Assessing Target Specificity of the Small Molecule Inhibitor MARIMASTAT to Snake Venom Toxins: A Novel Application of Thermal Proteome Profiling.

New treatments that circumvent the pitfalls of traditional antivenom therapies are critical to address the problem of snakebite globally. Numerous snake venom toxin inhibitors have shown promising cross-species neutralization of medically significant venom toxins in vivo and in vitro. The development of high-throughput approaches for the screening of such inhibitors could accelerate their identification, testing, and implementation and thus holds exciting potential for improving the treatments and outcomes of snakebite envenomation worldwide. Energetics-based proteomic approaches, including thermal proteome profiling and proteome integral solubility alteration (PISA) assays, represent "deep proteomics" methods for high throughput, proteome-wide identification of drug targets and ligands. In the following study, we apply thermal proteome profiling and PISA methods to characterize the interactions between venom toxin proteoforms in Crotalus atrox (Western Diamondback Rattlesnake) and the snake venom metalloprotease (SVMP) inhibitor marimastat. We investigate its venom proteome-wide effects and characterize its interactions with specific SVMP proteoforms, as well as its potential targeting of non-SVMP venom toxin families. We also compare the performance of PISA thermal window and soluble supernatant with insoluble precipitate using two inhibitor concentrations, providing the first demonstration of the utility of a sensitive high-throughput PISA-based approach to assess the direct targets of small molecule inhibitors for snake venom.

Deconvolution and Analysis of the 1H NMR Spectra of Crude Reaction Mixtures.

Nuclear magnetic resonance (NMR) spectroscopy is an important analytical technique in synthetic organic chemistry, but its integration into high-throughput experimentation workflows has been limited by the necessity of manually analyzing the NMR spectra of new chemical entities. Current efforts to automate the analysis of NMR spectra rely on comparisons to databases of reported spectra for known compounds and, therefore, are incompatible with the exploration of new chemical space. By reframing the NMR spectrum of a reaction mixture as a joint probability distribution, we have used Hamiltonian Monte Carlo Markov Chain and density functional theory to fit the predicted NMR spectra to those of crude reaction mixtures. This approach enables the deconvolution and analysis of the spectra of mixtures of compounds without relying on reported spectra. The utility of our approach to analyze crude reaction mixtures is demonstrated with the experimental spectra of reactions that generate a mixture of isomers, such as Wittig olefination and C-H functionalization reactions. The correct identification of compounds in a reaction mixture and their relative concentrations is achieved with a mean absolute error as low as 1%.

Prehospital hemorrhage management in low- and middle-income countries: A scoping review.

INTRODUCTION: Low- and middle-income countries (LMICs) account for 90% of deaths due to injury, largely due to hemorrhage. The increased hemorrhage mortality burden in LMICs is exacerbated by absent or ineffective prehospital care. Hemorrhage management (HM) is an essential component of prehospital care in LMICs, yet current practices for prehospital HM and outcomes from first responder HM training have yet to be summarized. METHODS: This review describes the current literature on prehospital HM and the impact of first responder HM training in LMICs. Articles published between January 2000 and January 2023 were identified using PMC, MEDLINE, and Scopus databases following PRISMA-ScR guidelines. Inclusion criteria spanned first responder training programs delivering prehospital care for HM. Relevant articles were assessed for quality using the Newcastle-Ottawa scale. RESULTS: Of the initial 994 articles, 20 met inclusion criteria representing 16 countries. Studies included randomized control trials, cohort studies, case control studies, reviews, and epidemiological studies. Basic HM curricula were found in 15 studies and advanced HM curricula were found in six studies. Traumatic hemorrhage was indicated in 17 studies while obstetric hemorrhage was indicated in three studies. First responders indicated HM use in 55%-76% of encounters, the most frequent skill they reported using. Mean improvements in HM knowledge acquisition post-course ranged from 23 to 58 percentage points following training for pressure and elevation, gauze application, and tourniquet application. CONCLUSIONS: Our study summarizes the current literature on prehospital HM in LMICs pertaining to epidemiology, interventions, and outcomes. HM resources should be a priority for further development.

Prodromes in demyelinating disorders, amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer's dementia.

