Food Insecurity and Hypoglycemia among Older Patients with Type 2 Diabetes Treated with Insulin or Sulfonylureas: The Diabetes & Aging Study.

BACKGROUND: Severe hypoglycemia is a serious adverse drug event associated with hypoglycemia-prone medications; older patients with diabetes are particularly at high risk. Economic food insecurity (food insecurity due to financial limitations) is a known risk factor for hypoglycemia; however, less is known about physical food insecurity (due to difficulty cooking or shopping for food), which may increase with age, and its association with hypoglycemia. OBJECTIVE: Study associations between food insecurity and severe hypoglycemia. DESIGN: Survey based cross-sectional study. PARTICIPANTS: Survey responses were collected in 2019 from 1,164 older (≥ 65 years) patients with type 2 diabetes treated with insulin or sulfonylureas. MAIN MEASURES: Risk ratios (RR) for economic and physical food insecurity associated with self-reported severe hypoglycemia (low blood glucose requiring assistance) adjusted for age, financial strain, HbA1c, Charlson comorbidity score and frailty. Self-reported reasons for hypoglycemia endorsed by respondents. KEY RESULTS: Food insecurity was reported by 12.3% of the respondents; of whom 38.4% reported economic food insecurity only, 21.1% physical food insecurity only and 40.5% both. Economic food insecurity and physical food insecurity were strongly associated with severe hypoglycemia (RR = 4.3; p = 0.02 and RR = 4.4; p = 0.002, respectively). Missed meals ("skipped meals, not eating enough or waiting too long to eat") was the dominant reason (77.5%) given for hypoglycemia. CONCLUSIONS: Hypoglycemia prevention efforts among older patients with diabetes using hypoglycemia-prone medications should address food insecurity. Standard food insecurity questions, which are used to identify economic food insecurity, will fail to identify patients who have physical food insecurity only.

Implementation of a Novel Prehospital Clinical Decision Tool and ECG Transmission for STEMI Significantly Reduces Door-to-Balloon Time and Sex-Based Disparities.

Background: An important method employed to reduce door to balloon time (DTBT) for ST segment elevation Myocardial Infarctions (STEMIs) is a prehospital MI alert. The purpose of this retrospective study was to examine the effects of an educational intervention using a novel decision support method of STEMI notification and prehospital electrocardiogram (ECG) transmission on DTBT.Methods: An ongoing database (4/4/2000 - present) is maintained to track STEMI alerts. In 2007, an MI alert program began; emergency medicine physicians could activate a "prehospital MI alert". In October 2015, modems were purchased for Emergency Medical Services personnel to transmit ECGs. There was concurrent implementation of a decision support tool for identifying STEMI. Sex was assigned as indicated in the medical record. Data were analyzed in two groups: Pre-2016 (PRE) and 2016-2022 (POST).Results: In total, 3,153 patients (1,301 PRE; 1,852 POST) were assessed; the average age was 65.2 years, 32.6% female, 87.7% white with significant differences in age and race between the two cohorts. Of the total 3,153 MI alerts, 239 were false activations, leaving 2,914 for analysis. 2,115 (72.6%) had cardiac catheterization while 16 (6.7%) of the 239 had a cardiac catheterization. There was an overall decrease in DTBT of 27.5% PRE to POST of prehospital ECG transmission (p <0.001); PRE median time was 74.5 minutes vs. 55 minutes POST. There was no significant difference between rates of cardiac catheterization PRE and POST for all patients. After accounting for age, race, and mode of arrival, DTBT was 12.2% longer in women, as compared to men (p < 0.001) PRE vs. POST. DTBT among women was significantly shorter when comparing PRE to POST periods (median 77 minutes vs. 60 minutes; p = 0.0001). There was no significant sex difference in the proportion of those with cardiac catheterization between the two cohorts (62.5% vs. 63.5%; p = 0.73).Conclusion: Introduction of a decision support tool with prehospital ECG transmission with prehospital ECG transmission decreased overall DTBT by 20 minutes (27.5%). Women in the study had a 17-minute decrease in DTBT (22%), but their DTBT remained 12.2% longer than men for reasons that remain unclear.

