Osseous and Cartilaginous Trochlear Development in the Pediatric Knee: A Cadaveric Computed Tomography Study.

Background: The anatomy of the trochlea plays a significant role in patellar stability. The developmental anatomy of the trochlea and its relationship to patellar stability remains poorly understood. Purpose: To describe the developmental changes of the osseous and cartilaginous trochlear morphology in skeletally immature specimens. Study Design: Descriptive laboratory study. Methods: A total of 65 skeletally immature cadaveric knees between the ages of 2 months and 11 years were evaluated using computed tomography scans. The measurements in the axial plane of both cartilage and bone include medial, central, and lateral trochlear height; sulcus height; medial and later trochlear facet length; trochlear sulcus angle; patellar sulcus angle; condylar height asymmetry; and trochlear facet asymmetry. Additional measurements included trochlear depth and lateral trochlear inclination angle. In the sagittal plane, measurements included curvilinear trochlear length, direct trochlear length, condylar height, and patellar sulcus angle. Results: Analysis of trochlear morphology using condylar height, condylar height asymmetry, and trochlear depth all increased with increasing age. The osseous and cartilaginous sulcus angles became deeper with age until age 8 and then plateaued. This corresponded with an increase in trochlear depth that also plateaued around age 8. Osseous condylar asymmetry increased with age but flipped from a larger medial condyle to a larger lateral condyle around age 8. The continued growth of the trochlea with age was further demonstrated in all measures in the sagittal view. Conclusion: This cadaveric analysis demonstrated that there is an increase in condylar height as age increased by all measurements analyzed. These changes in condylar height continued to be seen through age 11, suggesting a still-developing trochlea past this age. By age 8, a plateau in sulcus angle, and sulcus depth suggests more proportionate growth after this point. Similar changes in trochlear and patellar shape with age suggests that the 2 structures may affect each other during development. Clinical Relevance: This information can help design, develop, and determine timing of procedures that may alter the anatomy and stabilize the trochlear and patellofemoral joint.

Femorotibial rotation is Linearly Associated with Tibial Tubercle-Trochlear Groove Distance: A Cadaveric Study.

OBJECTIVES: A tibial tubercle-trochlear groove (TT-TG) distance of 20 millimeters (mm) is typically used when determining whether tibial tubercle medialization is performed for surgical treatment of patellar instability. Without knowledge of the variability of an individual's TT-TG distance influenced by through-the-knee femorotibial rotation, the use of a specific TT-TG distance during pre-operative planning for patellar instability may lead to incorrect decisions on the use of tibial tubercle medializtion. We hypothesized that knee joint IE rotation is related to the TT-TG distance. METHODS: Eight independent human cadaveric knee specimens (age: 32 ± 6 years; 4 males, 4 females) were utilized. A robotic manipulator (ZX165U, Kawasaki Robotics, Wixom, MI, USA) instrumented with a universal force/moment sensor was used to determine knee joint IE rotation under applied moments of ±5 newton-meters (Nm) at full extension. Two independent reviewers selected the trochlear groove and tibial tuberosity points on computerized tomography (CT) images of each specimen to define TT-TG. To determine the influence of knee joint IE rotation on TT-TG distance, three-dimensional (3D) models generated from CT scans were registered to tibiofemoral kinematics. Linear regression was performed to determine the relationship between knee joint IE rotation and TT-TG distance. The regression coefficient and standard error of measurement (α = 0.05), and coefficient of determination (r2) were reported. RESULTS: At 0° of rotation, the mean TT-TG distance was 14.2 ± 5.0 mm. Knee joint IE rotation averaged 23.0 ± 4.2°. For every degree of knee joint IE rotation, TT-TG distance changed by 0.52 mm. CONCLUSION: TT-TG distance was linearly dependent on knee joint IE rotation changing by 0.52 mm for every degree of knee joint IE rotation. Thus, an offset of IE rotation of 10° would lead to a change in TT-TG distance of 5.2 mm, enough to alter surgical decision-making for/or against tibial tubercle medialization. LEVEL OF EVIDENCE: IV: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15-24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin. However, these agents also cause rapid and significant loss of lean mass (∼10% or ∼6 kg), comparable to a decade or more of aging. Maintaining muscle mass and function as humans age is crucial to avoiding sarcopenia and frailty, which are strongly linked to morbidity and mortality. Studies indicate that supervised resistance exercise training interventions with a duration >10 weeks can elicit large increases in lean mass (∼3 kg) and strength (∼25%) in men and women. After a low-calorie diet, combining aerobic exercise with liraglutide improved weight loss maintenance compared with either alone. Retaining lean mass during incretin therapy could blunt body weight (and fat) regain on cessation of weight loss pharmacotherapy. We propose that tailored resistance exercise training be recommended as an adjunct to incretin therapy to optimize changes in body composition by preserving lean mass while achieving fat loss.

Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

Macrophage-fibroblast JAK/STAT dependent crosstalk promotes liver metastatic outgrowth in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease for which better therapies are urgently needed. Fibroblasts and macrophages are heterogeneous cell populations able to enhance metastasis, but the role of a macrophage-fibroblast crosstalk in regulating their pro-metastatic functions remains poorly understood. Here we deconvolve how macrophages regulate metastasis-associated fibroblast (MAF) heterogeneity in the liver. We identify three functionally distinct MAF populations, among which the generation of pro-metastatic and immunoregulatory myofibroblastic-MAFs (myMAFs) critically depends on macrophages. Mechanistically, myMAFs are induced through a STAT3-dependent mechanism driven by macrophage-derived progranulin and cancer cell-secreted leukaemia inhibitory factor (LIF). In a reciprocal manner, myMAF secreted osteopontin promotes an immunosuppressive macrophage phenotype resulting in the inhibition of cytotoxic T cell functions. Pharmacological blockade of STAT3 or myMAF-specific genetic depletion of STAT3 restores an anti-tumour immune response and reduces metastases. Our findings provide molecular insights into the complex macrophage-fibroblast interactions in tumours and reveal potential targets to inhibit PDAC liver metastasis.

Comparing the Impacts of Testosterone and Exercise on Lean Body Mass, Strength and Aerobic Fitness in Aging Men.

BACKGROUND: Based on the largely untested premise that it is a restorative hormone that may reverse the detrimental impacts of aging, prescription of testosterone (T) has increased in recent decades despite no new clinical indications. It is apparent that middle-aged and older men with low-normal serum T levels are considering T supplementation as an anti-aging strategy. At the same time, there is evidence that physical activity (PA) is at historical lows in the Western world. In this review, we compare the impacts of T treatment aimed at achieving physiological T concentrations in middle-aged and older men, alongside the impacts of ecologically relevant forms of exercise training. The independent, and possible combined, effects of T and exercise therapy on physiological outcomes such as aerobic fitness, body composition and muscular strength are addressed. MAIN BODY: Our findings suggest that both T treatment and exercise improve lean body mass in healthy older men. If improvement in lean body mass is the primary aim, then T treatment could be considered, and the combination of T and exercise may be more beneficial than either in isolation. In terms of muscle strength in older age, an exercise program is likely to be more beneficial than T treatment (where the dose is aimed at achieving physiological concentrations), and the addition of such T treatment does not provide further benefit beyond that of exercise alone. For aerobic fitness, T at doses aimed at achieving physiological concentrations has relatively modest impacts, particularly in comparison to exercise training, and there is limited evidence as to additive effects. Whilst higher doses of T, particularly by intramuscular injection, may have larger impacts on lean body mass and strength, this must be balanced against potential risks. CONCLUSION: Knowing the impacts of T treatment and exercise on variables such as body composition, strength and aerobic fitness extends our understanding of the relative benefits of physiological and pharmacological interventions in aging men. Our review suggests that T has impacts on strength, body composition and aerobic fitness outcomes that are dependent upon dose, route of administration, and formulation. T treatment aimed at achieving physiological T concentrations in middle-aged and older men can improve lean body mass, whilst exercise training enhances lean body mass, aerobic fitness and strength. Men who are physically able to exercise safely should be encouraged to do so, not only in terms of building lean body mass, strength and aerobic fitness, but for the myriad health benefits that exercise training confers.

Response of bilateral wilms tumor to chemotherapy suggests histologic subtype and guides treatment.