A prodrome is an early set of symptoms, which indicates the onset of a disease; these symptoms are often non-specific. Prodromal phases are now recognized in multiple central nervous system diseases. The depth of understanding of the prodromal phase varies across diseases, being more nascent for multiple sclerosis for example, than for Parkinson disease or Alzheimer's disease. Key challenges when identifying the prodromal phase of a disease include the lack of specificity of prodromal symptoms, and consequent need for accessible and informative biomarkers. Further, heterogeneity of the prodromal phase may be influenced by age, sex, genetics and other poorly understood factors. Nonetheless, recognition that an individual is in the prodromal phase of disease offers the opportunity for earlier diagnosis and with it the opportunity for earlier intervention.

Mass Spectrometry-Based Atlas of Extracellular Matrix Proteins across 25 Mouse Organs.

The extracellular matrix (ECM) is a critical non-cellular component of multicellular organisms containing a variety of proteins, glycoproteins, and proteoglycans which have been implicated in a wide variety of essential biological processes, including development, wound healing, and aging. Due to low solubility, many ECM proteins have been underrepresented in previous proteomic datasets. Using an optimized three-step decellularization and ECM extraction method involving chaotrope extraction and digestion via hydroxylamine hydrochloride, we have generated coverage of the matrisome across 25 organs. We observe that the top 100 most abundant proteins from the ECM fractions of all tissues are generally present in all tissues, indicating that tissue matrices are principally composed of a shared set of ECM proteins. However, these proteins vary up to 4000-fold between tissues, resulting in highly unique matrix profiles even with the same primary set of proteins. A data reduction approach was used to reveal related networks of expressed ECM proteins across varying tissues, including basement membrane and collagen subtypes.

Machine Learning Full NMR Chemical Shift Tensors of Silicon Oxides with Equivariant Graph Neural Networks.

The nuclear magnetic resonance (NMR) chemical shift tensor is a highly sensitive probe of the electronic structure of an atom and furthermore its local structure. Recently, machine learning has been applied to NMR in the prediction of isotropic chemical shifts from a structure. Current machine learning models, however, often ignore the full chemical shift tensor for the easier-to-predict isotropic chemical shift, effectively ignoring a multitude of structural information available in the NMR chemical shift tensor. Here we use an equivariant graph neural network (GNN) to predict full 29Si chemical shift tensors in silicate materials. The equivariant GNN model predicts full tensors to a mean absolute error of 1.05 ppm and is able to accurately determine the magnitude, anisotropy, and tensor orientation in a diverse set of silicon oxide local structures. When compared with other models, the equivariant GNN model outperforms the state-of-the-art machine learning models by 53%. The equivariant GNN model also outperforms historic analytical models by 57% for isotropic chemical shift and 91% for anisotropy. The software is available as a simple-to-use open-source repository, allowing similar models to be created and trained with ease.

Causes and diagnostic utility of musculoskeletal MRI recall examinations.

AIM: To determine the causes and diagnostic utility of musculoskeletal (MSK) magnetic resonance imaging (MRI) recall examinations. MATERIALS AND METHODS: An institutional review board-approved retrospective review was conducted of all MSK MRI examinations performed at a single academic institution over 10 years where radiologists requested the patient return for additional imaging. The reason for the recall was documented. Recalls were reviewed in consensus by two MSK radiologists to determine whether additional sequences resulted in a change in the final report. Recall causes were divided into four categories: (1) radiologist-related: incorrect field of view (FOV) or incorrect protocol; (2) technologist-related: incorrect FOV or incorrect/incomplete protocol performed, or technically poor-quality images; (3) patient-related motion artefact; (4) unexpected lesion discovered. Fisher's exact test was used to assess for statistical significance. RESULTS: The recall rate was 0.25% (156/62,930). Of the total 129 recalls returning for imaging, 42 (33%) were radiologist-related, 45 (35%) were technologist-related, six (5%) were patient-related, and 36 (28%) had an unexpected lesion requiring additional sequences. For clinical utility, 42% resulted in a change from the initial report. Recalls due to radiologist error, incorrect FOV, or unexpected lesion caused a significant change in the final report; however, recalls due to technologist error, patient motion artefact, or incorrect protocol did not. CONCLUSION: MRI MSK recalls are uncommon, and the most common reasons are incorrect FOV, incorrect protocol, and unexpected lesion. Radiologist-related errors in protocols and FOV led to a significant change in the final report and should be targeted as areas for improvement to reduce recall examinations.

Evaluation and Refinement of Sample Preparation Methods for Extracellular Matrix Proteome Coverage.

