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BACKGROUND: Recalcitrant plantar fasciitis (RPF) is characterized by its unresponsiveness to conservative treatments, and its surgical management remains controversial. Although there is some evidence to suggest that gastrocnemius recession can be an effective treatment for RPF, no large series of patients with mid- to long-term follow-up has been published. The objective of this study was to compare physical performance, as measured by the Foot and Ankle Ability Measure activities of daily living score (FAAM-ADL), and pain levels before and 1 year after undergoing proximal medial gastrocnemius recession (PMGR) as a treatment for RPF. Additionally, we aimed to assess this cohort of patients in the mid- to long-term follow-up. METHODS: This retrospective cohort study included 167 patients who underwent PMGR to address RPF between 2009 and 2021. Patients were examined with the FAAM ADL, visual analog scale (VAS) and satisfaction scores at baseline, 1 year, and at the end of follow-up. Other variables recorded were weight, duration of symptoms until surgery, time between surgery to substantial clinical improvement, calf power and Silfverskiold test, and postoperative complications. RESULTS: We observed that before surgery patients had an FAAM-ADL score of 22.5 (SD 11.1) and a VAS score of 8.6 (SD 9.3). One year after surgery, patients had an FAAM-ADL score of 89 (SD 17) and VAS of 1.33 (SD 2) (P < .01). We also observed that the FAAM-ADL score in the long-term follow-up (>12.5 years) group had a median of 86.4 (SD 22.6), the VAS score was 1.90 (SD 2.84), and the patient satisfaction score had a median of 1 (interquartile range 0-1). Regarding complications, we observed 1 lateral gastrocnemius recession and 1 sural nerve neuritis. CONCLUSION: Our study provides substantial evidence supporting the use of PMGR as an effective treatment for RPF. The long-term follow-up and large sample size of our series contribute to the existing literature on this topic.

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BACKGROUND: Few studies have assessed the ability of internal medicine residents to perform a cardiovascular physical examination using real patients. METHODS: First year internal medicine interns from 2 large academic medical centers in Maryland examined the same patient with aortic insufficiency as part of the Assessment of Physical Examination and Communication Skills (APECS). Interns were assessed on 5 clinical domains: physical exam technique, identifying physical signs, generating a differential diagnosis, clinical judgment, and maintaining patient welfare. Spearman's correlation test was used to describe associations between clinical domains. Preceptor comments were examined to identify common errors in physical exam technique and identifying physical signs. RESULTS: One hundred nine interns examined the same patient with aortic insufficiency across 14 APECS sessions. Only 58 interns (53.2%) correctly identified the presence of a diastolic murmur, and only 52 interns (47.7%) included aortic insufficiency on their differential diagnosis. There was a significant and positive correlation between physical exam technique and identification of the correct physical findings (r = 0.42, P < .001). Both technique (r = 0.34, P = .003) and identifying findings (r = 0.42, P < .001) were significantly associated with generating an appropriate differential diagnosis. Common errors in technique included auscultating over the gown, timing the cardiac cycle with the radial pulse, and failing to palpate for the apical impulse. CONCLUSIONS: Internal medicine interns had variable skills in performing and interpreting the cardiovascular physical exam. Improving cardiovascular exam skills would likely lead to increased identification of relevant cardiovascular findings, inform clinical decision making and improve overall patient care.

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Talocalcaneal coalitions (TCC) is the second most frequent tarsal coalition reported. Our aim was to review talocalcaneal coalition classifications and to propose a new classification emphasizing a therapeutic approach. None of the classifications described for TCC mention the presence of flatfoot or valgus hindfoot, which are the key elements when defining the optimal treatment of this disease. We defined five clinical and radiological factors that would guide the choice of surgical treatment and based on these, we proposed a new classification system.