OBJECTIVES: Patients with bilateral Wilms tumor (BWT) initially receive neoadjuvant chemotherapy to shrink the tumors and increase the likelihood of successful nephron-sparing surgery. Biopsy of poorly responding tumors is often done to better understand therapy resistance. The purpose of this retrospective, single-institution study was to determine whether initial chemotherapy response is associated with tumor histology, potentially obviating the need for biopsy or change in chemotherapy. METHODS: Patients with synchronous BWT who underwent surgery at St Jude Children's Research Hospital from January 2000 to March 2022 were considered for this study. A mixed-effects logistic regression model was used to evaluate the likelihood of the tumor being stromal predominant, as predicted by tumor response to neoadjuvant chemotherapy. RESULTS: Sixty-eight patients were eligible for this study. Tumors that increased in size had an odds ratio of 19.5 (95% CI: 2.46-155.03) for being stromal-predominant vs any other histologic subtype. Age at diagnosis was youngest in patients with stromal-predominant tumors, with a mean age of 18.8 months (SD = 14.1 months), compared to all other histologic subtypes (χ2=7.05, p = .07). The predictive value of a tumor growing, combined with patient age less than 18 months, for confirming stromal-predominant histology was 85.7% (95% CI: 57.18%-93.5%). CONCLUSIONS: Tumors that increased in size during neoadjuvant chemotherapy were most frequently stromal-predominant BWT, especially in younger patients. Therefore, nephron-sparing surgery, rather than biopsy, or extension or intensification of neoadjuvant chemotherapy, should be considered for bilateral BWT that increase in volume during neoadjuvant chemotherapy, particularly in patients younger than 18 months of age.

Hemiepiphysiodesis for Genu Valgum in Patients With Multiple Hereditary Exostoses.

BACKGROUND: Genu valgum is a well-known feature of multiple hereditary exostoses (MHE). Though prior reports have demonstrated successful treatment with hemiepiphysiodesis, details regarding the correction rate and comparison to an idiopathic population are lacking. This study aimed to detail our institution's experience with guided growth of the knee in patients with MHE and compare this to an idiopathic population. METHODS: All pediatric patients (age 18 and younger) with MHE who underwent lower extremity hemiepiphysiodesis at a tertiary care medical center between January 2016 and December 2022 were retrospectively reviewed. Preoperative and postoperative mechanical lateral distal femoral angle (mLDFA) and medial proximal tibial angle (MPTA, the primary outcomes) were measured in addition to mechanical axis deviation (MAD) and hip-knee-ankle angle (HKA). Patients were 1:2 matched based on age, sex, and physes instrumented to a cohort with idiopathic genu valgum. RESULTS: A total of 21 extremities in 16 patients with MHE underwent hemiepiphysiodesis of the distal femur, proximal tibia, and/or distal tibia. The mean age at surgery was 11.7±2.2 years. Mean MAD corrected from zone 1.9±0.7 to -0.3±1.5, while mLDFA corrected from 83.4±2.9 to 91.7±5.2 degrees and MPTA corrected from 95.3±3.6 to 90.5±4.0 degrees in distal femurs and proximal tibias undergoing guided growth, respectively. Three extremities (14.3%) experienced overcorrection ≥5 degrees managed with observation. There were no differences in correction rates per month for mLDFA (0.54±0.34 vs. 0.51±0.29 degrees, P =0.738) or MPTA (0.31±0.26 vs. 0.50±0.59 degrees, P =0.453) between MHE and idiopathic groups. For 11 extremities in the MHE group with open physes at hardware removal, they experienced a mean recurrence of HKA of 4.0±3.4 degrees at 19-month follow-up. CONCLUSION: Hemiepiphysiodesis corrects lower extremity malalignment in patients with MHE at a similar rate compared with an idiopathic coronal plane deformity population. Rebound deformity of 4 degrees at 19 months after hardware removal in patients with remaining open growth plates should make surgeons conscious of the remaining growth potential when planning deformity correction. LEVEL OF EVIDENCE: Level III.

Oxygen isotopes in orangutan teeth reveal recent and ancient climate variation.

