The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique

Objective To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. Methods Women aged 30­49 years were prospectively enrolled and offered primary HPV testing using either self- collected or provider- collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. Results Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30­49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self- collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV- positive patients, 2588 (92.3%) returned for all steps of their diagnostic work- up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty- one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. Conclusion It is feasible to perform cervical cancer screening with primary HPV testing and follow- up in low- resource settings. Participants preferred self- collection, and the majority of screen- positive patients completed all steps of their diagnostic work- up and treatment. Our findings provide important information for further implementation and scale- up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Substitutional/positional disorder of biguanide and guanylurea in the structure of a decavanadate complex [(Bg)(HV10O285-)]0.4[(HGU+)(V10O286-)]0.6(H2Met2+)2(H3O+)·8H2O.

A hydrated salt of decavanadate containing diprotonated metforminium(2+) (H2Met2+), hydronium (H3O+) and either neutral biguanide (Bg) or monoprotonated guanylurea (HGU+) exhibits a previously seen complex charge-stabilized hydrogen-bonded network [Chatkon et al. (2022). Acta Cryst. B78, 798-808]. Charge balance is achieved in two ways through substitutional disorder: a 0.6 occupied HGU+ cation is paired with a V10O286- anion, and a 0.4 occupied neutral Bg molecule is paired with a HV10O285- anion, with the remaining charge in both cases balanced by two H2Met2+ dications and one H3O+ monocation. Bg/HGU+ moieties exhibit bifurcated N-H...O hydrogen bonding to the H3O+ cation and are substitutionally/positionally disordered along with the H3O+ cation about an inversion center. The HGU+ V10O286- synthon seen in the previous study occurs again. Bg exhibits bifurcated hydrogen bonding from two amino groups to two rows of cluster O atoms running diagonally across the equatorial plane of the HV10O285- anion with a return hydrogen bond from the cluster H atom to the imino N atom of the Bg. Thus, a Bg...cluster synthon similar to the HGU+...cluster synthon previously reported is found. The disordered moieties occupy spaces with excess volume in the 3-D network structure. Interestingly, when the crystallographic unit cell of the current compound, whose X-ray data was collected at 100 K, is compared with that of a previous compound exhibiting the same supramolecular framework, unit-cell parameter c does not shorten as a and b expectantly do because of the lower data collection temperature. The lack of contraction on unit-cell parameter c is possibly due to the supramolecular structure.

Genetic Manipulation of Neisseria gonorrhoeae and Commensal Neisseria Species.

The sexually transmitted pathogen, Neisseria gonorrhoeae, undergoes natural transformation at high frequency. This property has led to the rapid dissemination of antibiotic resistance markers and the panmictic structure of the gonococcal population. However, high-frequency transformation also makes N. gonorrhoeae one of the easiest bacterial species to manipulate genetically in the laboratory. Techniques have been developed that result in transformation frequencies >50%, allowing the identification of mutants by screening and without selection. Constructs have been created to take advantage of this high-frequency transformation, facilitating genetic mutation, complementation, and heterologous gene expression. Similar methods have been developed for N. meningitidis and nonpathogenic Neisseria including N. mucosa and N. musculi. Techniques are described for genetic manipulation of N. gonorrhoeae and commensal Neisseria species, as well as for growth of these fastidious organisms. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Spot transformation of Neisseria gonorrhoeae on agar plates Basic Protocol 2: Spot transformation of commensal Neisseria on agar plates Basic Protocol 3: Transformation of Neisseria gonorrhoeae in liquid culture Basic Protocol 4: Electroporation of Neisseria gonorrhoeae Basic Protocol 5: Creation of unmarked mutations using a positive and negative selection cassette Basic Protocol 6: In vitro mutagenesis of Neisseria gonorrhoeae chromosomal DNA using EZ-Tn5 Basic Protocol 7: Chemical mutagenesis Basic Protocol 8: Complementation on the Neisseria gonorrhoeae chromosome Alternate Protocol 1: Complementation with replicating plasmids Alternate Protocol 2: Complementation on the Neisseria musculi or Neisseria mucosa chromosome Basic Protocol 9: Preparation of chromosomal DNA from Neisseria gonorrhoeae grown on solid medium Alternate Protocol 3: Preparation of chromosomal DNA from Neisseria gonorrhoeae grown in broth Support Protocol: Preparing PCR templates from Neisseria gonorrhoeae colonies.

Nicotine use during late adolescence and young adulthood is associated with changes in hippocampal volume and memory performance.

