed for 7 years from initial osteochondral talar allograft transplantation and for 2 years from conversion of ankle fusion to total ankle arthroplasty. It is important to understand the techniques, indications, and outcomes for the various revision options for talar allograft failure. This case report illustrates how multiple revision options can be used to provide the best outcome for the patient.

American College of Foot and Ankle Surgeons Clinical Consensus Statement: Appropriate Clinical Management of Adult-Acquired Flatfoot Deformity.

This clinical consensus statement of the American College of Foot and Ankle Surgeons focuses on the highly debated subject of the management of adult flatfoot (AAFD). In developing this statement, the AAFD consensus statement panel attempted to address the most relevant issues facing the foot and ankle surgeon today, using the best evidence-based literature available. The panel created and researched 16 statements and generated opinions on the appropriateness of the statements. The results of the research on this topic and the opinions of the panel are presented here.

Screw fixation diameter for fifth metatarsal jones fracture: a cadaveric study.

The fifth metatarsal Jones fracture is a well-documented injury occurring at the proximal diaphyseal-metaphyseal junction. Conservative versus surgical intervention has been discussed in published studies for the management of Jones fractures. Solid intramedullary fixation relies on accurate matching of the screw diameter to the intraosseous diameter. The purpose of the present cadaveric study was to determine the average intraosseous diameter of the proximal fifth metatarsal as it relates to screw size selection for Jones fracture stabilization. Twenty fresh-frozen cadaver legs were used for examination. The fifth metatarsal was completely dissected. A transverse osteotomy was performed from laterally to medially along the midline of the metatarsal. A digital caliper was used to measure the diameter of the medullary canal of the fifth metatarsal. The measurement was taken at the narrowest portion of the medullary canal just distal to the proximal metaphysis. The mean dorsal to plantar diameter of the fifth metatarsal was 6.475 ± 1.54 (range 4 to 12) mm and the mean medial to lateral diameter was 4.6 ± 0.85 (range 3 to 6) mm. Intramedullary screw fixation has shown beneficial results in the treatment protocol of fifth metatarsal Jones fractures. Our study has demonstrated that a 4.5-mm cannulated screw is the narrowest diameter screw that can be used in the average fifth metatarsal and still obtain adequate intraosseous purchase. When selecting the appropriate screw, the surgeon must be comfortable selecting the largest screw that will achieve the maximal interface with the dense cortical bone in both the medial to lateral and dorsal to plantar plane.

Medial double arthrodesis with lateral column sparing and arthrodiastasis: a radiographic and medical record review.

Correction of valgus hindfoot deformity can be successfully achieved with arthrodesis of the subtalar and talonavicular joints through a single medial based incision. The advantages of medial double arthrodesis compared with the standard triple arthrodesis 2-incision approach include the absence of a lateral incision and a few degrees of residual mobility through the unfused calcaneocuboid joint (CCJ). The CCJ has often been noted to distract and decompress with the abduction correction achieved through medial double fusion. The primary goal of the present retrospective study was to identify the frequency of CCJ decompression, measure the radiographic changes at the CCJ, and evaluate the flatfoot correction using this operative approach. A total of 46 patients (47 feet) were identified as possible subjects. Twenty patients (20 feet) with a mean follow-up period of 9.2 ± 4.1 (range 6 to 21) months met our inclusion criteria. Distraction of the CCJ using medial double fusion resulted in increased joint space and improvement of at least 1 grade of arthritis in 50% of the patients. In the patients with severe CCJ arthrosis, the improvement was less predictable, with only 20% showing radiographic improvement. Correction of flatfoot as measured on standard radiographs showed excellent results. Subchondral bone changes as measured by the CCJ arthrosis scale improved in patients with mild to moderate arthritis after distraction arthrodiastasis. However, those with severe preoperative CCJ had less predictable improvement. Medial double arthrodesis for severe flatfoot deformity provides predictable correction of the deformity and improvement in the CCJ arthritis scale when the preoperative arthritis of the CCJ is mild to moderate.

Ankle valgus after hindfoot arthrodesis: a radiographic and chart comparison of the medial double and triple arthrodeses.