The extracellular matrix is a key component of tissues, yet it is underrepresented in proteomic datasets. Identification and evaluation of proteins in the extracellular matrix (ECM) has proved challenging due to the insolubility of many ECM proteins in traditional protein extraction buffers. Here we separate the decellularization and ECM extraction steps of several prominent methods for evaluation under real-world conditions. The results are used to optimize a two-fraction ECM extraction method. Approximately one dozen additional parameters are tested, and recommendations for analysis based on overall ECM coverage or specific ECM classes are given. Compared with a standard in-solution digest, the optimized method yielded a fourfold improvement in unique ECM peptide identifications.

Editorial Commentary: Superior Capsular Reconstructions in Cases of Irreparable Rotator Cuff Tendons Only Partially Restore Anatomy, Yet Significantly Normalize Biomechanics-Without Resorting to Reverse Anatomy.

The goal of shoulder superior capsular reconstruction and/or anterior cable reconstructions, at least in terms of biomechanics, is to primarily restore a fulcrum to assist with pain control and functional optimization, with the secondary hope of maintaining cartilage. Fully restoring glenohumeral joint loads with SCR cannot be expected in the setting of persistent tendon insufficiency. Biomechanical studies characterizing shoulder capsular reconstructions have demonstrated anatomic and functional restorations toward normalization when tested with standard biomechanical methods. Glenohumeral abduction, superior humeral head migration, deltoid forces, and glenohumeral contact pressure and area, can be optimized toward the normal intact condition, as measured by motion tracking and pressure mapping in real time, using dynamic actuators. Insofar as restoring normal native anatomy is considered a fundamental priority, with the idea that joint functional longevity is enhanced by preserving anatomy, as surgeons, we should not lose sight of reconstruction over replacement (such as nonanatomic reverse total shoulder arthroplasty) as a favored goal. Anatomy-based reconstructions such as superior capsule or anterior cable reconstruction, may prove over time to be the best primary treatment as knowledge and innovations (technical and medical) develop, with nonanatomic arthroplasty truly being a last resort (yet a clinically viable option when indicated).

Anterior Cable Reconstruction: Prioritize Rotator Cable and Tendon Cord When Considering Superior Capsular Reconstruction.

Although distinct in name, the anterior cable of the superior capsule and tendon cord of the supraspinatus are structurally one in the same at the attachment on the greater tuberosity footprint. Force transmission through both structures where they converge and interdigitate at this location is disproportionately high, which has implications on functional impact. Superior capsule reconstruction, and, specifically, the anterior cable of the superior capsule, has been shown to assist in maintaining superior stability and a functional fulcrum of the glenohumeral joint, without overconstraining range of motion. Anterior cable reconstructions have been described for specific indications, including full-thickness tears of the supraspinatus and anterior one-half of the infraspinatus. Cord-like grafts, including long head biceps tendon autografts and semitendinosus allografts, can provide relative technical ease during surgery compared to sheet-like grafts for this indication. Side-to-side sutures between anterior cable reconstruction graft and posterosuperior capsule retension the native capsule to optimize its natural functional role. Accounting for abduction and rotation at the time of fixation and employing "loop-around" fixation sutures (no sutures through the graft), are critical concepts to consider in terms of kinematics and limiting graft failure. With both the biomechanically and clinically based literature demonstrating functionality with maintenance of the superior capsule (and specifically the anterior cable of the capsule), despite rotator cuff tendon insufficiency or irreparability, the anterior cable of the superior capsule should be prioritized when considering full-thickness rotator cuff tears that naturally involve both the capsular cable and the supraspinatus tendon cord. LEVEL OF EVIDENCE: Level V (expert opinion).

Biomechanical Assessment of a V-Shaped Semitendinosus Allograft Anterior Cable Reconstruction for Irreparable Rotator Cuff Tears.

