Giant diaphragmatic hernia surgical treatment by laparoscopic repair: a case report.

Diaphragmatic hernias occur in up to 10%-50% of the general population. Treatment of hiatal hernias depends on the type of hernia and the severity of the symptoms. We report the case of a 52-year-old woman with no significant history who presented for 1 year with non-specific chest pain, dyspnea, dysphagia, and heartburn. A thoracoabdominal tomography with contrast was performed, showing a diaphragmatic hernia containing the stomach, portions of the duodenum, pancreas, small intestine, and colon with a sac of up to 20 cm, which was successfully repaired laparoscopically.

The Combined Influence of Sleep Disturbance and Depression on 12-month Outcomes after Lumbar Spine Surgery.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: To examine the combined influence of preoperative sleep disturbance and depression on 12-month patient-reported outcomes after lumbar spine surgery (LSS). SUMMARY OF BACKGROUND DATA: Psychological and behavioral factors are considered major risk factors of poor outcome after LSS. However, there is a need to explore the combined effects of preoperative factors such as sleep disturbance and depression. Understanding the influence of sleep disturbance and depression can inform evidence-based preoperative assessment and shared-decision making of preoperative and postoperative treatment. METHODS: Data from 700 patients undergoing LSS were analyzed. Preoperative sleep disturbance and depression were assessed with PROMIS subscales. Established thresholds defined patients with moderate/severe symptoms. Outcomes for disability (Oswestry Disability Index) and back and leg pain (Numeric Rating Scales) were assessed preoperatively and at 12 months. Separate multivariable linear regressions examined the influence of each factor on 12-month outcomes with and without accounting for the other, and in combination as a 4-level variable: 1) moderate/severe sleep disturbance alone, 2) moderate/severe depression alone, 3) both moderate/severe sleep disturbance and depression, 4) no moderate/severe sleep disturbance or depression. RESULTS: Preoperative sleep disturbance and depression were associated with 12-month disability and pain (P<0.05). After accounting for depression, preoperative sleep disturbance remained associated with disability, while preoperative depression adjusting for sleep disturbance remained associated with all outcomes (P<0.05). Patients reporting both moderate/severe sleep disturbance and moderate/severe depression had 12.6 points higher disability and 1.5 points higher back and leg pain compared to patients without moderate/severe sleep disturbance or depression. CONCLUSION: The combination of sleep disturbance and depression impacts postoperative outcomes considerably. The high-risk group of patients with moderate/severe sleep disturbance and depression could benefit from targeted treatment strategies.

Disentangling top-down drivers of mortality underlying diel population dynamics of Prochlorococcus in the North Pacific Subtropical Gyre.

Photosynthesis fuels primary production at the base of marine food webs. Yet, in many surface ocean ecosystems, diel-driven primary production is tightly coupled to daily loss. This tight coupling raises the question: which top-down drivers predominate in maintaining persistently stable picocyanobacterial populations over longer time scales? Motivated by high-frequency surface water measurements taken in the North Pacific Subtropical Gyre (NPSG), we developed multitrophic models to investigate bottom-up and top-down mechanisms underlying the balanced control of Prochlorococcus populations. We find that incorporating photosynthetic growth with viral- and predator-induced mortality is sufficient to recapitulate daily oscillations of Prochlorococcus abundances with baseline community abundances. In doing so, we infer that grazers in this environment function as the predominant top-down factor despite high standing viral particle densities. The model-data fits also reveal the ecological relevance of light-dependent viral traits and non-canonical factors to cellular loss. Finally, we leverage sensitivity analyses to demonstrate how variation in life history traits across distinct oceanic contexts, including variation in viral adsorption and grazer clearance rates, can transform the quantitative and even qualitative importance of top-down controls in shaping Prochlorococcus population dynamics.

Are Formal and Informal Home Mindfulness Practice Quantities Associated With Outcomes? Results From a Pilot Study of a Four-Week Mindfulness Intervention for Chronic Pain Management.

