UnTWISTing the BALS: A study of predictive accuracy of clinical scoring tools for testicular torsion identification in adults.

OBJECTIVE: Testicular torsion is an uncommon but time-critical condition in EDs. If the diagnosis is missed or delayed, there are significant medicolegal and patient fertility implications. Scoring tools are advocated for use in children but have limited validation in adults. The aim of the present study was to explore the predictive accuracy of the testicular torsion scoring tools, Testicular Workup for Ischemia and Suspected Torsion (TWIST) and Boettcher Alert Score (BALS), in adult patients with a final ED diagnosis of torsion. METHODS: All patients with an ED working diagnosis of testicular torsion were identified retrospectively. Data collected from digital medical records included demographics, processes of care and clinical information. The outcome of interest was the predictive performance of the scores for a confirmed diagnosis of testicular torsion as adjudicated by an urologist or a surgeon. RESULTS: Fifty-four patients had complete clinical data, of whom 13 had confirmed torsion. The TWIST score had a high area under the receiver operating characteristics curve (AUROC) of 0.89 (95% confidence interval [CI] = 0.78-0.999) with a score of 6-7 corresponding to a positive predictive value (PPV) of 80% (95% CI = 38-96%). The BAL score had an AUROC of 0.79 (95% CI = 0.69-0.92). PPV for a score ≥2 was 38% (95% CI = 22-56%). CONCLUSION: A high TWIST score correlates to a high likelihood of torsion and can inform surgical decision-making in the absence of US.

Decreased Strength, Complication Rate and Higher Satisfaction in Conservative Treatment of Partial Distal Biceps Tendon Rupture Compared to Surgical Treatment: A Systematic Review.

Background: Treatment modalities for partial distal biceps tendon (DBT) ruptures include conservative management (immobilization, medication, and physical therapy) or surgery. Selecting treatment modality can present a challenge to both patient and provider. Hypothesis: It was hypothesized that patients undergoing surgical treatment for partial DBT rupture would have higher complications but better overall strength, range of motion (ROM), and patient satisfaction. Study Design: Systematic Review. Methods: A systematic review was performed in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane, Embase, and Medline databases were searched for studies published through May 2023. Studies were included if they examined patients with a partial DBT rupture who underwent treatment. Exclusion criteria were non-human studies, studies not in English, reviews, technical notes, letters to the editor, surgical technique papers, and studies reported in a prior review. Results: 13 studies consisting of 290 patients with a partial DBT tear were included in this review. 75% of the patients were male and the ages ranged from 23 - 75 years. The follow up for the patients ranged from 1 - 94 months. 55 patients underwent conservative treatment versus 256 patients underwent surgical treatment. Outcomes examined by the studies included pain, strength, range of motion (ROM), complications, patient reported outcomes (PROs), return to activity, and patient satisfaction. Conclusion: Treatment for partial DBT tear via surgery or conservative treatment both produce good clinical outcomes. There are similar outcomes between treatment options for pain and ROM. Conservative treatment had some poorer outcomes in terms of strength after treatment. Surgical treatment had more complications and a few patients with decreased satisfaction. Overall, both are viable treatment options, requiring a physician and patient discussion regarding the pros and cons of both options as a part of a shared decision-making process that incorporates patient priorities.

Dual Plating of Distal Femoral Fractures.