Studies of climate variation commonly rely on chemical and isotopic changes recorded in sequentially produced growth layers, such as in corals, shells, and tree rings, as well as in accretionary deposits-ice and sediment cores, and speleothems. Oxygen isotopic compositions (δ18O) of tooth enamel are a direct method of reconstructing environmental variation experienced by an individual animal. Here, we utilize long-forming orangutan dentitions (Pongo spp.) to probe recent and ancient rainfall trends on a weekly basis over ~3-11 years per individual. We first demonstrate the lack of any consistent isotopic enrichment effect during exclusive nursing, supporting the use of primate first molar teeth as environmental proxies. Comparisons of δ18O values (n=2016) in twelve molars from six modern Bornean and Sumatran orangutans reveal a high degree of overlap, with more consistent annual and bimodal rainfall patterns in the Sumatran individuals. Comparisons with fossil orangutan δ18O values (n=955 measurements from six molars) reveal similarities between modern and late Pleistocene fossil Sumatran individuals, but differences between modern and late Pleistocene/early Holocene Bornean orangutans. These suggest drier and more open environments with reduced monsoon intensity during this earlier period in northern Borneo, consistent with other Niah Caves studies and long-term speleothem δ18O records in the broader region. This approach can be extended to test hypotheses about the paleoenvironments that early humans encountered in southeast Asia.

When an animal drinks water, two naturally occurring variants of oxygen ­ known as oxygen-18 and oxygen-16 ­ are incorporated into its growing teeth. The ratio of these variants in water changes with temperature, rainfall and other environmental conditions and therefore can provide a record of the climate during an animal's life. Teeth tend to be well preserved as fossils, which makes it possible to gain insights into this climate record even millions of years after an animal's death. Orangutans are highly endangered great apes that today live in rainforests on the islands of Borneo and Sumatra. During a period of time known as the Pleistocene (around 2.6 million years to 12,000 years ago), these apes were more widely spread across Southeast Asia. Climate records from this area in the time before human-induced climate change are somewhat limited. Therefore, fossilized orangutan teeth offer a possible way to investigate past seasonal rainfall patterns and gain insight into the kind of environments early humans would have encountered. To address this question, Smith et al. measured oxygen-18 and oxygen-16 variants in thin slices of modern-day orangutan teeth using a specialized analytical system. This established that the teeth showed seasonal patterns consistent with recent rainfall trends, and that the ratio of these oxygen variants did not appear to be impacted by milk intake in young orangutans. These findings indicated that the oxygen variants could be a useful proxy for predicting prehistoric weather patterns from orangutan teeth. Further measurements of teeth from fossilized Sumatran orangutans showed broadly similar rainfall patterns to those of teeth from modern-day orangutans. On the other hand, fossilized teeth from Borneo suggested that the environment used to be drier, with less intense wet seasons. The approach developed by Smith et al. provides an opportunity for scientists to leverage new fossil discoveries as well as existing collections to investigate past environments. This could allow future research into how climate variation may have influenced the spread of early humans through the region, as well as the evolution of orangutans and other endangered animals.

Simultaneous MPFL reconstruction and guided growth result in low rates of recurrent patellofemoral instability.

PURPOSE: Implant-mediated guided growth (IMGG) is used to address coronal plane deformity in skeletally immature patients. Few studies have reported on IMGG and simultaneous medial patellofemoral ligament (MPFL) reconstruction for paediatric patients with concurrent genu valgum and patellofemoral instability (PFI). This study aimed to report on the outcomes of these simultaneous procedures. MATERIALS AND METHODS: This was a retrospective review of paediatric patients undergoing simultaneous MPFL reconstruction and IMGG between 2016 and 2023. Mechanical lateral distal femoral angle (mLDFA), hip-knee-ankle angle (HKA) and mechanical axis deviation (MAD) were measured on full-length hip-to-ankle plain radiographs. Measurements were taken preoperatively, prior to implant removal and/or at final follow-up with minimum 1-year clinical follow-up. RESULTS: A total of 25 extremities in 22 patients (10 female) underwent simultaneous IMGG and MPFL reconstruction. The mean age at surgery was 12.6 ± 1.7 years. The mean duration of implant retention was 18.6 ± 11.3 months. Nineteen extremities (76%) underwent implant removal by final follow-up. Preoperative HKA corrected from a mean of 5.8 ± 2.3° to -0.8 ± 4.5° at implant removal or final follow-up (p < 0.001), with mLDFA and MAD similarly improving (both p < 0.001). HKA corrected a mean of 0.7 ± 0.9° per month, while mLDFA and MAD corrected a mean of 0.5 ± 0.6°/month and 2 ± 3 mm/month, respectively. At the time of implant removal or final follow-up, 88% of patients demonstrated alignment within 5° of neutral. Only one extremity experienced subsequent PFI (4%). For 14 patients who underwent implant removal with further imaging at a mean of 7.8 ± 4.9 months, only one patient (7%) had a valgus rebound to an HKA > 5°. CONCLUSION: Simultaneous MPFL reconstruction and IMGG provided successful correction of lower extremity malalignment with only one recurrence of PFI. This approach is a reliable surgical option for skeletally immature patients with genu valgum and PFI. LEVEL OF EVIDENCE: Level 4 case series.

