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Allison Maher,1 Michelle Bennett,1 Hsin-Chia Carol Huang,1,2 Philip Gaughwin,1,3 Mary Johnson,1 Madeleine Brady,1 Kacie Patterson,1,3 Tanya Buettikofer,1,3 Jo Morris,1 Veronica Mary Rainbird,3 Imogen Mitchell,1,2 Bernie Bissett1,3 1Rehabilitation and Community Services / Respiratory Medicine, Canberra Health Services, Canberra ACT, Australia; 2College of Health and Medicine, Australian National University, Canberra ACT, Australia; 3Faculty of Health, University of Canberra, Canberra ACT, Bruce, AustraliaCorrespondence: Bernie Bissett, Email Bernie.Bissett@canberra.edu.auObjective: To describe our methodology and share the practical tools we have developed to operationalize a multidisciplinary Long COVID clinic that incorporates progressive, personalized exercise prescription as a cornerstone feature.Background: There is a lack of evidence-based guidance regarding optimal rehabilitation strategies for people with Long COVID. Existing guidelines lack precision regarding exercise dosage. As one of Australia’s few established multidisciplinary Long COVID clinics, we describe our novel approach to safely incorporating exercise of both peripheral and respiratory muscles, with essential monitoring and management of post-exertional symptom exacerbation.Methods: Working closely with primary health-care providers, our multidisciplinary team screens referrals for people aged 16 and older with Long COVID. Staff apply a three tier model of triage, dependent on the consumer’s presenting problems. Exercise-based interventions necessitate detailed monitoring for post-exertional symptom exacerbation both in the clinic and at home. Personalized exercise prescription includes resistance training at a submaximal threshold (4– 6 exercises, 3 days/week); whole-body endurance exercise titrated to the individual’s progress, at an intensity 4– 6/10 (Rate of Perceived Exertion); and for those limited by dyspnoea, high-intensity inspiratory muscle training using a threshold-based handheld device (30 repetitions per day, ≥ 50% of their maximum inspiratory pressure).Discussion: We have used these approaches for the past 2 years in 250 consumers with no serious adverse events and promising consumer feedback. Our exercise prescription is less conservative than the methods advocated in international guidelines for people with Long COVID, and these more progressive tools may be valuable in other contexts.Conclusion: In our experience, a multidisciplinary clinic-based approach to safely prescribing progressive exercise in Long COVID is feasible. Both peripheral and inspiratory muscle exercise can be effectively titrated to each individual’s symptoms, and careful monitoring for post-exertional symptom exacerbation is crucial.Plain Language Summary: Long COVID affects 5-10% of people following COVID infection. There is little specific guidance on how exercise can be safely prescribed in Long COVID. This paper is the first to provide a detailed description of an Australian multidisciplinary Long COVID clinic, including specific tools and guidance about how exercise can be prescribed while minimising post-exertional symptom exacerbation. The tools described could be valuable to other health facilities striving to optimise multidisciplinary care for people with Long COVID, incorporating safe exercise prescription.Keywords: COVID, rehabilitation, multidisciplinary care, physiotherapy, respiratory muscle training

Abstract T cell receptor (TCR) signaling regulates important developmental transitions, partly through induction of the E protein antagonist, Id3. Although normal γδ T cell development depends on Id3, Id3 deficiency produces different phenotypes in distinct γδ T cell subsets. Here, we show that Id3 deficiency impairs development of the Vγ3+ subset, while markedly enhancing development of NKγδT cells expressing the invariant Vγ1Vδ6.3 TCR. These effects result from Id3 regulating both the generation of the Vγ1Vδ6.3 TCR and its capacity to support development. Indeed, the Trav15 segment, which encodes the Vδ6.3 TCR subunit, is directly bound by E proteins that control its expression. Once expressed, the Vγ1Vδ6.3 TCR specifies the innate-like NKγδT cell fate, even in progenitors beyond the normally permissive perinatal window, and this is enhanced by Id3-deficiency. These data indicate that the paradoxical behavior of NKγδT cells in Id3-deficient mice is determined by its stereotypic Vγ1Vδ6.3 TCR complex.