PURPOSE: The purpose of this study was to biomechanically assess superior stability, subacromial contact pressures, and glenohumeral kinematics of a V-shaped anterior cable reconstruction with semitendinosus allograft (VST) in a massive rotator cuff tear (MCT) model. METHODS: Eight cadaveric shoulders (mean age, 66 years; range, 48 to 72 years) were tested with a custom testing system used to evaluate superior translation, subacromial contact pressure, and glenohumeral kinematics at 0°, 20°, and 40° glenohumeral abduction and 0°, 30°, 60°, and 90° of external rotation (ER). Conditions tested included (1) native state, (2) MCT (complete supraspinatus and ½ infraspinatus), a (3) VST. The VST was secured medially on the glenoid with 1 anchor and on the greater tuberosity with a double-row configuration using 4 anchors. RESULTS: The VST significantly decreased superior translation compared to the MCT at 0° and 20° glenohumeral abduction for 0°, 30°, and 60° humeral rotation and at 40° abduction and 0° degrees humeral rotation (P < .05). Superior translation following the VST remained significantly greater than the intact state at 0° abduction and 60° and 90° ER (P = .039 and 0.007, respectively) and 20° abduction and 30°, 60°, and 90° ER (P = .048, .003, and .004, respectively). The VST restored peak subacromial contact pressure to intact levels for all positions except 40° abduction and 60° ER. The VST did not statistically affect humeral head kinematics compared to the intact condition. CONCLUSIONS: In a biomechanical model, a VST anterior cable reconstruction partially restores superior stability and reduces peak subacromial contact pressure associated with an MCT, without affecting glenohumeral kinematics. The technique may be a consideration in the treatment of an irreparable MCT with isolated anterior cable disruption. CLINICAL RELEVANCE: The VST may provide an option for treatment of irreparable MCTs with anterior rotator cable disruption.

Outcomes and complications of primary reverse shoulder arthroplasty with minimum of 2 years' follow-up: a systematic review and meta-analysis.

BACKGROUND: Primary reverse shoulder arthroplasty (rTSA) is an effective treatment option for reducing pain and improving function for patients with rotator cuff tear arthropathy, irreparable rotator cuff tears, glenoid deformity, and other challenging clinical scenarios, including fracture sequelae and revision shoulder arthroplasty. There has been a wide range of reported outcomes and postoperative complication rates reported in the literature. The purpose of this systematic review and meta-analysis is to provide an updated review of the clinical outcomes and complication rates following primary rTSA. METHODS: A systematic review and meta-analysis was performed to evaluate outcomes and complications following primary rTSA according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Demographics, range of motion, patient-reported outcome measures (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form [ASES] and Constant scores), number of complications, and revisions were extracted, recorded, and analyzed from the included articles. RESULTS: Of the 1415 studies screened, 52 studies met the inclusion criteria comprising a total of 5824 shoulders. The mean age at the time of surgery was 72 years (range: 34-93), and the mean follow-up was 3.9 years (range: 2-16). Patients demonstrated a mean improvement of 56° in active flexion, 50° in active abduction, and 14° in active external rotation. Regarding functional outcome scores, rTSA patients demonstrated a mean clinically significant improvement of 37 in Constant score (minimal clinically important difference [MCID] = 5.7) and ASES score (42.0; MCID = 13.6). The overall complication rate for rTSA was 9.4% and revision rate of 2.6%. Complications were further subdivided into major medical complications (0.07%), shoulder- or surgical-related complications (5.3%), and infections (1.2%). The most frequently reported shoulder- or surgical-related complications were scapular notching (14.4%), periprosthetic fracture (0.8%), glenoid loosening (0.7%), and prosthetic dislocation (0.7%). DISCUSSION: Primary rTSA is a safe and reliable procedure with low complication, revision, infection, and scapular notching rates. Additionally, patients demonstrated clinically significant improvements in both range of motion and clinical outcome scores.

The novel interaction between Neisseria gonorrhoeae TdfJ and human S100A7 allows gonococci to subvert host zinc restriction.

Neisseria gonorrhoeae causes the sexually-transmitted infection gonorrhea, a global disease that is difficult to treat and for which there is no vaccine. This pathogen employs an arsenal of conserved outer membrane proteins called TonB-dependent transporters (TdTs) that allow the gonococcus to overcome nutritional immunity, the host strategy of sequestering essential nutrients away from invading bacteria to handicap infectious ability. N. gonorrhoeae produces eight known TdTs, of which four are utilized for acquisition of iron or iron chelates from host-derived proteins or xenosiderophores produced by other bacteria. Of the remaining TdTs, two of them, TdfH and TdfJ, facilitate zinc uptake. TdfH was recently shown to bind Calprotectin, a member of the S100 protein family, and subsequently extract its zinc, which is then internalized by N. gonorrhoeae. Like Calprotectin, other S100s are also capable of binding transition metals such as zinc and copper, and thus have demonstrated growth suppression of numerous other pathogens via metal sequestration. Considering the functional and structural similarities of the TdTs and of the S100s, as well as the upregulation in response to Zn limitation shown by TdfH and TdfJ, we sought to evaluate whether other S100s have the ability to support gonococcal growth by means of zinc acquisition and to frame this growth in the context of the TdTs. We found that both S100A7 and S10012 are utilized by N. gonorrhoeae as a zinc source in a mechanism that depends on the zinc transport system ZnuABC. Moreover, TdfJ binds directly to S100A7, from which it internalizes zinc. This interaction is restricted to the human version of S100A7, and zinc presence in S100A7 is required to fully support gonococcal growth. These studies highlight how gonococci co-opt human nutritional immunity, by presenting a novel interaction between TdfJ and human S100A7 for overcoming host zinc restriction.