Impact of active surveillance and decolonization strategies for methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.

OBJECTIVE: To assess the impact of active surveillance and decolonization strategies on methicillin-resistant Staphylococcus aureus (MRSA) infection rates in a NICU. STUDY DESIGN: MRSA infection rates were compared before (2014-2016) and during (2017-2022) an active surveillance program. Eligible infants were decolonized with chlorohexidine gluconate (CHG) bathing and/or topical mupirocin. Successful decolonization and rates of recolonization were assessed. RESULTS: Fifty-two (0.57%) of 9 100 hospitalized infants had invasive MRSA infections from 2014 to 2022; infection rates declined non-significantly. During the 6-year surveillance program, the risk of infection was 16.9-times [CI95 8.4, 34.1] higher in colonized infants than uncolonized infants. Those colonized with mupirocin-susceptible MRSA were more likely successfully decolonized (aOR 9.7 [CI95 4.2, 22.5]). Of 57 infants successfully decolonized who remained hospitalized, 34 (60%) became recolonized. CONCLUSIONS: MRSA infection rates did not significantly decline in association with an active surveillance and decolonization program. Alternatives to mupirocin and CHG are needed to facilitate decolonization.

Cardiac functional adaptation to resistance and endurance exercise training: a randomized crossover study.

Few training studies have assessed the impact of different modes of exercise on changes in cardiac function. This study investigated changes in left ventricular (LV) systolic and diastolic function following endurance (END) and resistance (RES) training in healthy participants. Sixty-four individuals participated in a randomized crossover design trial, involving 12 wk of END and RES training, separated by a 12-wk washout. Echocardiograms assessed systolic function [ejection fraction (EF) and global longitudinal strain (GLS)], diastolic function [mitral valve early velocity (E), tissue Doppler velocity (e'), their ratio (E/e')], and left atrial volume indexed to body surface area (LA ESVi). LV mass (LVM) increased with both RES (Δ5.3 ± 11.9, P = 0.001) and END (Δ7.5 ± 13.9, P < 0.001). Once adjusted for lean body mass (LVMi), changes remained significant following END. E/e' improved following END (Δ-0.35 ± 0.98, P = 0.011) not RES (Δ0.35 ± 1.11, P =0.157; P = 0.001 between modes). LA ESVi increased with END (Δ2.0 ± 6.1, P = 0.019) but not RES (Δ1.7 ± 5.7, P = 0.113). EF and GLS were not impacted significantly by either mode of training. Adaptation in LVM and LA volumes, as well as diastolic function, was exercise mode specific. Twelve weeks of intensive END increased LVM, LA volumes, and increased diastolic function. Following RES, LVM increased, although this was attenuated after accounting for changes in lean body mass. There were no changes in systolic function following either mode of exercise training.NEW & NOTEWORTHY Different types of exercise training induce distinct physiological adaptations however few exercise training studies have assessed the impact of different modes of exercise on cardiac function. This study investigated changes in left ventricular systolic and diastolic function following exercise training. Participants completed both endurance and resistance training separated by a 12-wk washout period so each participant is their own control. We present adaptations in cardiac structure and diastolic function are exercise mode specific.

Timing and clinical risk factors for early acquisition of gut pathogen colonization with multidrug resistant organisms in the intensive care unit.