Objective: Laparoscopic surgery (MIS) offers equivalent oncologic outcomes as compared to open surgery, while causing lesser morbidity and resulting in a faster recovery. Vaginal extraction of specimens may cause vaginal or perineal lacerations (VL). The objective of this retrospective study was to assess local recurrence rates compared between cases with vaginal laceration (VL) or without vaginal lacerations (NL). Methods: We identified patients with endometrial cancer who underwent MIS between 2014 and 2018. We assessed the rate of local recurrence between patients in VL and NL cohorts. The study included all histologic subtypes and stages while benign final pathology, synchronous primaries or cases that required laparotomy for extraction were excluded. Results: 338 MIS cases were evaluable of which 40 cases had a vaginal laceration during specimen extraction. There was no significant difference in age, race, presence of LVSI, stage, grade, histology or use of vaginal brachytherapy between cohorts. Cases with vaginal lacerations were significantly associated with a higher median BMI and larger uterine size. The VL cohort was more likely to have received adjuvant treatment. In early stage disease, more cases had non-endometrioid histology in the VL group and had increased incidence of chemotherapy and radiation use as well. There were no cases of isolated vaginal recurrence (0/40) in the VL group as compared to an incidence of 2 % (7/298) in the NL group with a relative risk of 0.48 (CI: 0.03–8.36, p = 0.62). There were 4 cases of pelvic recurrence (4/40) in the VL group and 2 cases in the NL group (2/298) with a relative risk of 2.13 (CI: 0.46–9.89, p = 0.34). Conclusions: In endometrial cancer cases, we did not observe a significantly increased risk of vaginal or pelvic recurrence after a vaginal laceration at the time of specimen removal.

Loss of the tumour suppressor gene PTEN leads to the activation of pro-tumourigenic signalling pathways. Here, the authors analyse sequencing data from a large cohort of colorectal cancer patients harbouring PTEN mutations and identify distinct patterns of associations with genomic and clinical features.

Following herniation of the intervertebral disc, there is a need for advanced surgical strategies to protect the diseased tissue from further herniation and to minimize further degeneration. Accordingly, a novel tissue engineered implant for annulus fibrosus (AF) repair was fabricated via three-dimensional fiber deposition and evaluated in a large animal model. Specifically, lumbar spine kinetics were assessed for eight (n = 8) cadaveric ovine lumbar spines in three pure moment loading settings (flexion-extension, lateral bending, and axial rotation) and three clinical conditions (intact, with a defect in the AF, and with the defect treated using the AF repair implant). In ex vivo testing, seven of the fifteen evaluated biomechanical measures were significantly altered by the defect. In each of these cases, the treated spine more closely approximated the intact biomechanics and four of these cases were also significantly different to the defect. The same spinal kinetics were also assessed in a preliminary in vivo study of three (n = 3) ovine lumbar spines 12 weeks post-implantation. Similar to the ex vivo results, functional efficacy of the treatment was demonstrated as compared to the defect model at 12 weeks post-implantation. These promising results motivate a future large animal study cohort which will establish statistical power of these results further elucidate the observed outcomes, and provide a platform for clinical translation of this novel AF repair patch strategy. Ultimately, the developed approach to AF repair holds the potential to maintain the long-term biomechanical function of the spine and prevent symptomatic re-herniation.

Streamlit is an open-source Python coding framework for building web-applications or “web-apps” and is now being used by researchers to share large data sets from published studies and other resources. Here we present Stmol, an easy-to-use component for rendering interactive 3D molecular visualizations of protein and ligand structures within Streamlit web-apps. Stmol can render protein and ligand structures with just a few lines of Python code by utilizing popular visualization libraries, currently Py3DMol and Speck. On the user-end, Stmol does not require expertise to interactively navigate. On the developer-end, Stmol can be easily integrated within structural bioinformatic and cheminformatic pipelines to provide a simple means for user-end researchers to advance biological studies and drug discovery efforts. In this paper, we highlight a few examples of how Stmol has already been utilized by scientific communities to share interactive molecular visualizations of protein and ligand structures from known open databases. We hope Stmol will be used by researchers to build additional open-sourced web-apps to benefit current and future generations of scientists.

