Retraction: A Cautionary Tale of a Complex Peri-Trochanteric Fracture in a Very Important Person (VIP) Patient at a Community-Based Hospital: A Case Report.

[This retracts the article DOI: 10.7759/cureus.33150.].

Improvement of Pretibial Myxedema Following Administration of Teprotumumab.

Pretibial myxedema (PTM) is a rare complication of Graves' disease. It is characterized by non-pitting edema with hyperpigmented hyperkeratotic papules and plaques on bilateral lower legs. Effective treatments for patients with PTM are lacking. The etiology of PTM is unknown; however, it may be similar to the mechanism of thyroid-associated ophthalmopathy (TAO). Activated fibroblasts produce inflammatory cytokines and synthesize excessive glycosaminoglycans (GAG) that accumulate in the dermis and subcutaneous tissue. A recent, novel pathway implicates IGF-1 receptor as a mediator in this process. We present two patients with refractory PTM that improved following treatment with teprotumumab, an IGF-1 receptor inhibitor approved for use in TAO. J Drugs Dermatol. 2022;21(11):1252-1254. doi:10.36849/JDD.6854.

Effects of Cervical Spine Exercise Protocol on Neck Pain, Pericervical Muscle Endurance, and Range of Motion in Medical Students: A Prospective Study.

Introduction Neck pain is a common and debilitating ailment that places a significant burden on the healthcare system. No practical protocols have been published utilizing a portable, commercially available, and affordable device that significantly reduces acute and chronic neck pain. Methods Forty-six young adults with or without mild-to-moderate neck pain completed a six-week neck stretching and strengthening protocol with a portable cervical stretching and strengthening device. The primary outcome was changes to pericervical muscle endurance. Secondary outcomes were changes to cervical range of motion (ROM), neck length, circumference, and subjective pain, flexibility, and strength. Measurements were obtained on study days 0, 21, and 42. Results A significant increase in pericervical muscle endurance was demonstrated across all planes of cervical motion, ranging from 84% to 105%. Cervical ROM improved across all planes of motion but was only significant in right-side bending (5.3°), left rotation (6.2°), and right rotation (7.8°). Subjective pain evaluated via the Numeric Rating Scale (NRS) saw statistically significant improvement as well (1.33 to 0.51). Subjective assessment of participant cervical pain, strength, and flexibility improved 61.3%, 95.7%, and 97.8%, respectively. Conclusions A six-week pericervical muscle stretching and strengthening program increased pericervical endurance and ROM in young adults. Decreased cervical pain was seen using the NRS and modified pain scale across most participants.

Impact of medical scribes on physician and patient satisfaction in dermatology.

Physician burnout and its association with the use of electronic health records (EHRs) is well known. The impact of scribes for academic dermatologists and their patients needs to be explored. As physician burnout increases, system-based solutions are needed. To assess the impact of a scribe on physician and patient satisfaction at an academic dermatology clinic. Prospective, pre-post-pilot intervention study. During the pilot intervention, clinicians had clinic sessions with and without a scribe. We assessed changes in (1) clinician satisfaction and burnout, (2) time spent on EHR, and (3) patient satisfaction. An electronic 7-item baseline survey, 23-item mid-study survey, and a 22-item end-of-study survey to assess clinician burnout and feedback on satisfaction with medical scribes. A 19-item post visit satisfaction survey was given to patients. EHR was queried to compare amount of time spent on EHR, closure of charts, and number of patients seen during scribe coverage and at baseline. Of the six clinicians, 100% felt that there was value to scribe support. Physician burnout was low at baseline and did not change post-pilot. Active documentation time, on average, decreased by 67% per patient with a 28% increase in patients seen per clinic. Over 88% of patients disagreed with the statement, "I was uncomfortable disclosing personal information when a scribe was present" (p < 0.001). In an academic dermatology and Mohs surgery setting, medical scribes increased clinician satisfaction without compromising patient satisfaction.

A Cautionary Tale of a Complex Peri-Trochanteric Fracture in a Very Important Person (VIP) Patient at a Community-Based Hospital: A Case Report.