BACKGROUND: Microbiome restitution therapies are being developed to prevent gut pathogen colonization among patients in the intensive care unit (ICU) and in other select populations. If preventive therapies are to be effective, they must be administered prior to pathogen acquisition. The timing and risk factors for early acquisition of gut pathogen colonization (within 72 h) are currently unknown and could be helpful to guide ICU trial design. METHODS: This was a prospective cohort study. Patients in the ICU had deep rectal swabs performed within 4 h of ICU admission and exactly 72 h later. Early gut pathogen colonization was classified as the new presence (based on culture of rectal swabs) of one or more of the following organisms of interest: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant (VRE), and Gram-negative bacteria that showed multidrug resistance (MDR) or third generation Cephalosporin resistance (Ceph-R). Clinical risk factors for early acquisition of gut pathogen colonization were captured using the Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scoring system. FINDINGS: Among 131 patients who were swabbed at ICU admission and 72 h later, the rates of gut pathogen colonization at ICU admission were 11.4%, 10.6%, 38.6%, and 8.3% for MRSA, VRE, MDR and Ceph-R Gram-negatives respectively. Among the patients who were negative for a given pathogen at ICU admission, the rates of early acquisition of gut pathogen colonization were 7.8% for MRSA (95% CI 3.6 to 14.2%), 7.7% for VRE (95% CI 3.6 to 14.1%), 11.3% for MDR Gram-negatives (95% CI 4.4 to 18.8%), and 4.2% for Ceph-R Gram-negatives (95% CI 1.4 to 9.5%). There were no clinical risk factors which independently predicted early acquisition of gut pathogen colonization. INTERPRETATION: Early gut pathogen colonization was common in the ICU, but our single-center study could not identify any clinical risk factors which were significantly associated with acquisition of gut pathogens.

MPFL Reconstruction and Implant-Mediated Guided Growth in Skeletally Immature Patients With Patellar Instability and Genu Valgum.

BACKGROUND: There is a higher rate of failure of isolated MPFL reconstruction in skeletally immature patients with patellar instability compared to skeletally mature patients. Genu valgum is a known risk factor for patellar instability. There is potential for concomitant surgical correction of genu valgum to achieve better clinical outcomes and to decrease failure rates of MPFL reconstruction. PURPOSE: To evaluate outcomes of combined medial patellofemoral ligament (MPFL) reconstruction and implant-mediated guided growth (IMGG) in skeletally immature patients with patellar instability and genu valgum. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: In a multicenter study, all skeletally immature patients with recurrent patellar instability and genu valgum who underwent MPFL reconstruction using hamstring graft and IMGG using a transphyseal screw or tension band plate for the distal femur and/or proximal tibia were included. The knee valgus angle and mechanical axis were measured on full-length radiographs and anatomic risk factors were measured on MRI. Patients were followed until correction of their lower limb alignment and implant removal or until skeletal maturity. Clinical outcomes, including complications, were analyzed. RESULTS: A total of 31 patients (37 knees) were included in the study. The mean age and skeletal age of the cohort were 12.4 and 12.9 years, respectively. Simultaneous MPFL reconstruction and IMGG were performed in 26 of 37 knees; 11 underwent staged procedures. Twenty knees had transphyseal screws and 17 knees had tension band plates for IMGG. The knee valgus corrected from a mean of 12.4° to 5.1° in 12.1 months. Implants were removed from 22 of 37 knees once genu valgum was corrected. There was no significant difference (P = .65) in the correction rate between plates (0.7 deg/month) and screws (0.6 deg/month). Ten complications occurred in 4 patients (7 knees) and included 5 patellar redislocations, 2 rebound valgus, 1 varus overcorrection, 1 knee arthrofibrosis, and 1 implant loosening. For children <10 years of age, 3 of 6 (50%) knees had patellar redislocations and 5 of 6 knees had a complication. This was statistically significant (P = .003) compared with patients >10 years of age. Similarly, for patients with bilateral knee involvement, 5 of 12 (42%) knees had patellar redislocations and a total of 8 complications occurred in this subset. This was statistically significant (P < .001) compared with patients with unilateral involvement. CONCLUSION: IMGG with plates or screws in the setting of combined MPFL reconstruction improves genu valgum. Children <10 years of age and those with bilateral instability with genu valgum remain difficult subsets to treat with higher complication rates.

Recommendations for surveillance of pulmonary dysfunction among childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors.

Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial.

INTRODUCTION: Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC. METHODS AND ANALYSIS: In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient's baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model. ETHICS AND DISSEMINATION: The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT: 2019-002485-12; NCT04259138.

Decreased Effective Patellar Tendon Length following Distalization Tibial Tubercle Osteotomy without Patellar Tendon Tenodesis.

