Surgical management of the diabetic foot: The current evidence.

The prevalence of diabetes mellitus and its associated complications, particularly diabetic foot pathologies, poses significant healthcare challenges and economic burdens globally. This review synthesises current evidence on the surgical management of the diabetic foot, focusing on the interplay between neuropathy, ischemia, and infection that commonly culminates in ulcers, infections, and, in severe cases, amputations. The escalating incidence of diabetes mellitus underscores the urgency for effective management strategies, as diabetic foot complications are a leading cause of hospital admissions among diabetic patients, significantly impacting morbidity and mortality rates. This review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers, infections, and skeletal pathologies such as Charcot arthropathy, emphasising the critical role of early diagnosis, comprehensive management strategies, and interdisciplinary care in mitigating adverse outcomes. In addressing surgical interventions, this review evaluates conservative surgeries, amputations, and reconstructive procedures, highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot pathologies. The integration of advanced diagnostic tools, novel surgical techniques, and postoperative care, including offloading and infection control, are discussed in the context of optimising healing and preserving limb function.

Distribution of prostatic markers in glands of the female urethra and anterior vaginal wall-a rapid autopsy study.

BACKGROUND: There are varying reports of immunohistochemically detected prostatic marker protein distribution in glands associated with the female urethra that may be related to tissue integrity at the time of fixation. AIM: In this study we used tissue derived from rapid autopsies of female patients to determine the distribution of glandular structures expressing prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) along the female urethra and in surrounding tissues, including the anterior vaginal wall (AVW). METHODS: Tissue blocks from 7 donors that contained the entire urethra and adjacent AVW were analyzed. These tissue samples were fixed within 4-12 hours of death and divided into 5-mm transverse slices that were paraffin embedded. Sections cut from each slice were immunolabeled for PSA or PSAP and a neighboring section was stained with hematoxylin and eosin. The sections were reviewed by light microscopy and analyzed using QuPath software. OBSERVATIONS: In tissue from all donors, glandular structures expressing PSA and/or PSAP were located within the wall of the urethra and were present along its whole length. RESULTS: In the proximal half of the urethra from all donors, small glands expressing PSAP, but not PSA, were observed adjacent to the and emptying into the lumen. In the distal half of the urethra from 5 of the 7 donors, tubuloacinar structures lined by a glandular epithelium expressed both PSA and PSAP. In addition, columnar cells at the surface of structures with a multilayered transitional epithelium in the distal half of the urethra from all donors expressed PSAP. No glands expressing PSA or PSAP were found in tissues surrounding the urethra, including the AVW. CLINICAL IMPLICATIONS: Greater understanding of the distribution of urethral glands expressing prostatic proteins in female patients is important because these glands are reported to contribute to the female sexual response and to urethral pathology, including urethral cysts, diverticula, and adenocarcinoma. STRENGTHS AND LIMITATIONS: Strengths of the present study include the use of rapid autopsy to minimize protein degradation and autolysis, and the preparation of large tissue sections to demonstrate precise anatomical relations within all the tissues surrounding the urethral lumen. Limitations include the sample size and that all donors had advanced malignancy and had undergone previous therapy which may have had unknown tissue effects. CONCLUSION: Proximal and distal glands expressing prostate-specific proteins were observed in tissue from all donors, and these glands were located only within the wall of the urethra.

Evaluation of a Linkage to care Quality Improvement Initiative for People with HIV.