Background: With the advent of electronic nicotine delivery systems, the use of nicotine and tobacco products (NTPs) among adolescents and young adults remains high in the US. Use of e-cigarettes additionally elevates the risk of problematic use of other substances like cannabis, which is often co-used with NTPs. However, their effects on brain health, particularly the hippocampus, and cognition during this neurodevelopmental period are poorly understood. Methods: Healthy late adolescents/young adults (N = 223) ages 16-22 completed a structural MRI to examine right and left hippocampal volumes. Memory was assessed with the NIH Toolbox Picture Sequence Memory Test (PSMT) and Rey Auditory Verbal Learning Test (RAVLT). Cumulative 6-month NTP and cannabis episodes were assessed and modeled continuously on hippocampal volumes. Participants were then grouped based on 6-month NTP use to examine relationships with the hippocampus and memory: current users (CU) endorsed weekly or greater use; light/abstinent users (LU) endorsed less than weekly; and never users (NU). Results: NTP use predicted larger hippocampal volumes bilaterally while cannabis use had no impact nor interacted with NTP use. For memory, larger left hippocampal volumes were positively associated with PSMT performance, RAVLT total learning, short delay and long delay recall for the NU group. In contrast, there was a negative relationship between hippocampal volumes and performances for LU and CU groups. No differences were detected between NTP-using groups. Conclusion: These results suggest that the hippocampus is sensitive to NTP exposure during late adolescence/young adulthood and may alter typical hippocampal morphometry in addition to brain-behavior relationships underlying learning and memory processes.

Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926.

PURPOSE: To investigate the use of radiation with radiosensitizing chemotherapy following repeated transurethral resection (trimodality therapy) as an alternative to radical cystectomy in T1 bladder cancer which has failed Bacillus Calmette-Guerin (BCG). PATIENTS AND METHODS: Patients with recurrent T1 bladders who had failed BCG and were recommended to undergo cystectomy were treated with trimodality therapy. The primary end point was 3-year freedom from cystectomy. Secondary end points were distant metastasis at 3 and 5 years, local recurrence, disease-specific and overall survival (OS), and safety. RESULTS: This single-arm phase II study enrolled 37 patients. Efficacy and safety were evaluated in 34 patients after three exclusions. The median follow-up was 5.1 years. The 3-year freedom from cystectomy rate was 88% (lower one-sided 97.5% confidence limit [CI], 72%), meeting the primary study goal. OS at 3 and 5 years was 69% (95% CI, 54 to 85) and 56% (95% CI, 39 to 74), respectively. The distant metastasis rates at 3 and 5 years were 12% (95% CI, 4 to 26) and 19% (95% CI, 7 to 34), respectively. Eight patients died due to urothelial cancer, 12 exhibited local recurrence at 3 years (cumulative incidence: 32%; 95% CI, 17 to 48), 18 experienced grade 3 adverse events, mostly hematological, and one developed grade 4 neutropenia. CONCLUSION: Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder. At 3 years, 88% of the patients remained free of cystectomy.

Age differences in BOLD modulation to task difficulty as a function of amyloid burden.

Effective cognitive performance often requires the allocation of additional neural resources (i.e. blood-oxygen-level-dependent [BOLD] activation) as task demands increase, and this demand-related modulation is affected by amyloid-beta deposition and normal aging. The present study investigated these complex relationships between amyloid, modulation, and cognitive function (i.e. fluid ability). Participants from the Dallas Lifespan Brain Study (DLBS, n = 252, ages 50-89) completed a semantic judgment task during functional magnetic resonance imaging (fMRI) where the judgments differed in classification difficulty. Amyloid burden was assessed via positron emission tomography (PET) using 18F-florbetapir. A quadratic relationship between amyloid standardized value uptake ratios (SUVRs) and BOLD modulation was observed such that modulation was weaker in those with moderately elevated SUVRs (e.g. just reaching amyloid-positivity), whereas those with very high SUVRs (e.g. SUVR > 1.5) showed strong modulation. Greater modulation was related to better fluid ability, and this relationship was strongest in younger participants and those with lower amyloid burden. These results support the theory that effective demand-related modulation contributes to healthy cognitive aging, especially in the transition from middle age to older adulthood, whereas high modulation may be dysfunctional in those with substantial amyloid deposition.

The Role of Bone Grafting vs. Bone Cement in the Treatment of Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis on the Risk of Recurrence in 1,454 Patients.

