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Approaches to manage nonalcoholic fatty liver disease (NAFLD) are limited by an incomplete understanding of disease pathogenesis. The aim of this study was to identify hepatic gene-expression patterns associated with different patterns of liver injury in a high-risk cohort of adults with obesity. Using the NanoString Technologies (Seattle, WA) nCounter assay, we quantified expression of 795 genes, hypothesized to be involved in hepatic fibrosis, inflammation, and steatosis, in liver tissue from 318 adults with obesity. Liver specimens were categorized into four distinct NAFLD phenotypes: normal liver histology (NLH), steatosis only (steatosis), nonalcoholic steatohepatitis without fibrosis (NASH F0), and NASH with fibrosis stage 1-4 (NASH F1-F4). One hundred twenty-five genes were significantly increasing or decreasing as NAFLD pathology progressed. Compared with NLH, NASH F0 was characterized by increased inflammatory gene expression, such as gamma-interferon-inducible lysosomal thiol reductase (IFI30) and chemokine (C-X-C motif) ligand 9 (CXCL9), while complement and coagulation related genes, such as C9 and complement component 4 binding protein beta (C4BPB), were reduced. In the presence of NASH F1-F4, extracellular matrix degrading proteinases and profibrotic/scar deposition genes, such as collagens and transforming growth factor beta 1 (TGFB1), were simultaneously increased, suggesting a dynamic state of tissue remodeling. Conclusion: In adults with obesity, distinct states of NAFLD are associated with intrahepatic perturbations in genes related to inflammation, complement and coagulation pathways, and tissue remodeling. These data provide insights into the dynamic pathogenesis of NAFLD in high-risk individuals.

Surgical repair of massive and chronic rotator cuff tears is difficult due to tendon retraction and severe atrophy, and the resultant retear rate in the structurally weak tendons is high. Commercially available patches and bioinductive scaffolds have been used to provide strength and superior healing environment in partial and complete rotator cuff tears. Biological biceps autograft has been used for superior capsular reconstruction, and the subacromial bursa has been shown to have significant pluripotent stem cell potency for tendon healing. We describe our technique for combined use of the long biceps tendon (LBT) and vasculature-preserved subacromial bursa as autografts in rotator cuff repair augmentation. The technique involves obtaining a LBT graft of sufficient length using a “traction and tenodesis” technique. The subacromial bursa is mobilized as a continuous layer (vascular bursal duvet) by maintaining its medial and lateral vascularity. All-suture anchors are used to minimize the insertion apertures (3 mm) in tuberosity. The bursa is advanced laterally, and the mobilized cuff is repaired together as a biceps-cuff-bursa composite unit. Combined use of the biceps and bursa as biological autografts has the advantage of structural and regenerative augmentation, and the autografts are easily accessible without added cost., Technique Video Video 1 The surgical technique is demonstrated in a right shoulder in the beach-chair position. Sutures from subscapularis repair are passed around LBT, and the tendon is tenodesed after maximal intraarticular tractional pull. LBT is then detached just proximal to tenodesis sutures and the proximal stump is used as augmentation autograft. Next, the subacromial bursa is mobilized as a continuous layer and medial and lateral attachments of the bursal layer are preserved. A high posterolateral (HPL) portal is created and used for visualization throughout the procedure. Three all-suture anchors are inserted in a single-row configuration, and sutures are passed through the LBT-supraspinatus- bursa composite anteriorly, and through the infraspinatus-bursa complex posteriorly. Sliding knots are used to secure the biceps-cuff-bursa composite to the tuberosity. Dynamic flexion-extension and rotational assessment is finally performed to ensure correct tension on the composite repair.

Background Distal biceps endoscopy has emerged as a minimally invasive alternative to open procedures for distal biceps tendon (DBT) pathology. The purpose of this study was to systematically describe the static and dynamic appearance and variations of the DBT insertional region using a standardized endoscopic technique and dissection in healthy cadaveric elbows. Methods Endoscopic assessment of the DBT insertional region was performed using a standard proximal parabiceps portal in 20 fresh frozen cadaveric upper extremities. A 6-point endoscopic evaluation of the DBT and bicipitoradial bursa was performed in a static supination position and with dynamic rotation. Anatomic variations in the DBT insertional characteristics, as well as the extent and appearance of the intrabursal space, were documented. Each cadaver was then dissected to correlate endoscopic findings with gross anatomic structures. Results A bare oval tuberosity area (n = 20) bounded by the supinator and DBT was observed. The DBT inserted ulnar to the bare area (n = 16) and the presence of an intervening wide (n = 1) or narrow (n = 3) tuberosity sulcus were documented. The dorsoradial DBT surface was consistently intrabursal and was differentiated into 2-5 fiber bundles (n = 15). The volar-ulnar DBT surface was always extrabursal and was associated with endoscopically identifiable proximal and distal fat pads. The bicipitoradial bursa formed a bursal sac that was attached to the dorsoradial (n = 13) or volar (n = 7) aspect of the tuberosity and extended proximally along the DBT for 3-5 cm (parabiceps space). A distinct ligament-like band (transverse radioulnar ligament) extended transversely across the proximal radioulnar space and appeared to form a sling that provided ulnar support to the DBT during dynamic rotation. The intact DBT surface was robust and could not be breached, even with firm pressure using a probe. Conclusions The bare tuberosity area, the bursal sac, and the parabiceps space are consistent anatomic landmarks that can be used during DBT endoscopy. An insertional tuberosity sulcus and DBT surface differentiation are normal anatomic variations. The transverse radioulnar ligament provides ulnar support for the DBT during pronation and forms a pulley mechanism for smooth tendon gliding motion.