A Case of Cutaneous Leishmaniasis with Mucosal Involvement in the Northern United States.

BACKGROUND: Cutaneous leishmaniasis (CL) is a vector-borne parasitic infection endemic to many sub-tropical regions worldwide. In the Americas, Leishmania braziliensis is responsible for most reported CL cases. Variable symptom presentation and susceptibility to secondary infection make diagnosing CL a difficult proposition for physicians who may not encounter cases frequently. CASE REPORT: We present the case of a 50-year-old man with multiple progressive lesions, diagnosed initially as a bacterial infection, who presented to a North American emergency department after several unsuccessful trials of antibiotic therapy. Eventually, polymerase chain reaction testing of a wound biopsy sample confirmed the presence of L. braziliensis. After a complicated course, the patient's infection resolved after tailored antiparasitic therapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the need to include travel history in the evaluation of atypical dermatologic infections.

Electromechanical Coupling and Anatomy of the In-Vivo Gastroduodenal Junction.

INTRODUCTION: Few biomarkers support diagnosis and treatment of disorders of gut-brain interaction (DGBI), although gastroduodenal junction (GDJ) electromechanical coupling is a target for novel interventions. Rhythmic 'slow waves', generated by interstitial cells of Cajal (ICC), and myogenic 'spikes' are bioelectrical mechanisms underpinning motility. In this study, simultaneous in-vivo high-resolution electrophysiological and impedance planimetry measurements were paired with immunohistochemistry to elucidate GDJ electromechanical coupling. METHODS: Following ethical approval, the GDJ of anaesthetized pigs (N=12) was exposed. Anatomically-specific, high-resolution electrode arrays (256 electrodes) were applied to the serosa. EndoFLIP catheters (16 electrodes; Medtronic, MN, USA) were positioned luminally to estimate diameter. Post-mortem tissue samples were stained with Masson's trichrome and Ano1 to quantify musculature and ICC. RESULTS: Electrical mapping captured slow-waves (N=512) and spikes (N=1071). Contractions paralleled electrical patterns. Localized slow waves and spikes preceded rhythmic contractions of the antrum, and non-rhythmic contractions of the duodenum. Slow-wave and spike amplitudes were correlated in the antrum (r=0.74, p<0.001) and duodenum (r=0.42, p<0.001). Slow-wave and contractile amplitudes were correlated in the antrum (r=0.48, p<0.001) and duodenum (r=0.35, p<0.001). Distinct longitudinal and circular muscle layers of the antrum and duodenum had a total thickness of (2.8 ± 0.9) mm and (0.4 ± 0.1) mm, respectively. At the pylorus, muscle layers merged and thickened to (3.5 ± 1.6) mm. Pyloric myenteric ICC covered less area (1.5 ± 1.1 %) compared to the antrum (4.2 ± 3.0 %) and duodenum (5.3 ± 2.8 %). CONCLUSIONS: Further characterization of electromechanical coupling and ICC biopsies may generate DGBI biomarkers.

Children with perinatally acquired HIV exhibit distinct immune responses to 4CMenB vaccine.

Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy-treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.

Evaluation of Ergot Resistance in Hard Red Spring Wheat in North Dakota.