BACKGROUND: Giant cell tumor of bone (GCTB) presents a challenge in management due to its invasive nature and propensity for local recurrence. While either bone grafting (BG) or bone cement (BC) can be utilized to fill defects after intralesional curettage, the optimal treatment remains contested. The purpose of this study was to examine the impact of defect filling with BC compared with BG on recurrence rates in patients with GCTB following intralesional curettage. METHODS: A random-effects model binary outcome meta-analysis was performed utilizing recurrence rate for the BC and BG groups to evaluate the risk ratio (p < 0.05 considered significant). There were 1,454 patients included. RESULTS: Intralesional curettage with BG had a recurrence risk ratio of 1.68 (95% confidence interval [CI], 1.22-2.31, p = 0.001) when compared with BC. The overall rate of recurrence for GCTB after intralesional curettage with BC was 20.05% vs. 29.74% with BG (95% CI, 0.17-0.23 vs. 0.26-0.33, p < 0.001). CONCLUSION: Intralesional curettage with BC for the treatment of GCTB demonstrated lower recurrence rates than intralesional curettage with BG. However, the rates of recurrence remain substantial for both groups, necessitating careful consideration of the benefits and potential pitfalls associated with BC vs. BG when considering salvage options after recurrences. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Metabolic Choreography of Energy Substrates During DCD Heart Perfusion.

Background: The number of patients waiting for heart transplant far exceeds the number of hearts available. Donation after circulatory death (DCD) combined with machine perfusion can increase the number of transplantable hearts by as much as 48%. Emerging studies also suggest machine perfusion could enable allograft "reconditioning" to optimize outcomes. However, a detailed understanding of the energetic substrates and metabolic changes during perfusion is lacking. Methods: Metabolites were analyzed using 1-dimensional 1H and 2-dimensional 13C-1H heteronuclear spectrum quantum correlation nuclear magnetic resonance spectroscopy on serial perfusate samples (N = 98) from 32 DCD hearts that were successfully transplanted. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test for significant differences in metabolite resonances during perfusion and network analysis was used to uncover altered metabolic pathways. Results: Metabolite differences were observed comparing baseline perfusate to samples from hearts at time points 1-2, 3-4, and 5-6 h of perfusion and all pairwise combinations. Among the most significant changes observed were a steady decrease in fatty acids and succinate and an increase in amino acids, especially alanine, glutamine, and glycine. This core set of metabolites was also altered in a DCD porcine model perfused with a nonblood-based perfusate. Conclusions: Temporal metabolic changes were identified during ex vivo perfusion of DCD hearts. Fatty acids, which are normally the predominant myocardial energy source, are rapidly depleted, while amino acids such as alanine, glutamine, and glycine increase. We also noted depletion of ketone, ß-hydroxybutyric acid, which is known to have cardioprotective properties. Collectively, these results suggest a shift in energy substrates and provide a basis to design optimal preservation techniques during perfusion.

Vascular Complications in Extracorporeal Membrane Oxygenation-A Narrative Review.

The establishment of a peripheral ECMO circuit can lead to significant arterial and venous complications in 10-30% of patients. Vascular complications, particularly acute limb ischemia, are associated with worsening overall outcomes. Limb ischemia occurs significantly more frequently in the early stages of VA ECMO than in VV ECMO. Mechanisms of limb ischemia include arterial obstruction, cannulation injury, loss of pulsatile flow, thromboembolism, venous stasis from compressive obstruction with large venous cannulas, and systemic vasoconstriction due to shock and pharmacologic vasoconstriction. The care team may use several mitigation strategies to prevent limb ischemia. Arterial and venous complications can be mitigated by careful access site selection, minimizing cannula size, placement of distal perfusion and/or outflow catheter(s), and continuous NIRS monitoring. Rapid intervention, when ischemia or compartment syndrome occurs, can reduce limb loss but may not affect the mortality and morbidity of the ECMO patient in the long term due to their underlying conditions and the etiology of the ECMO need.

Immunotherapy and transarterial embolization in patients with metastatic melanoma: a retrospective cohort study.

Aim: To investigate how the sequence of checkpoint immunotherapy (CPI) and transarterial embolization (TAE) affects overall survival (OS) of patients with metastatic melanoma.Materials & methods: This retrospective cohort study included 65 patients with metastatic melanoma who underwent both TAE and CPI between September 2011 and January 2022.Results: Significantly higher OS was seen in patients who received CPI before and after embolization (22 months, 95% CI 14-NR, p < 0.001) compared with only before embolization (4.5 months 95% CI, 14-NR). ≤3 hepatic metastasis (p < 0.01), more TAE procedures (p < 0.001) and CPI sequence (before and after embolization) (p < 0.001) were independent predictors of survival.Conclusion: Metastatic melanoma patients who underwent TAE have longer survival when CPI was sequenced both before and after embolization.