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BACKGROUND: Previous retrospective results are evaluated prospectively and blinded. METHODS: A total of 221 eyes previously classified as normal (G1), 279 as moderate risk of glaucoma (G2) and 217 as high risk (G3) according to the Globin Discriminant Function (GDF) Laguna-ONhE index were examined with OCT Spectralis- Results: In G1, the Bruch's Membrane Opening Minimum Rim Width (BMO-MRW) was 332 ± 55 microns; in G2, it was 252 ± 47 (p < 0.0001); and in G3, 231 ± 44 (p < 0.0001). In G1, the 1% and 5% percentiles were 233 and 248, respectively; in G2, they were lower in 28.80% and 42.29% of cases, respectively; and in G3, in 50.23% and 63.59% of cases, respectively. Most of the cases were normal-tension glaucomas. Laguna-ONhE indices showed a curvilinear correlation with BMO-MRW results. The Retinal Nerve Fibre Layer (RNFL) showed a poor relationship with BMO. Assuming G1 to be truly normal, BMO-MRW would have a Receiver operating characteristic (ROC) curve area of 0.901 for G2 and G3 and 0.651 for RNFL. A significant reduction in pixels corresponding to vessels was found in G2 and G3 vs. G1 (p < 0.0001). CONCLUSIONS: In some cases, these defects appear to be mainly glaucomatous, and in others, they are associated with diabetic microangiopathy. In normal tension glaucoma, RNFL defects may be less severe than those inside the nerve.

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CD56+ T cells are generally recognized as a distinct population of T cells and are categorized as NKT-like cells. Although our understanding of NKT-like cells is far from satisfactory, it has been shown that aging and a number of disease situations have impacted these cells. To construct an overview of what is currently known, we reviewed the literature on human NKT-like cells. NKT-like cells are highly differentiated T cells with "CD1d-independent" antigen recognition and MHC-unrestricted cell killing. The genesis of NKT-like cells is unclear; however, it is proposed that the acquisition of innate characteristics by T cells could represent a remodeling process leading to successful aging. Additionally, it has been shown that NKT-like cells may play a significant role in several pathological conditions, making it necessary to comprehend whether these cells might function as prognostic markers. The quantification and characterization of these cells might serve as a cutting-edge indicator of individual immune health. Additionally, exploring the mechanisms that can control their killing activity in different contexts may therefore result in innovative therapeutic alternatives in a wide range of disease settings.

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In a scenario with declining biodiversity and habitat loss, botanic gardens could serve as refuges for invertebrates, but the opportunities they offer for animal conservation are still poorly understood. Odonata is a good model group for conservation studies, because it includes threatened species and responses to habitat disturbance are well documented. In this study, we assessed the role of the botanic garden of Castilla-La Mancha in Spain as a refuge for members of Odonata by analysing their taxonomic and functional diversity. We explored if the small size of the botanic garden might constrain the taxonomic diversity of Odonata and if low habitat diversity might limit their functional diversity. We sampled adult Odonata from five water bodies along a gradient of human impact and characterized the Odonata communities based on 12 functional traits in Odonata. We used a species-area relationship to control for differences in the size of water bodies. Compared with natural lakes, the Odonata communities contained less species and their functional diversity was lower in the botanic garden ponds, where generalist species were basically hosted. Despite these limitations, the botanic garden ponds hosted the number of species expected for natural water bodies with the moderate surface area and functional diversity, thereby demonstrating that they are a valuable habitat for Odonata in an urban environment. Appropriate management involving the removal of exotic fish and habitat diversification, including creating lotic environments, would increase the taxonomic and functional diversity of Odonata in this urban system. Supplementary Information: The online version contains supplementary material available at 10.1007/s10201-022-00704-3.

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Background: Laguna ONhE provides a globin distribution function (GDF), in which a glaucoma discriminator based on deep learning plays an important role, and there is also an optimized globin individual pointer (GIP) for progression analysis. Methods: Signs of optic nerve glaucoma were identified in 1,124,885 fundus images from 203,115 diabetics obtained over 15 years and 117,813 control images. Results: A total of 743,696 images from 313,040 eyes of 173,661 diabetics were analysed. Some exclusions occurred due to excessive illumination, poor quality, or the absence of optic discs. Suspicion of glaucoma was reported in 6.70%, for an intended specificity of 99% (GDF < −15). More signs of glaucoma occur in diabetics as their years of disease increase, and after age 60, compared to controls. The GIP detected progression (p < 0.01) in 2.59% of cases with 4 controls and in 42.6% with 14 controls was higher in cases with lower GDF values. The GDF was corrected for the disc area and proved to be independent of it (r = 0.001925; p = 0.2814). Conclusions: The GDF index suggests a higher and increasing glaucoma probability in diabetics over time. Doubling the number of check-ups from four to eight increases the ability to detect GIP index progression by a factor of 5.