Abstract Background In tissue engineering (TE) strategies, cell processes are regulated by mechanical stimuli. Although TE scaffolds have been developed to replicate tissue‐level mechanical properties, it is intractable to experimentally measure and prescribe the cellular micromechanical environment (CME) generated within these constructs. Accordingly, this study aimed to fill this lack of understanding by modeling the CME in TE scaffolds using the finite element method. Methods A repeating unit of composite fiber scaffold for annulus fibrosus (AF) repair with a fibrin hydrogel matrix was prescribed a series of loading, material, and architectural parameters. The distribution of CME in the scaffold was predicted and compared to proposed target mechanics based on anabolic responses of AF cells. Results The multi‐axial loading modality predicted the greatest percentage of cell volumes falling within the CME target envelope (%PTE) in the study (65 %PTE for 5.0% equibiaxial tensile strain with 50 kPa radial‐direction compression; 7.6 %PTE without radial pressure). Additionally, the architectural scale had a moderate influence on the CME (maximum of 17 %PTE), with minimal change in the tissue‐level properties of the scaffold. Scaffold materials and architectures had secondary influences on the predicted regeneration by modifying the tissue‐level scaffold mechanics. Conclusions Scaffold loading modality was identified as the critical factor for TE the AF. Scaffold materials and architecture were also predicted to modulate the scaffold loading and, therefore, control the CME indirectly. This study facilitated an improved understanding of the relationship between tissue‐level and cell‐level mechanics to drive anabolic cell responses for tissue regeneration.

Enhanced Recovery after Surgery (ERAS) is an evidence-based approach that aims to reduce narcotic use and maintain anabolic balance to enable full functional recovery. Our primary aim was to determine the effect of ERAS on narcotic usage among patients who underwent exploratory laparotomy by gynecologic oncologists. We characterized its effect on length of stay, intraoperative blood transfusions, bowel function, 30-day readmissions, and postoperative complications. A retrospective cohort study was performed at Abington Hospital-Jefferson Health in gynecologic oncology. Women who underwent an exploratory laparotomy from 2011 to 2016 for both benign and malignant etiologies were included before and after implementation of our ERAS protocol. Patients who underwent a bowel resection were excluded. A total of 724 patients were included: 360 in the non-ERAS and 364 in the ERAS cohort. An overall reduction in narcotic usage, measured as oral morphine milliequivalents (MMEs) was observed in the ERAS relative to the non-ERAS group, during the entire hospital stay (MME 34 versus 68, p

This report documents a rare case of an extracranial meningioma on the posterior scalp without apparent dural connection. Additionally, a sebaceous steatocystoma of the anterior scalp presented alongside the meningioma. A steatocystoma localized to the scalp is also remarkably rare. To our knowledge, this is the first report documenting both an extracranial meningioma and a steatocystoma presenting concurrently on the scalp. A male patient in his thirties presented with a mass lesion on the scalp. A CT scan revealed one posterior scalp mass with no intracranial abnormalities. Post excision histologic examination confirmed an extracranial meningioma (meningothelial variant, WHO Grade I). A second anterior scalp mass, not revealed by CT scan, was discovered during surgery. It was excised and diagnosed as a steatocystoma. Meningiomas predominantly occur intracranially but, in some instances, may present as a standalone extracranial tumor without intracranial abnormalities. Because extracranial meningioma is uncommon, it may be overlooked during clinical diagnosis of scalp masses. We recommend that this neoplasm be routinely considered in the differential diagnosis of extracranial tumors. The discovery of another rare tumor—a steatocystoma located in immediate proximity on the scalp—is further remarkable. We briefly review relevant case reports and etiologies and consider a potential relationship between the two neoplasms. However, it remains more likely that the concurrence of these tumors in our patient was simply coincidental.

Medial meniscal root tears are often disabling injuries that can occur in isolation during low-velocity, deep knee flexion maneuvers in middle-aged patients. The most common meniscal root tear pattern is a radial tear near the root attachment (type II). Root tears are often associated with meniscal extrusion, identified on magnetic resonance imaging. Relocation of the meniscal root to its anatomic center is a reported current difficulty faced by surgeons during surgical repair. However, this can be achieved via sufficient peripheral release of the posteromedial capsular attachment of the medial meniscus. The purpose of this Technical Note is to describe the authors' current surgical technique for medial meniscus root repair with a peripheral release for addressing meniscal extrusion. Classifications: level I (knee); level II (meniscus).