While neural networks achieve state-of-the-art performance for many molecular modeling and structure–property prediction tasks, these models can struggle with generalization to out-of-domain examples, exhibit poor sample efficiency, and produce uncalibrated predictions. In this paper, we leverage advances in evidential deep learning to demonstrate a new approach to uncertainty quantification for neural network-based molecular structure–property prediction at no additional computational cost. We develop both evidential 2D message passing neural networks and evidential 3D atomistic neural networks and apply these networks across a range of different tasks. We demonstrate that evidential uncertainties enable (1) calibrated predictions where uncertainty correlates with error, (2) sample-efficient training through uncertainty-guided active learning, and (3) improved experimental validation rates in a retrospective virtual screening campaign. Our results suggest that evidential deep learning can provide an efficient means of uncertainty quantification useful for molecular property prediction, discovery, and design tasks in the chemical and physical sciences., A fast, scalable approach for uncertainty quantification in neural networks enables uncertainty-aware molecular property prediction, accelerated property optimization, and guided virtual screening.

Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization and the opportunity to monitor response to therapy. Here, we report a multimodal nanosensor engineered to target tumours through acidosis, respond to proteases in the microenvironment to release urinary reporters and (optionally) carry positron emission tomography probes to enable localization of primary and metastatic cancers in mouse models of colorectal cancer. We present a paradigm wherein this multimodal sensor can be employed longitudinally to assess burden of disease non-invasively, including tumour progression and response to chemotherapy. Specifically, we showed that acidosis-mediated tumour insertion enhanced on-target release of matrix metalloproteinase-responsive reporters in urine. Subsequent on-demand loading of the radiotracer 64Cu allowed pH-dependent tumour visualization, enabling enriched microenvironmental characterization when compared with the conventional metabolic tracer 18F-fluorodeoxyglucose. Through tailored target specificities, this modular platform has the capacity to be engineered as a pan-cancer test that may guide treatment decisions for numerous tumour types.

INTRODUCTION The American Academy of Orthopaedic Surgeons (AAOS) Annual Meeting provides an opportunity for clinicians to attain the most recent advancements in the orthopaedic field. However, the most recent study analyzing publication rates from the 2001 Annual Meeting determined that only 49% of the podium and poster abstracts were eventually published. The purpose of this study was to determine the publication rate, likelihood of publication based on the presentation format, and time to publication for abstracts presented at the 2014 to 2017 AAOS Annual Meetings. METHODS We did a comprehensive search of PubMed and Google Scholar to determine whether abstracts presented in the podium, poster, and scientific exhibit formats from the 2014 to 2017 AAOS Annual Meetings were published in a peer-reviewed journal. Abstract title, authors, and keywords were used to query for publication status and date of publication. RESULTS We analyzed 5,902 abstracts from the 2014 to 2017 AAOS Annual Meetings. The overall publication rate for podium and poster presentations was 69.9%, with individual publication rates at 73.0% and 65.1%, respectively. A higher likelihood of publication in the podium format was noted with odds ratio 1.45 (P < 0.0001). Scientific exhibits displayed a publication rate of 46.9%. Most publications in all formats occurred within 2 years. CONCLUSION A large increase was noted in the quality of research being presented at the AAOS Annual Meeting. With 69.9% of podium and poster presentations from the 2014 to 2017 Annual Meetings being published in a peer-reviewed journal, clinicians can use the data presented as an up-to-date, adjunct source of guidance for their clinical practices.