Xenobiotic metabolism and transport in Caenorhabditis elegans.

Caenorhabditis elegans has emerged as a major model in biomedical and environmental toxicology. Numerous papers on toxicology and pharmacology in C. elegans have been published, and this species has now been adopted by investigators in academic toxicology, pharmacology, and drug discovery labs. C. elegans has also attracted the interest of governmental regulatory agencies charged with evaluating the safety of chemicals. However, a major, fundamental aspect of toxicological science remains underdeveloped in C. elegans: xenobiotic metabolism and transport processes that are critical to understanding toxicokinetics and toxicodynamics, and extrapolation to other species. The aim of this review was to initially briefly describe the history and trajectory of the use of C. elegans in toxicological and pharmacological studies. Subsequently, physical barriers to chemical uptake and the role of the worm microbiome in xenobiotic transformation were described. Then a review of what is and is not known regarding the classic Phase I, Phase II, and Phase III processes was performed. In addition, the following were discussed (1) regulation of xenobiotic metabolism; (2) review of published toxicokinetics for specific chemicals; and (3) genetic diversity of these processes in C. elegans. Finally, worm xenobiotic transport and metabolism was placed in an evolutionary context; key areas for future research highlighted; and implications for extrapolating C. elegans toxicity results to other species discussed.

Neonatal outcome by planned mode of delivery in women with a body mass index of 35 or more: a retrospective cohort study.

OBJECTIVE: To compare neonatal outcomes of women with a body mass index (BMI) of ≥35 kg/m2 who underwent a trial of labour with those of women who underwent a planned primary caesarean section (CS). DESIGN: A retrospective cohort study of births between April 2012 and March 2014. SETTING: A provincial database: Better Outcomes Registry & Network (BORN) Ontario, Canada. POPULATION: A cohort of 8752 women with a BMI of ≥35 kg/m2 who had a singleton birth at 38-42 weeks of gestation. METHODS: Neonatal outcomes were compared between women who underwent a trial of labour (with either a successful vaginal birth or intrapartum CS) and those who underwent a planned CS. MAIN OUTCOME MEASURE: A composite of any of the following outcomes: intrapartum neonatal death, neonatal intensive care unit admission, 5-minute Apgar score of <7 or umbilical artery pH of <7.1. RESULTS: During the study period, 8433 (96.4%) women had a trial of labour and 319 (3.6%) had a planned CS. Intrapartum CS was performed in 1644 (19.5%) cases. There was no association between planned mode of delivery and the primary outcome (aOR 0.80, 95% CI 0.59-1.07). The primary outcome was lower among women who had a successful trial of labour (aOR 0.67, 95% CI 0.50-0.91) and was higher among women who had a failed trial of labour (aOR 1.74, 95% CI 1.21-2.48), compared with women who underwent a planned CS. CONCLUSIONS: In women with a BMI of ≥35 kg/m2 at a gestational age of 38-42 weeks, neonatal outcomes are comparable between planned vaginal delivery and planned CS, although a failed trial of labour is at risk of adverse neonatal outcome. TWEETABLE ABSTRACT: Neonatal outcomes are not affected by planned mode of delivery in women who are obese, with a BMI of ≥35 kg/m2 .

Pregnancy and COVID-19: pharmacologic considerations.