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BACKGROUND: Between October 2018, and February 2020, the United States saw an unprecedented increase in the number of asylum seekers and refugees arriving unexpectedly at international crossings along the US-Mexico Border. Many of these migrants needed proper medical attention, and consequently created significant pressure on local health systems. In El Paso, Texas, volunteer clinicians, collaborating closely with religious organizations and non-governmental organizations, provided outpatient medical care for the new arrivals; the county hospital provided in-patient care at local tax payers' expense. The objective of this study was to estimate costs of healthcare services offered by these volunteers in order to formulate sustainable and appropriate healthcare policies to address the needs of refugees and asylum seekers in the United States. METHODS: A mixed methods approach was used including personal interviews with stakeholders, and follow up surveys with volunteer clinicians. The cost analysis was done from the payer perspective using Medicaid reimbursement rates. RESULTS: Total costs of care provided to asylum seekers and refugees varied between $1.9MM to $4.4MM during the study period. The number of patient visits was estimated at 15,736 to 19,236, and cost per patient ranged between $99 and $281. Most common conditions treated by volunteer providers were abdominal pain, dermatological conditions, headaches, dehydration and hypertension. CONCLUSIONS: This is the first study looking at the cost of healthcare for refugees and asylum seekers provided by volunteer clinicians, in a binational context. The resources invested by volunteer providers were significant, and essential to meet medical needs of migrant populations. Without appropriate financial support, a strategy relying on volunteer and local community resources will prove unsustainable in the long term. Findings from this study will help formulate federal and local policies to support local health systems along the US-Mexico Border in providing care to future migrations into the United States.

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Leprosy is a chronic disease and also a global health issue, with a high number of new cases per year. Toll-like receptors can respond to mycobacterial molecules in the early stage of infection. As important components of the innate immune response, alterations in genes coding for these receptors may contribute to susceptibility/protection against diseases. In this context, we used a case-control study model (183 leprosy cases vs. 185 controls) to investigate whether leprosy patients and the control group, in southern Brazil, have different frequencies in TLR1 (TLR1 G>T; rs5743618), TLR2 (TLR2 T>C, rs1816702 and rs4696483), and TLR4 (TLR4 A>G, rs1927911) polymorphisms. Analysis of the TLR1 1805G>T polymorphism presented the G/G genotype more frequently in the control group. TLR2 T>C rs1816702 and TLR2 T>C rs4696483, the T/T and C/T genotype, respectively, were more frequent in the control group than in leprosy patients, suggesting protection from leprosy when the T allele is present (rs4696483). Haplotype analyses between TLR1 (rs5743618) and TLR2 (rs1816702 and rs4696483) polymorphisms suggest risk for the presence of the TCC haplotype and protection in the presence of the TCT haplotype. This study suggests that polymorphisms in TLR1 and TLR2 are factors that may contribute to development/resistance of leprosy.

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OBJECTIVE: To describe a new method to estimate the frequency distribution of optic nerve disc area, using digital retinographic images. METHODS AND ANALYSIS: We analysed 492 023 fundus images obtained with seven fundus cameras, mainly in Caucasian subjects. They were grouped by resolution and zoom. They were automatically segmented by identifying the inner edge of the Elschnig scleral ring. For this purpose, a neural network trained by deep learning previously described was used. The number of pixels contained within the segmentation and their frequency distribution were calculated. The results of each camera, using different number of images, were compared with the global results using the Kolmogorov-Smirnov test to confront frequency distributions. RESULTS: The frequency distribution was non-Gaussian, more limited in small sizes than in large ones. If the median is assigned a theoretical value of 1.95 mm2, the 1th, 5th, 25th, 50th, 75th, 95th and 99th percentiles would correspond to 1.29, 1.46, 1.73, 1.95, 2.20, 2.64 and 3.03 mm2 in all the dataset. The overall differences were significant for the smaller series, but for each percentile their mean value was only 0.01 mm2 and the maximum 0.10 mm2, so they can be considered similar for practical purposes in all cameras. CONCLUSION: By automatically segmenting the edges of the optic nerve and observing the frequency distribution of the number of pixels it delimits, it is possible to estimate the frequency distribution of the disc area in the population as a whole and that of each individual case.