Higher levels of ergot (Claviceps purpurea (Fr.)) Tul. were reported in North Dakota hard red spring wheat (HRSW) in 2018, leading to questions pertaining to management and cultivar resistance. To better understand pathogen and HRSW cultivar responses, greenhouse experiments were conducted from 2020 to 2021 to evaluate aggressiveness of nine C. purpurea isolates and ergot resistance in 21 HRSW cultivars. Results from the aggressiveness assay indicated significant cultivar by isolate interactions for total weight of sclerotia produced and ergot incidence. Mean data across all cultivar by isolate combinations suggested isolates CC-3 and IA-Tim were the most aggressive and subsequently used in ergot resistance experiments. Results from ergot resistance screening indicated none of the HRSW cultivars were immune to C. purpurea as all cultivars produced sclerotia. However, differences in ergot incidence, kernel incidence, aborted kernel incidence, total sclerotia weight, sclerotia length, and sclerotia width occurred among cultivars. Both 'ND-Frohberg' and 'TCG-Spitfire' had the lowest ergot incidence values and were among the lowest in total sclerotia weight. 'Waldron' and 'LCS-Trigger' had the highest ergot incidence and the highest total sclerotia weight. Given that most concerns with ergot occur post-harvest, we suggest two categories to describe ergot resistance: host resistance (fate of inoculation for a stigma) and logistical resistance (size characteristics of a sclerotium that influence its ability to remain with a seed lot after harvest and cleaning). This research provides a strong foundation on our understanding of HRSW resistance to ergot that will influence variety decisions in ergot-prone areas in North Dakota.

Changes in the term neonatal electroencephalogram with general anesthesia - a systematic review with narrative synthesis.

While effects of general anesthesia on neuronal activity in the human neonatal brain are incompletely understood, electroencephalography (EEG) provides some insight and may identify age-dependent differences. A systematic search (MEDLINE, Embase, PUBMED, Cochrane Library to November 2023) retrieved English language publications reporting EEG during general anesthesia for cardiac or non-cardiac surgery in term neonates (37 to 44 weeks post-menstrual age). Data were extracted and risk of bias (ROBINS-I Cochrane tool) and quality of evidence (GRADE checklist) assessed. From 1155 abstracts, nine publications (157 neonates; 55.7% male) fulfilled eligibility criteria. Data were limited and study quality was very low. The occurrence of discontinuity, a characteristic pattern of alternating higher and lower amplitude EEG segments, was reported with general anesthesia (94 of 119 neonates, six publications) and with hypothermia (23 of 23 neonates, two publications). Decreased power in the delta (0.5-4Hz) frequency range was also reported with increasing anesthetic dose (39 neonates; three publications). While evidence gaps were identified, both increasing sevoflurane concentration and decreasing temperature are associated with increasing discontinuity.

Air-liquid intestinal cell culture allows in situ rheological characterization of intestinal mucus.

Intestinal health heavily depends on establishing a mucus layer within the gut with physical properties that strike a balance between being sufficiently elastic to keep out harmful pathogens yet viscous enough to flow and turnover the contents being digested. Studies investigating dysfunction of the mucus layer in the intestines are largely confined to animal models, which require invasive procedures to collect the mucus fluid. In this work, we develop a nondestructive method to study intestinal mucus. We use an air-liquid interface culture of primary human intestinal epithelial cells that exposes their apical surface to allow in situ analysis of the mucus layer. Mucus collection is not only invasive but also disrupts the mucus microstructure, which plays a crucial role in the interaction between mucus and the gut microbiome. Therefore, we leverage a noninvasive rheology technique that probes the mechanical properties of the mucus without removal from the culture. Finally, to demonstrate biomedical uses for this cell culture system, we characterize the biochemical and biophysical properties of intestinal mucus due to addition of the cytokine IL-13 to recapitulate the gut environment of Nippostrongylus brasiliensis infection.

Identifying Population-Level and Within-Hospital Disparities in Surgical Care.

INTRODUCTION: The lack of consensus on equity measurement and its incorporation into quality-assessment programs at the hospital and system levels may be a barrier to addressing disparities in surgical care. This study aimed to identify population-level and within-hospital differences in the quality of surgical care provision. METHODS: The analysis included 657 National Surgical Quality Improvement Program participating hospitals with over 4 million patients (2014-2018). Multi-level random slope, random intercept modeling was used to examine for population-level and in-hospital disparities. Disparities in surgical care by Area Deprivation Index (ADI), race, and ethnicity were analyzed for five measures: all-case inpatient mortality, all-case urgent readmission, all-case postoperative surgical site infection, colectomy mortality, and spine surgery complications. RESULTS: Population-level disparities were identified across all measures by ADI, two measures for Black race (all-case readmissions and spine surgery complications), and none for Hispanic ethnicity. Disparities remained significant in the adjusted models. Prior to risk-adjustment, in all measures examined, within-hospital disparities were detected in: 25.8-99.8% of hospitals for ADI, 0-6.1% of hospitals for Black race, and 0-0.8% of hospitals for Hispanic ethnicity. Following risk-adjustment, in all measures examined, fewer than 1.1% of hospitals demonstrated disparities by ADI, race, or ethnicity. CONCLUSIONS: Following risk adjustment, very few hospitals demonstrated significant disparities in care. Disparities were more frequently detected by ADI than by race and ethnicity. The lack of substantial in-hospital disparities may be due to the use of postoperative metrics, small sample sizes, the risk adjustment methodology, and healthcare segregation. Further work should examine surgical access and healthcare segregation.