In this review, we summarize evidence regarding the use of routine and investigational pharmacologic interventions for pregnant and lactating patients with coronavirus disease 2019 (COVID-19). Antenatal corticosteroids may be used routinely for fetal lung maturation between 24 and 34 weeks' gestation, but decisions in those with critical illness and those < 24 or > 34 weeks' gestation should be made on a case-by-case basis. Magnesium sulfate may be used for seizure prophylaxis and fetal neuroprotection, albeit cautiously in those with hypoxia and renal compromise. There are no contraindications to using low-dose aspirin to prevent placenta-mediated pregnancy complications when indicated. An algorithm for thromboprophylaxis in pregnant patients with COVID-19 is presented, which considers disease severity, timing of delivery in relation to disease onset, inpatient vs outpatient status, underlying comorbidities and contraindications to the use of anticoagulation. Nitrous oxide may be administered for labor analgesia while using appropriate personal protective equipment. Intravenous remifentanil patient-controlled analgesia should be used with caution in patients with respiratory depression. Liberal use of neuraxial labor analgesia may reduce the need for emergency general anesthesia which results in aerosolization. Short courses of non-steroidal anti-inflammatory drugs can be administered for postpartum analgesia, but opioids should be used with caution due to the risk of respiratory depression. For mechanically ventilated pregnant patients, neuromuscular blockade should be used for the shortest duration possible and reversal agents should be available on hand if delivery is imminent. To date, dexamethasone is the only proven and recommended experimental treatment for pregnant patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen. Although hydroxycholoroquine, lopinavir/ritonavir and remdesivir may be used during pregnancy and lactation within the context of clinical trials, data from non-pregnant populations have not shown benefit. The role of monoclonal antibodies (tocilizumab), immunomodulators (tacrolimus), interferon, inhaled nitric oxide and convalescent plasma in pregnancy and lactation needs further evaluation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Oxytocin at elective caesarean delivery: a dose-finding study in women with obesity.

Prophylactic oxytocin administration at the third stage of labour reduces blood loss and the need for additional uterotonic drugs. Obesity is known to be associated with an increased risk of uterine atony and postpartum haemorrhage. It is unknown whether women with obesity require higher doses of oxytocin in order to achieve adequate uterine tone after delivery. The purpose of this study was to establish the bolus dose of oxytocin required to initiate effective uterine contraction in 90% of women with obesity (the ED90 ) at elective caesarean delivery. We conducted a double-blind dose-finding study using the biased coin up-down design method. Term pregnant women with a BMI ≥ 40 kg.m-2 undergoing elective caesarean delivery under regional anaesthesia were included. Those with conditions predisposing to postpartum haemorrhage were not included. Oxytocin was administered as an intravenous bolus over 1 minute upon delivery of the fetus. With the first woman receiving 0.5 IU, oxytocin doses were administered according to a sequential allocation scheme. The primary outcome measure was satisfactory uterine tone, as assessed by the operating obstetrician 2 minutes after administration of the oxytocin bolus. Secondary outcomes included the need for rescue uterotonic drugs, adverse effects and estimated blood loss. We studied 30 women with a mean (SD) BMI of 52.3 (7.6) kg.m-2 . The ED90 for oxytocin was 0.75 IU (95%CI 0.5-0.93 IU) by isotonic regression and 0.78 IU (95%CI 0.68-0.88 IU) by the Dixon and Mood method. Our results suggest that women with a BMI ≥ 40 kg.m-2 require approximately twice as much oxytocin as those with a BMI < 40 kg.m-2 , in whom an ED90 of 0.35 IU (95%CI 0.15-0.52 IU) has previously been demonstrated.

Editorial Commentary: Anterior Cable Reconstruction for the Shoulder Superior Capsule: Time for "Indication Rounds".

Anterior cable reconstruction (ACR) techniques for the superior capsule are multiple and varied. To optimize patient outcomes, technical considerations must be supported by basic science, both anatomically and biomechanically. ACR was designed to treat only partially repairable rotator cuff tendon tears, to provide a static support to a dynamic partial (and therefore "nonanatomic") repair, and to treat tears that could not be treated by transosseous-equivalent footprint-restoring "anatomic" repairs (both capsule and tendon repaired), but were also not so large as to necessitate superior capsule reconstruction. ACR allows restoration of posterosuperior capsular function with side-to-side repair sutures, and much of the biomechanical functionality comes from using whatever inherent native superior capsule is available. Cable reconstructions should be secured to normal attachment sites on the glenoid and greater tuberosity sulcus. Also, graft tension must be accounted for when considering humeral motion such as rotation and adduction. The indications for ACR need to be carefully considered and account for both anatomic and biomechanical rationales. In the face of new ACR techniques, the need to discern what is possible versus what procedure is indicated cannot be overlooked.