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OBJECTIVE: To identify age-related vascular changes in the optic discs of patients with diabetes with and without signs of glaucoma. METHODS AND ANALYSIS: A total of 2153 eyes of 1797 patients with diabetes without significant retinopathy were monitored with 10 Topcon-NW400 images obtained over 10.27±1.58 years. 571 non-diabetics eyes were selected as controls. Laguna ONhE uses convolutional neural networks to identify optic disc edges, vessels, cup and rim, and provides a glaucoma assessment index-Globin Distribution Function (GDF). RESULTS: In the first image, vessel pixels accounted for 33.88% of the disc area (SD=3.72) in non-glaucoma (DN) and 31.35% (SD=4.05; p<0.0001) in glaucoma cases (DG). This number of pixels was reduced by -0.55% each year (SD=0.77) in the DN and -0.76% (SD=0.86; p=0.0014) in the DG. In the first image, 76.55% of the disc pixels (SD=11.13) belonged to the rim in the DN and 62.05% (SD=11.00; p=0.0014) in the DG, decreasing annually by -0.33% (SD=0.99) in the DN and -0.68% (SD=1.08; p<0.00001) in the DG groups. All rim sectors were reduced over time in the DG group, particularly superotemporal (41°-80°) and inferotemporal (271°-310°). The reduction was smaller in DN, presenting as progressive thickening of the temporal sector (311°-40°). No changes in age were observed in healthy controls. CONCLUSION: Patients with diabetes show progressive reduction of vessels and neuroretinal rim at the optic disc, which is more intense in association with glaucoma. In the absence of glaucoma, the temporal sector of the diabetic rim was not reduced but thickened, displacing the cup nasally.

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The role of the immune system, and hence inflammation, in the pathophysiology of hypertensive patients is not clear. Until now, most clinical and biochemical parameters have failed to predict a positive response to renal denervation (RDN). Our aim was to evaluate the immune response in a cohort of patients treated by RDN, through the analysis of cytokine, chemokine, and growth factor behavior. A population of 21 resistant hypertension patients, treated by RDN, was evaluated at six months and one year. Response was defined as a drop of ≥5 mmHg in ambulatory blood pressure monitoring. Sixty-seven percent and 81% of patients clinically responded after six months and one year, respectively. There were no complications or safety issues. Plasmatic levels of 45 cytokine, chemokine, and growth factors were quantified at four different times, pre- and post-procedure. Baseline characteristics were similar between groups, except that active smoking was more frequent in non-responders at one year. Regulated on activation, normal T cell expressed, and secreted (RANTES/CCL5) levels were significantly lower in responders, both at baseline and at 30 days (p = 0.037), and a level ≤15,496 pg/mL was the optimal cutoff, for prediction of a response. IL-15, IL-17A, IL-27, and leukemia inhibitory factor varied significantly in time, with an acute rise being observed 24 h after RDN. Our group has previously showed that HLA-DR+ double-negative (DN) T cells were significantly lower in responders. There was a positive correlation between IL-13, -27, and -4, and DN T cells, and a negative correlation between the latter and SDF-1α and TNF-α, at baseline. Low plasmatic levels of the chemokine RANTES/CCL5 was the most significant result associated with RDN response and may help to identify the best candidates among patients with true resistant hypertension. Pro-inflammatory cytokines correlated negatively with DN T cells in responders, a finding compatible with an enhanced inflammatory milieu present in this extremely high cardiovascular risk cohort.