Safety And Efficacy Of Combination Lurbinectedin Plus Doxorubicin From A Phase 1b Trial In Patients With Advanced/Metastatic Soft Tissue Sarcoma.

PURPOSE: While cytotoxic chemotherapy is standard first-line treatment for patients with metastatic soft tissue sarcoma (STS), clinical outcomes remain suboptimal. Our prior study showed lurbinectedin plus doxorubicin is well-tolerated with promising clinical activity in STS. We designed this phase 1b trial to optimize dosing as the basis for a randomized trial in leiomyosarcoma (LMS) and to further explore the safety profile and efficacy signal. PATIENTS AND METHODS: Patients had advanced/metastatic STS and no prior anthracycline/lurbinectedin/trabectedin. Escalation followed a 3+3 design with 3-week cycles: lurbinectedin (3.2 mg/m2 day 1) and two doxorubicin levels (DL1: 25 mg/m2 day 1; DL2 25 mg/m2 days 1 and 8). The primary objectives were to identify the maximum tolerated dose (MTD) and recommended dose for subsequent randomized trials. RESULTS: Ten patients were enrolled in a 6-month period. The most common treatment-emergent adverse events (TEAE) were grade (G) 2 fatigue and nausea, and G2 cytopenias with no febrile neutropenia events. There were 2 dose-limiting toxicities (DLTs) at DL2 (day 8 [G2 ALT/AST increase, G3 neutropenia]), and 1 DLT in DL1 (G3 ALT increase). These were reversible and all patients continued the study. DL1 was chosen for further study. At the time of data cutoff, the estimated median PFS is 16.5 months (95%CI 6.0-ND). The ORR was 60% (6/10 confirmed partial responses [PR]). CONCLUSIONS: In this phase 1b study, the recommended dose is lurbinectedin 3.2 mg/m2 in combination with doxorubicin 25 mg/m2 every 3 weeks. The study combination was well-tolerated and demonstrated intriguing clinical activity.

Phase II Clinical Trial of Intravenous Levothyroxine to Mitigate Pharyngocutaneous Fistula in Euthyroid Patients Undergoing Salvage Laryngectomy.

PURPOSE: Patients undergoing head and neck cancer surgery after prior radiation or chemoradiation are at high risk for wound complications. Hypothyroidism is a known risk factor for wound complications, especially fistulae after salvage total laryngectomy. The purpose of this phase II clinical trial is to investigate the effect of peri-operative intravenous levothyroxine supplementation on wound complications in patients undergoing salvage total laryngectomy. PATIENTS AND METHODS: Euthyroid patients previously treated with radiation/chemoradiation undergoing total laryngectomy were prospectively recruited (n=72). Post-operatively, intravenous levothyroxine was administered at a weight-based dose (1.3 mcg/kg/day) and transitioned to enteral dosing on day 7. Free T3, T4, and thyroid stimulating hormone (TSH) were collected and dosing was adjusted accordingly. The primary endpoints were rates of fistula and fistula requiring re-operation, compared to matched historical controls. All patients were monitored for adverse effects. RESULTS: The rate of post-operative hypothyroidism was 21% compared to 49% in a matched historic cohort. The rate of fistula was 18.1% while the rate of fistula requiring re-operation was 4.2%, significantly lower than rates in our historic cohort (34.6% and 14.8% respectively, p=0.02 and 0.01). Post-operative hypothyroidism and recurrent clinical stage predicted fistula requiring re-operation in multivariate analysis; other acute phase reactants were not predictive. There were no observed adverse events related to levothyroxine supplementation. CONCLUSIONS: Post-operative intravenous levothyroxine supplementation reduced rates of acute hypothyroidism, fistula, and fistula requiring re-operation in patients undergoing salvage total laryngectomy without adverse effects. Intravenous levothyroxine is a viable strategy to reduce wound complications in this high-risk patient population.