This study looked at how the order of two treatments, called checkpoint immunotherapy (CPI) and transarterial embolization (TAE), affects how long people with metastatic melanoma live. Sixty-five patients who had both treatments between September 2011 and January 2022 took part in the study. Patients with fewer than three liver metastases, cancer in just one part of the liver, and who had more TAE treatments tended to live longer. Patients who got CPI both before and after TAE lived longer compared with those who only got CPI before TAE.

Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial.

Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies1-4. A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound5-7. Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2. The primary endpoints were safety, tolerability and pharmacokinetics, and the secondary endpoints in part 2 were antiviral activity following ART discontinuation, changes in CD4+ T cell counts and development of HIV-1 sequence mutations associated with bNAb resistance. The trial met its prespecified endpoints. The bNAb treatment was generally safe and well tolerated. In part 2, 83% of participants (10 of 12) maintained virologic suppression for the duration of antibody therapy for at least 28 weeks, and 42% of participants (5 of 12) showed virologic suppression for at least 38-44 weeks, despite the decline of serum bNAb concentrations to low or undetectable levels. In exploratory analyses, early viral rebound in two individuals correlated with baseline resistance to PGT121 and PGDM1400, whereas long-term virologic control in five individuals correlated with reduced immune activation, T cell exhaustion and proinflammatory signaling following bNAb therapy. Our data show the potential of a triple bNAb cocktail to suppress HIV-1 in the absence of ART. ClinicalTrials.gov registration: NCT03721510 .

Risk of Incident Psychosis and Mania With Prescription Amphetamines.

OBJECTIVE: Amphetamine prescribing has increased in the United States in recent years. Previous research identified an increased risk of incident psychosis with prescription amphetamines. The purpose of this study was to examine the impact of dose levels of prescription amphetamines on the risk of this rare but serious adverse outcome. METHODS: A case-control study using electronic health records was conducted to compare the odds of incident psychosis or mania with past-month exposure to prescription amphetamines. Case subjects were patients ages 16-35 hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. Control subjects were patients with an initial psychiatric hospitalization for other reasons, most commonly depression and/or anxiety. Amphetamine doses were converted to dextroamphetamine equivalents and divided into terciles. Secondary analyses evaluated the odds of psychosis or mania with methylphenidate use. RESULTS: Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for individuals with past-month prescription amphetamine use compared with no use (adjusted odds ratio=2.68, 95% CI=1.90-3.77). A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with 5.28-fold increased odds of psychosis or mania. Past-month methylphenidate use was not associated with increased odds of psychosis or mania compared with no use (adjusted odds ratio=0.91, 95% CI=0.54-1.55). CONCLUSIONS: Although use of hospitalized control subjects excludes individuals with less severe disease, leading to selection bias, the study results suggest that caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania.

Benzodiazepine Initiation Effect on Mortality Among Medicare Beneficiaries Post Acute Ischemic Stroke.

