Metatarsal Fractures.

Metatarsal fractures are some of the most common fractures reported in the human body. Recent advances in surgical techniques and fixation have helped facilitate healing and improved outcomes for our patients. The treatment goals of metatarsal fractures are to maintain the metatarsal parabola, sagittal position of the metatarsal heads, and a congruent metatarsophalangeal joint. Most of these injuries can be treated nonoperatively, but displaced fractures require surgical intervention to preserve normal gait biomechanics.

Management of Pilon Fractures.

Pilon fractures are complex injuries that can be difficult to treat and lead to severe complications if not managed appropriately. A thorough examination for polytraumatic injuries, neurovascular status, and skin condition should be done. A variety of approaches can be chosen based on fracture pattern, including staging, incisional approach, and no-touch technique. This article discusses various ways to manage pilon fractures.

Access to care by Medicare beneficiaries in the U.S. with diabetes and multiple chronic conditions during the COVID-19 pandemic.

OBJECTIVE: Determine characteristics of Medicare beneficiaries with diabetes and multiple chronic conditions (MCC) associated with being unable to obtain medical services during COVID-19. RESEARCH DESIGN AND METHODS: Retrospective cohort study of data from COVID-19 Supplements of Medicare Current Beneficiary Surveys administered in Summer (N = 11,114, unweighted) and Fall (N = 9686, unweighted) 2020, and Winter 2021 (N = 11,107, unweighted). Binary logistic regression was used to model for adjusted odds of self-reports of being unable to access different types of care. RESULTS: In three time periods from March 2020 through March/April 2021 beneficiaries with diabetes plus MCC combinations reported being unable to get medical care, compared to beneficiaries with diabetes alone. Notably, patterns persisted at the 12-month mark with beneficiaries with diabetes plus cancer (OR = 1.24), and diabetes plus cancer/stroke (OR = 2.53) experiencing increased odds of being unable to get care because of COVID-19, compared to beneficiaries with diabetes alone. By March/April 2021 beneficiaries with diabetes plus COPD (OR = 1.08), diabetes plus stroke (OR = 1.49), and diabetes plus Alzheimer's (OR = 1.09) experienced increased odds of being unable to get treatment for ongoing conditions. Beneficiaries with diabetes plus Alzheimer's (OR = 1.40) also experienced increased odds of being unable to get a regular check-up 12 months into the pandemic. Finally, members of racial/ethnic minority groups experienced increased odds of being unable to obtain services at various times during the pandemic compared to non-Hispanic Whites, with increased odds persisting at 12 months for non-Hispanic Blacks and Hispanics. CONCLUSIONS: Beneficiaries with MCC, and minorities, experienced increased odds of being unable to obtain some services during COVID-19, even when controlling for similar diabetes and MCC combinations. Work remains for providers and public health systems to dismantle and reimagine systems to provide equitable access to care.

A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques.

The rising global HIV-1 burden urgently requires vaccines capable of providing heterologous protection. Here, we developed a clade C HIV-1 vaccine consisting of priming with modified vaccinia Ankara (MVA) and boosting with cyclically permuted trimeric gp120 (CycP-gp120) protein, delivered either orally using a needle-free injector or through parenteral injection. We tested protective efficacy of the vaccine against intrarectal challenges with a pathogenic heterologous clade C SHIV infection in rhesus macaques. Both routes of vaccination induced a strong envelope-specific IgG in serum and rectal secretions directed against V1V2 scaffolds from a global panel of viruses with polyfunctional activities. Envelope-specific IgG showed lower fucosylation compared with total IgG at baseline, and most of the vaccine-induced proliferating blood CD4+ T cells did not express CCR5 and α4ß7, markers associated with HIV target cells. After SHIV challenge, both routes of vaccination conferred significant and equivalent protection, with 40% of animals remaining uninfected at the end of six weekly repeated challenges with an estimated efficacy of 68% per exposure. Induction of envelope-specific IgG correlated positively with G1FB glycosylation, and G2S2F glycosylation correlated negatively with protection. Vaccine-induced TNF-α+ IFN-γ+ CD8+ T cells and TNF-α+ CD4+ T cells expressing low levels of CCR5 in the rectum at prechallenge were associated with decreased risk of SHIV acquisition. These results demonstrate that the clade C MVA/CycP-gp120 vaccine provides heterologous protection against a tier2 SHIV rectal challenge by inducing a polyfunctional antibody response with distinct Fc glycosylation profile, as well as cytotoxic CD8 T cell response and CCR5-negative T helper response in the rectum.