Background: Dual plating of the distal femur is indicated for the treatment of complex intra-articular fractures, supracondylar femoral fractures, low periprosthetic fractures, and nonunions. The aim of this procedure is anatomical alignment of the articular surface, restoration of the articular block, and prevention of varus collapse. Description: Following preoperative planning, the patient is positioned supine with the knee flexed at 30°. The lateral incision is made first, with a mid-lateral incision that is in line with the femoral shaft. If intra-articular work is needed this incision can be extended by curving anteriorly over the lateral femoral condyle. Next, the iliotibial band is transected in line with its fibers. The vastus lateralis fascia is incised and elevated off the septum, working distal to proximal. Care should be taken to maintain hemostasis when encountering femoral artery perforating vessels. Once there is adequate exposure, several reduction aids can be utilized, including a bump under the knee, Schanz pins, Kirschner wires, and reduction clamps. A lateral precontoured plate is placed submuscularly, and the most proximal holes are filled percutaneously. The medial incision begins distally at the adductor tubercle and is a straight incision made proximally in line with the femoral shaft. The underlying fascia is transected in line with the skin incision, and the vastus medialis is elevated. Care should be taken to avoid the descending geniculate artery, as well as its articular branch and the muscular branch to the vastus medialis. A lateral tibial plateau plate is contoured and placed. Alternatives: Nonoperative treatment of distal femoral fractures is rare, but relative indications for nonoperative treatment include frailty of the patient, lack of ambulatory status, a non-reconstructible fracture, or a stable fracture. These patients are placed in a long-leg cast followed by a hinged knee brace1. There are several other surgical fixation options, including lateral plating, retrograde intramedullary nailing, distal femoral replacement, and augmentation of a retrograde nail with a plate. Rationale: Dual plating has several benefits, depending on the clinical scenario. Biomechanical studies have found that dual plating results in increased stiffness and construct strength2,3. Additional construct stability can be offered through the use of locking plates, particularly in osteoporotic bone. Taken together, this increased stability and construct strength can allow for earlier weight-bearing, which is particularly important for fractures in the geriatric population. Furthermore, the increased stiffness and construct strength make this procedure a favorable treatment option for nonunion, and it has been shown to result in lower rates of postoperative nonunion compared with lateral plating alone4-7. Adjunctive use of a medial plate also has been suggested to prevent varus collapse, particularly with metaphyseal comminution and poor bone quality2,3,8. Finally, in the periprosthetic fracture population, dual plating also removes the concern of incompatibility with a retrograde nail. Expected Outcomes: The outcomes of dual plating are promising, given the severity of the injury. When comparing operative to nonoperative treatment outcomes, nonoperatively managed patients had worse functional outcomes and higher rates of complications related to immobility1. Dual plating of supracondylar fractures and intra-articular distal femoral fractures yields nonunion rates ranging from 0% to 12.5%, lower than the 18% to 20% reported with lateral locking plates4-7,9-12. This reduction in nonunions has been shown to lead to fewer revisions when compared with single-plating techniques7. In prior studies, 95% of nonunions treated with the dual-plating technique achieved union postoperatively11. One concern when utilizing the medial approach is critical damage to medial vascularity; however, this result has not been reported in the literature, and there is a safe operating window13. Despite the benefits of dual plating, there are relatively high rates of infection following dual plating (0% to 16.7%) compared with lateral plating alone (3.6% to 8.5%)5,14-17. However, many of these studies are small case series, highlighting that a surgeon's comfort and skill with these procedures is paramount to patient outcomes. Important Tips: Meticulous placement and contouring of lateral and medial plates are required to prevent malreduction of the articular block that creates a "golf-club deformity."18,19During the medial approach, be aware of descending geniculate artery-particularly its muscular branch, which is ∼5 cm from the adductor tubercle/medial epicondyle, and its root, which enters the compartment at the adductor hiatus at ∼16 cm13.

NSQIP data collection up to 30 postoperative days is sufficient to capture some complications in orthopedic surgeries.

PURPOSE: The primary aim of this study is to determine if the 30-day follow-up period used by the National Surgical Quality Improvement Program (NSIQP) is an appropriate timeframe to capture complications after orthopedic surgeries. METHODS: The 2019 NSQIP data were used. The independent variables were complication type. The dependent variable was days to complication. A Shapiro-Wilk test was used to determine if the data were normally distributed. RESULTS: 271,397 orthopedic cases were included. Myocardial infarction, pneumonia, ventilator over 48 h, progressive renal insufficiency, acute renal failure, stroke, and cardiac arrest had positive skewness and positive kurtosis. Deep incisional surgical site infection (SSI), organ/space SSI, wound disruption, unplanned reoperation one, unplanned reoperation two, readmission two, and readmission three had negative kurtosis and negative skewness. Complications with positive kurtosis and positive skewness are more likely to be confined to the 30-day postoperative period, whereas complications with negative skewness and negative kurtosis may be underreported within the 30-day follow-up. CONCLUSIONS: These findings are useful in their ability to inform future orthopedic research using NSQIP which continues to generate new data for surgeons to consider for their postoperative care and complication management.

Femoral rotational osteotomy for femoroacetabular impingement: A systematic review.