Anterior Cable Reconstruction of the Superior Capsule Using Semitendinosus Allograft for Large Rotator Cuff Defects Limits Superior Migration and Subacromial Contact Without Inhibiting Range of Motion: A Biomechanical Analysis.

PURPOSE: To biomechanically assess translation, contact pressures, and range of motion for anterior cable reconstruction (ACR) using hamstring allograft for large to massive rotator cuff tears. METHODS: Eight cadaveric shoulders (mean age, 68 years) were tested with a custom testing system. Range of motion (ROM), superior translation of the humeral head, and subacromial contact pressure were measured at 0°, 30°, 60°, and 90° of external rotation (ER) with 0°, 20°, and 40° of glenohumeral abduction. Three conditions were tested: intact, stage III tear (supraspinatus + anterior half of infraspinatus), and stage III tear + allograft ACR (involving 2 supraglenoid anchors for semitendinosus tendon allograft fixation. Allograft ACR included loop-around fixation using 3 side-to-side sutures and an anchor at the articular margin to restore capsular anatomy along the anterior edge of the cuff defect. RESULTS: ACR with allograft for stage III tears showed significantly higher total ROM compared with intact at all angles (P ≤ .028). Augmentation significantly decreased superior translation for stage III tears at 0°, 30°, and 60° ER for both 0° and 20° abduction, and at 0° and 30° ER for 40° abduction (P ≤ .043). Augmentation for stage III tears significantly reduced overall subacromial contact pressure at 30° ER with 0° and 40° abduction, and at 60° ER with 0° and 20° abduction (P ≤ .016). CONCLUSION: Anterior cable reconstruction using cord-like allograft semitendinosus tendon can biomechanically improve superior migration and subacromial contact pressure (primarily in the lower combined abduction and rotation positions), without limiting range of motion for large rotator cuff tendon defects or tears. CLINICAL RELEVANCE: In patients with superior glenohumeral instability, using hamstring allograft for ACR may improve rotator cuff tendon defect longevity by providing basic static ligamentous support to the dynamic tendon while helping to limit superior migration, without restricting glenohumeral kinematics.

Biomechanical analysis of progressive rotator cuff tendon tears on superior stability of the shoulder.

BACKGROUND: The biomechanical relationship between irreparable rotator cuff tear size and glenohumeral joint stability in the setting of superiorly directed forces has not been characterized. The purpose of this study was to quantify kinematic alterations of the glenohumeral joint in response to superiorly directed forces in a progressive posterosuperior rotator cuff tear model. METHODS: Nine fresh-frozen cadaveric shoulders (mean age; 58 years) were tested with a custom shoulder testing system. Three conditions were tested: intact, stage II (supraspinatus) tear, stage III (supraspinatus + anterior half of infraspinatus) tear. At each condition, range of motion and humeral head positions were measured with a "balanced" loading condition, and with a superiorly directed force ("unbalanced loading condition"). At each of the 0°, 20°, and 40° of glenohumeral abduction positions, all measurements were made at 0°, 30°, 60°, and 90° of external rotation (ER). Two-way repeated measures analysis of variance with Tukey post hoc tests were performed for statistical analyses. RESULTS: With the balanced load, no significant change in superior humeral head position was observed in stage II tears. Stage III tears significantly changed the humeral head position superiorly at 30° and 60° ER at each abduction angle compared with the intact condition (P ≤ .028). With superiorly directed load, stage II and stage III tears both showed statistically significant increases in superior translation at all degrees of ER for all degrees of abduction (P ≤ .035), except stage II tears at 0° ER and 40° abduction (P = .185) compared with the intact condition. Stage II tears showed posterior translations with 30° and 60° ER, both at 20° and 40° of abduction. Stage III tears also showed posterior translations with 90° ER for all abduction angles (P ≤ .039). CONCLUSION: With superiorly directed loads, complete supraspinatus tendon tears created superior translations at all abduction angles, and posterior instability in the middle ranges of rotation for 20° and 40° of abduction. Larger tears involving the anterior half of the infraspinatus tendon caused significant superior and posterior translations within the middle ranges of ER for all abduction angles. In addition to superior instability, posterior translation should be considered when selecting or developing surgical techniques for large posterosuperior rotator cuff tears.