Bacterial infections are re-emerging as substantial threats to global health due to the limited selection of antibiotics that are capable of overcoming antibiotic-resistant strains. By deterring such mutations whilst minimizing the need to develop new pathogen-specific antibiotics, immunotherapy offers a broad-spectrum therapeutic solution against bacterial infections. In particular, pathology resulting from excessive immune response (i.e. fibrosis, necrosis, exudation, breath impediment) contributes significantly to negative disease outcome. Herein, we present a nanoparticle that is targeted to activated macrophages and loaded with siRNA against the Irf5 gene. This formulation is able to induce >80% gene silencing in activated macrophages in vivo, and it inhibits the excessive inflammatory response, generating a significantly improved therapeutic outcome in mouse models of bacterial infection. The versatility of the approach is demonstrated using mice with antibiotic-resistant Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) muscle and lung infections, respectively. Effective depletion of the Irf5 gene in macrophages is found to significantly improve the therapeutic outcome of infected mice, regardless of the bacteria strain and type.

All patients with acute complete distal biceps tendon ruptures who are not low demand or medically unfit to proceed with surgery are offered operative repair. This restores arm shape, supination strength and function, and decreases their cramping symptoms. Surgical repair technique varies significantly depending on location and training centre. Nuances in technique and appropriate implant selection need to be noted in order to achieve a strong repair allowing early active range of motion. Intimate knowledge of distal biceps tendon anatomy is key to avoid complications associated with the different approaches. The cumulative body of evidence on complications, coupled with knowledge of the different biomechanical construct strengths of the alternative methods of fixation, points to the use of the cortical button technique without the addition of an interference screw. Subtle variations in drill hole positioning on the bicipital tuberosity secures either an anatomic or non-anatomic repair. Anatomic repair results in greater supination peak torque and fatigue strength, and in greater flexion fatigue strength. It is advisable to perform an anatomic repair in elite athletes or those patients who significantly rely on supination strength and endurance for their livelihood. A universal postoperative protocol is suggested for all repairs.

The ongoing coronavirus disease 2019 (COVID-19) pandemic poses a severe threat to public health worldwide. We combine data on demography, contact patterns, disease severity, and health care capacity and quality to understand its impact and inform strategies for its control. Younger populations in lower-income countries may reduce overall risk, but limited health system capacity coupled with closer intergenerational contact largely negates this benefit. Mitigation strategies that slow but do not interrupt transmission will still lead to COVID-19 epidemics rapidly overwhelming health systems, with substantial excess deaths in lower-income countries resulting from the poorer health care available. Of countries that have undertaken suppression to date, lower-income countries have acted earlier. However, this will need to be maintained or triggered more frequently in these settings to keep below available health capacity, with associated detrimental consequences for the wider health, well-being, and economies of these countries.

Human breath contains many volatile metabolites. However, few breath tests are currently used in the clinic to monitor disease due to bottlenecks in biomarker identification. Here we engineered breath biomarkers for respiratory disease by local delivery of protease-sensing nanoparticles to the lungs. The nanosensors shed volatile reporters upon cleavage by neutrophil elastase, an inflammation-associated protease with elevated activity in lung diseases such as bacterial infection and alpha-1 antitrypsin deficiency. After intrapulmonary delivery into mouse models with acute lung inflammation, the volatile reporters are released and expelled in breath at levels detectable by mass spectrometry. These breath signals can identify diseased mice with high sensitivity as early as 10 min after nanosensor administration. Using these nanosensors, we performed serial breath tests to monitor dynamic changes in neutrophil elastase activity during lung infection and to assess the efficacy of a protease inhibitor therapy targeting neutrophil elastase for the treatment of alpha-1 antitrypsin deficiency. Volatile reporter molecules released by protease-sensing nanoparticles can serve as breath biomarkers for monitoring respiratory disease.

Significance Checkpoint inhibitor (CPI) immunotherapies have revolutionized the treatment of a wide array of cancers, but their utility remains limited to a subset of patients with favorable disease phenotypes. We show that the generation of peptide-based nanocomplexes carrying immunostimulatory oligonucleotides dramatically increases the potency of certain of these compounds to stimulate toll-like receptor signaling. The administration of immunostimulatory nanocomplexes carrying CpG oligonucleotides generates antitumor effects and enhances the efficacy of checkpoint inhibitor antibody therapy in mouse models of cancer, and the nanocomplex formulation enables drastic reductions in the dose required to generate therapeutic effects., The recent advent of immune checkpoint inhibitor (CPI) antibodies has revolutionized many aspects of cancer therapy, but the efficacy of these breakthrough therapeutics remains limited, as many patients fail to respond for reasons that still largely evade understanding. An array of studies in human patients and animal models has demonstrated that local signaling can generate strongly immunosuppressive microenvironments within tumors, and emerging evidence suggests that delivery of immunostimulatory molecules into tumors can have therapeutic effects. Nanoparticle formulations of these cargoes offer a promising way to maximize their delivery and to enhance the efficacy of checkpoint inhibitors. We developed a modular nanoparticle system capable of encapsulating an array of immunostimulatory oligonucleotides that, in some cases, greatly increase their potency to activate inflammatory signaling within immune cells in vitro. We hypothesized that these immunostimulatory nanoparticles could suppress tumor growth by activating similar signaling in vivo, and thereby also improve responsiveness to immune checkpoint inhibitor antibody therapies. We found that our engineered nanoparticles carrying a CpG DNA ligand of TLR9 can suppress tumor growth in several animal models of various cancers, resulting in an abscopal effect on distant tumors, and improving responsiveness to anti-CTLA4 treatment with combinatorial effects after intratumoral administration. Moreover, by incorporating tumor-homing peptides, immunostimulatory nucleotide-bearing nanoparticles facilitate antitumor efficacy after systemic intravenous (i.v.) administration.