Purpose: To synthesize existing literature regarding the indications and outcomes of femoral rotational osteotomies (FDO) for femoroacetabular impingement (FAI) due to. Methods: Medline, Cochrane, and Embase were searched using keywords "femoroacetabular impingement", "rotational osteotomy" and others to identify FAI patients undergoing FDO. Double-screened studies were reviewed by blinded authors according to inclusion criteria. Data from full texts was extracted including study type, number of patients, sex, mean age, surgical indication, type of dysplasia, associated pathology, surgical technique, follow-up, and pre-op/post-op evaluations of the following: impingement test, femoral version (FV), 'other angles measured', outcome scores, range of motion (ROM). Results: 7 studies including 91 patients (97 FDO surgeries), 73 females (80 %) with mean age of 28.3 years, and follow-up mean of 2.44 ± 2.83 years. Pain or impingement was the most common clinical indication, while others included aberrant FV and ROM measurements for both anteverted and retroverted femurs. There were reports of FDO being performed with concomitant procedures addressing other pathology. Various outcome scores and ROM measurements showed postoperative improvement after FDO. Complication data was sparse, preventing aggregation. The rate of unplanned reoperation was 40 % (where reported), with 'hardware removal' being the most common. Conclusions: FDO is effective in treating FAI due to increased FV, improving clinical symptoms, and potentially delaying articular degeneration. Hardware removal surgery remains an inherent risk in undergoing FDO. Further work is needed to discover indications warranting FDO as a primary treatment versus hip arthroscopy. Level of evidence: This review contains 4 studies with Level IV evidence and 3 studies with Level III evidence.

Crowdsourcing temporal transcriptomic coronavirus host infection data: Resources, guide, and novel insights.

The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) reawakened the need to rapidly understand the molecular etiologies, pandemic potential, and prospective treatments of infectious agents. The lack of existing data on SARS-CoV-2 hampered early attempts to treat severe forms of coronavirus disease-2019 (COVID-19) during the pandemic. This study coupled existing transcriptomic data from severe acute respiratory syndrome-related coronavirus 1 (SARS-CoV-1) lung infection animal studies with crowdsourcing statistical approaches to derive temporal meta-signatures of host responses during early viral accumulation and subsequent clearance stages. Unsupervised and supervised machine learning approaches identified top dysregulated genes and potential biomarkers (e.g. CXCL10, BEX2, and ADM). Temporal meta-signatures revealed distinct gene expression programs with biological implications to a series of host responses underlying sustained Cxcl10 expression and Stat signaling. Cell cycle switched from G1/G0 phase genes, early in infection, to a G2/M gene signature during late infection that correlated with the enrichment of DNA damage response and repair genes. The SARS-CoV-1 meta-signatures were shown to closely emulate human SARS-CoV-2 host responses from emerging RNAseq, single cell, and proteomics data with early monocyte-macrophage activation followed by lymphocyte proliferation. The circulatory hormone adrenomedullin was observed as maximally elevated in elderly patients who died from COVID-19. Stage-specific correlations to compounds with potential to treat COVID-19 and future coronavirus infections were in part validated by a subset of twenty-four that are in clinical trials to treat COVID-19. This study represents a roadmap to leverage existing data in the public domain to derive novel molecular and biological insights and potential treatments to emerging human pathogens.

Midwave resonant cavity infrared detectors (RCIDs) with suppressed background noise.

We report a resonant cavity infrared detector (RCID) with an InAsSb/InAs superlattice absorber with a thickness of only ≈ 100 nm, a 33-period GaAs/Al0.92Ga0.08As distributed Bragg reflector bottom mirror, and a Ge/SiO2/Ge top mirror. At a low bias voltage of 150 mV, the external quantum efficiency (EQE) reaches 58% at the resonance wavelength λres ≈ 4.6 µm, with linewidth δλ = 19-27 nm. The thermal background current for a realistic system scenario with f/4 optic that views a 300 K scene is estimated by integrating the photocurrent generated by background spanning the entire mid-IR spectral band (3-5 µm). The resulting specific detectivity is a factor of 3 lower than for a state-of-the-art broadband HgCdTe device at 300 K, where dark current dominates the noise. However, at 125 K where the suppression of background noise becomes critical, the estimated specific detectivity D* of 5.5 × 1012 cm Hz½/W is more than 3× higher. This occurs despite a non-optimal absorber cut-off that causes the EQE to decrease rapidly with decreasing temperature, e.g., to 33% at 125 K. The present RCID's advantage over the broadband device depends critically on its low EQE at non-resonance wavelengths: ≤ 1% in the range 3.9-5.5 µm. Simulations using NRL MULTIBANDS indicate that impact ionization in the bottom contact and absorber layers dominates the dark current at near ambient temperatures. We expect future design modifications to substantially enhance D* throughout the investigated temperature range of 100-300 K.

Effects of Development on Bone Mineral Density and Mechanical Properties in the Aquatic Frog, Xenopus Laevis, and a Terrestrial Frog, Lithobates Catesbianus.