Background: The association between home mindfulness practice quantity in standard length mindfulness-based interventions (MBIs) and chronic pain outcomes is variable. Few studies focus on abbreviated MBIs (< 8 weeks) and distinguish between formal guided practices and informal practices in daily life. Objectives: To characterize home mindfulness practice and explore associations between home practice quantity and pre-to-post-outcome changes after an MBI for chronic pain. Methods: In this single-arm study, 21 adults with chronic pain (mean age = 54 years, 81% White, mean pain duration = 7 years) completed an MBI with four weekly group sessions. Pre and post self-report measures of pain intensity/interference, physical function, depression, anxiety, positive affect, sleep disturbance (all PROMIS measures), and pain acceptance, catastrophizing, perceived stress and mindfulness were completed, along with daily surveys of formal (mindfulness of breath, body scan) and informal (breathing space, mindfulness of daily activities) practice. Bivariate correlations and multivariable regression models were used to assess the association between days and minutes of practice and change in outcomes. Results: On average, formal practice was completed on 4.3 days per week and 13.5 minutes per day. Informal practice was completed on 3.5 days per week and 8.6 minutes per day. Formal practice was not significantly correlated with outcomes (Spearman's ρ = |.01|-|.32|), whereas informal practice was correlated with multiple outcomes (ρ = |.04|-|.66|). Number of days practiced informally was associated with improved pain interference, physical function, sleep disturbance, and catastrophizing (p's ≤ .05). Number of minutes practiced informally was associated with improved pain interference, anxiety, positive affect, and catastrophizing (p's ≤ .05). Conclusion: Informal home practice quantity, but not formal practice quantity, is associated with improved outcomes during an abbreviated MBI for chronic pain. For these MBIs, it is important to evaluate the distinct roles of formal and informal practice. ClinicalTrialsgov Registration: NCT03495856.

Metapopulation model of phage therapy of an acute Pseudomonas aeruginosa lung infection.

Infections caused by multi-drug resistant (MDR) pathogenic bacteria are a global health threat. Phage therapy, which uses phage to kill bacterial pathogens, is increasingly used to treat patients infected by MDR bacteria. However, the therapeutic outcome of phage therapy may be limited by the emergence of phage resistance during treatment and/or by physical constraints that impede phage-bacteria interactions in vivo. In this work, we evaluate the role of lung spatial structure on the efficacy of phage therapy for Pseudomonas aeruginosa infection. To do so, we developed a spatially structured metapopulation network model based on the geometry of the bronchial tree, and included the emergence of phage-resistant bacterial mutants and host innate immune responses. We model the ecological interactions between bacteria, phage, and the host innate immune system at the airway (node) level. The model predicts the synergistic elimination of a P. aeruginosa infection due to the combined effects of phage and neutrophils given sufficiently active immune states and suitable phage life history traits. Moreover, the metapopulation model simulations predict that local MDR pathogens are cleared faster at distal nodes of the bronchial tree. Notably, image analysis of lung tissue time series from wild-type and lymphocyte-depleted mice (n=13) revealed a concordant, statistically significant pattern: infection intensity cleared in the bottom before the top of the lungs. Overall, the combined use of simulations and image analysis of in vivo experiments further supports the use of phage therapy for treating acute lung infections caused by P. aeruginosa while highlighting potential limits to therapy given a spatially structured environment, such as impaired innate immune responses and low phage efficacy.

Macrophage-induced reduction of bacteriophage density limits the efficacy of in vivo pulmonary phage therapy.

The rise of antimicrobial resistance has led to renewed interest in evaluating phage therapy. In murine models highly effective treatment of acute pneumonia caused by Pseudomonas aeruginosa relies on the synergistic antibacterial activity of bacteriophages with neutrophils. Here, we show that depletion of alveolar macrophages (AM) shortens the survival of mice without boosting the P. aeruginosa load in the lungs. Unexpectedly, upon bacteriophage treatment, pulmonary levels of P. aeruginosa were significantly lower in AM-depleted than in immunocompetent mice. To explore potential mechanisms underlying the benefit of AM-depletion in treated mice, we developed a mathematical model of phage, bacteria, and innate immune system dynamics. Simulations from the model fitted to data suggest that AM reduce bacteriophage density in the lungs. We experimentally confirmed that the in vivo decay of bacteriophage is faster in immunocompetent compared to AM-depleted animals. These findings demonstrate the involvement of feedback between bacteriophage, bacteria, and the immune system in shaping the outcomes of phage therapy in clinical settings.

Impact of Racial/Ethnic Disparities on Patient-Reported Outcomes Following Cervical Spine Surgery: QOD Analysis.