The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains poor despite decades of effort. The abundant extracellular matrix (ECM) in PDAC comprises a major fraction of the tumor mass and plays various roles in promoting resistance to therapies. However, nonselective depletion of ECM has led to poor patient outcomes. Consistent with that observation, we previously showed that individual matrisome proteins derived from stromal cells correlate with either long or short patient survival. In marked contrast, those derived from cancer cells correlate strongly with poor survival. Here, we studied three cancer cell–derived matrisome proteins that are significantly overrepresented during PDAC progression, AGRN (agrin), SERPINB5 (serine protease inhibitor B5), and CSTB (cystatin B). Using both overexpression and knockdown experiments, we demonstrate that all three are promoters of PDAC metastasis. Furthermore, these proteins operate at different metastatic steps. AGRN promoted epithelial-to-mesenchymal transition in primary tumors, whereas SERPINB5 and CSTB enhanced late steps in the metastatic cascade by elevating invadopodia formation and in vivo extravasation. All three genes were associated with a poor prognosis in human patients and high levels of SERPINB5, secreted by cancer cells and deposited in the ECM, correlated with poor patient prognosis. This study provides strong evidence that cancer cell–derived matrisome proteins can be causal in promoting tumorigenesis and metastasis and lead to poor patient survival. Therefore, compared with the bulk matrix, mostly made by stromal cells, precise interventions targeting cancer cell–derived matrisome proteins, such as AGRN, SERPINB5, and CSTB, may represent preferred potential therapeutic targets. Significance: This study provides insights into the biological roles of cancer cell–derived matrisome proteins in PDAC and supports the notion that these proteins are protumorigenic and better therapeutic targets.

Background: In the past decade, there has been an increase in the number and types of bariatric procedures in India. It is, thus, important to monitor prevalent bariatric practices. Aim: To identify prevalent pre- and post-operative dietary practices by bariatric professionals across India. Materials and Methods: Data regarding various pre- and post-surgery dietary practices were collected using an Internet-based survey. Thirty-three bariatric professionals including dietitians (n = 25) and surgeons (n = 8) across the country participated in the survey. The data were analysed, and prevalent dietary practices were identified. Results: Five (20%) dietitians were not involved in the pre-surgery consultation. Nineteen (70%) professionals put all patients on a low-calorie pre-surgery diet regardless of their body mass index, with a preference (n = 21; 77.7%) for liquid diet. Twenty-three (70%) professionals put patients on post-surgery liquid diet for 1–2 weeks. Thereafter, 28 (84.8%) professionals recommended soft diet for 2–4 weeks. Twenty-seven (81%) professionals used protein shakes (as opposed to dietary sources) as their primary source of protein for the first 3 months post-surgery. Fourteen (36%) professionals stopped protein shake supplements within 6 months post-surgery. Ten (30%) professionals reported whey protein aversions in >25% of the patients. Twenty-three (71%) professionals advocated a meal with

Peripartum cardiomyopathy is a form of dilated cardiomyopathy. It is a systolic heart failure of unknown aetiology and poorly understood pathophysiology. The prognosis of patients with PPCM is generally good with 70-80% recovering with ejection fraction >50% at the end of 6 months. However, the intrapartum period, especially in case of operative delivery, is fraught with danger

Recent months have demonstrated that emerging variants may set back the global COVID-19 response. The ability to rapidly assess the threat of new variants in real-time is critical for timely optimisation of control strategies.We extend the EpiEstim R package, designed to estimate the time-varying reproduction number (Rt), to estimate in real-time the effective transmission advantage of a new variant compared to a reference variant. Our method can combine information across multiple locations and over time and was validated using an extensive simulation study, designed to mimic a variety of real-time epidemic contexts.We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29, (95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and France respectively. We further estimate that Beta and Gamma combined are 1.25 (95% CrI 1.24-1.27) times more transmissible than the wildtype (France data). All results are in line with previous estimates from literature, but could have been obtained earlier and more easily with our off-the-shelf open-source tool.Our tool can be used as an important first step towards quantifying the threat of new variants in real-time. Given the popularity of EpiEstim, this extension will likely be used widely to monitor the co-circulation and/or emergence of multiple variants of infectious pathogens.Significance StatementEarly assessment of the transmissibility of new variants of an infectious pathogen is critical for anticipating their impact and designing appropriate interventions. However, this often requires complex and bespoke analyses relying on multiple data streams, including genomic data. Here we present a novel method and software to rapidly quantify the transmission advantage of new variants. Our method is fast and requires only routinely collected disease surveillance data, making it easy to use in real-time. The ongoing high level of SARS-CoV-2 circulation in a number of countries makes the emergence of new variants highly likely. Our work offers a powerful tool to help public health bodies monitor such emerging variants and rapidly detect those with increased transmissibility.