Adherence to antiretroviral therapy (ART) and engagement in HIV care is critical to decrease HIV transmissions and optimize outcomes in people with HIV (PWH). In 2016, the CDC reported that 63% of incident HIV diagnoses were transmitted by PWH who were aware of their status but not virally suppressed. Adult Special Care Clinic (ASCC) designed and implemented a quality improvement (QI) program to facilitate linkage and increase viral suppression rates in PWH. ASCC utilized identified barriers to create a Linkage to Care (LTC) program with multiple components, including a LTC coordinator, proactive outreach, and standardized protocols. Logistic regression was used to compare 395 PWH enrolled during the post-QI phase (01 January 2019-31 December 2021) to 337 PWH enrolled during the pre-QI phase (01 January 2016-31 December 2018). Newly diagnosed PWH enrolled during the post-QI phase had significantly higher odds of achieving viral suppression compared to those enrolled during the pre-QI phase (aOR 2.22, 95% CI 1.37-3.59, p = .001). There was no significant difference between previously diagnosed but unengaged PWH enrolled during pre- and post-QI phases, although absolute viral suppression increased from 66.1 to 71.5% in this group. Both increasing age and having private insurance increased the likelihood of achieving viral suppression. Results highlight the potential impact on linkage to care and viral suppression rates of a standardized LTC program, addressing barriers to care for PWH. Additional focus should be placed on previously diagnosed but unengaged PWH to determine what parts of the intervention may be modified to increase viral suppression rates.

Long-acting Injectable Cabotegravir/Rilpivirine Effective in a Small Patient Cohort With Virologic Failure on Oral Antiretroviral Therapy.

We report 12 patients with persistent viremia on oral antiretroviral therapy who were initiated on injectable cabotegravir/rilpivirine (iCAB/RPV) without oral lead-in. All patients achieved viral suppression without any virologic rebound. iCAB/RPV may be considered as an option for patients unable to maintain suppression on oral antiretroviral therapy.

Immune mechanisms of depression in rheumatoid arthritis.

Depression is a common and disabling comorbidity in rheumatoid arthritis that not only decreases the likelihood of remission and treatment adherence but also increases the risk of disability and mortality in patients with rheumatoid arthritis. Compelling data that link immune mechanisms to major depressive disorder indicate possible common mechanisms that drive the pathology of the two conditions. Preclinical evidence suggests that pro-inflammatory cytokines, which are prevalent in rheumatoid arthritis, have various effects on monoaminergic neurotransmission, neurotrophic factors and measures of synaptic plasticity. Neuroimaging studies provide insight into the consequences of inflammation on the brain (for example, on neural connectivity), and clinical trial data highlight the beneficial effects of immune modulation on comorbid depression. Major depressive disorder occurs more frequently in patients with rheumatoid arthritis than in the general population, and major depressive disorder also increases the risk of a future diagnosis of rheumatoid arthritis, further highlighting the link between rheumatoid arthritis and major depressive disorder. This Review focuses on interactions between peripheral and central immunobiological mechanisms in the context of both rheumatoid arthritis and major depressive disorder. Understanding these mechanisms will provide a basis for future therapeutic development, not least in depression.

Surgical Interventions for Chronic Ulnar Collateral Ligament Injuries of the Thumb: A Systematic Review.

Background: There is no consensus for the appropriate surgical management of symptomatic chronic ulnar collateral ligament (UCL) injuries of the thumb. The aim of this study is to systematically review the treatment of chronic thumb metacarpophalangeal (MCP) joint UCL injuries to determine the optimal approach to treatment. Methods: A systematic review of PubMed, Medline, Embase and ePub Ahead of Print was performed in accordance with Preferred Reporting of Items in Systematic Review and Meta-Analysis (PRISMA) guidelines. Results: Data from 11 studies using various surgical techniques in 245 thumbs were heterogenous and meta-analysis of results not possible. These data were qualitatively assessed. Direct repair, reconstruction with free tendon grafts and arthrodesis all demonstrated favourable outcomes with patient-reported outcome measures (PROMs). Conclusions: Direct repair can be safely performed more than 2 months following injury. Arthrodesis may be considered in heavy manual labourers or those with osteoarthrosis. Tendon grafting is safe, yet the optimal type and configuration are yet to be determined for reconstructive methods. Level of Evidence: Level III (Therapeutic).

Considerations for PrEP Implementation at Federally Qualified Health Centers in Mississippi: Perspectives From Staff and Patients.