The medial double arthrodesis, comprised of subtalar and talonavicular joint fusions, has become a popular way to correct hindfoot deformity. There is potential concern for an increase in ankle valgus postoperatively owing to extended medial dissection and possible disruption of the deltoid ligament. Although this approach is often used to correct a valgus hindfoot, little attention has been paid to date on this procedure's effect on the tibiotalar joint. Although the medial double arthrodesis has been shown to produce reproducible outcomes without violating the lateral hindfoot structures, our hypothesis was that this approach would increase the ankle valgus deformity compared with its triple counterpart. The primary goal of the present retrospective study was to identify the frequency and severity of ankle valgus after the medial double arthrodesis compared with the triple arthrodesis. A total of 77 patients (78 feet) met our inclusion criteria. Their mean age was 61.3 ± 10.7 (range 27 to 79) years, and the follow-up period was 15.7 ± 9.9 (range 6 to 46) months. There were 16 and 61 patients (62 feet) in the medial double and triple arthrodesis groups, respectively. Overall, the preoperative ankle valgus was 1.24° ± 2.02° (range 0° to 6°), and there was no statistical difference of preoperative ankle valgus noted between groups (p = .060). Collectively, postoperative ankle valgus was 3.01° ± 3.54° (0° to 17°) with an increase in ankle valgus in 4 of 16 medial double and 34 of 62 triple arthrodesis patients. With a mean follow-up of 8.75 ± 4.02 (6 to 21) months, the medial double arthrodesis cohort's ankle valgus increased from 0.5° ± 1.55° (0° to 6°) to 1.5° ± 3.14° (1° to 10°) postoperatively. The triple arthrodesis group had a mean follow-up 17.53 ± 10.17 (6 to 46) months and ankle valgus increased from 1.44° ± 2.09° (0 to 6°) to 3.40° ± 3.56° (0° to 17°). Postoperative ankle valgus was statistically significant between groups (U = 303.50, p = .013). The odds of having an increase in the valgus ankle angle for patients in the triple group was 3.64 times that for patients in the double group, while holding all other variables in the model constant.

Structures at risk with medial double hindfoot fusion: a cadaveric study.

Although discussed as an alternative to triple arthrodesis for hindfoot correction, the published data surrounding the medial double arthrodesis, or fusion of the subtalar and talonavicular joints, has not addressed the proximity of the anatomic structures at risk. A total of 10 cadaver specimens were used to examine the risk of damage to the neurovascular and tendinous structures of the posterior medial hindfoot when performing the medial double arthrodesis. The distance of the reviewed structures was measured in relation to the standardized point of the middle facet of the calcaneus (mean ± standard deviation and range). The proximity of the middle facet to the posterior tibial tendon was 1.88 ± 2.65 (range 0 to 6.65) mm, to the flexor digitorum longus tendon was 5.34 ± 4.79 (range -3.14 to 12.79) mm, to the flexor hallucis longus tendon was 19.08 ± 4.84 (range 13.04 to 27.31) mm, and to the neurovascular bundle was 21.19 ± 7.84 (range 8.36 to 34.26) mm. At the level of the middle facet, the posterior tibial tendon was the largest tendon, measuring 7.14 ± 2.21 (range 3.31 to 10.23) mm by 2.95 ± 0.88 mm (range 1.86 to 4.24 mm; area 22.37 ± 12.23 mm(2), range 6.16 to 43.38 mm) followed by the flexor digitorum longus tendon at 4.25 ± 1.25 (range 1.74 to 5.95) mm by 2.25 ± 0.96 mm (range 1.41 to 4.79 mm; area 8.88 ± 2.62 mm(2), range 6.12 to 14.52 mm) and flexor hallucis longus tendon at 5.75 ± 2.05 (range 2.27 to 8.91) mm by 2.75 ± 0.82 mm (range 1.35 to 4.13 mm; area 16.81 ± 10.05 mm(2), range 4.81 to 36.80 mm). During dissection for the medial double arthrodesis, one can encounter critical anatomic structures, including artery, vein, nerve, and tendon. Our cadaveric investigation found a mean safe distance of more than 2 cm between the middle facet of the talocalcaneal articulation and the inferiorly located neurovascular bundle using the medial double arthrodesis approach.

Inspiration4 data access through the NASA Open Science Data Repository.

The increasing accessibility of commercial and private space travel necessitates a profound understanding of its impact on human health. The NASA Open Science Data Repository (OSDR) provides transparent and FAIR access to biological studies, notably the SpaceX Inspiration4 (I4) mission, which amassed extensive data from civilian astronauts. This dataset encompasses omics and clinical assays, facilitating comprehensive research on space-induced biological responses. These data allow for multi-modal, longitudinal assessments, bridging the gap between human and model organism studies. Crucially, community-driven data standards established by NASA's OSDR Analysis Working Groups empower artificial intelligence and machine learning to glean invaluable insights, guiding future mission planning and health risk mitigation. This article presents a concise guide to access and analyze I4 data in OSDR, including programmatic access through GLOpenAPI. This pioneering effort establishes a precedent for post-mission health monitoring programs within space agencies, propelling research in the burgeoning field of commercial space travel's impact on human physiology.

Longitudinal multi-omics analysis of host microbiome architecture and immune responses during short-term spaceflight.

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning.

Calcaneal Z osteotomy for extra-articular correction of hindfoot valgus.

The lateral column lengthening procedure has been used in the surgical management of congenital and adult-acquired pes planus. Lateral column lengthening allows correction of the abducted forefoot and subsequent improvement in the medial longitudinal arch. However, owing to the inconsistent healing times and complications, we opted to pursue a novel approach to the lateral column lengthening procedure, the calcaneal Z osteotomy.