Noninvasive detection of nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease, promises to improve patient screening, accelerate drug trials, and reduce health care costs. On the basis of protease dysregulation of the biological pathways of fibrotic NASH, we developed the Glympse Bio Test System (GBTS) for multiplexed quantification of liver protease activity. GBTS-NASH comprises a mixture of 19 mass-barcoded PEGylated peptides that is administered intravenously and senses liver protease activity by releasing mass-barcoded reporters into urine for analysis by mass spectrometry. To identify a protease signature of NASH, transcriptomic analysis of 355 human liver biopsies identified a 13-protease panel that discriminated clinically relevant NASH ≥F2 fibrosis from F0-F1 with high classification accuracy across two independent patient datasets. We screened 159 candidate substrates to identify a panel of 19 peptides that exhibited high activity for our 13-protease panel. In the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) mouse model, binary classifiers trained on urine samples discriminated fibrotic NASH from simple steatosis and healthy controls across a range of nondisease conditions and indicated disease regression upon diet change [area under receiver operating characteristics (AUROCs)0.97]. Using a hepatoprotective triple combination treatment (FXR agonist, ACC and ASK1 inhibitors) in a rat model of NASH, urinary classification distinguished F0-F1 from ≥F2 animals and indicated therapeutic response as early as 1 week on treatment (AUROCs0.91). Our results support GBTS-NASH to diagnose fibrotic NASH via an infusion of peptides, monitor changes in disease severity, and indicate early treatment response.

Intraosseous ganglion (IOG) cysts in the lunate can be decompressed using open and arthroscopic approaches. A direct “cystoscopic” approach to the IOG is minimally invasive and provides excellent visualization of the cyst from within. Direct visualization access is obtained via a 3 mm cortical tunnel in the lunate, and ensures complete intracystic excision of lining and contents. Bone grafting of a large cyst may be performed using the same approach if necessary.

Radial neck fractures are common injuries in children. Surgery is necessary for displaced fractures that cannot be closed reduced; however, open surgery is associated with suboptimal outcomes and potential complications. Arthroscopic fixation of radial neck fractures is a minimally invasive technique for repositioning the radial head in correct alignment. Reduction of the radial head is performed under direct visualization to restore the congruency of proximal radioulnar and radiocapitellar joints and K-wires can be passed under visualization via safe portals for fixation.

A chronic perilunate dislocation is a disabling wrist injury that involves complete midcarpal separation and loss of contact between the lunate and capitate for a period of 6 weeks or more. Arthroscopic reduction is possible after perilunate adhesiolysis and percutaneous K-wire stabilization of the carpal rows maintains the reduction until soft tissue healing is achieved. This chapter describes the technical steps of the procedure that are necessary to achieve and maintain carpal alignment.

Partial tears of the distal biceps tendon (DBT) are overuse injuries and surgical intervention may be necessary for symptomatic relief. The two-portal “all-endoscopic” approach is a safe and minimally invasive procedure for diagnosis, classification, and definitive treatment of partial DBT tears and avoids the necessity of a more extensive open procedure. The “endoscopic probe test” is described for evaluation of severity (low vs high grade) of partial DBT tears. Technical steps for endoscopic debridement and DBT repair are presented.

Chronic ruptures of the distal biceps tendon (DBT) are characterized by severe retraction and a severe Popeye deformity. Often these tears are irreparable due to muscle atrophy, tendon degeneration, and deficient tendon length. Surgical intervention involves extensive open procedures using autografts or allografts for augmentation and restoration of tendon length. This chapter presents an all-endoscopic autograft reconstruction technique for chronic irreparable DBT ruptures.

Endoscopic-assisted distal biceps tendon (DBT) procedures are performed by using a single anterior incision similar to the open surgical approach for DBT tears [1–4]. The arthroscope and working instruments are used via the same incision during the procedure. Endoscopic magnification via the incision permits clear visualization of the anatomy and optimizes debridement and tendon repair (Fig. 52.1).