Pre-exposure prophylaxis (PrEP) uptake remains low in the southeastern United States ("the South"), likely owing to overlapping structural barriers, including the lack of nearby PrEP providers. Federally qualified health centers (FQHCs) are potential sites through which to expand PrEP availability in the South, and telemedicine is promising for these services. This study investigated considerations for PrEP implementation at FQHCs and the use of telemedicine through qualitative interviews with 19 FQHC staff and 17 PrEP-eligible patients in Mississippi. Results indicated that existing infrastructure and policies at FQHCs can support PrEP implementation and that additional needed resources include more education for providers and strategies to advertise PrEP services. Findings suggest that using telemedicine for PrEP can address some regional implementation barriers (e.g., transportation problems and confidentiality concerns) but may present new ones (e.g., concerns about patients performing home HIV/STI testing procedures). Results can inform future PrEP implementation efforts in the South.

Acceptability and Comfort Regarding Remotely Delivered PrEP Services in Mississippi.

Despite the prevalence of human immunodeficiency virus (HIV) in Mississippi, access to pre-exposure prophylaxis (PrEP) is mostly limited to urban areas. Remote PrEP care via telemedicine, HIV self-testing, and prescription mail delivery can improve care in underserved communities. This mixed methods study assessed the acceptability and feasibility of using remote PrEP care, compared to alternatives. This consisted of (1) a cross-sectional survey and (2) interviews. PrEP-eligible adults were recruited from community-based organizations across Mississippi while accessing HIV testing between December 2019 and May 2022. Those surveyed (n = 63) indicated the greatest comfort in receiving PrEP via mail delivery (m = 5.14) and telemedicine (m = 4.89) and least comfort at gyms (m = 3.92). Comfort significantly differed between mail delivery and gyms (F = 2.90; P < .01). Those interviewed (n = 26) expressed relatively high comfort with remote PrEP care citing enhanced accessibility, privacy, simplicity, and quality. Remote PrEP services were acceptable and feasible among our sample, thus, should be expanded in Mississippi to address unmet needs.

How a Chain Can Be Extended While Its Bonds Are Compressed.

Extending polymer chains results in a positive chain tension, fch, primarily due to conformational restrictions. At the level of individual bonds, however, tension, fb, is either negative or positive and depends on both chain tension and bulk pressure. Typically, the chain and bond tension are assumed to be directly related. In specific systems, however, this dependence may not be intuitive, whereby fch increases while fb decreases; i.e., the entire chain is extended while bonds are compressed. Specifically, increasing the grafting density of a polymer brush results in chain extension along the direction perpendicular to the grafting surface while the underlying bonds are compressed. Similarly, upon compression of polymer networks, the extension of chains oriented in the "free" direction increases while their bonds are getting more compressed. We demonstrate this phenomenon in molecular dynamics simulations and explain it by the fact that the pressure contribution to fb is dominant over a wide range of network deformations and brush grafting densities.

Mapping Implementation Science with Expert Recommendations for Implementing Change (MIS-ERIC): Strategies to Improve PrEP Use among Black Cisgender Women Living in Mississippi.

BACKGROUND: Black women are disproportionately affected by the HIV epidemic. Strategies to increase Black women's use of pre-exposure prophylaxis (PrEP) are needed. METHODS: Interviews were conducted in Mississippi (MS) with Black, cisgender women at risk for HIV, and community healthcare clinic (CHC) staff who work directly with this population. Reflexive thematic analysis was used to identify barriers and select appropriate implementation strategies to increase PrEP care. RESULTS: Twenty Black women and twelve CHC staff were interviewed. PrEP use barriers resulted from low HIV risk awareness, lack of PrEP knowledge, and structural and stigma-related barriers. Methods for PrEP education and motivation included normalizing PrEP in public communications, providing education at places where women congregate, and tailoring PrEP content with Black women as educators. The Expert Recommendations for Implementing Change (ERIC) project provides a way for implementation scientists to select strategies that are consistent within research and practice across studies. Strategies from the ERIC project were selected to address implementation barriers. CONCLUSIONS: Tailoring PrEP implementation protocols to increase Black women's access, engagement, and adherence to PrEP is needed. This is one of the first implementation studies to incorporate these four implementation concepts into a single study: (1) implementation outcomes, (2) i-PARIHS, (3) ERIC's strategy list, and (4) operationalizing the strategies using the Proctor et al., guidelines. Results provide an in-depth comprehensive list of implementation strategies to increase PrEP uptake for Black women in MS.