The limb bones of vertebrates have a critical role in supporting the weight of the body and transmitting forces that power locomotion. The loads that limb bones experience can vary in association with a range of factors, including locomotor environment or developmental stage. Limbed vertebrates that are habitually found in environments with low locomotor loads (e.g., water) might be predicted to also exhibit limb bones with less elevated mechanical properties, such as yield stiffness and yield stress. Frogs provide a distinctive case, in which these ideas can be tested as they experience changes in both locomotor style and habitat as they develop. However, while many frog taxa shift from aquatic to terrestrial habitats as they metamorphose, some lineages, such as pipids, maintain an aquatic lifestyle even after metamorphosis, providing a comparative framework for the effects of habitat shifts on developing limbs in vertebrates. This study compares the material composition and mechanical properties of the femur between frog species that are aquatic specialists (Xenopus laevis) vs generalists that spend considerable time both on land and in water (Lithobates catesbeianus) as they transition from metamorphic tadpoles to fully grown adults. MicroCT scanning was used to determine changes in bone density related to developmental stage and hindlimb use during swimming. Microindentation was then used to collect hardness values from the cortical bone of each femur, which was used to evaluate bone material properties. We found that aquatic frogs had less overall bone mineral density (BMD) than terrestrial frogs and that BMD was more elevated in the cortical region of the diaphysis than trabeculae and distal and proximal epiphyses. Despite its less elevated BMD, bone mechanical properties were not significantly different in aquatic specialist X. laevis than in more terrestrial L. catesbeianus. Our results suggest that the limb bones of aquatic frogs may experience compensatory effects through development to offset their lower BMD. Furthermore, changes in bone density and material properties across development may help to explain some of the differences in locomotor performance found between aquatic and terrestrial metamorphic frogs, providing insight into how environmental factors might correlate with bone ossification.

Surgical Outcomes and Associated Injuries of Anterior Labroligamentous Periosteal Sleeve Avulsion (ALPSA) Lesions: A Systematic Review.

Introduction: Anterior Labroligamentous Periosteal Sleeve Avulsion (ALPSA) lesions can lead to chronic shoulder instability and repetitive dislocations in active populations. Objective: The purpose of this systematic review was to evaluate associated injuries and postoperative outcomes following ALPSA lesion repairs. Methods: Medline, Embase, Cochrane, and Web of Science were searched through May 2022 for studies that investigated management and surgical outcomes of ALPSA lesion repair. Data was extracted on the following topics: surgical management, surgical complications, associated injuries, follow-up duration, and outcome parameters, including recurrence rates, functional outcome scores, range-of-motion (ROM), and return to activity. Results: A total of 6 studies covering 202 patients met the inclusion criteria. In the included studies, 79% of patient were male with a mean age of 25.1 years. A total of 192 associated injuries were reported amongst 176 patients with the most common being Hill Sachs lesions (84, 43.8%), synovitis (35, 18.2%), SLAP tears (32, 16.7%) and glenoid erosions or lesions (30, 15.6%). All 202 patients were treated arthroscopically with no reported complications. 26 patients (12.9%) experienced operative failure as evidenced by recurrence of shoulder instability over a mean follow-up of 4.3 years. Various clinical outcome scores showed postoperative functional improvement and one study reported a 100% return to activity rate in 26 patients. Conclusion: Our findings suggest a high 12.9 % risk of recurrence following ALPSA repair but satisfactory functional outcomes, both of which should be weighed by physicians when considering arthroscopic repair. Physicians should also be cognizant of co-pathologies when examining patients with suspected ALPSA lesions.

Return to sport and active military duty after cervical disc arthroplasty: A systematic review.

Introduction: Cervical disc arthroplasty (CDA) has been established as an effective treatment for cervical disc degeneration or herniation in the general population. Return to sport (RTS) outcomes in athletes remain unclear. Objective: The purpose of this review was to evaluate RTS following single-level, multi-level, or hybrid CDA, with additional return to activity context provided by return to duty (RTD) outcomes in active-duty military. Methods: Medline, Embase, and Cochrane were searched through August 2022 for studies that reported RTS/RTD after CDA in athletic or active-duty populations. Data was extracted on the following topics: surgical failures/reoperations, surgical complications, RTS/RTD, and postoperative time to RTS/RTD. Results: Thirteen papers covering 56 athletes and 323 active-duty members were included. Athletes were 59% male with a mean age of 39.8 years and active-duty members were 84% male with a mean age of 40.9 years. Only 1 of 151 cases required reoperation and only 6 instances of surgical complications were reported. Classified as return to general sporting activity, RTS was observed in 100% of patients (n = 51/51) after an average of 10.1 weeks to training and 30.5 weeks to competition. RTD was observed in 88% of patients (n = 268/304) after an average of 11.1 weeks. Average follow-up was 53.1 months for athletes and 13.4 months for the active-duty population. Conclusion: CDA displays excellent RTS and RTD rates in physically demanding populations at rates superior or equivalent to alternative treatments. Surgeons should consider these findings when determining the optimal cervical disc treatment approach in active patients.

