1) Quantify the intensity of bone marrow oedema (BMO) present in the lumbar vertebrae of asymptomatic elite adult fast bowlers; 2) relate the intensity of BMO to bowling workload and lumbar bone ...stress injury (LBSI), and; 3) evaluate the utility of MRI screening to reduce the risk of LBSI.
Thirty-eight elite Australian fast bowlers (21.6 ± 3.7 years) completed 48 screening MRI over 3 years. BMO intensity was quantified on MRI retrospectively. Standard practices for bowling workload monitoring and injury diagnosis were followed.
Clinically significant BMO (signal intensity ratio ≥ 2.0) was observed in 22 (46%, 95% CI 31–61) screening MRI. These bowlers had a total of 77 (IQR 45–115) days off between seasons, compared to 66 (IQR 41–94) days off for bowlers with a BMO intensity less than 2.0 (p = 0.510). Fifteen bowlers received follow up MRI as part of individualised management based on their screening MRI, of which less than five went on to develop LBSI in the subsequent season. There was no difference in days or balls bowled in the 12 months following screening MRI between those who sustained LBSI and those who did not.
BMO is common in asymptomatic bowlers. Identification of high-risk bowlers using screening MRI informs individualised management and may prevent progression to LBSI.
•Bone marrow oedema is common in asymptomatic elite adult fast bowlers•Quantifying bone marrow oedema intensity on MRI has excellent reliability regardless of radiological experience•MRI may be used as a screening tool to guide individualised management and reduce the risk of severe lumbar bone stress
Background
Mitotic rate is a strong, independent prognostic factor in patients with melanoma. However, incorporating it into the melanoma staging system has proved challenging.
Methods
The prognostic ...impact of mitotic rate was assessed in a melanoma cohort comprising 5050 patients from 2 geographically distinct populations. Computer‐generated cut points for mitotic rate were constructed to determine its impact on melanoma‐associated survival using Kaplan‐Meier and multivariate regression analyses. The impact of mitotic rate also was assessed in randomly split training and validation sets.
Results
Mitotic rate had a nonlinear impact on survival, as evidenced by unequally spaced cut points. An index incorporating these cut points that was constructed from one population produced significantly more accurate predictions of survival in the other population than using the entire scale of mitotic rate. An index constructed from the combined cohort was found to be independently predictive of survival, with an impact comparable to that of ulceration. Optimal high‐versus‐low cut points for mitotic rate were generated separately for each T category (<2 mitoses/mm2 vs ≥2 mitoses/mm2 for T1 melanoma, <4 mitoses/mm2 vs ≥4 mitoses/mm2 for T2 melanoma, <6 mitoses/mm2 vs ≥6/mitoses/mm2 for T3 melanoma, and <7 mitoses/mm2 vs ≥7 mitoses/mm2 for T4 melanoma). Using Kaplan‐Meier analysis, elevated mitotic rate was found to have an impact on survival comparable to that of ulceration within each T category. Application of the index for mitotic rate that was constructed from the training data set demonstrated an independent impact in the validation data set, with a significance similar to that of ulceration.
Conclusions
The results of the current study demonstrated the comparable prognostic impact of mitotic rate and ulceration, providing support for its reincorporation into the T category.
The identification of computer‐generated, optimal high‐risk versus low‐risk cut points for mitotic rate, separately within each T category, demonstrates a prognostic significance that is similar to that of ulceration in the prediction of melanoma‐associated survival. The results of the current study also indicate that mitotic rate has an overall prognostic impact on survival similar to that of ulceration, thereby justifying further its incorporation into the T category of the melanoma staging system, resulting in improved predictive accuracy for individual patients.
The purpose of this study was to evaluate the safety and efficacy of intra-articular injections of autologous peripheral blood stem cells (PBSCs) plus hyaluronic acid (HA) after arthroscopic ...subchondral drilling into massive chondral defects of the knee joint and to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than HA plus physiotherapy.
This is a dual-center randomized controlled trial (RCT). Sixty-nine patients aged 18 to 55 years with International Cartilage Repair Society grade 3 and 4 chondral lesions (size ≥3 cm2) of the knee joint were randomized equally into (1) a control group receiving intra-articular injections of HA plus physiotherapy and (2) an intervention group receiving arthroscopic subchondral drilling into chondral defects and postoperative intra-articular injections of PBSCs plus HA. The coprimary efficacy endpoints were subjective International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS)–pain subdomain measured at month 24. The secondary efficacy endpoints included all other KOOS subdomains, Numeric Rating Scale (NRS), and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores.