STUDY DESIGN: Retrospective analysis of data from the cervical module of a National Spine Registry, the Quality Outcomes Database. OBJECTIVE: To examine the association of race and ethnicity with patient-reported outcome measures (PROMs) at one year after cervical spine surgery. SUMMARY OF BACKGROUND DATA: Evidence suggests that Black individuals are 39% to 44% more likely to have postoperative complications and a prolonged length of stay after cervical spine surgery compared with Whites. The long-term recovery assessed with PROMs after cervical spine surgery among Black, Hispanic, and other non-Hispanic groups ( i.e . Asian) remains unclear. MATERIALS AND METHODS: PROMs were used to assess disability (neck disability index) and neck/arm pain preoperatively and one-year postoperative. Primary outcomes were disability and pain, and not being satisfied from preoperative to 12 months after surgery. Multivariable logistic and proportional odds regression analyses were used to determine the association of racial/ethnic groups [Hispanic, non-Hispanic White (NHW), non-Hispanic Black (NHB), and non-Hispanic Asian (NHA)] with outcomes after covariate adjustment and to compute the odds of each racial/ethnic group achieving a minimal clinically important difference one-year postoperatively. RESULTS: On average, the sample of 14,429 participants had significant reductions in pain and disability, and 87% were satisfied at one-year follow-up. Hispanic and NHB patients had higher odds of not being satisfied (40% and 80%) and having worse pain outcomes (30%-70%) compared with NHW. NHB had 50% higher odds of worse disability scores compared with NHW. NHA reported similar disability and neck pain outcomes compared with NHW. CONCLUSIONS: Hispanic and NHB patients had worse patient-reported outcomes one year after cervical spine surgery compared with NHW individuals, even after adjusting for potential confounders, yet there was no difference in disability and neck pain outcomes reported for NHA patients. This study highlights the need to address inherent racial/ethnic disparities in recovery trajectories following cervical spine surgery.

Combining Wearable Technology and Telehealth Counseling for Rehabilitation After Lumbar Spine Surgery: Feasibility and Acceptability of a Physical Activity Intervention.

OBJECTIVE: The purpose of this study was to examine the feasibility and acceptability of a wearable device and telehealth counseling physical activity intervention early after lumbar spine surgery. METHODS: Sixteen patients were randomized to an 8-session physical activity intervention or to usual postoperative care after surgery. The intervention included a wearable device (ie, Fitbit) and telehealth counseling by a licensed physical therapist. The feasibility of study procedures was assessed through recruitment, randomization, retention, and participation rates. Acceptability was assessed through a satisfaction survey and median within-participant change in objective physical activity (steps per day and time spent in moderate-to-vigorous physical activity [MVPA]) and patient-reported outcomes. RESULTS: Of 64 participants who were eligible, recruitment and randomization rates were 41 and 62%, respectively. Retention for objective physical activity and patient-reported outcomes was 94 and 100%, respectively, at 6-month follow-up. Seven (88%) participants in the intervention group completed all telehealth sessions, and 6 (75%) met step goals over the 8 sessions. All participants in the intervention group found the wearable device and telehealth counseling to be helpful and reported it much or somewhat more important than other postoperative services. Median within-participant change for steps per day improved from baseline (preoperative) to 6 months after surgery for both the intervention (1070) and usual care (679) groups, while MVPA only improved for the intervention group (2.2. minutes per day). Improvements in back and leg pain and disability were noted for both groups. No adverse events were reported in the study. CONCLUSION: Combining wearable technology and telehealth counseling is a feasible approach to promote the physical activity during the early postoperative period after spine surgery. Future randomized controlled trials are needed to investigate the efficacy of leveraging wearables and telehealth during postoperative rehabilitation. IMPACT: This study has implications for the clinical dissemination of physical activity strategies in the rehabilitation setting.

Discriminative multimodal learning via conditional priors in generative models.

Deep generative models with latent variables have been used lately to learn joint representations and generative processes from multi-modal data, which depict an object from different viewpoints. These two learning mechanisms can, however, conflict with each other and representations can fail to embed information on the data modalities. This research studies the realistic scenario in which all modalities and class labels are available for model training, e.g. images or handwriting, but where some modalities and labels required for downstream tasks are missing, e.g. text or annotations. We show, in this scenario, that the variational lower bound limits mutual information between joint representations and missing modalities. We, to counteract these problems, introduce a novel conditional multi-modal discriminative model that uses an informative prior distribution and optimizes a likelihood-free objective function that maximizes mutual information between joint representations and missing modalities. Extensive experimentation demonstrates the benefits of our proposed model, empirical results show that our model achieves state-of-the-art results in representative problems such as downstream classification, acoustic inversion, and image and annotation generation.