Impact of Homophobia and Racism on Comfort Receiving Pre-exposure Prophylaxis at Various Locations Among Black MSM in Mississippi.

Pre-exposure prophylaxis (PrEP) is underutilized among Black men who have sex with men (BMSM) in the Southern United States. We assessed comfort receiving PrEP at various locations among 65 BMSM. Chi-square and t-tests explored associations between demographics, experienced homophobia and racism, and comfort receiving PrEP. BMSM with greater experienced homophobia were less comfortable at academically affiliated clinics [X2(2, N = 59) = 10.61, p = 0.01], CBOs [X2(3, N = 59) = 10.02, p = 0.02], and STI/HIV clinics [X2(3, N = 59) = 8.63, p = 0.04]. Those with greater experienced racism were more comfortable receiving PrEP by mail [X2(3, N = 61) = 9.40, p = 0.02]. Homophobia and racism influence preferences of BMSM for where and how they receive PREP care. Private modes of PrEP delivery and interventions targeting provider and organizational bias should be explored.

Supervision of Surgical Trainees During Operative Procedures: Implementation of a Formal Preoperative Surgical Checklist.

Background Trainers in surgery have an educational obligation to train trainees in performing operative procedures. Objective We hypothesized that poor concordance manifests as discrepancies between the trainee and the trainer, with an associated reduction in satisfaction with the training experience, perception of training quality, and completion of workplace-based assessments (WBAs). This study also aimed to validate the novel Supervised Training Operative Procedure (STOP) online tool. Method We developed an online proforma (STOP online tool) and conducted a prospective, single-blinded study of 53 orthopedic operative procedures with 53 trainees between January 19, 2019, and August 27, 2019. Results Forty-four (82%) trainees were listed as the primary surgeon. The overall mean trainee satisfaction (on a 0-10 Likert scale) was 8.25 (range: 3-10), and the mean trainer satisfaction was 8.28 (range: 4-10). A preoperative discussion between the trainee and the trainer occurred in 96.2% of the cases. Forty-eight (91%) trainers preoperatively established trainees' objectives and 91% (n = 48) of the cases showed postoperative completion of objectives. Forty-four (83%) trainers anticipated workplace-based assessment (WBA) completion for trainees, and this translated into 41 (77%) completed WBAs. Overall, 47 (92.9%) trainees felt that the STOP tool would be useful as a surgical training checklist and in the completion of WBAs. Conclusion The STOP checklist is useful in understanding qualitative and quantitative measures of the overall trainee performance of an operative case. This holistic approach will enable us to establish a structured perioperative surgical training checklist, as trainee and trainer requirements are dependent on one another.

Tibial Intramedullary Nailing by Suprapatellar Approach: Is It Quicker and Safer?

Background With the increasingly accepted method of suprapatellar tibial nailing for tibial shaft fractures, we aimed to compare intraoperative and postoperative outcomes of infrapatellar (IP) vs suprapatellar (SP) tibial nails. Methods This is a retrospective cohort analysis of 34 SP tibial nails over three years vs 24 IP tibial nails over a similar time frame. We compared total radiation dose (TRD), patient positioning time (PPT), fracture healing and follow up time. Knee pain in the SP group was evaluated utilising the Hospital for Special Surgery (HSS) Knee Injury and Osteoarthritis Outcome Score (KOOS). Results Fifty-eight patients with a mean age of 43 years were included. Mean intraoperative radiation dose for SP nails was 61.78 cGy (range: 11.60-156.01 cGy) vs 121.09 cGy (range: 58.01-18.03 cGy) for IP nails (p < 0.05). Mean PPT for SP nails was 10 minutes vs 18 minutes for IP nails (p < 0.05). All fractures united in the SP group vs one non-union in the IP group. Mean follow up was 5.5 months vs 11 months in the IP and SP groups, respectively. Mean KOOS was 7 (range: 0-22) at six months for the SP group. Conclusion The semi-extended position (SP group) leads to reduced TRD because of ease of imaging. Patients showed improved outcomes with shorter follow up and fracture union in all patients (SP group). The KOOS revealed that SP nail patients had minimal pain and good knee function. This study establishes a management and patient-reported outcome measures (PROMs) baseline for ongoing evaluation of SP nails.