Anterolateral rotational instability may persist after anterior cruciate ligament (ACL) reconstruction for a variety of reasons including damage to lateral or posterolateral structures, injury to the meniscus, disruption of anterolateral soft tissue structures, or increased tibial slope. In the setting of revision or primary ACL reconstruction with persistent anterolateral laxity, despite repair or reconstruction of other injured structures or in the setting of increased tibial slope, a lateral extra-articular tenodesis procedure can be used to augment an ACL reconstruction to aid in restoring anterolateral rotational stability and to upload the ACL reconstruction graft. This article details our technique for performing a modified Lemaire lateral extra-articular tenodesis using iliotibial band autograft as an adjunct to ACL reconstruction.

Chondral defects of the patellofemoral joint remain a difficult-to-treat pathology with limited long-term results. Currently available techniques to treat large or unipolar chondral defects of the patella include autologous chondrocyte implantation and osteochondral allograft transplantation. Despite the recent advances in orthobiologic adjuncts, there is no single gold-standard surgical approach to this difficult-to-treat pathology in patients who are frequently young, active, and demanding on their bodies. We describe a technique for osteochondral allograft transplantation to the patella for an isolated patellar chondral lesion (unipolar).

Combined posterior cruciate ligament (PCL) and medial collateral ligament (MCL) injuries represent a complex pathology that requires a thorough clinical and radiographic examination to diagnose and identify all injured structures. Anatomic reconstruction of the injured ligaments is recommended, including double-bundle PCL reconstruction and superficial MCL augmentation. In the setting of this complex reconstruction, several technical aspects require consideration and preoperative planning, including the risk of femoral tunnel convergence on the medial aspect of the femoral condyle. This article details our technique for combined anatomic double-bundle PCL reconstruction and superficial MCL augmentation to avoid tunnel convergence. Level I (knee); level II (PCL).

Increased sagittal plane posterior tibial slope has been identified as a risk factor for primary anterior cruciate ligament reconstruction (ACLR) failure. Although ACLR failure is multifactorial, correction of sagittal plane posterior tibial slope should be evaluated in patients with an ACLR graft rupture. There are limited technical descriptions of proposed decreasing tibial slope osteotomy procedures; therefore, the purpose of this Technical Note is to describe the current senior author's technique of performing an anterior closing wedge proximal tibial osteotomy to decrease sagittal plane tibial slope in patients requiring a revision ACLR.

Recurrent multidirectional shoulder instability (MDI) is a challenging clinical problem, particularly in the setting of connective tissue diseases, and there is a distinct lack of literature discussing strategies for operative management of this unique patient group. These patients frequently present with significant glenoid bone loss, patulous and abnormal capsulolabral structures, and a history of multiple failed arthroscopic or open instability procedures. Although the precise treatment algorithm requires tailoring to the individual patient, we have shown successful outcomes in correcting recurrent MDI in the setting of underlying connective tissue disorders by means of a modified T-plasty capsular shift and rotator interval closure in conjunction with distal tibial allograft bony augmentation. The purpose of this Technical Note was to describe a technique that combines a fresh distal tibial allograft for glenoid bony augmentation with a modified T-plasty capsular shift and rotator interval closure for the management of recurrent shoulder MDI in patients presenting with Ehlers-Danlos syndrome or other connective tissue disorders after failed Latarjet stabilization.

Extension loss due to patella baja is a rare but devastating postoperative complication associated with knee surgery. The most common causes of patella baja are prolonged postoperative immobilization, over-distalization of the patellar tendon during patella-related surgical procedures (i.e., tibial tubercle osteotomy and patellar tendon reconstruction), and inadequate knee range-of-motion exercises postoperatively. Patella baja can cause significant functional limitations owing to knee-related stiffness, pain, and weakness. Arthroscopy with scar tissue debridement is the standard of care for patients with arthrofibrosis in whom conservative treatment has failed. However, when this surgical approach fails, patients with continued patella baja may be candidates for open patellar tendon tenotomy as a salvage procedure.