An overview of systematic reviews examining the quantitative sensory testing-derived hypoalgesic effects of manual therapy for musculoskeletal pain.

BACKGROUND: Changes in quantitative sensory testing (QST) after manual therapy can provide insight into pain relief mechanisms. Prior systematic reviews have evaluated manual-therapy-induced QST change. This overview of systematic reviews aims to consolidate this body of literature and critically review evidence on the hypoalgesic effects of manual therapy in clinical populations. METHODS: A comprehensive search was conducted on PubMed, CINAHL, PsycInfo, and Embase. Peer-reviewed systematic reviews with or without meta-analysis were eligible if the reviews examined the effect of manual therapy compared to non-manual therapy interventions on QST outcomes in clinical populations. Methodological quality was assessed with the AMSTAR 2 tool. Meta-analysis results and qualitative (non-meta-analysis) interpretations were summarized by type of manual therapy. Overlap of studies was examined with the corrected covered area (CCA) index. RESULTS: Thirty systematic reviews, including 11 meta-analyses, met inclusion. There was a slight overlap in studies (CCA of 1.72% for all reviews and 1.69% for meta-analyses). Methodological quality was predominantly low to critically low. Eight (27%) reviews examined studies with a range of manual therapy types, 13 (43%) reviews focused on joint-biased manual therapy, 7 (23%) reviews focused on muscle-biased manual therapy, and 2 (7%) reviews focused on nerve-biased manual therapy. Twenty-nine (97%) reviews reported on pressure pain threshold (PPT). Meta-analytic results demonstrated conflicting evidence that manual therapy results in greater hypoalgesic effects compared to other interventions or controls. CONCLUSION: Our overview of QST effects, which has relevance to mechanisms underlying hypoalgesia, shows conflicting evidence from mostly low to critically low systematic reviews.

Central Sensitization: The Missing Link Between Psychological Distress and Poor Outcome Following Primary Total Knee Arthroplasty.

BACKGROUND: While preoperative psychological distress is known to predict risk for worse total knee arthroplasty (TKA) outcomes, distress may be too broad and nonspecific a predictor in isolation. We tested whether there are distinct preoperative TKA patient types based jointly on psychological status and measures of altered pain processing that predict adverse clinical outcomes. METHODS: In 112 TKA patients, we preoperatively assessed psychological status (depression, anxiety, and catastrophizing) and altered pain processing via a simple quantitative sensory testing protocol capturing peripheral and central pain sensitization. Outcomes (pain, function, opioid use) were prospectively evaluated at 6 weeks and 6 months after TKA. Cluster analyses were used to empirically identify TKA patient subgroups. RESULTS: There were 3 distinct preoperative TKA patient subgroups identified from the cluster analysis. A low-risk (LR) group was characterized by low psychological distress and low peripheral and central sensitization. In addition, 2 subgroups with similarly elevated preoperative psychological distress were identified, differing by pain processing alterations observed: high-risk centralized pain and high-risk peripheral pain. Relative to LR patients, high-risk centralized pain patients displayed significantly worse function and greater opioid use at 6 months after TKA (P values <.05). The LR and high-risk peripheral pain patient subgroups had similar 6-month outcomes (P values >.05). CONCLUSIONS: Among patients who have psychological comorbidity, only patients who have central sensitization were at elevated risk for poor functional outcomes and increased opioid use. Central sensitization may be the missing link between psychological comorbidity and poor TKA clinical outcomes. Preoperative testing for central sensitization may have clinical utility for improving risk stratification in TKA patients who have psychosocial risk factors.

Development and validation of a pentaplex assay for the identification of antibodies against common viral diseases in cattle.