Rationale: Despite guideline warnings, older acute ischemic stroke (AIS) survivors still receive benzodiazepines (BZD) for agitation, insomnia, and anxiety despite being linked to severe adverse effects, such as excessive somnolence and respiratory depression. Due to polypharmacy, drug metabolism, comorbidities, and complications during the sub-acute post-stroke period, older adults are more susceptible to these adverse effects. We examined the impact of receiving BZDs within 30 days post-discharge on survival among older Medicare beneficiaries after an AIS. Methods: Using the Medicare Provider Analysis and Review (MedPAR) dataset, Traditional fee-for-service Medicare (TM) claims, and Part D Prescription Drug Event data, we analyzed a random 20% sample of TM beneficiaries aged 66 years or older who were hospitalized for AIS between July 1, 2016, and December 31, 2019. Eligible beneficiaries were enrolled in Traditional Medicare Parts A, B, and D for at least 12 months before admission. We excluded beneficiaries who were prescribed a BZD within 90 days before hospitalization, passed away during their hospital stay, left against medical advice, or were discharged to institutional post-acute care. Our primary exposure was BZD initiation within 30 days post-discharge, and the primary outcome was 90-day mortality risk differences (RD) from discharge. We followed a trial emulation process involving cloning, weighting, and censoring, plus we used inverse-probability-of-censoring weighting to address confounding. Results: In a sample of 47,421 beneficiaries, 826 (1.74%) initiated BZD within 30 days after discharge from stroke admission or before readmission, whichever occurred first, and 6,392 (13.48%) died within 90 days. Our study sample had a median age of 79, with an inter-quartile range (IQR) of 12, 55.3% female, 82.9% White, 10.1% Black, 1.7% Hispanic, 2.2% Asian, 0.4% American Native, 1.5% Other and 1.1% Unknown. After standardization based on age, sex, race/ethnicity, length of stay in inpatient, and baseline dementia, the estimated 90-day mortality risk was 159 events per 1,000 (95% CI: 155, 166) for the BZD initiation strategy and 133 events per 1,000 (95% CI: 132, 135) for the non-initiation strategy, with an RD of 26 events per 1,000 (95% CI: 22, 33). Subgroup analyses showed RDs of 0 events per 1,000 (95% CI: -4, 11) for patients aged 66-70, 3 events per 1,000 (95% CI: -1, 13) for patients aged 71-75, 10 events per 1,000 (95% CI: 3, 23) for patients aged 76-80, 27 events per 1,000 (95% CI: 21, 46) for patients aged 81-85, and 84 events per 1,000 (95% CI: 73, 106) for patients aged 86 years or older. RDs were 34 events per 1,000 (95% CI: 26, 48) and 20 events per 1,000 (95% CI: 11, 33) for males and females, respectively. RDs were 87 events per 1,000 (95% CI: 63, 112) for patients with baseline dementia and 18 events per 1,000 (95% CI: 13, 21) for patients without baseline dementia. Conclusion: Initiating BZDs within 30 days post-AIS discharge significantly increased the 90-day mortality risk among Medicare beneficiaries aged 76 and older and for those with baseline dementia. These findings underscore the heightened vulnerability of older adults, especially those with cognitive impairment, to the adverse effects of BZDs.

Regulatory Pathways for Qualification and Acceptance of Digital Health Technology-Derived Clinical Trial Endpoints: Considerations for Sponsors.

Despite widespread interest and substantial investment in the adoption of sensor-based digital health technologies (sDHTs) for remote data capture in drug development trials, no drug has been approved based on an sDHT-derived primary endpoint in the United States (US). One reason for this lack of advancement is the complexity of obtaining regulatory endorsement for those endpoints within current US regulatory pathways. The goal of our review is to describe the two choices currently available to pharmaceutical study Sponsors: (i) they may navigate the traditional route of compiling the evidence to support the sDHT-derived endpoint in their investigational new drug (IND) application, requiring specific expertise and substantial resources; or (ii) they may navigate the drug development tool (DDT) pathway with the goal of qualifying their sDHT-derived endpoint as a biomarker or clinical outcome assessment applicable to a broader context of use (COU), either alone or as part of a partnership or consortium. We describe the nuances of each pathway; the evidentiary requirements for supporting an sDHT-derived endpoint and the technology used to capture it; and the impact that an sDHT's regulatory status may have on a Sponsor's decision to use it for data capture. By systematically comparing the IND and DDT pathways, our over-arching goals are to support the increasing deployment of sDHTs within the clinical research setting and help advance regulatory science in the field of digital medicine.

Lower Extremity Amputation in Fracture-Related Infection.

OBJECTIVES: To analyze demographics, comorbidities, fracture characteristics, presenting characteristics, microbiology, and treatment course of patients with fracture-related infections (FRIs) to determine risk factors leading to amputation. DESIGN: Retrospective cohort. SETTING: Single Level I Trauma Center (2013-2020). PATIENT SELECTION CRITERIA: Adults with lower extremity (femur and tibia) FRIs were identified through a review of an institutional database. Inclusion criteria were operatively managed fracture of the femur or tibia with an FRI and adequate documentation present in the electronic medical record. This included patients whose primary injury was managed at this institution and who were referred to this institution after the onset of FRI as long as all characteristics and risk factors assessed in the analysis were documented. Exclusion criteria were infected chronic osteomyelitis from a non-fracture-related pathology and a follow-up of less than 6 months. OUTCOME MEASURES AND COMPARISONS: Risk factors (demographics, comorbidities, and surgical, injury, and perioperative characteristics) leading to amputation in patients with FRIs were evaluated. RESULTS: A total of 196 patients were included in this study. The average age of the study group was 44±16 years. Most patients were men (63%) and White (71%). The overall amputation rate was 9.2%. There were significantly higher rates of chronic kidney disease (CKD; P = 0.039), open fractures (P = 0.034), transfusion required during open reduction internal fixation (P = 0.033), Gram-negative infections (P = 0.048), and FRI-related operations (P = 0.001) in the amputation cohort. On multivariate, patients with CKD were 28.8 times more likely to undergo amputation (aOR = 28.8 [2.27 to 366, P = 0.010). A subanalysis of 79 patients with either a methicillin-sensitive Staphylococcus aureus or methicillin-resistant S. aureus (MRSA) infection showed that patients with MRSA were significantly more likely to undergo amputation compared with patients with methicillin-sensitive Staphylococcus aureus (P = 0.031). MRSA was present in all cases of amputation in the Staphylococcal subanalysis. CONCLUSIONS: Findings from this study highlight CKD as a risk factor of amputation in the tibia and femur with fracture-related infection. In addition, MRSA was present in all cases of Staphylococcal amputation. Identifying patients and infection patterns that carry a higher risk of amputation can assist surgeons in minimizing the burden on these individuals. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