Oral care practices and hospital-acquired pneumonia prevention: A national survey of Australian nurses.

BACKGROUND: Hospital-acquired pneumonia (HAP) also known as non-ventilator associated pneumonia, is one of the most common infections acquired in hospitalised patients. Improving oral hygiene appears to reduce the incidence of HAP. This study aimed to describe current practices, barriers and facilitators, knowledge and educational preferences of registered nurses performing oral health care in the Australian hospital setting, with a focus on the prevention of HAP. We present this as a short research report. METHODS: We undertook a cross sectional online anonymous survey of Australian registered nurses. Participants were recruited via electronic distribution through existing professional networks and social media. The survey used was modified from an existing survey on oral care practice. RESULTS: The survey was completed by 179 participants. Hand hygiene was considered a very important strategy to prevent pneumonia (n = 90, 58%), while 45% (n = 71) felt that oral care was very important. The most highly reported barriers for providing oral care included: an uncooperative patient; inadequate staffing; and a lack of oral hygiene requisite. Patients' reminders, prompts and the provision of toothbrushes were common ways believed to help facilitate improvements in oral care. CONCLUSION: Findings from this survey will be used in conjunction with consumer feedback, to help inform a planned multi-centre randomised trial, the Hospital Acquired Pneumonia PrEveNtion (HAPPEN) study, aimed at reducing the incidence of HAP. Findings may also be useful for informing studies and quality improvement initiatives aimed at improving oral care to reduce the incidence of HAP.

Lifileucel: the first cellular therapy approved for solid tumours.

The US Food and Drug Administration (FDA) approval of lifileucel, for advanced melanoma, represents the first cellular therapy to reach the clinic for solid cancers. Here, we summarise this landmark approval, consider the associated regulatory pathway, and evaluate the challenges that remain to ensure effective implementation of this advanced 'living' therapy.

Web-based intervention for young adults experiencing anxiety and hazardous alcohol use: Study protocol for an 18-month randomized controlled trial.

BACKGROUND AND AIMS: Alcohol use and anxiety often co-occur, causing increased severity impairment. This protocol describes a randomized controlled trial (RCT) that aims to test the efficacy and cost-effectiveness of a web-based, self-guided alcohol and anxiety-focused program, compared with a web-based brief alcohol-focused program, for young adults who drink at hazardous levels and experience anxiety. It will also test moderators and mechanisms of change underlying the intervention effects. DESIGN: This RCT will be conducted with a 1:1 parallel group. SETTING: The study will be a web-based trial in Australia. PARTICIPANTS: Individuals aged 17-30 years who drink alcohol at hazardous or greater levels and experience at least mild anxiety (n = 500) will be recruited through social media, media (TV, print) and community networks. INTERVENTION AND COMPARATOR: Participants will be randomly allocated to receive a web-based, integrated alcohol-anxiety program plus technical and motivational telephone/e-mail support (intervention) or a web-based brief alcohol-feedback program (control). MEASUREMENTS: Clinical measures will be assessed at baseline, post-intervention (2 months), 6 months (primary end-point), 12 months and 18 months. Co-primary outcomes are hazardous alcohol consumption and anxiety symptom severity. Secondary outcomes are binge-drinking frequency; alcohol-related consequences; depression symptoms; clinical diagnoses of alcohol use or anxiety disorder (at 6 months post-intervention), health-care service use, educational and employment outcomes; and quality of life. Mediators and moderators will also be assessed. Efficacy will be tested using mixed models for repeated measures within an intention-to-treat framework. The economic evaluation will analyze individual-level health and societal costs and outcomes of participants between each trial arm, while mediation models will test for mechanisms of change. COMMENTS: This will be the first trial to test whether a developmentally targeted, web-based, integrated alcohol-anxiety intervention is effective in reducing hazardous alcohol use and anxiety severity among young adults. If successful, the integrated alcohol-anxiety program will provide an accessible intervention that can be widely disseminated to improve wellbeing of young adults, at minimal cost.