Posterior elbow impingement is an overuse injury associated with valgus-extension overload in several throwing and non-throwing sports. Impingement pathology is variable and includes olecranon tip overgrowth, trochlear and fossa osteophytes, synovial hypertrophy, osteophyte fracture, and olecranon stress fractures. Arthroscopy is useful for evaluation, and arthroscopic dynamic tracking permits identification of impinging regions. Arthroscopic resection results in predictable symptomatic relief and early return to competitive sports.

The diagnosis of chronic elbow instability is based on meticulous clinical and radiological evaluation. Arthroscopy is a valuable adjunct to clinical signs and imaging, and an alteration in arthroscopically visualized radiocapitellar and ulnotrochlear relations after external manipulation can be quantified. This chapter presents a ten-point arthroscopic assessment technique that is useful in the diagnosis and possibly grading of medial and lateral elbow instability. Systematic evaluation of anterior and posterior compartments is performed and six anterior and four posterior compartment signs are described.

Degenerative arthritis of trapeziometacarpal joint (TMJ) often necessitates surgical management and trapezium-sparing procedures are associated with satisfactory outcomes. Arthroscopic partial trapeziectomy is performed via specialized TMJ portals; approximately 4–6 mm of distal trapezium is excised and peripheral ligaments and capsular attachments are preserved. This chapter presents the arthroscopic anatomy and technical steps of TMJ arthroscopy and partial trapeziectomy.

Triceps tendon tear is an uncommon injury and is usually associated with systemic diseases and anabolic steroid use. Surgical repair is necessary to restore strength and optimal function. Transosseous repair of triceps tendon is an all-suture repair technique that can be configured to provide a broad footprint-like approximation at the olecranon. The technique is useful in partial and acute retracted tears, and in acute bony avulsions. Chronic retracted tears that can be mobilized and reduced to the olecranon can be repaired and augmented using this technique.

The distal biceps tendon (DBT) anatomy is complex; the tendon passes through different planes across the arm and cubital fossa and inserts into a distinct footprint at the bicipital tuberosity. The DBT is closely related to several vital neurovascular structures along its course, and these structures are potentially at-risk during open and endoscopic surgery. Dynamic rotation draws the DBT through the narrow proximal radioulnar space and predisposes the tendon to impingement and wear. Dynamic rotation significantly alters the relationship of DBT insertion with the adjacent neurovascular structures and the insertion can be used as an intraoperative reference point for predicting the position of major neurovascular structures during surgery. Detailed knowledge of the structural morphometry and neurovascular anatomy of the DBT is necessary to safely replicate DBT kinematics during repair and reconstructive surgery for distal biceps pathology.

The metacarpophalangeal joint (MCP) is frequently involved in sports injuries, and in degenerative and inflammatory conditions of small joints of hand. MCP arthroscopy is useful for diagnostic evaluation and advances in small joint instrumentation now permit therapeutic arthroscopic procedures as well. This chapter presents the portal placement and access techniques for MCP arthroscopy, and describes the intraarticular anatomy in detail. Additionally, a four-point evaluation technique is described, and management of instability, chondral defects, and fractures is discussed.

Volar dislocation of the distal radioulnar joint (DRUJ) is an unusual injury and occasionally may be irreducible. Arthroscopic reduction is a minimally invasive alternative for mobilization and reduction of the impacted ulnar head and percutaneous transfixation K-wires maintain the reduction until soft tissues have healed. This chapter describes the surgical technique for arthroscopic management of this unusual DRUJ dislocation.

Capitellum fractures are uncommon injuries and osteosynthesis is necessary for displaced fractures. Arthroscopic capitellum excision is indicated in comminuted fractures and those with inadequate bone for stable fixation. Arthroscopy is also useful for removal of fixation screws and capitellar debridement in postsurgical collapse and avascular necrosis of the fragment. Capitellum fractures that are missed on radiological imaging may present much later with a malunion or a nonunion of the fragment and an arthroscopic capitelloplasty may be performed for pain relief and restoration of range.

The all-endoscopic distal biceps approach is a safe and reproducible technique for management of distal biceps pathology. The technique is based on portals placed in safe zones around the complex cubital-fossa anatomy for extra-articular viewing and working. This chapter classifies portals used in the all-endoscopic approach and the associated neurovascular anatomy-at-risk is described.

The all-endoscopic distal biceps repair is a minimally invasive technique for acute and chronic retracted tendon tears. The procedure involves endoscopic mobilization and retrieval of the retracted tendon using arm endoscopy. The tendon is then shuttled through safe zones into the deeper plane of the cubital fossa and is repaired to the tuberosity under endoscopic visualization using suture anchors or buttons. This chapter describes technical steps and safety guidelines for the all-endoscopic distal biceps repair.