Peri-trochanteric fractures with an extension into the femoral neck are relatively rare. Due to the lack of a defined treatment in the literature, these fractures pose a challenge to orthopedic surgeons. This case report highlights the value of timing to surgical intervention, choosing the appropriate operative course, not treating very important person (VIP) patients differently than standard patients, and decreasing unnecessary costs for the patient and the US healthcare system. An 85-year-old male VIP patient presented to the emergency department (ED) with a left peri-trochanteric fracture with an extension into the ipsilateral femoral neck. The initial plan was to perform arthroplasty with diaphyseal fixation. However, the community-based hospital would have to wait two to three days for the proper implants, and the patient insisted on being treated at this hospital. Due to concerns about increased mortality with delayed treatment, the patient underwent short cephalomedullary nail (CMN) fixation the next day. On postoperative day (POD) 49, a pop was heard and felt while ambulating, and radiographs revealed substantial lateral cutout of the CMN and subsidence of the femoral head. On POD 54, the patient underwent a successful left total hip arthroplasty using a modular diaphyseal press-fit femoral component, which resulted in an uneventful recovery. This case illustrates a cautionary tale in choosing the appropriate operative course for a VIP patient with a peri-trochanteric fracture extending into the femoral neck (a relatively rare fracture type that has no clearly defined treatment option). This is imperative to reduce pain and length of stay for the patient, postoperative complications, and cost. Based on the results from the second procedure and weighing the risk of prolonged treatment, the authors believe that this patient would likely have benefited from a primary arthroplasty procedure given his body habitus and complex fracture pattern.

Predominant risk factors for tick-borne co-infections in hunting dogs from the USA.

BACKGROUND: Both incidence and geographical range of tick-borne disease has increased across the USA. Similar to people, dogs are hosts for Anaplasma spp., Babesia spp., Ehrlichia spp. and Borrelia burgdorferi. Dogs also share our homes and beds, making them both a sentinel for the ticks in our backyards but also increasing our exposure to ticks. Measures to better track, prevent, and/or treat tick-borne diseases in companion animals can lead to better control and prevention of human tick-borne disease. This study identifies demographic and co-infection risk factors for canine seropositivity to tick-borne infections in a cohort of hunting dogs across the USA. RESULTS: Human patterns of tick-borne disease co-infection in the USA have been predominantly driven by the geographical distribution of the tick vector. Dogs who tested seropositive for Anaplasma spp. were 1.40 times more likely (P = 0.0242) to also test seropositive for Babesia spp. and vice versa (1.60 times more likely, P = 0.0014). Dogs living in the West had 5% lower risk (P = 0.0001) for Ehrlichia spp. seropositivity compared to other regions. Controlling for age and Anaplasma spp. seroprevalence, dogs in all three other regions were 2.30 times more likely (P = 0.0216) to test seropositive for B. burgdorferi than dogs in the West. Dogs seropositive for B. burgdorferi were 1.60 times more likely (P = 0.0473) to be seropositive for Anaplasma spp. CONCLUSIONS: Tick geographical distributions have a prominent impact on the regional distribution of hunting dog exposure to tick-borne diseases. Education concerning regional tick prevalence and disease risk is important for everyone, but particularly dog owners, regarding ticks in their region and protection from infection and co-infection of tick-borne pathogens as they travel or move with their dogs. Dogs are sentinel species for human exposure to ticks, and as such surveillance of canine tick-borne infections and understanding the probability that these infections might be seen together as co-infections helps predict emerging areas where people are more likely to be exposed as well.

ERK Inhibitor LY3214996 Targets ERK Pathway-Driven Cancers: A Therapeutic Approach Toward Precision Medicine.

The ERK pathway is critical in oncogenesis; aberrations in components of this pathway are common in approximately 30% of human cancers. ERK1/2 (ERK) regulates cell proliferation, differentiation, and survival and is the terminal node of the pathway. BRAF- and MEK-targeted therapies are effective in BRAF V600E/K metastatic melanoma and lung cancers; however, responses are short-lived due to emergence of resistance. Reactivation of ERK signaling is central to the mechanisms of acquired resistance. Therefore, ERK inhibition provides an opportunity to overcome resistance and leads to improved efficacy. In addition, KRAS-mutant cancers remain an unmet medical need in which ERK inhibitors may provide treatment options alone or in combination with other agents. Here, we report identification and activity of LY3214996, a potent, selective, ATP-competitive ERK inhibitor. LY3214996 treatment inhibited the pharmacodynamic biomarker, phospho-p90RSK1, in cells and tumors, and correlated with LY3214996 exposures and antitumor activities. In in vitro cell proliferation assays, sensitivity to LY3214996 correlated with ERK pathway aberrations. LY3214996 showed dose-dependent tumor growth inhibition and regression in xenograft models harboring ERK pathway alterations. Importantly, more than 50% target inhibition for up to 8 to 16 hours was sufficient for significant tumor growth inhibition as single agent in BRAF- and KRAS-mutant models. LY3214996 also exhibited synergistic combination benefit with a pan-RAF inhibitor in a KRAS-mutant colorectal cancer xenograft model. Furthermore, LY3214996 demonstrated antitumor activity in BRAF-mutant models with acquired resistance in vitro and in vivo. Based on these preclinical data, LY3214996 has advanced to an ongoing phase I clinical trial (NCT02857270).

Improvised Inguinal Junctional Tourniquets: Recommendations From the Special Operations Combat Medical Skills Sustainment Course.