The Role of Cryotherapy After Total Knee Arthroplasty: A Systematic Review.

BACKGROUND: Previous research shows conflicting evidence regarding the postoperative role of cryotherapy after total knee arthroplasty (TKA). This systematic review aims to further investigate the effect of various methods of cryotherapy on the following: (1) pain; (2) swelling; (3) postoperative opioid use; and (4) range of motion (ROM). METHODS: A strategic keyword search of Medline, Cochrane, Embase, and CINAHL retrieved randomized controlled trials examining cryotherapy following TKA published between February 1, 2017, and February 24, 2022. The studied outcomes included pain ratings, knee/limb swelling, opioid use, and ROM. Six studies were selected for inclusion in this review. RESULTS: Opioid use was significantly decreased in cryotherapy groups compared to noncryotherapy groups within the first postoperative week only (P < .05). This effect may be augmented by the use of computer-assisted (temperature regulated) cryotherapy devices, compared to other modalities including ice packs. Pain ratings also decrease, but this decrease may not be clinically relevant. Cryotherapy appears to confer no consistent benefit to ROM and swelling at any time point. Computer-assisted cryotherapy may be associated with decreased opioid consumption after TKA compared to traditional ice packs. CONCLUSION: Cryotherapy's role after TKA appears to be in decreasing opioid consumption primarily in the first postoperative week. Pain ratings also decrease consistently with cryotherapy use, but this decrease may not be clinically relevant. Study heterogeneity requires further research focusing on optimizing cryotherapy modalities within the first postoperative week, and analyzing cost associated with modern outpatient postoperative TKA protocols.

Posterior Approach for Open Reduction and Internal Fixation for Scapular Fractures.

Background: This technique utilizes a full-thickness flap to provide a posterior approach to the scapula for open reduction and internal fracture fixation. The present video article outlines the Judet approach along with an incision modification tip for the surgeon's consideration. Description: Prior to making the incision, perform preoperative planning, patient and C-arm positioning, and identification of the primary fragments of the fracture that necessitate fixation on imaging. The Judet incision is made, and the full-thickness flap is retracted laterally (also described as a "boomerang-shaped" incision, allowing for the flap to be reflected medially). Next, detach and reflect the deltoid off the scapular spine superolaterally to reveal the internervous plane between the infraspinatus and teres minor. Utilize this interval to access the fracture sites while making sure to reflect the infraspinatus cranially, carefully minding the suprascapular neurovascular bundle, and the teres minor inferiorly, protecting the axillary nerve. A longitudinal arthrotomy may then be created parallel to the posterior border of the glenoid, with careful attention paid toward protecting the labrum from iatrogenic injury. The arthrotomy will allow for intra-articular evaluation of the reduction if needed. Primary fractures are then reduced. Reduction is confirmed with use of fluoroscopy, and fixation is applied to maintain the reduction. Alternatives: Most scapular fractures do well with nonoperative treatment, and this has been well documented in the literature. Open reduction and internal fixation has been shown to offer good-to-excellent clinical outcomes with minimal risk of complications in patients with traumatic scapular fractures that necessitate operative treatment1. In certain fractures of the glenoid fossa, operative treatment is necessary to restore normal anatomy, provide stability to the glenohumeral joint, and facilitate functional rehabilitation. Operative treatment is typically reserved for injuries with intra-articular involvement that results in joint incongruity or joint instability2,3. When operative treatment is indicated, an open posterior approach is utilized for some fractures. The posterior Judet approach is the best-known operative technique for such fractures, while other modifications of the Judet technique have also been described in the literature3-5. Rationale: Reports state that scapular body or neck and glenoid fossa fractures account for up to 80% of scapular fractures6. Open reduction and internal fixation of the scapula is an invasive procedure, requiring large incisions and manipulation of soft tissues to expose the various possible fracture sites on the scapula. Thus, numerus surgical techniques have been described that allow surgeons to best tailor treatment to their patients on a case-by-case basis. However, the Judet approach is the workhorse approach for the operative treatment of scapular fractures and is a technique that should be mastered7. The Judet approach allows access to the posterior scapula and provides excellent exposure for fractures that require posterior fixation. The alternative boomerang-shaped incision represents a mirrored version of the Judet incision, with the skin flap reflected medially. The benefit of this modified approach is that it increases the degree of lateral surgical exposure of the scapula and provides easier access to the glenohumeral joint. Expected Outcomes: With this technique for open reduction and internal fixation of scapular fractures, patients can expect comparable outcomes to those described in the literature for the standard Judet technique. These outcomes have been reported as clinical scores and defined as good-to-excellent in a few retrospective case series1,2. Given the variability in scapular fracture morphology, a trauma surgeon should have a strong repertoire of approaches to address these fractures on a case-by-case basis. The Judet approach is one of these necessary approaches and has been shown in the literature to have acceptable outcomes1-3,7. Important Tips: Placing the vertical limb of the boomerang incision too medial can limit lateral exposure of the scapula and make glenohumeral joint access difficult. To avoid this, be sure that the vertical limb of the incision remains in line with the posterior axillary fold.Wound-healing complications can occur following such an extensive surgical approach. A thorough and secure wound closure with repair of the deltoid back to the scapular spine may avoid these problems.Difficulty with intra-articular visualization may occur. Placing a threaded pin into the humeral head or a small distractor across the glenohumeral joint (with a pin in the extra-articular proximal humerus) may improve visualization. Manipulation of the arm can also be beneficial in this regard.Lateral positioning offers easier imaging and allows for exposure to the coracoid or clavicle if these structures are also injured and require operative fixation.Drawing a boomerang-shaped incision with the horizontal limb paralleling the scapular spine and vertical limb along the posterior axillary fold of the arm allows the skin flap to be reflected medially, increasing the degree of lateral surgical exposure of the scapula.After identifying the internervous plane between the infraspinatus and teres minor, take care to reflect the infraspinatus cranially, protecting the suprascapular neurovascular bundle, and the teres minor inferiorly, protecting the axillary nerve. Acronyms and Abbreviations: ORIF = open reduction and internal fixationK-wire = Kirschner wire.