Arthroscopy of the small joints of the hand has evolved with advances in arthroscopes and instruments. Arthroscopic access to trapeziometacarpal (TMJ), metacarpophalangeal (MCP), and the proximal and distal interphalangeal joints (PIP, DIP) is difficult due to the narrow joint spaces and proximity to neurovascular structures and tendons. Specialized portals for thumb and finger joints permit arthroscopic visualization of these joints and complex therapeutic procedures can be performed. Each of these joints has a unique bony, soft-tissue, and neurovascular anatomy and familiarity with anatomic landmarks and neurovascular structures is necessary for accurate and safe portal placement.

Thenar endoscopy is an evolving technique that may be used for treatment of specific pathological conditions involving thenar musculature and deep spaces. Proximal and distal thenar portals provide access to intermuscular planes and intramuscular cysts. “Cystoscopic” visualization is useful for obtaining biopsy of cyst tissues under direct vision and the communication with the adjacent joint can be identified. Excision of cyst lining and septae ensures complete excision of the ganglion cyst.

Arthroscopic radial head resection is a minimally invasive alternative to open excision in acute fractures and chronic pathology of the radiocapitellar joint. Access to the entire radial head via standard portals is difficult and the “radial head portal” devised by the author provides safe access for rapid resection and removal of large fragments. This chapter describes the arthroscopic resection technique in acute comminuted radial head fractures and in chronic radiocapitellar pathology.

Arthroscopy in scaphoid fracture fixation has the advantage of visualization of the fracture reduction and bone grafting the fracture site if necessary. In most arthroscopic techniques, fixation is performed by passing the screw percutaneously from volar or dorsal aspects. Arthroscopic fixation via standard dorsal portals is difficult as the proximal scaphoid is covered by the dorsal radial rim, and therefore the angulation necessary for wire passage along the central axis of the scaphoid is difficult to achieve. This chapter describes a modified arthroscopic technique that utilizes a “scaphoid portal” for dorsal antegrade screw fixation (proximal to distal). The technique is especially useful in proximal pole scaphoid fractures as the scapholunate ligament is identified and the precise entry point and screw passage centered on the proximal scaphoid pole can be arthroscopically visualized.

Common extensor tendinopathy (lateral epicondylitis/tennis elbow) is an overuse enthesopathy of the extensor carpi radialis brevis (ECRB) and extensor digitorum communis (EDC) tendons. Refractory lateral epicondylitis with disabling symptoms often necessitates an open or arthroscopic debridement of the pathology. The arthroscopic anatomic insertional release (AAIR) procedure devised by the author involves accurate identification and release of ECRB and EDC tendon insertional footprints, and associated intra-articular pathology can be identified and treated simultaneously.

Metacarpal head fractures are infrequent sports injuries and accurate reduction and fixation of these intraarticular fractures is necessary. Metacarpophalangeal joint (MCP) arthroscopy provides excellent visualization of the fracture geometry and evaluation of soft-tissue injuries. Accurate articular reduction and fixation with percutaneous K-wires can be performed under arthroscopic and fluoroscopic guidance. Arthroscopic fixation results in minimal soft-tissue scarring and faster recovery of range of motion and function.

Arthroscopic surgery of the elbow, wrist, and hand is evolving rapidly, and there has never been a more exciting time to be a surgeon of the upper limb. What began as simple intra-articular visualization has evolved to complex minimally invasive reconstruction, and procedures that were once exclusively the domain of the subspecialist are becoming increasingly utilized by more and more surgeons, bringing minimally invasive upper extremity care to a greater number of patients worldwide. Advances in anesthetic techniques including regional blocks and wide-awake surgery are making arthroscopy safer and more affordable for patients. Small-joint instrumentation technology continues to evolve, making arthroscopy and endoscopy of the upper limb safer and less-invasive. Innovative techniques that utilize dry-arthroscopy and endoscopy are being developed, expanding the traditional boundaries of the arthroscope to allow procedures that once required extensive open dissection to be performed through smaller incisions. Lastly, biologics and stem cell augmentation holds promise to help improve healing rates and recovery after upper limb surgery. As surgeons around the world become increasingly familiar with small joint arthroscopy, the future of hand, elbow, and wrist arthroscopy shines bright.

Arthroscopic elbow adhesiolysis is an effective intervention for refractory elbow stiffness and adequate anterior capsulectomy is a crucial step in the procedure. Anterior capsulectomy is usually performed using an inside-out technique; however, joint access is difficult in severe stiffness and altered neurovascular relationships may result in iatrogenic injury. This chapter presents an all-endoscopic anterior capsulectomy technique developed by the author that utilizes the sub-brachialis space for an outside-in capsular resection under vision. Standard anatomic landmarks are identified and are used as a guide for safe resection in a central to peripheral direction.