At 24 months, the mean IKDC scores for the control and intervention groups were 48.1 and 65.6, respectively (P < .0001). The mean for KOOS-pain subdomain scores were 59.0 (control) and 86.0 (intervention) with P < .0001. All other KOOS subdomain, NRS, and MOCART scores were statistically significant (P < .0001) at month 24. Moreover, for the intervention group, 70.8% of patients had IKDC and KOOS-pain subdomain scores exceeding the minimal clinically important difference values, indicating clinical significance. There were no notable adverse events that were unexpected and related to the study drug or procedures.
Arthroscopic marrow stimulation with subchondral drilling into massive chondral defects of the knee joint followed by postoperative intra-articular injections of autologous PBSCs plus HA is safe and showed a significant improvement of clinical and radiologic scores compared with HA plus physiotherapy.
Level I, RCT.
This study presents seven seasons of injury surveillance data for both elite Australian male and female cricket players, revealing injury statistics and allowing for comparison between sexes.
...Retrospective cohort.
Participants were elite Australian male and female cricket players who were contracted to play for a national and/or state/territory team and/or T20 franchise between 2015–16 and 2021–22 (7 seasons). Injury data was recorded in Cricket Australia's Athlete Management System database and combined with match data. The STROBE-SIIS statement was used as the relevant guideline for this study.
Data for 1345 male player seasons and 959 female player seasons revealed sex-related differences in the injury incidence rates and prevalence. Males had higher incidence (average 136 vs 101 injuries per 1000 match days) and prevalence of match time-loss injuries (average 10.4% vs 6.5% players unavailable). However, the overall incidence of all medical attention injuries were similar between sexes (Incidence Rate Ratio (IRR) 0.9, 95%CI 0.8–1.0). The most frequent match time-loss injuries for males were hamstring strains (7.4 new injuries per 100 players per season), side and abdominal strains (5.5), concussion (5.0), lumbar stress fractures (4.3), and wrist and hand fractures (3.9). The most frequent match time-loss injuries for females over the 7 seasons were hamstring strains (3.1), concussion (2.3), quadriceps strains (2.4) and shin/foot/ankle stress fractures (2.0). The IRR of medical attention injuries for males compared to females was higher for lumbosacral stress fractures (IRR 2.3), elbow and forearm injuries (1.5), and concussion (1.4), and lower for lower leg, foot, and ankle stress fractures (0.6), shoulder and upper arm injuries (0.7), and quadriceps strains (0.6).
Robust long-term injury surveillance enabled the injury profiles of elite Australian male and female cricket players to be understood and compared. Males had a higher incidence and prevalence of match time-loss injuries, likely reflecting a higher match exposure.
The F1FO‐ATP synthase is required for growth and viability of Mycobacterium tuberculosis and is a validated clinical target. A mycobacterium‐specific loop of the enzyme's rotary γ subunit plays a ...role in the coupling of ATP synthesis within the enzyme complex. We report the discovery of a novel antimycobacterial, termed GaMF1, that targets this γ subunit loop. Biochemical and NMR studies show that GaMF1 inhibits ATP synthase activity by binding to the loop. GaMF1 is bactericidal and is active against multidrug‐ as well as bedaquiline‐resistant strains. Chemistry efforts on the scaffold revealed a dynamic structure activity relationship and delivered analogues with nanomolar potencies. Combining GaMF1 with bedaquiline or novel diarylquinoline analogues showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. These results suggest that GaMF1 presents an attractive lead for the discovery of a novel class of anti‐tuberculosis F‐ATP synthase inhibitors.
TB or not TB: The antimycobacterial compound GaMF1 inhibits the mycobacterial F‐ATP synthase by binding to a specific loop of subunit γ, preventing ATP synthesis. GaMF1 is active against multidrug‐resistant Mycobacterium tuberculosis strains and increases the potency of the TB drug bedaquiline and its analogues, thereby offering potential for an efficient multidrug combination. Medicinal chemistry efforts gave analogues with nanomolar potency.
Toxic peripheral neuropathies have been described, and are typically cumulative in their pathophysiology. Cranial neuropathies secondary to medication toxicity are extremely rare. Use of ...emtricitabine/tenofovir as pre-exposure prophylaxis (PrEP) is recommended as standard of care for people at risk of HIV infection. Cranial neuropathies as an adverse effect of this drug have only been described once in the literature (Van Slyke, 2018). We present the case of a 22-year-old information technology worker who developed acute right trigeminal neuritis within 24 hours of initiating emtricitabine/tenofovir. MRI with gadolinium contrast demonstrated abnormal T2 signal hyperintensity and enhancement affecting the maxillary and mandibular divisions of the right trigeminal nerve, with the ophthalmic division involved to a lesser degree. Symptoms resolved within 6 weeks following medication cessation and repeat MRI imaging showed near resolution of enhancement. Despite advice, the patient rechallenged the medication and within 24 hours his symptoms recurred. The proposed mechanism of trigeminal neuropathy is a toxic neuritis due to tenofovir, with some studies showing modulation of mitochondrial biogenesis and inflammatory pathways (Fields, 2019).ReferencesVan Slyke L, Scott M. Acute trigeminal neuralgia associated with initiation of emtricitabine/tenofovir for HIV pre-exposure prophylaxis. J Int Assoc Provid AIDS Care. 2018;17:2325958218760846.Fields JA, Swinton MK, Carson A, Soontornniyomkij B, Lindsay C, Han MM, Frizzi K, Sambhwani S, Murphy A, Achim CL, Ellis RJ, Calcutt NA. Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice. Sci Rep. 2019 Nov 20;9(1).
Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, ...alterations in these "non-smoking-related oncogenes" (NSROs) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared to typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and non-smokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC datasets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to regulation of the cell cycle. These findings suggest that, while the genomic landscape is similar between NSRO-driven NSCLC in smokers and non-smokers, smoking still affects the tumor phenotype independently of genomic alterations.
Purpose
In sentinel node-positive (SN+ve) melanoma patients, active surveillance with regular ultrasound examination of the node field has become standard, rather than completion lymph node ...dissection (CLND). A proportion of these patients now receive adjuvant systemic therapy and have routine cross-sectional imaging (computed tomography CT or positron emission tomography PET/CT). The role of concurrent ultrasound (US) surveillance in these patients is unclear. The purpose of our study was to describe the modality of detection of nodal recurrence in SN+ve node fields.
Methods
SN+ve melanoma patients who did not undergo CLND treated at a single institution from January 1, 2016 to December 31, 2020 were included.
Results
A total of 225 SN+ve patients with a median follow-up of 23 months were included. Of these, 119 (53%) received adjuvant systemic therapy. Eighty (36%) developed a recurrence at any site; 24 (11%) recurred first in the SN+ve field, of which 12 (5%) were confirmed node field recurrence only at 2 months follow-up. The nodal recurrences were first detected by ultrasound in seven (3%), CT in seven (3%), and PET/CT in seven (3%) patients. All nodal recurrences evident on US were also evident on PET/CT and vice versa.
Conclusions
The high rate of recurrences outside the node field and the identification of all US-detected nodal recurrences on concurrent cross-sectional imaging modalities suggest that routine concurrent ultrasound surveillance of the node-positive field may be unnecessary for SN+ve melanoma patients having routine cross-sectional imaging.
The Pan American Health Organization/World Health Organization (PAHO/WHO) Anti-Infodemic Virtual Center for the Americas (AIVCA) is a project led by the Department of Evidence and Intelligence for ...Action in Health, PAHO and the Center for Health Informatics, PAHO/WHO Collaborating Center on Information Systems for Health, at the University of Illinois, with the participation of PAHO staff and consultants across the region. Its goal is to develop a set of tools-pairing AI with human judgment-to help ministries of health and related health institutions respond to infodemics. Public health officials will learn about emerging threats detected by the center and get recommendations on how to respond. The virtual center is structured with three parallel teams: detection, evidence, and response. The detection team will employ a mixture of advanced search queries, machine learning, and other AI techniques to sift through more than 800 million new public social media posts per day to identify emerging infodemic threats in both English and Spanish. The evidence team will use the EasySearch federated search engine backed by AI, PAHO's knowledge management team, and the Librarian Reserve Corps to identify the most relevant authoritative sources. The response team will use a design approach to communicate recommended response strategies based on behavioural science, storytelling, and information design approaches.
ObjectivesLumbar bone stress injury (‘bone stress injury’) is common in junior fast bowlers. The repetitive loading of cricket fast bowling may cause bone marrow oedema (BMO), detectable on MRI, ...before the bowler suffers from symptomatic bone stress injury. We investigated the temporal relationship between BMO, bone stress injury, along with bowling workload correlates, in elite junior fast bowlers throughout a cricket season.Methods65 junior fast bowlers were prospectively monitored for one 8-month cricket season. For research purposes, participants had up to six MRI scans at set times in the season; findings were withheld from them and their clinicians. Standard practices for bowling workload monitoring and injury diagnosis were followed.Results15 (23%) participants developed bone stress injury during the study. All 15 of these participants had BMO detected on at least one of the preceding MRI scans, including the scan immediately prior to diagnosis. The risk of BMO progressing to bone stress injury during the season was greatest for participants with BMO present 2 weeks prior to the national championship tournament (period of high load) (RR=18.9, OR=44.8). Both bone stress injury and BMO were associated with bowling a higher percentage of days in training and having a shorter bowling break during the season. The number of balls bowled and acute-to-chronic workload were not associated with imaging abnormalities or injury.ConclusionThe presence of BMO on MRI in asymptomatic junior cricket fast bowlers confers a very high risk for bone stress injury. The risk may be managed by MRI screening and monitoring bowling frequency.
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