Effectively and rapidly controlling significant junctional hemorrhage is an important effort of Tactical Combat Casualty Care (TCCC) and can potentially contribute to greater survival on the battlefield. Although the US Food and Drug Administration (FDA) has approved labeling of four devices for use as junctional tourniquets, many Special Operations Forces (SOF) medics do not carry commercially marketed junctional tourniquets. As part of ongoing educational improvement during Special Operations Combat Medical Skills Sustainment Courses (SOCMSSC), the authors surveyed medics to determine why they do not carry commercial tourniquets and present principles and methods of improvised junctional tourniquet (IJT) application. The authors describe the construction and application of IJTs, including the use of available pressure delivery devices and emphasizing that successful application requires sufficient and repetitive training.

Comorbid infections induce progression of visceral leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL) is a vector borne zoonotic disease endemic in humans and dogs in Brazil. Due to the increased risk of human infection secondary to the presence of infected dogs, public health measures in Brazil mandate testing and culling of infected dogs. Despite this important relationship between human and canine infection, little is known about what makes the dog reservoir progress to clinical illness, significantly tied to infectiousness to sand flies. Dogs in endemic areas of Brazil are exposed to many tick-borne pathogens, which are likely to alter the immune environment and thus control of L. infantum. RESULTS: A cross-sectional study of 223 dogs from an area of Natal, in the Rio Grande do Norte, Brazil, were studied to determine the association between comorbid tick-borne disease and Leishmania infection in this endemic area. The risk of Leishmania seropositivity was 1.68× greater in dogs with tick-borne disease seropositivity compared to those without (Adjusted RR: 1.68, 95% CI: 1.09-2.61, P = 0.019). A longitudinal study of 214 hunting dogs in the USA was conducted to determine the causal relationship between infection with tick-borne diseases and progression of VL. Hunting dogs were evaluated three times across a full tick season to detect incident infection with tick-borne diseases. A logistic regression model with generalized estimating equations to estimate the parameters was used to determine how exposure to tick-borne disease altered VL progression over these three time points when controlling for other variables. Dogs infected with three or more tick-borne diseases were 11× more likely to be associated with progression to clinical VL than dogs with no tick-borne disease (Adjusted RR: 11.64, 95% CI: 1.22-110.99, P = 0.03). Dogs with exposure to both Leishmania spp. and tick-borne diseases were five times more likely to die during the study period (RR: 4.85, 95% CI: 1.65-14.24, P = 0.0051). CONCLUSIONS: Comorbid tick-borne diseases dramatically increased the likelihood that a dog had clinical L. infantum infection, making them more likely to transmit infection to sand flies and people. As an important consequence, reduction of tick-borne disease exposure through topical or oral insecticides may be an important way to reduce progression and transmissibility of Leishmania infection from the canine reservoir to people.

Thermal Reshaping Dynamics of Gold Nanorods: Influence of Size, Shape, and Local Environment.

The thermal reshaping of gold nanorods in a polymer matrix is an important phenomenon for many potential applications. However, a fundamental understanding of the various mechanisms that govern the nanorod reshaping dynamics is still lacking. Here, we provide evidence for a phenomenological model of the gold nanorod shape transformation based on the measurements and detailed analysis of the time-resolved thermal reshaping for a variety of gold nanorods having different geometries (aspect ratio, volume, diameter) in a cross-linked epoxy matrix at application relevant temperatures (120-220 °C). Our analysis suggests that (a) the nanorod reshaping dynamics consist of two temporal regimes that are governed by different phenomena and (b) the ultimate amount of reshaping at a given temperature depends strongly on the initial particle geometry and the mechanical stiffness of its surroundings. At short times, the shape transformation is dominated by a curvature-induced surface diffusion process, in which the activation energy for diffusion depends on curvature. At long times, however, the surrounding environment plays a key role in slowing the diffusion and stabilizing the nanorod shape. We show that the long-time behavior can be well described using a modified surface diffusion model that takes into account the slowing of atomic diffusivity as a result of external forces arising from mechanical constraints. The ability to tune both the final shape and the reshaping dynamics in nanocomposites opens up new possibilities in tailoring the optical properties of these materials.

Randomized, controlled, double-blinded field trial to assess Leishmania vaccine effectiveness as immunotherapy for canine leishmaniosis.

Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009-1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185-8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.

Gastrointestinal Histoplasmosis Presenting as an Acute Abdomen with Jejunal Perforation.