The pisiform bone forms a mobile articulation with the triquetrum that is stabilized by several ligaments and flexor carpi ulnaris tendon. The inherent mobility predisposes the joint to instability and wear and results in ulnar-sided wrist pain. Arthroscopy of the PTJ is a minimally invasive approach to evaluation and treatment of PTJ pain and results in predictable outcomes and early return to sports. This chapter describes a safe approach to the pisotriquetral articulation using standard portals and various therapeutic techniques are presented.

Ganglion cyst of the elbow is an uncommon benign lesion and surgical excision is necessary for a symptomatic and progressively enlarging cyst. Arthroscopic transarticular cyst excision is a minimally invasive technique and is performed using standard portals and intraoperative anatomical landmarks for safety. A 70° arthroscope is used for “cystoscopic” visualization of the cyst interior and complete intracystic excision of cyst contents and membranes is possible via this approach.

Benign tumours and tumour-like lesions are occasionally seen in the intra-articular region of the elbow and clinically present with chronic disabling pain and progressive stiffness. Arthroscopic excision is possible when the lesion is focal and in an accessible location. This chapter presents the arthroscopic findings and technique for excision of three different intra-articular bony and soft-tissue lesions.

The elbow is a complex anatomical region formed by a multilayered soft-tissue sleeve of muscles, ligaments, and neurovascular structures. The anatomical locations of these structures are unpredictable due to paucity of anatomical landmarks and frequent variations; to add to this variability, dynamic movement at the joint further changes the surface markings for most structures. The layered approach to elbow anatomy is useful during minimally invasive open, endoscopic assisted, and all-endoscopic procedures around the elbow. Each layer is formed by specific muscles and/or ligaments, and neurovascular structures course through or in between these layers from proximal to distal. The distal biceps tendon traverses the layers from superficial to deep planes, and even extends to the posterior aspect in full pronation. The “parabiceps space” is therefore a useful and safe passage across anatomic planes in the lower arm and cubital fossa for elbow endoscopy. Consistent anatomic landmarks across the four layers are useful intraoperative indicators of neurovascular structures in each layer. Lastly, the major nerves are at risk of entrapment during their course, and anatomical structures that predispose to compression must be evaluated and released during surgery.

IntroductionNon-pharmaceutical interventions (NPIs) are a crucial suite of measures to prevent and control infectious disease outbreaks. They are particularly important for crisis-affected populations that typically reside in settings characterised by overcrowding, inadequate access to healthcare and resource limitations. To describe the landscape of research and identify evidence gaps concerning the acceptability, feasibility, and effectiveness of NPIs among crisis-affected populations and informal settings, we conducted a systematic scoping review of the published evidence.MethodsWe systematically reviewed peer-reviewed articles published between 1970 and 2020 to collate available evidence on the feasibility, acceptability, and effectiveness of NPIs in crisis-affected populations and informal settlements. We performed quality assessments of each study using a standardised questionnaire.ResultsOur review included 158 studies published in 85 peer-reviewed articles. Most research used low quality study designs. The acceptability, feasibility, and effectiveness of NPIs was highly context dependent. In general, simple and cost-effective interventions such as community-level environmental cleaning and provision of water, sanitation and hygiene services, and distribution of items for personal protection such as insecticide-treated nets, were both highly feasible and acceptable. Logistical, financial, and human resource constraints affected both the implementation and sustainability of measures. Community engagement emerged as a strong factor contributing to the effectiveness of NPIs. Conversely, measures that involve potential restriction on personal liberty such as case isolation were found to be less acceptable to the community.ConclusionOverall, the evidence base was patchy, with substantial knowledge gaps between differing between settings and pathogens. Although implementation of NPIs presents unique practical challenges, it is critical that the lessons learned are shared with the wider community to build a robust evidence base.Summary boxWhat is already known?- NPIs are a crucial suite of tools for the prevention and control of infectious diseases, either as a complement to, or in the absence of, effective pharmaceutical interventions (i.e., therapeutics and vaccination).- Despite being disproportionately vulnerable, crisis-affected populations and those living in informal settlements are often neglected by research and guidance. NPIs are, however, vital and adaptation is necessary within these settings due to poor living conditions and resource limitations that intensify disease transmission risk.What are the new findings?- We conducted a scoping review to produce a landscape analysis of the existing evidence concerning NPIs within crisis-affected settings and informal settlements.- The existing evidence is patchy, uneven, occasionally contradictory, and of generally low quality, but building over time.- Although limited, some findings are generalisable across settings, populations and NPIs.What do the new findings imply?- There is a need for greater investments in research to strengthen the guidance and policies on NPIs in these settings.- In particular, upstream pilot feasibility and acceptability studies should be conducted prior to the widespread roll-out of interventions to ensure they are feasible, acceptable, and ultimately effective for the target populations.