Animal welfare and economic implications of infectious diseases in cattle demand an efficient surveillance as the foundation for control and eradication programmes. Bovine respiratory syncytial virus (BRSV), Parainfluenza virus type 3 (PI3V), Bovine herpes virus-1 (BoHV-1), Bovine viral diarrhoea virus (BVDV), and Enzootic bovine leukosis virus (EBLV) cause common and often underdiagnosed diseases in cattle that are endemic in most countries [1]. A hallmark of individual exposure to a viral pathogen is the presence of antibodies directed towards that virus. The aim of this study was to develop and validate a pentaplex assay to simultaneously detect and quantify antibodies against BRSV, PI3V, BoHV-1, BVDV and EBLV in serum, as an efficient tool to yield epidemiological data. Monoplex assays were initially developed using either complete BRSV or BoHV-1 viral lysates, or recombinant proteins for BVDV, EBLV or PI3V as capture antigens. In addition, 125 serum samples from unvaccinated cattle, which were classified as positive or negative for each of the viruses by commercial ELISA kits, were used for validation. Conditions established for the Luminex monoplex assays were adopted for the pentaplex assay. The accuracy, determined by the area under the ROC curve, was greater than 0.97, and assay diagnostic sensitivities and specificities were over 95 and 90%, respectively, for all antigens. Intra (r) and interassay (R) coefficients of variation were under 10 and 20 %, respectively. Selectivity towards target viruses was shown by binding inhibition assays where unbound viruses reduced fluorescence intensities. Diagnostic agreement for samples analysed simultaneously in the monoplex and multiplex assays was almost perfect. In conclusion, a highly sensitive pentaplex assay was validated for the simultaneous identification of antibodies directed against BVDV, BoHV-1, PI3V, BRSV and EBLV in serum. The developed pentaplex assay complies with performance characteristics established by international guidelines for diagnostic tests and may be used as a tool for the implementation of epidemiological surveillance.

Effect of Cervicothoracic Junction LIV Selection on Posterior Cervical Fusion Mechanical Failure: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and Meta-analysis. OBJECTIVE: Analyze and summarize literature evaluating the role of C7, T1, and T2 lowest instrumented vertebra (LIV) selection in posterior cervical fusion (PCF) and if this affects the progression of mechanical failure and revision surgery. SUMMARY OF BACKGROUND DATA: Literature evaluating mechanical failure and adjacent segment disease in the setting of PCF at or nearby the cervicothoracic junction (CTJ) remains limited with studies reporting conflicting results. MATERIALS AND METHODS: Two reviewers conducted a detailed systematic review using EMBASE, PubMed, Web of Science, and Google Scholar on June 28, 2021, for primary research articles comparing revision and complication rates for posterior fusions ending in the lower cervical spine (C7) and upper thoracic spine (T1-T2). The initial systematic database yielded 391 studies, of which 10 met all inclusion criteria. Random effects meta-analyses compared revision and mechanical failure rates between patients with an LIV above the CTJ and patients with an LIV below the CTJ. RESULTS: Data from 10 studies (total sample=2001, LIV above CTJ=1046, and LIV below CTJ=955) were meta-analyzed. No differences were found between the 2 cohorts for all-cause revision [odds ratio (OR)=0.75, 95% CI=0.42-1.34, P<0.0001] and construct-specific revision (OR=0.62, 95% CI=0.25-1.53, P<0.0001). The odds of total mechanical failure in the LIV below CTJ cohort compared with the LIV above CTJ cohort were significantly lower (OR=0.38, 95% CI=0.18-0.81, P<0.0001). CONCLUSION: The results show patients with PCFs ending below the CTJ have a lower risk of undergoing total mechanical failure compared with fusions ending above the CTJ. This is important information for both physicians and patients to consider when planning for operative treatment. LEVEL OF EVIDENCE: Level I.

Outcomes of Activity-Related Lower Extremity Muscle Tears After Application of the British Athletics Muscle Injury Classification: A Systematic Review.