Age, sex, and lung volume dependence of dissolved xenon-129 MRI gas exchange metrics.

PURPOSE: To characterize the dependence of Xe-MRI gas transfer metrics upon age, sex, and lung volume in a group of healthy volunteers. METHODS: Sixty-five subjects with no history of chronic lung disease were assessed with 129Xe-MRI using a four-echo 3D radial spectroscopic imaging sequence and a dose of xenon titrated according to subject height that was inhaled from a lung volume of functional residual capacity (FRC). Imaging was repeated in 34 subjects at total lung capacity (TLC). Regional maps of the fractions of dissolved xenon in red blood cells (RBC), membrane (M), and airspace (Gas) were acquired at an isotropic resolution of 2 cm, from which global averages of the ratios RBC:M, RBC:Gas, and M:Gas were computed. RESULTS: Data from 26 males and 36 females with a median age of 43 y (range: 20-69 y) were of sufficient quality to analyze. Age (p = 0.0006) and sex (p < 0.0001) were significant predictors for RBC:M, and a linear regression showed higher values and steeper decline in males: RBC:M(Males) = -0.00362 × Age + 0.60 (p = 0.01, R2 = 0.25); RBC:M(Females) = -0.00170 × Age + 0.44 (p = 0.02, R2 = 0.15). Similarly, age and sex were significant predictors for RBC:Gas but not for M:Gas. RBC:M, M:Gas and RBC:Gas were significantly lower at TLC than at FRC (plus inhaled volume), with an average 9%, 30% and 35% decrease, respectively. CONCLUSION: Expected age and sex dependence of pulmonary function concurs with 129Xe RBC:M imaging results, demonstrating that these variables must be considered when reporting Xe-MRI metrics. Xenon doses and breathing maneuvers should be controlled due to the strong dependence of Xe-MRI metrics upon lung volume.

Sex-specific cardiac magnetic resonance pulmonary capillary wedge pressure.

Aims: Heart failure (HF) with preserved ejection fraction disproportionately affects women. There are no validated sex-specific tools for HF diagnosis despite widely reported differences in cardiac structure. This study investigates whether sex, as assigned at birth, influences cardiac magnetic resonance (CMR) assessment of left ventricular filling pressure (LVFP), a hallmark of HF agnostic to ejection fraction. Methods and results: A derivation cohort of patients with suspected pulmonary hypertension and HF from the Sheffield centre underwent invasive right heart catheterization and CMR within 24 h of each other. A sex-specific CMR model to estimate LVFP, measured as pulmonary capillary wedge pressure (PCWP), was developed using multivariable regression. A validation cohort of patients with confirmed HF from the Leeds centre was used to evaluate for the primary endpoints of HF hospitalization and major adverse cardiovascular events (MACEs). Comparison between generic and sex-specific CMR-derived PCWP was undertaken. A total of 835 (60% female) and 454 (36% female) patients were recruited into the derivation and validation cohorts respectively. A sex-specific model incorporating left atrial volume and left ventricular mass was created. The generic CMR PCWP showed significant differences between males and females (14.7 ± 4 vs. 13 ± 3.0 mmHg, P > 0.001), not present with the sex-specific CMR PCWP (14.1 ± 3 vs. 13.8 mmHg, P = 0.3). The sex-specific, but not the generic, CMR PCWP was associated with HF hospitalization (hazard ratio 3.9, P = 0.0002) and MACE (hazard ratio 2.5, P = 0.001) over a mean follow-up period of 2.4 ± 1.2 years. Conclusion: Accounting for sex improves precision and prognostic performance of CMR biomarkers for HF.