Does the Lauge-Hansen Injury Mechanism Predict Posterior Malleolar Fracture Morphology?

The Lauge-Hansen ankle fracture classification system is widely accepted and is utilized to describe and predict ankle fracture patterns based on the mechanism of injury. Multiple studies have shown inconsistencies in the Lauge-Hansen's ability to predict fracture patterns based on the mechanism of injury. We set out to determine if the posterior malleolar fracture pattern is associated with the fracture types described by Lauge-Hansen. In this retrospective cohort study, we reviewed 153 patients with trimalleolar ankle fractures as diagnosed using computed tomography scans. Timing of injury was from February 2013 to August 2017. Patient ages ranged between 18 and 89 years old. Each patient had a complete clinical and radiographic workup including a preoperative computed tomographic scan following initial fracture reduction in the emergency room. We classified each ankle fracture based on plain film radiographs using the Lauge-Hansen classification scheme. Each individual posterior malleolar fracture was evaluated on computed tomography imaging and described using both the Haraguchi and Bartonicek-Rammelt classification systems. Of the 153 patients identified with trimalleolar ankle fractures, 70% were female (±20%), the mean age was 51 y (±8 y), and the mean body mass index was 30 kg/m2 (±3 kg/m2). We did not observe a significant association between the Lauge-Hansen injury mechanism and either the Bartonicek-Rammelt or the Haraguchi trimalleolar ankle fracture classification systems (chi-square correlation tests p > .05).

Erratum: Addendum: Outcomes of a Five-Year Formal Ophthalmology Residency Mentorship Program.

[This corrects the article DOI: 10.1055/s-0042-1756133.].

Outcomes of a Five-Year Formal Ophthalmology Residency Mentorship Program.

Objective: This article describes a formal ophthalmology residency mentorship program, identifies its strengths and weaknesses over 5 years of implementation, and proposes strategies to improve qualitative outcomes of the mentorship program. Design: Cross-sectional anonymous online survey. Subjects: All current and former mentees and mentors at the Casey Eye Institute (CEI) residency program from 2016 to 2021. Methods: All eligible participants were contacted via email to complete a survey to describe and analyze their experiences with the CEI's formal residency mentorship program. Results: Of the 65 surveyed participants, 82% preferred in-person meetings and met up from 2 to 3 times (44%) to 4 to 6 times (38.5%) annually at 15 minutes to 1 hour (48%) or 1 to 2 hours (42%) duration. Sixty-two percent of meetings were initiated by mentors, 8% by mentees, and 32% shared responsibilities equally. Participants also identified the three most important qualities for successful mentor-mentee relationship as personality (33.6%), communication styles (29.2%), and extracurricular interests/hobbies (16.8%). Mentees valued career advising, networking, and wellness support over academic and research mentorship. Subjective outcomes showed 25% of the mentee and 43% of the mentors agreed the mentorship program was a valuable experience. Comparably, 14% of the mentees and 38% of the mentors prioritized the relationship. There was a strong correlation between participants who prioritized the relationship and acknowledged it as a valuable experience (p < 0.01). Eighteen percent of the mentees and 43% of the mentors found the relationship effective and met their expectations. Twenty-one percent of the mentees and 38% of the mentors believed they had the tools and skills necessary to be effective in their respective roles. Conclusion: Our survey identified that weaknesses of the mentorship program include ineffective communications, inadequate preparation in their respective roles, and lack of priority focus on the relationship. We propose strategies to strengthen our program through creating workshops to clarify roles and responsibilities, emphasizing accountability with a contract statement, and implementing a new matching algorithm to customize participants' experience. Additional studies from other residencies with formal mentorship programs are warranted to identify, strategize, and foster high-quality mentorship.

Assuring Access to Safe Medicines in Pregnancy and Breastfeeding.