CONTEXT: Muscle injury classification and grading systems have been reported for >100 years; yet it offer limited evidence relating the clinical or radiological qualities of a muscle injury to the pathology or clinical outcome. The British Athletics Muscle Injury Classification (BAMIC) incorporates recent predictive features of muscle injuries and provides a precise radiographic framework for clinical prediction and management. OBJECTIVE: To investigate clinical outcomes, particularly time to return to play (RTP), reinjury rate (RIR), and prognostic value of specific magnetic resonance imaging (MRI) findings, of activity-related muscle injuries (tears) in athletes after application of the BAMIC. DATA SOURCES: A search of PubMed (NLM), EMBASE (Ovid), Web of Science (Clarivate), Cochrane Library (Wiley), and ClinicalTrials.gov from the inception date of each database through August 31, 2022, was conducted. Keywords included the BAMIC. STUDY SELECTION: All English language studies evaluating clinical outcomes of RTP and RIR after activity-related muscle injuries and where BAMIC was applied were included. A total of 136 articles were identified, and 11 studies met inclusion criteria. STUDY DESIGN: Systematic review (PROSPERO: CRD42022353801). LEVEL OF EVIDENCE: Level 2. DATA EXTRACTION: Two reviewers independently screened studies for eligibility and extracted data. Methodological quality of included study was assessed independently by 2 reviewers with the Newcastle-Ottawa Quality Scale (NOS); 11 good quality studies (4 prospective cohort studies, 7 retrospective cohort studies) with 468 athletes (57 female) and 574 muscle injuries were included. RESULTS: All studies reported a statistically significant relationship between BAMIC grade, BAMIC injury site, and/or combined BAMIC grade and injury site with RTP. A statistically significant increased RIR was reported by BAMIC grade and BAMIC injury site in 2 of 4 and 3 of 4 studies, respectively. The prognostic value of individual MRI criteria was limited. CONCLUSION: Consistent evidence suggests that BAMIC offers prognostic and therapeutic guidance for clinical outcomes, particularly RTP and RIR, after activity-related muscle injuries in athletes that may be superior to previous muscle injury classification and grading systems.

Identification of Eimeria tenella sporozoite immunodominant mimotopes by random phage-display peptide libraries-a proof of concept study.

Introduction: Coccidiosis, caused by parasites of numerous Eimeria species, has long been recognized as an economically significant disease in the chicken industry worldwide. The rise of anti-coccidian resistance has driven a search for other parasite management techniques. Recombinant antigen vaccination presents a highly feasible alternative. Properly identifying antigens that might trigger a potent immune response is one of the major obstacles to creating a viable genetically modified vaccine. Methods: This study evaluated a reverse immunology approach for the identification of B-cell epitopes. Antisera from rabbits and hens inoculated with whole-sporozoites of E. tenella were used to identify Western blot antigens. The rabbit IgG fraction from the anti-sporozoite serum exhibited the highest reactogenicity; consequently, it was purified and utilized to screen two random Phage-display peptide libraries (12 mer and c7c mer). After three panning rounds, 20 clones from each library were randomly selected, their nucleotide sequences acquired, and their reactivity to anti-sporozoite E. tenella serum assessed. The selected peptide clones inferred amino acid sequences matched numerous E. tenella proteins. Results and Conclusions: The extracellular domain of the epidermal growth factor-like (EGF-like) repeats, and the thrombospondin type-I (TSP-1) repeats of E. tenella micronemal protein 4 (EtMIC4) matched with the c7c mer selected clones CNTGSPYEC (2/20) and CMSTGLSSC (1/20) respectively. The clone CSISSLTHC that matched with a conserved hypothetical protein of E. tenella was widely selected (3/20). Selected clones from the 12-mer phage display library AGHTTQFNSKTT (7/20), GPNSAFWAGSER (2/20) and HFAYWWNGVRGP (8/20) showed similarities with a cullin homolog, elongation factor-2 and beta-dynein chain a putative E. tenella protein, respectively. Four immunodominant clones were previously selected and used to immunize rabbits. By ELISA and Western blot, all rabbit anti-clone serums detected E. tenella native antigens. Discussion: Thus, selected phagotopes contained recombinant E. tenella antigen peptides. Using antibodies against E. tenella sporozoites, this study demonstrated the feasibility of screening Phage-display random peptide libraries for true immunotopes. In addition, this study looked at an approach for finding novel candidates that could be used as an E. tenella recombinant epitope-based vaccine.

A synthetic biology approach to engineering circuits in immune cells.