INTRODUCTION: Gastrointestinal histoplasmosis (GH) is a well-described albeit uncommon disease. It is found almost exclusively in the immunocompromised host, especially those with untreated HIV and low CD4 counts. Presentation with intestinal perforation is seen mostly commonly in the colon. We present a patient with jejunal perforation, and there have been only 3 previous cases reported in the literature. CASE: A 39-year-old male with known, untreated HIV presented to the ED with an acute abdomen after experiencing worsening intermittent abdominal pain for 2 months before that was associated with nausea, vomiting, diarrhea, and weight loss. CT of the abdomen and pelvis revealed evidence of gas in the mesentery, small bowel thickening, edema, and free fluid in the abdomen. Emergency exploratory laparotomy was conducted. Intraoperative findings included a perforated jejunum that was studded with nodular lesions as well as mesenteric masses. Histopathologic exam of these mesenteric masses and jejunal lesions were positive for histoplasmosis. CONCLUSION: Disseminated histoplasmosis is a life-threatening disease that occurs nearly exclusively in immunocompromised hosts. Untreated, mortality is as high as 80%. This rare presentation with jejunal perforation highlights the need for awareness of histoplasmosis involvement throughout the entirety of the GI tract.

Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class transforming growth factor-ß receptor type I inhibitor.

Transforming growth factor-ß (TGFß) is an important driver of tumor growth via intrinsic and extrinsic mechanisms, and is therefore an attractive target for developing cancer therapeutics. Using preclinical models, we characterized the anti-tumor activity of a small molecule inhibitor of TGFß receptor I (TGFßRI), galunisertib (LY2157299 monohydrate). Galunisertib demonstrated potent and selective inhibition of TGFßRI with corresponding inhibition of downstream signaling via inhibition of SMAD phosphorylation (pSMAD). Galunisertib also inhibited TGFß-induced pSMAD in vivo, which enabled a pharmacokinetic/pharmacodynamic profile in Calu6 and EMT6-LM2 tumors. Galunisertib demonstrated anti-tumor activity including inhibition of tumor cell migration and mesenchymal phenotype, reversal of TGFß-mediated immune-suppression, and tumor growth delay. A concentration-effect relationship was established with a dosing schedule to achieve the optimal level of target modulation. Finally, a rat model demonstrated a correlation between galunisertib-dependent inhibition of pSMAD in tumor tissues and in PBMCs, supporting the use of PBMCs for assessing pharmacodynamic effects. Galunisertib has been tested in several clinical studies with evidence of anti-tumor activity observed in subsets of patients. Here, we demonstrate that galunisertib inhibits a number of TGFß-dependent functions leading to anti-tumor activity. The enhanced understanding of galunisertib provides rationale for further informed clinical development of TGFß pathway inhibitors.

Synthesis and chemical transformation of Ni nanoparticles embedded in silica.

Ni nanoparticles (NPs) catalyze many chemical reactions, in which they can become contaminated or agglomerate, resulting in poorer performance. We report deposition of silica (SiO2) onto Ni NPs from tetraethyl orthysilicate (TEOS) through a reverse microemulsion approach, which is accompanied by an unexpected etching process. Ni NPs with an average initial diameter of 27 nm were embedded in composite SiO2-overcoated Ni NPs (SiO2-Ni NPs) with an average diameter of 30 nm. Each SiO2-Ni NP contained a ∼7 nm oxidized Ni core and numerous smaller oxidized Ni NPs with diameters of ∼2 nm distributed throughout the SiO2 shell. Etching of the Ni NPs is attributed to use of ammonium hydroxide as a catalyst for deposition of SiO2. Aliquots acquired during the deposition and etching process reveal agglomeration of SiO2 and Ni NPs, followed by dissociation into highly uniform SiO2-Ni NPs. This etching and embedding process may also be extended to other core materials. The stability of SiO2-Ni NPs was also investigated under high-temperature oxidizing and reducing environments. The structure of the SiO2-Ni NPs remained significantly unchanged after both oxidation and reduction, which suggests structural durability when used for catalysis.

The Use of Remifentanil as the Primary Agent for Analgesia in Parturients.

Pain control in parturients can be particularly challenging for the hospital staff. To achieve optimal outcomes in anesthesia patients, it is important to consider multiple options for pain control, especially when traditional options pose a problem or are not options. In particular, there are parturient clients for whom the use of neuraxial anesthesia (epidural and spinal blockade) is not an option. One option that warrants consideration for patient centered anesthesia practice is the use of remifentanil.

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone.

There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

Malignant melanoma-The cradle of anti-neoplastic immunotherapy.

One of the defining characteristics of the malignant phenotype is the ability to evade the host immune system. Immunotherapy as a treatment modality represents a new dawn in the way we think about the treatment of a variety of malignancies. The story of immunotherapy traces its roots to its relationship with malignant melanoma. In this article, we review the intertwined history of immunotherapy and melanoma, including the early significant history, a discussion on immune mechanisms, resistance, local and systemic immunotherapeutic modalities, and speculate on possible novel future treatment options.