Scientists and regulators in Europe and the United States continue to seek methods and strategies to improve knowledge on rational use of medicines for pregnant and breastfeeding populations, an important subset of women's health. Regulatory agencies have made strides toward improvement, but much more is needed. Recognizing the importance of international collaboration, we have begun to consider how to address these important public health issues more globally. The health of the child begins with the health of the mother.

Elevated Extracellular cGMP Produced after Exposure to Enterotoxigenic Escherichia coli Heat-Stable Toxin Induces Epithelial IL-33 Release and Alters Intestinal Immunity.

Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen in children in low- to middle-income countries. Previous studies identified heat-stable enterotoxin (ST)-producing ETEC as a prevalent diarrheal pathogen in children younger than 5 years. While many studies have evaluated the interaction of ETEC heat-labile enterotoxin (LT) with host epithelium and immunity, few investigations have attempted similar studies with ST. To further understand ST pathogenesis, we examined the impact of ST on cGMP localization, epithelial cell cytokine production, and antibody development following immunization. In addition to robust intracellular cGMP in T84 cells in the presence of phosphodiesterase inhibitors (PDEis) that prevent the breakdown of cyclic nucleotides, we found that prolonged ST intoxication induced extracellular cGMP accumulation in the presence or absence of PDEis. Further, ST intoxication induced luminal cGMP in vivo in mice, suggesting that secreted cGMP may have other cellular functions. Using transcriptome sequencing (RNA-seq) and quantitative PCR (qPCR), we demonstrated that ST intoxication, or treatment with the clinically used ST mimic linaclotide, altered inflammatory cytokine gene expression, including the interleukin 1 (IL-1) family member IL-33, which could also be induced by cell-permeative 8-Br-cGMP. Finally, when present during immunization, ST suppressed induction of antibodies to specific antigens. In conclusion, our studies indicate that ST modulates epithelial cell physiology and the interplay between the epithelial and immune compartments.

Early Complications With Preloaded Descemet Membrane Endothelial Keratoplasty Are Not Dependent on Optisol-GS Washout or Trypan Blue Restaining.

PURPOSE: To describe the intraoperative and early postoperative complications using preloaded Descemet membrane endothelial keratoplasty (DMEK) grafts with intraocular injection of the graft in Optisol-GS and omission of trypan blue restaining. METHODS: This is a retrospective case series of 132 consecutive eyes with Fuchs endothelial dystrophy or endothelial failure who underwent DMEK using preloaded donor tissue prepared as previously described. The graft was not restained with trypan blue by the surgeon, and Optisol-GS was injected with the graft into the eye instead of being rinsed from the injector. Early postoperative complications (0-8 wk) including intraoperative fibrin formation, intraocular inflammation, elevated intraocular pressure, partial graft detachment requiring rebubble, and early graft failure were recorded. RESULTS: No eyes developed intraoperative fibrin formation or postoperative inflammation (such as toxic anterior segment syndrome) or elevated intraocular pressure. For eyes with Fuchs corneal dystrophy, our rebubble rate was 21% (22/106 eyes). Early graft failure was noted in 2% (3/132 eyes), which is similar to previous reports. CONCLUSIONS: Our results suggest that injection of Optisol-GS into the anterior chamber during DMEK graft injection does not lead to increases in intraoperative or early postoperative complications. Trypan blue restaining is not necessary for intraoperative visualization. This simplification can reduce graft manipulation and save time and resources for this procedure.

Dupilumab-Associated Ocular Surface Disease: Clinical Characteristics, Treatment, and Follow-Up.

PURPOSE: A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated. METHODS: A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted. RESULTS: Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms). CONCLUSIONS: This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult.

Race Disparities in the Use of Prevention, Screening, and Monitoring Services in Michigan Medicare Beneficiaries With Type 2 Diabetes and Combinations of Multiple Chronic Conditions.

People with diabetes need routine health care to prevent potential exacerbations of diabetes and detect or prevent the development of additional chronic conditions that can worsen the course of diabetes. Using 2012 Medicare claims data from the State of Michigan for 443,932 beneficiaries with type 2 diabetes, we determined that there are differences between white and racial/ethnic minority people with diabetes in accessing any preventive care and in the amount of service used once they do access care, even after adjusting for the presence of multiple chronic conditions.

Differences in spending for diabetes and multiple chronic conditions in Michigan Medicare beneficiaries.