Background: Distalization tibial tubercle osteotomy (TTO) is an effective treatment for improving patellar height in patients with patella alta associated with patellofemoral instability and cartilage lesions. The addition of a patellar tendon tenodesis has been suggested; nonetheless, concerns exist regarding possible increased patellofemoral cartilage stresses. Purpose: To evaluate pre- and postoperative patellar tendon length and alignment parameters on magnetic resonance imaging (MRI), as well as patient-reported outcome measures (PROMs) after distalization TTO without patellar tendon tenodesis. Study Design: Case series; Level of evidence, 4. Methods: Twenty skeletally mature patients who underwent distalization TTO with or without anteromedialization at our institution between December 2014 and August 2021 were included. All patients underwent pre- and postoperative MRIs of the affected knee. The Caton-Deschamps index (CDI), the axial and sagittal tibial tubercle-trochlear groove (TT-TG) distances, the distances from the tibial plateau to the patellar tendon insertion and the tibial tubercle, and the patellar tendon length were assessed. PROMs included the International Knee Documentation Committee Subjective Knee Evaluation Form, the Knee injury and Osteoarthritis Outcome Score-Quality of Life subscale, the Kujala Anterior Knee Pain Scale, and the Veterans RAND 12-Item Health Survey mental and physical component scores. Results: The mean patient age at surgery was 27.4 years (range, 14-42 years). Radiographic parameters demonstrated improved patellar height (CDI decreased from 1.36 to 1.11; P < .001) after distalization TTO. The distance from the tibial plateau to the patellar tendon insertion significantly decreased from 20.1 mm preoperatively to 17.9 mm postoperatively (P < .020), and the patellar tendon length decreased from 53.4 mm preoperatively to 46.0 mm postoperatively (P < .001). The patellar tendon insertion was not distalized after distalization TTO, likely because of scarring of the patellar tendon proximal to the osteotomy site. Patients demonstrated significant pre- to postoperative improvements on all PROMs (P≤ .024 for all ). There were 4 (20%) complications-2 cases of arthrofibrosis, 1 postoperative infection, and 1 osteotomy delayed union. Conclusion: Distalization TTO without patellar tendon tenodesis was associated with improved radiographic outcomes and PROMs. It provides an additional tool for surgical management of patellofemoral pathology with associated patella alta.

Association of Quadriceps Tendon Harvest for ACL Reconstruction With Development of Osteochondritis Dissecans of the Patella in Pediatric Patients.

Background: There are various reported complications after primary anterior cruciate ligament reconstruction (ACLR) necessitating additional surgery in skeletally immature patients, regardless of technique and autograft type. Purpose: To analyze the rate and type of complications encountered with soft tissue quadriceps tendon autograft (QTA) for ACLR in patients ≤18 years as well as the overall rate of second surgery, unrelated to the use of the QTA. Study Design: Case series; Level of evidence, 4. Methods: A total of 141 patients ≤18 years who underwent ACLR with a QTA and had minimum 6-month follow-up were included. All patients underwent ACLR by utilizing a full-thickness soft tissue QTA. Complications associated with the QTA harvest site and use of QTA were reported. Results: The mean age of the included cohort (84 men, 57 women) was 14.8 ± 1.6 years. The average follow-up was of 2.0 ± 1.2 years. A total of 30 (21%) patients had a subsequent complication that required surgical intervention; in 11 (8%) patients, the complication was specifically associated with the use of a QTA, whereas in 19 (13%) patients, the complication was related to the ACLR. In addition, 13 (9%) patients underwent a contralateral ACLR procedure. Of the QTA-related complications, 2 patients developed osteochondritis dissecans (OCD)-like lesions in the superior aspect of the patella, 2 patients had injured their quadriceps extensor mechanism and required surgical repair, and 8 patients had a subsequent procedure to remove nonabsorbable sutures used for donor site quadriceps tendon closure. One of the patients who underwent the removal of nonabsorbable sutures also had an arthroscopic debridement of patellar chondral damage. Conclusion: We reported complications encountered with soft tissue QTA for ACLR. The complication rate for QTA harvest was 8%. However, given that the removal of nonabsorbable sutures from the donor site was caused by the surgical technique used, the revised nonsuture-related complication rate for QTA graft harvest was 2%. Although the use of a QTA has recently gained popularity due to its high return-to-sport and low graft-failure rates, surgeons should be aware of the complications associated with using this graft type.