Role of cellular allograft containing mesenchymal stem cells in high-risk foot and ankle reconstructions.

The use of cellular allograft containing mesenchymal stem cells is gaining popularity as an augmentation to foot and ankle arthrodesis. Those with underlying comorbidities (diabetes mellitus, Charcot osteoarthropathy, smoking, suppressive medication, increased body mass index) are more likely to require surgical revision procedures and typically have a greater rate of nonunion than their healthy counterparts. We believe that the use of a mesenchymal stem cell graft will increase the likelihood of a successful fusion during the primary procedure. The present study reviewed the use of stem cell grafting in hindfoot and ankle surgery and the healing times in high-risk patients. Successful fusion was defined as bridging across 3 cortices. In this patient group, the average interval to radiologic union was 11.1 ± 2.0 (range 8 to 15) weeks. The interval to partial weightbearing was 5.5 ± 1.8 (range 3 to 12) weeks, to full weightbearing was 8.4 ± 1.9 (range 5 to 14) weeks, and to shoe wearing was 13.6 ± 3.0 (range 10 to 20) weeks.

Strength evaluation of lateral calcaneal wall with circular external fixation application in cadaveric specimens.

Circular external fixation is a useful treatment option for the correction of complex trauma, extremity deformity, osteomyelitis, and reconstruction of the foot and ankle. The goal of the present study was to determine the degrees of bolt rotation required to create enough wire tension to cause structural failure of the lateral calcaneal wall when stressed with both olive and smooth wires in a cadaveric model. Ten fresh, thawed, below-the-knee specimens were tested at the San Diego Cadaveric Academic Research Symposium. The mean bolt rotation required to pull an olive wire through the lateral wall of the calcaneus was 79.8° ± 32.81°, and the mean bolt rotation required to "walk" a skinny wire (narrow diameter) and create 1 mm of cortical bone failure was 50.5° ± 30.91°. The results of the present investigation further define and elucidate the appropriate "Russian tensioning" technique applicable for external fixation of the calcaneus using olive or skinny wires in the case of fracture repair or compression arthrodesis.

The Posttraumatic Tarsometatarsal Joints.

Tarsometatarsal joint injuries can be painful and debilitating and are most commonly due to direct or indirect trauma. Posttraumatic arthritis is a well-known long-term complication, with incidence as high as 58%. Conservative treatment options include shoe modifications, orthotic inserts, topical or oral anti-inflammatories, and intra-articular corticosteroid injections. There are various joint prep and fixation techniques reported in the literature, many with positive clinical and radiographic outcomes. This article discusses nonoperative and operative management of posttraumatic tarsometatarsal joint arthritis, reviews available literature, and includes the authors' tips and techniques.

Management of Subchondral Lesions in the Foot and Ankle.

The treatment of subchondral lesions is an area with limited focus within the foot and ankle literature. The literature has shown an association between disruption of the subchondral bone plate and the formation of subchondral cysts. The primary causes of subchondral lesions are acute trauma, repetitive microtrauma, as well as idiopathic means. Evaluation of these injuries should be done carefully and often requires advanced imaging including MRI and computed tomography. Treatment does vary depending on the presentation of the subchondral lesion with or without the presence of an osteochondral lesion.

A Comparison of Ankle Fractures Relative to Other Fragility Fractures: A Review and Analysis of the American Orthopaedic Association's Own the Bone Database.

BACKGROUND: Ankle fragility fractures (AFX) continue to increase in the elderly population. There is limited knowledge of AFX characteristics compared to nonankle fragility fractures (NAFX). The American Orthopaedic Association's Own the Bone (OTB) is a fragility fracture initiative. This robust data set was used to examine and compare characteristics of patients presenting with AFX to those with NAFX. METHODS: The OTB database contained 72,617 fragility fractures between January 2009 and March of 2022 and were reviewed in our secondary cohort comparative analysis. After exclusions, AFX accounted for 3229 patients and 54,772 patients were in the NAFX cohort. Bivariate analysis and logistic regression compared the AFX and NAFX groups concerning demographics, bone health factors, medication use, and prior fragility fracture. RESULTS: AFX patients were found to have a higher likelihood to be younger (67.6 years old), female (81.4%), non-Caucasian (11.7%) and have a higher BMI (30.6) compared to NAFX. Prior AFX predicted the risk of a future AFX. The probability of an AFX increased with increased age and BMI. CONCLUSION: A prior AFX is independently predictive of subsequent AFX. Therefore, these fractures should be considered a sentinel event. These patients are more likely to have higher BMI, to be of female gender, non-Caucasian race, and are younger compared to patients with NAFX. LEVEL OF EVIDENCE: Level III, retrospective cohort.