A synthetic circuit in a biological system involves the designed assembly of genetic elements, biomolecules, or cells to create a defined function. These circuits are central in synthetic biology, enabling the reprogramming of cellular behavior and the engineering of cells with customized responses. In cancer therapeutics, engineering T cells with circuits have the potential to overcome the challenges of current approaches, for example, by allowing specific recognition and killing of cancer cells. Recent advances also facilitate engineering integrated circuits for the controlled release of therapeutic molecules at specified locations, for example, in a solid tumor. In this review, we discuss recent strategies and applications of synthetic receptor circuits aimed at enhancing immune cell functions for cancer immunotherapy. We begin by introducing the concept of circuits in networks at the molecular and cellular scales and provide an analysis of the development and implementation of several synthetic circuits in T cells that have the goal to overcome current challenges in cancer immunotherapy. These include specific targeting of cancer cells, increased T-cell proliferation, and persistence in the tumor microenvironment. By harnessing the power of synthetic biology, and the characteristics of certain circuit architectures, it is now possible to engineer a new generation of immune cells that recognize cancer cells, while minimizing off-target toxicities. We specifically discuss T-cell circuits for antigen density sensing. These circuits allow targeting of solid tumors that share antigens with normal tissues. Additionally, we explore designs for synthetic circuits that could control T-cell differentiation or T-cell fate as well as the concept of synthetic multicellular circuits that leverage cellular communication and division of labor to achieve improved therapeutic efficacy. As our understanding of cell biology expands and novel tools for genome, protein, and cell engineering are developed, we anticipate further innovative approaches to emerge in the design and engineering of circuits in immune cells.

Clinical measurement of functional dart thrower's motion in patients with unilateral wrist conditions undergoing nonoperative or postoperative hand therapy.

STUDY DESIGN: Cross-sectional and descriptive study BACKGROUND: Functional dart thrower's motion (F-DTM) is an obliquely oriented wrist motion that occurs in activities such as throwing and drinking from a cup. There is limited data on clinical measurement of F-DTM. PURPOSE OF THE STUDY: The purpose of this study was to 1) describe and establish reference scores for F-DTM measurement for nonoperative and postoperative wrist patients 2) compare F-DTM between the affected and nonaffected sides and 3) determine F-DTM score agreement across three consecutive trials. METHODS: Two certified hand therapists evaluated F-DTM in consecutive adult patients with a unilateral wrist condition undergoing nonoperative or postoperative therapy. Three trials of goniometer measurements for radial extension (RE) and ulnar flexion (UF) were assessed on the nonaffected and affected wrists. A total arc F-DTM was computed. Mean, 95% confidence intervals (CI), and Cohen's d effect size described side-to-side differences in RE, UF, and total arc F-DTM. Agreement in scores across trials was assessed with an intraclass correlation coefficient (ICC). RESULTS: Thirty-one nonoperative (mean ± SD age = 40.0 ± 13.9 years, 74% female, 94% right hand dominant) and 44 postoperative patients (mean ± SD age = 44.9 ± 14.9 years, 66% female, 84% right hand dominant) were enrolled. The average side-to-side difference, in degrees, in the nonoperative group was -6.4 (95% CI: -9.4 to -3.4, Cohen's d = 0.8) for RE, -10.4 (-16.7 to -4.0, d = 0.6) for UF, and -16.8 (-24.3 to -9.2, d = 0.8) for total arc F-DTM. The average side-to-side difference in the postoperative group was -33.6 (-38.8 to -28.3, d = 1.9) for RE, -34.7 (-40.6 to -28.7, d = 1.8) for UF, and -68.2 (-77.9 to -58.5, d = 2.1) for total arc F-DTM. The range of ICCs for F-DTM measurements was 0.82-0.96. CONCLUSIONS: Goniometer measurement of F-DTM is a clinically feasible method to quantify functional motion loss in an injured wrist population, particularly patients with postoperatively managed wrist conditions.

Could Novel Radiographic Findings Help Identify Aseptic Tibial Loosening?

BACKGROUND: Aseptic loosening following total knee arthroplasty remains one of the leading causes of long-term failure. Radiographic identification of loose implants can be challenging with standard views. The purpose of this study was to compare the incidence of novel radiographic findings of anterior heterotopic bone formation and medial or lateral cyst formation in patients who have aseptic loosening to patients who have well-fixed implants. METHODS: A retrospective radiographic review was performed on 48 patients' revised secondary to aseptic tibial loosening. This cohort was compared to two additional cohorts; 48 patients returning for routine postoperative follow-up (control 1), and 48 patients revised secondary to infection or instability who had well-fixed implants (control 2). RESULTS: There were 41 of 48 (85%) patients who had implant loosening and were noted to have anterior heterotopic bone formation compared to 1 of 48 (2%) patients in control 1 and 3 of 48 (6%) patients in control 2 (P ≤ .0001). There were 43 of 48 (90%) patients who had implant loosening and had medial cyst formation compared to 3 of 48 (6%) patients in control 1 and 5 of 48 (10%) in control 2 (P ≤ .0001). There were 42 of 48 (88%) patients who had implant loosening and had lateral cyst formation compared to 2 of 48 (4%) patients in control 1 and 4 of 48 (8%) in control 2 (P ≤ .0001). CONCLUSION: In this study, we describe novel radiographic findings of anterior heterotopic bone formation and cysts that develop in patients who have aseptic loosening following primary total knee arthroplasty. We believe that these radiographic features may lead to easier identification of aseptic loosening.