MTG16 regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors.

Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium-induced (DSS-induced) colitis. Transcriptomic analyses implicated increased Ephrussi box-binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a mouse model with a point mutation that attenuates MTG16:E protein interactions (Mtg16P209T), we showed that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein-mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared with unaffected controls. Finally, uncoupling MTG16:E protein interactions partially phenocopied the enhanced tumorigenicity of Mtg16-/- colon in the azoxymethane/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets, is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.

Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues.

Macrophages are versatile cells of the innate immune system that perform diverse functions by responding to dynamic changes in their microenvironment. While the effects of soluble cues, including cytokines and chemokines, have been widely studied, the effects of physical cues, including mechanical stimuli, in regulating macrophage form and function are less well understood. In this study, we examined the effects of static and cyclic uniaxial stretch on macrophage inflammatory and healing activation. We found that cyclic stretch altered macrophage morphology and responses to IFNγ/LPS and IL4/IL13. Interestingly, we found that both static and cyclic stretch suppressed IFNγ/LPS induced inflammation. In contrast, IL4/IL13 mediated healing responses were suppressed with cyclic but enhanced with static stretch conditions. Mechanistically, both static and cyclic stretch increased expression of the integrin CD11b (αM integrin), decreased expression of the mechanosensitive ion channel Piezo1, and knock down of either CD11b or Piezo1 through siRNA abrogated stretch-mediated changes in inflammatory responses. Moreover, we found that knock down of CD11b enhanced the expression of Piezo1, and conversely knock down of Piezo1 enhanced CD11b expression, suggesting the potential for crosstalk between integrins and ion channels. Finally, stretch-mediated differences in macrophage activation were also dependent on actin, since pharmacological inhibition of actin polymerization abrogated the changes in activation with stretch. Together, this study demonstrates that the physical environment synergizes with biochemical cues to regulate macrophage morphology and function, and suggests a role for CD11b and Piezo1 crosstalk in mechanotransduction in macrophages.

VAAFT for complex anal fistula: a useful tool, however, cure is unlikely.