Simultaneous Bilateral Anterior Inferior Iliac Spine Avulsion Injury in an Adolescent Cross-Country Runner.

Introduction: Pelvic apophyseal injuries are common in young athletes where muscle strength exceeds the tensile strength of the physis. Sequential bilateral injuries are exceedingly rare, and little is known of their mechanism. Case Presentation: A 15-year-old male cross-country runner presented with bilateral hip pain after sprint training. The patient describes going "flat out" and "overstriding" before collapsing with immediate pain. MRI imaging confirmed an acute bilateral Anterior Inferior Iliac Spine Injury (AIIS). Conservative management included protected weight-bearing, a hip strengthening program and graded return to play. At 6 months, the patient returned to full sporting activities with no symptoms. Conclusion: We present a unique case of bilateral AIIS avulsion that offers insight into the potential mechanisms and adds to the evidence that these injuries may be managed successfully with conservative treatment.

Generation of Allogeneic CAR T Cells through Specific Degradation of the T Cell Antigen Receptor by E3 Ubiquitin Ligase Fusion Proteins.

Receptor downregulation is instrumental for many therapeutic interventions. Receptor knockout through gene-editing technologies is efficient but can introduce off-target mutations and chromothripsis. Regulation of gene expression at the protein level is a promising alternative. Here, we present results showing the targeted T cell antigen receptor (TCR) degradation using chimeric E3 fusion proteins that we call Receptor Targeting Chimeras (ReceptorTAC). We show that TCR degradation is dependent on enzymatically active, membrane-anchored E3 ligase variants. TCR specificity was achieved by direct fusion of an E3 domain to the CD3ζ transmembrane sequence. Jurkat and primary T cells stably expressing the ReceptorTAC constructs showed significantly reduced responses to TCR stimulation. We also used our ReceptorTAC technology to generate TCR-deficient, claudin18.2-specific CAR T cells, where the activity of the CAR was unaffected by the expression of the ReceptorTAC. These data indicate that our ReceptorTAC molecule can be used to generate allogeneic CAR T cells.

A Pilot Study of a Patient Navigation Intervention to Improve HIV Pre-exposure Prophylaxis Persistence Among Black/African American Men Who Have Sex With Men.

BACKGROUND: Suboptimal HIV pre-exposure prophylaxis (PrEP) care outcomes among Black/African American men who have sex with men (MSM) limits its population-level effects on HIV incidence. We conducted a pilot study of a brief patient navigation intervention aimed at improving PrEP initiation and persistence among Black/African American MSM in the Southern United States. SETTING: Community health center in Jackson, MS. METHODS: We recruited 60 Black/African American MSM aged 18-34 years who were newly prescribed PrEP. Participants were randomized to receive the clinic's current standard of care or an intervention condition including a single patient navigation session to discuss and address perceived barriers to initiating and maintaining access to PrEP and biweekly check-ins. Participants were followed over 6 months using survey assessments, medical chart review, and pharmacy purchase records to ascertain PrEP initiation and persistence. RESULTS: Participants in the intervention condition were more likely to pick up their initial PrEP prescription [RR: 1.47; 95% confidence interval (CI): 1.10 to 1.97], be retained in PrEP care at 3 months (RR: 1.62; 95% CI: 1.01 to 2.59) and 6 months (RR: 1.38; 95% CI: 0.64 to 2.93), and have access to PrEP medications greater than 80% of all study days based on pharmacy fill records (RR: 3.00; 95% CI: 1.50 to 5.98). CONCLUSION: A brief patient navigation intervention demonstrated proof-of-concept in improving PrEP initiation and persistence among Black/African American MSM in the Southern United States.

The role for JAK inhibitors in the treatment of immune-mediated rheumatic and related conditions.