Fibular collateral ligament (FCL) injuries can present as lateral-sided knee pain with feelings of side-to-side instability during activity. Patients with FCL injuries can have accompanying symptoms related to irritation of the common peroneal nerve. Preoperative diagnosis is imperative and should include a thorough physical examination complemented with varus stress radiographs before surgical reconstruction is indicated. In the adolescent cohort, surgical planning can be complicated by the presence of open physes, and caution must be taken to avoid drilling through or placing screw fixation across the physes. Potential complications include growth arrest and limb length discrepancy. Therefore, the purpose of this Technical Note is to describe an anatomic FCL reconstruction technique in the skeletally immature adolescent patient.

Anterior shoulder instability often results from avulsion of the anterior inferior glenohumeral ligament (aIGHL) off its insertion on the glenoid, yielding a Bankart lesion. Although less common, avulsion of the ligament attachment to the humerus results in a humeral avulsion of the glenohumeral ligament (HAGL) lesion. Combined Bankart and HAGL lesions, also termed the “floating aIGHL,” create a complex pathology that is not detailed significantly in the literature. We believe a mini-open approach is a viable and reproducible procedure for treatment because it allows for protection of the axillary nerve and other neurovascular structures while providing optimal exposure to both the humeral insertion site of the distal aIGHL and the Bankart lesion, ensuring anatomic restoration. The purpose of this Technical Note is to describe our preferred technique to surgically treat the floating aIGHL, consisting of an anterior HAGL and concomitant Bankart lesion repair through a mini-open approach.

Instability of the proximal tibiofibular joint (PTFJ) can present as frank dislocations, vague symptoms of lateral knee pain, discomfort during activity, or symptoms related to irritation of the common peroneal nerve. An accurate preoperative diagnosis is imperative and should include a trial of taping of the PTFJ for a 4- to 6-week time frame before surgical reconstruction is indicated. In the adolescent population, surgical planning can be complicated by the presence of open physes; therefore, caution must be taken to avoid drilling through or placing screw fixation across the physes. Potential complications include growth arrest and limb length discrepancy. Therefore, the purpose of this Technical Note is to describe the surgical technique for addressing PTFJ instability in adolescent patients.

Margot Green1, Vince Marzano1, I Anne Leditschke2,3, Imogen Mitchell2,3, Bernie Bissett1,4,5 1Physiotherapy Department, Canberra Hospital, Canberra, ACT, Australia; 2Intensive Care Unit, Canberra Hospital, Canberra, ACT, Australia; 3School of Medicine, Australian National University, Canberra, ACT, Australia; 4Discipline of Physiotherapy, University of Canberra, Canberra, ACT, Australia; 5School of Medicine, University of Queensland, Brisbane, QLD, Australia Objectives: To describe our experience and the practical tools we have developed to facilitate early mobilization in the intensive care unit (ICU) as a multidisciplinary team.Background: Despite the evidence supporting early mobilization for improving outcomes for ICU patients, recent international point-prevalence studies reveal that few patients are mobilized in the ICU. Existing guidelines rarely address the practical issues faced by multidisciplinary ICU teams attempting to translate evidence into practice. We present a comprehensive strategy for safe mobilization utilized in our ICU, incorporating the combined skills of medical, nursing, and physiotherapy staff to achieve safe outcomes and establish a culture which prioritizes this intervention.Methods: A raft of tools and strategies are described to facilitate mobilization in ICU by the multidisciplinary team. Patients without safe unsupported sitting balance and without ≥3/5 (Oxford scale) strength in the lower limbs commence phase 1 mobilization, including training of sitting balance and use of the tilt table. Phase 2 mobilization involves supported or active weight-bearing, incorporating gait harnesses if necessary. The Plan B mnemonic guides safe multidisciplinary mobilization of invasively ventilated patients and emphasizes the importance of a clearly articulated plan in delivering this valuable treatment as a team.Discussion: These tools have been used over the past 5 years in a tertiary ICU with a very low incidence of adverse outcomes (

A snapping biceps tendon is an infrequently seen and commonly misdiagnosed pathology, leaving patients with persistent symptoms that can be debilitating. Patients will present with a visible, audible, and/or painful snap over the lateral aspect of their knee when performing squats, sitting in low seats, or participating in activities with deep knee flexion. A thorough knowledge of the anatomy is essential for surgical treatment of this pathology, which is caused by a detachment of the direct arms of the long and short heads of the biceps femoris off the fibular styloid. This Technical Note provides a diagnostic approach, postoperative management, and details of a surgical technique to treat a snapping biceps tendon with an anatomic repair of the long and short head attachments of the biceps femoris to the posterolateral fibular styloid.