BACKGROUND: Therapeutic options for complex anal fistula (CAF) are limited. Video-assisted anal fistula treatment (VAAFT) allows examination of these anatomically complex fistulae from within. The aim of the present study was to evaluate outcomes of VAAFT for a series of CAF. METHODS: A retrospective study was conducted on consecutive patients at a single centre with complex anal cryptoglandular and Crohn's fistulae managed with VAAFT from June 2016 to June 2019. CAF was diagnosed as high intersphincteric/transsphincteric tract, multiple/secondary tracts, horseshoe or anovaginal fistulae. Patients were treated with 'therapeutic intent' if the internal opening was closed at the time of ablation and 'diagnostic/staged/palliative' VAAFT if there was no ablation/partial treatment/ablation-only, respectively. Symptom improvement was a reduction in reported pain, discharge, or pad use. RESULTS: Eighty-four patients (73 cryptoglandular, 11 Crohn's, M:F 2.5:1, median age 43 [22-77] years), underwent 105 VAAFT procedures. Twenty patients had > 1 VAAFT. Median follow-up was 8 (1-46) months. 40 (48%) had multiple or secondary tracts; an additional 16 (19%) had horseshoe and 3 (4%) anovaginal fistulae. Of the 84 patients, 19 [16/73 (22%) cryptoglandular and 3/11 (27%) Crohn's fistulae] healed. 34 (40%) unhealed reported improved symptoms; 23 (27%) no improvement; and 6 (7%) were worse. Sixteen (19%) had CAF > 5 years of whom none healed, albeit 50% reported symptom improvement. Five patients (6%) developed faecal incontinence: 2 temporary, 1 to flatus only and 1 to liquid and 1 to solid, all managed conservatively. CONCLUSIONS: VAAFT is a useful minimally invasive procedure for complex fistula with no other minimally invasive options. Complete healing is rare, and, although symptoms can be improved in a number of cases, there is a small risk of incontinence.

Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies.

BACKGROUND: Cancer is a multistep process involving genetic and epigenetic changes in the somatic genome. Genetic mutations as well as environmental factors lead to the initiation, promotion, and progression of cancer. Metastasis allows cancer cells to spread via circulatory and lymphatic systems; secondary tumorigenesis typically leads to a fatal outcome. Recent experimental evidence suggests that Cancer Stem Cells (CSCs) play a pivotal role in tumor progression. A tumor is heterogeneous and composed of different cell types. CSCs are a subpopulation of tumor cells possessing abilities to self-renew and differentiate. OBJECTIVE: The aim of this study was to present repurposed drugs, and potential candidates, that can serve as anticancer medications intended to target resistant cancer cells, i.e. CSCs. METHODS: Research publications, FDA filings, and patents have been reviewed for repurposed drugs or drug combinations that can act to improve cancer treatment and care. RESULTS: Drugs that act against CSCs include ones approved for treatment of diabetes (metformin & thiazolidinediones), parasitic diseases (chloroquine, niclosamide, mebendazole & pyrvinium), psychotic disorders (thioridazine, clomipramine & phenothiazines), alcoholism (disulfiram), lipid disorder (statins), inflammatory diseases (tranilast, auranofin, acetaminophen & celecoxib), antibiotics (azithromycin), and other disorders. Current research findings advocate the existence of beneficial effects by combining these repurposed drugs, and also through their complementary use with conventional cancer therapies. CONCLUSION: Repurposing FDA-approved medications towards cancer care, by targeting the resistant CSCs, will allow for a quicker, cheaper development and approval process. A larger drug library available to physicians will allow for increased efficacy during both first-line and recurrent cancer treatments.

Flexor Digitorum Superficialis Tendon Transfer for Wrist Extension.