Impact of organic phosphates on the structure and composition of short-range ordered iron nanophases.

Organic phosphates (OP) are important nutrient components for living cells in natural environments, where they readily interact with ubiquitous iron phases such as hydrous ferric oxide, ferrihydrite (FHY). FHY partakes in many key bio(geo)chemical reactions including iron-mediated carbon storage in soils, or iron-storage in living organisms. However, it is still unknown how OP affects the formation, structure and properties of FHY. Here, we document how ß-glycerophosphate (GP), a model OP ligand, affects the structure and properties of GP-FHY nanoparticles synthesized by coprecipitation at variable nominal molar P/Fe ratios (0.01 to 0.5). All GP-FHY precipitates were characterized by a maximum solid P/Fe ratio of 0.22, irrespective of the nominal P/Fe ratio. With increasing nominal P/Fe ratio, the specific surface area of the GP-FHY precipitates decreased sharply from 290 to 3 m2 g-1, accompanied by the collapse of their pore structure. The Fe-P local bonding environment gradually transitioned from a bidentate binuclear geometry at low P/Fe ratios to monodentate mononuclear geometry at high P/Fe ratios. This transition was accompanied by a decrease in coordination number of edge-sharing Fe polyhedra, and the loss of the corner-sharing Fe polyhedra. We show that Fe(iii) polymerization is impeded by GP, and that the GP-FHY structure is highly dependent on the P/Fe ratio. We discuss the role that natural OP-bearing Fe(iii) nanophases have in biogeochemical reactions between Fe-P and C species in aquatic systems.

Clinical Outcome following Management of Severe Osteomyelitis due to Pin Site Infection.

Aim: This study has investigated cases of pin site infection (PSI) which required surgery for persistent osteomyelitis (OM) despite pin removal. Materials and methods: Patients requiring surgery for OM after PSI between 2011 and 2021 were included in this retrospective cohort study. Single-stage surgery was performed in accordance with a protocol at one institution. This involved deep sampling, debridement, implantation of local antibiotics, culture-specific systemic antibiotics and soft tissue closure. A successful outcome was defined as an infection-free interval of at least 24 months following surgery. Results: Twenty-seven patients were identified (the sites were 22 tibias, 2 humeri, 2 calcanei, 1 radius); about 85% of them were males with a median age of 53.9 years. The majority of infections (21/27) followed fracture treatment. Fifteen patients were classified as BACH uncomplicated and 12 were BACH complex. Staphylococci were the most common pathogens, polymicrobial infections were detected in five cases (19%). Seven patients required flap coverage which was performed in the same operation.After a median of 3.99 years (2.00-8.05) follow-up, all patients remained infection free at the site of the former OM. Wound leakage after local antibiotic treatment was seen in 3/27 (11.1%) cases but did not require further treatment. Conclusion: Osteomyelitis after PSI is uncommon but has major implications for the patient as 7 patients needed flap coverage. This reinforces the need for careful pin placement and pin site care to prevent deep infection. These infections were treated in accordance with a protocol and were not managed simply by curettage. All patients treated in this manner remained infection-free after a minimum follow-up of 2 years suggesting that this protocol is effective. Clinical significance: Pin site infection is a very common complication in external fixation. The sequela of a chronic pin site OM is rare but the implications to the patient are huge. In this series, more than a quarter of patients required flap coverage as part of the treatment of the deep infection. How to cite this article: Frank FA, Pomeroy E, Hotchen AJ, et al. Clinical Outcome following Management of Severe Osteomyelitis due to Pin Site Infection. Strategies Trauma Limb Reconstr 2024;19(1):21-25.

An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery.

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40-50 times greater reporter expression in the CNS of human TFRC knock-in mice. The enhanced tropism was CNS-specific and absent in wild type mice. When used to deliver GBA1, mutations of which cause Gaucher disease and are linked to Parkinson's disease, BI-hTFR1 substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared to AAV9. These findings establish BI-hTFR1 as a potential vector for human CNS gene therapy.