OBJECTIVES: To determine which combinations of type 2 diabetes (T2D) and multiple chronic conditions (MCC) contribute to total spending and differences in spending between groups based on sex, race/ethnicity, and rural residency. STUDY DESIGN: Retrospective cohort study using 2012 Medicare claims data from beneficiaries in Michigan with T2D. METHODS: Zero-inflated Poisson regression models to estimate relationships of demographic characteristics and MCC combinations on hospital outpatient, acute inpatient, skilled nursing, hospice, and Part D drug spending. RESULTS: Across most MCC combinations, there are lower odds of no spending, with a concurrent increase in the expected mean of actual spending when payments are made, except for hospital outpatient costs. For hospital outpatient services, we observed lower spending across all MCC combinations. When controlling for MCC, we generally found that compared with White beneficiaries, Black, Asian/Pacific Islander, and Hispanic beneficiaries experience increased odds of no spending, but when payments were made, payments generally increased. American Indian/Alaska Native beneficiaries are the exception; they experience decreased odds of no payments for hospital outpatient and acute inpatient services, with a concurrent decrease in mean expected payments. CONCLUSIONS: When considering a range of MCC combinations, we observed differences in total payments between racial/ethnic minority groups and White beneficiaries. Our results highlight the ongoing need to make changes in the health care system to make the system more accessible to racial/ethnic minority groups.

Some thermodynamic effects of varying nonpolar surfaces in protein-ligand interactions.

Understanding how making structural changes in small molecules affects their binding affinities for targeted proteins is central to improving strategies for rational drug design. To assess the effects of varying the nature of nonpolar groups upon binding entropies and enthalpies, we designed and prepared a set of Grb2-SH2 domain ligands, Ac-pTyr-Ac6c-Asn-(CH2)n-R, in which the size and electrostatic nature of R groups at the pTyr+3 site were varied. The complexes of these ligands with the Grb2-SH2 domain were evaluated in a series of studies in which the binding thermodynamics were determined using isothermal titration calorimetry, and binding interactions were examined in crystallographic studies of two different complexes. Notably, adding nonpolar groups to the pTyr+3 site leads to higher binding affinities, but the magnitude and energetic origins of these effects vary with the nature of the R substituent. For example, enhancements to binding affinities using aliphatic R groups are driven by more favorable changes in binding entropies, whereas aryl R groups improve binding free energies through a combination of more favorable changes in binding enthalpies and entropies. However, enthalpy/entropy compensation plays a significant role in these associations and mitigates against any significant variation in binding free energies, which vary by only 0.8 kcal•mol-1, with changes in the electrostatic nature and size of the R group. Crystallographic studies show that differences in ΔG° or ΔH° correlate with buried nonpolar surface area, but they do not correlate with the total number of polar or van der Waals contacts. The relative number of ordered water molecules and relative order in the side chains at pTyr+3 correlate with differences in -TΔS°. Overall, these studies show that burial of nonpolar surface can lead to enhanced binding affinities arising from dominating entropy- or enthalpy-driven hydrophobic effects, depending upon the electrostatic nature of the apolar R group.

Rural, urban, and teaching hospital differences in hip fracture mortality.

INTRODUCTION: Hip fractures remain one of the most prevalent and deadly conditions afflicting those 65 years and older. For other health conditions (e.g. myocardial infarction), hospital location is associated with poorer health outcomes. To our knowledge, no study has investigated the relationship between hip fracture morality rate in the United States between urban and rural hospital settings. METHODS: A retrospective cohort study was conducted to examine differences in in-hospital mortality between groups treated in rural, urban-teaching, and urban-non-teaching hospitals, as well as public and private hospitals. Mortality rates were also compared for variances between surgical treatment, sex, insurance, patient location, race, and income. Discharge data was collected for 256,240 inpatient stays from the 2012 National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. RESULTS: Odds of mortality were 14.6% greater in rural hospital hip fracture patients compared to Urban/Non-Teaching centers (p < 0.05). CONCLUSIONS: Results from this study lend support to necessitate further research investigating prospective barriers to care of those in rural settings. This may point to limitations in resources and trained medical and surgical specialists in rural hospitals and need for continued research to mitigate such findings.