Peripheral nerve injuries are among the most complex conditions facing upper-extremity surgeons. Loss of wrist extension can result in marked limitations, including loss of pinch and grip strength with discoordination of grasp and release. Tendon transfers represent the mainstay of operative treatment and have proven to be an effective method for restoring loss of wrist extension. The literature describes myriad techniques to restore loss of wrist extension. The best choice of transfers is dependent on what is available, depending on the level of injury. The present article describes a novel technique of transferring 2 flexor digitorum superficialis (FDS) tendons for wrist extension for patients with radial nerve lesions. The technique involves direct transfer of the long and ring finger FDS tendons to the third metacarpal bone. One FDS is routed through the interosseous membrane while the second FDS tendon is routed radially around the wrist to prevent a net supination or pronation force. If needed, the tendons can be alternatively routed to augment either pronation or supination. Passing both FDS tendons through the interosseous membrane creates a supination moment of the forearm, whereas routing both around the radius adds pronation. This article will review the relevant anatomy, indications, contraindications, operative technique, postoperative management, and outcomes. DESCRIPTION: The present article describes the technique of transferring 2 FDS tendons to restore wrist extension in patients who have lost wrist extension secondary to nerve lesions, such as radial nerve palsy and brachial plexus injuries. This technique involves the transfer of the long and ring finger FDS tendons around the base of the long metacarpal. One FDS tendon is routed through the interosseous membrane, and the second FDS tendon is routed radially around the wrist to add a pronation moment to the transfer. ALTERNATIVES: Alternatives include nerve transfers and tendon transfers1-5, such as:pronator teres to extensor carpi radialis longus and extensor carpi radialis brevis,palmaris longus to flexor carpi radialis,flexor carpi ulnaris to extensor digitorum communis III-V3,flexor carpi radialis to extensor indicis proprius, extensor digitorum communis, and extensor pollicis longus. RATIONALE: The pronator teres tendon has been the primary donor described to restore wrist extension. However, this tendon is often inadequate and requires a periosteal extension. In addition, the pronator muscle may be involved in brachial plexus injures and unavailable as a donor. Lastly, the FDS is synergistic with wrist extension, which facilitates rehabilitation. EXPECTED OUTCOMES: Child and adult patients are expected to have good control of function at 3 months postoperatively, with a full recovery at 6 months postoperatively. Because the FDS is synergistic with wrist extension, rehabilitation is straightforward. The wrist is immobilized in a sugar-tong for 3 to 4 weeks postoperatively, followed by the use of a removable thermoplastic wrist brace for 4 weeks full-time, except when bathing and performing physical therapy, and then for 4 weeks at night only. Physical therapy should focus on activation and training of the FDS under therapist supervision. Supervised active extension exercises can be initiated after week 4 postoperatively, taking care to avoid wrist flexion beyond neutral and resistive exercises. Functional exercises can be initiated at 6 weeks postoperatively, with light resistance only until week 12, coinciding with the discontinued use of the wrist brace. IMPORTANT TIPS: Surgery is performed through 4 primary incisions:○ a volar oblique incision in the distal palmar crease at the base of the long and ring fingers,○ a volar transverse incision at the mid-forearm,○ a dorsal transverse incision over the midshaft of the third metacarpal,○ a dorsal forearm transverse incision opposite to the volar forearm incision to shuttle the FDS tendon.The FDS donor tendons to the long and ring fingers are isolated first.Any adhesions between the FDS and flexor digitorum profundus are divided.The FDS tendons are left in the wounds until later to prevent desiccation.On occasion, the FDS tendons can become caught in the carpal canal during harvesting and will need to be pulled back into the distal palmar incision for further lysis of connections between the FDS and flexor digitorum profundus tendons.A wide window, not a slit, is cut in the interosseous membrane to pass 1 of the FDS tendons.A counter incision in the dorsal forearm is made with use of a long, curved clamp through the interosseous membrane. A Penrose drain is then passed through this tendon portal.Our preferred site for the FDS tendon attachments is around the base of the long metacarpal. ACRONYMS AND ABBREVIATIONS: FDS = flexor digitorum superficialisPT = pronator teresECRL = extensor carpi radialis longusECRB = extensor carpi radialis brevisFCU = flexor carpi ulnarisEDC = extensor digitorum communisFCR = flexor carpi radialisEIP = extensor indicis propriusEPL = extensor pollicis longusFDP = flexor digitorum profundusMC = metacarpal.

Flexor Tenosynovectomy for Recurrent Carpal Tunnel Syndrome: A Retrospective Case Series of 108 Hands.

Background: The etiology of recurrent carpal tunnel syndrome (CTS) is unclear, and outcomes following secondary surgery in this demographic have been poorer than primary surgery. Fibrosis and hypertrophy have been identified in the flexor tenosynovium in these patients. The authors use flexor tenosynovectomy (FTS) for recurrent CTS after primary carpal tunnel release and present a review of these patients. Methods: A retrospective chart review was performed of 108 cases of FTS for recurrent CTS from 1995 to 2015 by 4 attending surgeons at one institution. Demographic information, symptoms, and outcomes were among the data recorded. A phone survey was conducted on available patients where the shortened version of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH) and satisfaction were assessed. Results: Average office follow-up was 12 months. Average age was 57.5 years. A total of 104 (96%) reported symptom improvement and 48 (44%) reported complete symptom resolution. Forty patients were available for long-term follow-up at an average 6.75 years postoperatively via phone interview. Average QuickDASH score was 31.2 in these patients. Thirty-six (90%) of 40 patients were initially satisfied at last office visit, and 31 (78%) of 40 were satisfied at average 6.9 years, a maintenance of satisfaction of 86%. Satisfied patients were older (58 years) than unsatisfied patients (51 years). Conclusion: Both long-term satisfaction and QuickDASH scores in our cohort are consistent with or better than published results from nerve-shielding procedures. The authors believe a decrease in both carpal tunnel volume and potential adhesions of fibrotic or inflammatory synovium contributes to the benefits of this procedure. This remains our procedure of choice for recurrent CTS.