A hop testing alternative for functional performance following anterior cruciate ligament reconstruction.

The purpose of this work was to provide a simple method to determine reactive strength during the 6-meter timed hop test (6mTH) and evaluate its association with isokinetic peak torque in patients following anterior cruciate ligament reconstruction (ACLR). Twenty-nine ACLR patients who were at least four months from surgery were included in this analysis. Participants were brought into the laboratory on one occasion to complete functional testing. Quadriceps and hamstring isokinetic testing was completed bilaterally at 60, 180, and 300 deg∙s-1, using extension peak torque from each speed as the outcome measure. The 6mTH was completed bilaterally using a marker-based motion capture system, and reactive strength ratio (RSR) was calculated from the vertical velocity of the pelvis during the test. An adjustment in RSR was made using the velocity of the 6mTH test to account for different strategies employed across participants. Repeated measures correlations were used to determine associations among isokinetic and hop testing variables. A two-way mixed analysis of variance was used to determine differences in isokinetic and hop testing variables between operated and non-operated legs and across male and female participants. Moderate positive associations were found between RSR (and adjusted RSR) and isokinetic peak torque at all speeds (r = .527 to .577). Mean comparisons showed significant main effects for leg and sex. Patients showed significant deficits in their operated versus non-operated legs in all isokinetic and hop testing variables, yet only isokinetic peak torque and timed hop time showed significant differences across male and female groups. Preliminary results are promising but further development is needed to validate other accessible technologies available to calculate reactive strength during functional testing after ACLR. Pending these developments, the effects of movement strategies, demographics, and levels of participation on RSR can then be explored to translate this simple method to clinical environments.

Focused Ultrasound: Noninvasive Image-Guided Therapy.

ABSTRACT: Invasive open surgery used to be compulsory to access tumor mass to perform excision or resection. Development of minimally invasive laparoscopic procedures followed, as well as catheter-based approaches, such as stenting, endovascular surgery, chemoembolization, brachytherapy, which minimize side effects and reduce the risks to patients. Completely noninvasive procedures bring further benefits in terms of reducing risk, procedure time, recovery time, potential of infection, or other side effects. Focusing ultrasound waves from the outside of the body specifically at the disease site has proven to be a safe noninvasive approach to localized ablative hyperthermia, mechanical ablation, and targeted drug delivery. Focused ultrasound as a medical intervention was proposed decades ago, but it only became feasible to plan, guide, monitor, and control the treatment procedures with advanced radiological imaging capabilities. The purpose of this review is to describe the imaging capabilities and approaches to perform these tasks, with the emphasis on magnetic resonance imaging and ultrasound. Some procedures already are in clinical practice, with more at the clinical trial stage. Imaging is fully integrated in the workflow and includes the following: (1) planning, with definition of the target regions and adjacent organs at risk; (2) real-time treatment monitoring via thermometry imaging, cavitation feedback, and motion control, to assure targeting and safety to adjacent normal tissues; and (3) evaluation of treatment efficacy, via assessment of ablation and physiological parameters, such as blood supply. This review also focuses on sonosensitive microparticles and nanoparticles, such as microbubbles injected in the bloodstream. They enable ultrasound energy deposition down to the microvascular level, induce vascular inflammation and shutdown, accelerate clot dissolution, and perform targeted drug delivery interventions, including focal gene delivery. Especially exciting is the ability to perform noninvasive drug delivery via opening of the blood-brain barrier at the desired areas within the brain. Overall, focused ultrasound under image guidance is rapidly developing, to become a choice noninvasive interventional radiology tool to treat disease and cure patients.