Blood flow restriction (BFR) training involves occluding venous outflow while maintaining arterial inflow by the application of an extremity tourniquet after surgery. BFR ultimately reduces oxygen delivery to muscle cells, similar to an anaerobic environment, and allows patients to exercise with low resistance and stimulates muscle hypertrophy and strength using heavy resistance. Thus orthopaedic surgeons and physical therapists are incorporating this type of training into their postoperative rehabilitation protocols, particularly after injuries or surgical procedures about the knee joint. The purpose of this Technical Note is to describe a BFR clinical application technique and to report on the indications, safety considerations, and postoperative knee surgery rehabilitation protocols for BFR.

It is well known that the posterior cruciate ligament (PCL) is the main stabilizer to posterior tibial translation in the knee. Anatomic double-bundle reconstruction has recently been proposed to best restore posterior and rotational tibial instability, especially compared with a single-bundle PCL reconstruction (PCLR). Most publications in the peer-reviewed literature on double-bundle PCLR have used allografts. However, in many countries, allografts are not available. This Technical Note describes an all-autograft arthroscopic technique for PCLR using the quadriceps and semitendinosus tendons.

Increasing infectious disease deaths, the emergence of new infections, and bioterrorism have made surveillance for infectious diseases a public health concern. Medical examiners and coroners certify approximately 20% of all deaths that occur within the United States and can be a key source of information regarding infectious disease deaths. We hypothesized that a computer-assisted search tool (algorithm) could detect infectious disease deaths from a medical examiner database, thereby reducing the time and resources required to perform such surveillance manually. We developed two algorithms, applied them to a medical examiner database, and verified the cases identified against the opinion of a panel of experts. The algorithms detected deaths with infectious components with sensitivities from 67% to 94%, and predictive value positives ranging from 8% to 49%. Algorithms can be useful for surveillance in medical examiner offices that have limited resources or for conducting surveillance across medical examiner jurisdictions.

After public notification of confirmed cases of bioterrorism-related anthrax, the Centers for Disease Control and Prevention’s Emergency Operations Center responded to 11,063 bioterrorism-related telephone calls from October 8 to November 11, 2001. Most calls were inquiries from the public about anthrax vaccines (58.4%), requests for general information on bioterrorism prevention (14.8%), and use of personal protective equipment (12.0%); 882 telephone calls (8.0%) were referred to the state liaison team for follow-up investigation. Of these, 226 (25.6%) included reports of either illness clinically confirmed to be compatible with anthrax or direct exposure to an environment known to be contaminated with Bacillus anthracis. The remaining 656 (74.4%) included no confirmed illness but reported exposures to “suspicious” packages or substances or the receipt of mail through a contaminated facility. Emergency response staff must handle high call volumes following suspected or actual bioterrorist attacks. Standardized health communication protocols that address contact with unknown substances, handling of suspicious mail, and clinical evaluation of suspected cases would allow more efficient follow-up investigations of clinically compatible cases in high-risk groups.

The need for a new surveillance approach to understand the clinical outcomes and behaviors of people in care for HIV evolved from the new challenges for monitoring clinical outcomes in the HAART era, the impact of the epidemic on an increasing number of areas in the US, and the need for representative data to describe the epidemic and related resource utilization and needs. The Institute of Medicine recommended that the Centers for Disease Control and Prevention and the Heath Resources and Services Administration coordinate efforts to survey a random sample of HIV-infected persons in care, in order to more accurately measure the need for prevention and care services. The Medical Monitoring Project (MMP) was created to meet these needs. This manuscript describes the evolution and design of MMP, a new nationally representative clinical outcomes and behavioral surveillance system, and describes how MMP data will be used locally and nationally to identify care and treatment utilization needs, and to plan for prevention interventions and services.