A Conceptual Model for Spine Surgery Recovery: A Qualitative Study of Patients' Expectations, Experiences, and Satisfaction.

STUDY DESIGN: Qualitative interview study. OBJECTIVE: The aim was to develop a conceptual model for Spine Surgery Recovery in order to better understand why patients undergo lumbar spine surgery and what factors influence patient satisfaction. SUMMARY OF BACKGROUND DATA: Quantitative studies have assessed patients' expectations for lumbar spine surgery outcomes, with greater expectation fulfillment leading to higher satisfaction. However, there is limited literature using qualitative methods to understand the patient perspective from the decision to undergo lumbar spine surgery through long-term recovery. MATERIALS AND METHODS: Semistructured phone interviews were conducted with 20 participants (nine females, mean age ±SD=61.2±11.1 yr) and three focus groups with 12 participants (nine females, mean age ±SD=62.0±10.9 yr). Sessions were audio recorded and transcribed. Two independent researchers coded the transcripts using a hierarchical coding system. Major themes were identified and a conceptual model was developed. RESULTS: A total of 1355 coded quotes were analyzed. The decision to have lumbar spine surgery was influenced by chronic pain impact on daily function, pain coping, and patient expectations. Results demonstrated that fulfilled expectations and setting realistic expectations are key factors for patient satisfaction after surgery, while less known constructs of accepting limitations, adjusting expectations, and optimism were found by many patients to be essential for a successful recovery. Emotional factors of fear, anxiety, and depression were important aspects of presurgical and postsurgical experiences. CONCLUSION: Our Spine Surgery Recovery conceptual model provides guidance for future research and clinical practice to optimize treatment and improve overall patient satisfaction. Recommendations based on this model include the assessment of patient expectations and mental well-being throughout postoperative recovery as well as preoperatively to help set realistic expectations and improve satisfaction. Educational, acceptance-based or positive psychological interventions may be potentially beneficial for addressing key factors identified in this model.

Comparing Calcaneus Fracture Radiographic Outcomes and Complications after Percutaneous Pin versus Screw Fixation.

Calcaneus fracture fixation is associated with high rates of morbidity and disability from wound complications, infection, subtalar arthritis, and malunion. Percutaneous fixation with Kirshner wires (K-wires) or screws may be implemented when soft tissue injury precludes an open approach. Although screws are thought to provide greater stability, limited data exists directly comparing fixation success of these implants. Medical record data from 53 patients (62 total fractures) surgically treated with percutaneous screws (28 fractures) or K-wires (34 fractures) for joint-depression calcaneus fractures at a large tertiary hospital were retrospectively reviewed. Bohler's angle and calcaneal varus were assessed from available radiographs at time of injury, postoperatively, and at final follow-up, and joint congruity was assessed postoperatively and at final follow-up. Complications were also extracted. There were no statistical differences in patient characteristics between surgical groups although a higher proportion of patients treated with K-wires compared to screws had other associated injuries (79% vs 42%, p = .01). A higher proportion of fractures treated with screws compared to K-wires maintained joint congruity at the final follow-up (69% vs 32%, p = .005). However, there were no statistically detectable differences in other postoperative radiographic metrics (p > .05). In conclusion, joint congruity was more often maintained with screw fixation although there was no statistical difference in restoration and maintenance of Bohler's angle or varus alignment. The difference in radiographic metrics was not correlated with secondary procedures, namely subtalar arthrodesis, and may not be clinically significant. Neither group was completely effective in attaining and maintaining reduction, and additional fixation strategies should be considered if feasible based on patient, injury, and soft tissue characteristics.