JAK inhibitors (JAKIs) are a new class of targeted therapy that have entered clinical practice for the treatment of immune-mediated rheumatic conditions. JAKIs can block the signaling activity of a variety of proinflammatory cytokines and therefore have the potential to mediate therapeutic benefits across a wide range of immune-mediated conditions. Several JAKIs are licensed, and many more are undergoing clinical trials. Here we provide a narrative review of the current and upcoming JAKIs for adult immune-mediated rheumatic and related conditions, with a specific focus on efficacy in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, psoriasis, and inflammatory bowel disease. The overall safety profile of JAKIs appears largely comparable to that of existing biologic cytokine-targeting agents, particularly, TNF inhibitors, apart from risk of herpes zoster, which is increased for JAKIs. Importantly however, unresolved safety concerns remain, particularly relating to increased venous thromboembolism.

Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy.

Few instances of treatment-emergent resistance to bictegravir have been reported in the literature. We describe a case of treatment-emergent resistance to bictegravir in a person recently diagnosed with human immunodeficiency virus who developed M184V and R263K mutations while on therapy.

Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle.

Zinc, an abundant transition metal, serves as a signalling molecule in several biological systems. Zinc transporters are genetically associated with cardiovascular diseases but the function of zinc in vascular tone regulation is unknown. We found that elevating cytoplasmic zinc using ionophores relaxed rat and human isolated blood vessels and caused hyperpolarization of smooth muscle membrane. Furthermore, zinc ionophores lowered blood pressure in anaesthetized rats and increased blood flow without affecting heart rate. Conversely, intracellular zinc chelation induced contraction of selected vessels from rats and humans and depolarized vascular smooth muscle membrane potential. We demonstrate three mechanisms for zinc-induced vasorelaxation: (1) activation of transient receptor potential ankyrin 1 to increase calcitonin gene-related peptide signalling from perivascular sensory nerves; (2) enhancement of cyclooxygenase-sensitive vasodilatory prostanoid signalling in the endothelium; and (3) inhibition of voltage-gated calcium channels in the smooth muscle. These data introduce zinc as a new target for vascular therapeutics.

Epidemiology, Clinical Features, and Outcomes of Hospitalized Adults with COVID-19: Early Experience from an Academic Medical Center in Mississippi.

OBJECTIVES: To describe the demographics, clinical characteristics, and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) in an academic medical center in the southern United States. METHODS: Retrospective, observational cohort study of all adult patients (18 years and older) consecutively admitted with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 infection between March 13 and April 25, 2020 at the University of Mississippi Medical Center. All of the patients either survived to hospital discharge or died during hospitalization. Demographics, body mass index, comorbidities, clinical manifestations, and laboratory findings were collected. Patient outcomes (need for invasive mechanical ventilation and in-hospital death) were analyzed. RESULTS: One hundred patients were included, 53% of whom were women. Median age was 59 years (interquartile range 44-70) and 66% were younger than 65. Seventy-five percent identified themselves as Black, despite representing 58% of hospitalized patients at our institution in 2019. Common comorbid conditions included hypertension (68%), obesity (65%), and diabetes mellitus (31%). Frequent clinical manifestations included shortness of breath (76%), cough (75%), and fever (64%). Symptoms were present for a median of 7 days (interquartile range 4-7) on presentation. Twenty-four percent of patients required mechanical ventilation and, overall, 19% died (67% of those requiring mechanical ventilation). Eighty-four percent of those who died were Black. On multivariate analysis, ever smoking (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.6) and history of diabetes mellitus (OR 5.9, 95% CI 1.5-24.3) were associated with mortality, and those admitted from home were less likely to die (vs outside facility, OR 0.2, 95% CI 0.0-0.7). Neither age, sex, race, body mass index, insurance status, nor rural residence was independently associated with mortality. CONCLUSIONS: Our study adds evidence that Black patients appear to be overrepresented in those hospitalized with and those who die from COVID-19, likely a manifestation of adverse social determinants of health. These findings should help guide preventive interventions targeting groups at higher risk of acquiring and developing severe COVID-19 disease.