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Osteosarcoma (OST) is the most common type of high-grade primary bone tumor, which mainly affects young adults. The current standard of care for OST combines surgical resection with chemotherapy. The clinical outcomes and the current options to treat OST patients are unsatisfactory and novel treatment strategies are needed. The crosstalk between tumor cells and immune cells is essential to the OST microenvironment. Despite the efforts that have been made to address the importance of immune-related factors in OST, there is still a lot to understand. The purpose of the current study was to evaluate the tumor-infiltrating lymphocytes (TIL), the expression of proteins involved in tumor biology, and their impact on the clinical outcome of OST patients. We studied 93 samples of OST patients using immunohistochemistry and histomorphometry. We looked for the infiltration of CD3+, CD4+, CD8+, TIA1+ and CD20+ cells and for the expression of CD44 standard (CD44s) and variant 6 (CD44v6), CD95/Fas, Fas-L, p53 and p-glycoprotein. All the parameters were analyzed for the influence on the occurrence of death and metastasis, plus patient overall survival (OS) and progression-free survival (PFS). The effect of sex, age, tumor location (distal femur or proximal tibia) and the combination with neoadjuvant chemotherapy was also assessed. Our results suggest that the presence of tumor-infiltrating CD4+ cells provides protection to OST patients, and that CD8+ cells have a significant impact on the patient's overall survival (OS) and progression-free survival (PFS), which is more evident in male patients. In addition, a strong association between tumor-infiltrating CD4+ cells and the presence of CD44s expression in tumor samples was observed. Analysis of TIL and tumor markers related to tumor biology could be useful to stratify patients and monitor the response to therapy, as well as to assist with the development of immunotherapy strategies to improve the effects of cytotoxic TIL to eradicate the tumor cells.

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Soft-tissue sarcomas (STS) represent about 80% of sarcomas, and are a heterogeneous group of rare and malignant tumors. STS arise from mesenchymal tissues and can grow into structures such as adipose tissue, muscles, nervous tissue and blood vessels. Morphological evaluation has been the standard model for the diagnosis of sarcomas, and even in samples with similar characteristics, they present a diversity in cytogenetic and genetic sequence alterations, which further increases the diversity of sarcomas. This variety is one of the main challenges for the classification and understanding of STS patterns, as well as for their respective treatments, which further decreases patient survival (<5 years). Despite some studies, little is known about the immunological profile of STS. As for the immunological profile of STS in relation to NK cells, there is also a shortage of studies. Observations made in solid tumors show that the infiltration of NK cells in tumors is associated with a good prognosis of the disease. Notwithstanding the scarcity of studies to characterize NK cells, their receptors, and ligands in STS, it is noteworthy that the progression of these malignancies is associated with altered NK phenotypes. Despite the scarcity of information on the function of NK cells, their phenotypes and their regulatory pathways in STS, the findings of this study support the additional need to explore NK cell-based immunotherapy in STS further. Some clinical trials, very tentatively, are already underway. STS clinical trials are still the basis for adoptive NK-cell and cytokine-based therapy.

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Soft Tissue Sarcomas (STS) are a heterogeneous and rare group of tumors. Immune cells, soluble factors, and immune checkpoints are key elements of the complex tumor microenvironment. Monitoring these elements could be used to predict the outcome of the disease, the response to therapy, and lead to the development of new immunotherapeutic approaches. Tumor-infiltrating B cells, Natural Killer (NK) cells, tumor-associated neutrophils (TANs), and dendritic cells (DCs) were associated with a better outcome. On the contrary, tumor-associated macrophages (TAMs) were correlated with a poor outcome. The evaluation of peripheral blood immunological status in STS could also be important and is still underexplored. The increased lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR), higher levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and Tim-3 positive CD8 T cells appear to be negative prognostic markers. Meanwhile, NKG2D-positive CD8 T cells were correlated with a better outcome. Some soluble factors, such as cytokines, chemokines, growth factors, and immune checkpoints were associated with the prognosis. Similarly, the expression of immune-related genes in STS was also reviewed. Despite these efforts, only very little is known, and much research is still needed to clarify the role of the immune system in STS.

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BACKGROUND: Laguna-ONhE is an application for the colorimetric analysis of optic nerve images, which topographically assesses the cup and the presence of haemoglobin. Its latest version has been fully automated with five deep learning models. In this paper, perimetry in combination with Laguna-ONhE or Cirrus-OCT was evaluated. METHODS: The morphology and perfusion estimated by Laguna ONhE were compiled into a "Globin Distribution Function" (GDF). Visual field irregularity was measured with the usual pattern standard deviation (PSD) and the threshold coefficient of variation (TCV), which analyses its harmony without taking into account age-corrected values. In total, 477 normal eyes, 235 confirmed, and 98 suspected glaucoma cases were examined with Cirrus-OCT and different fundus cameras and perimeters. RESULTS: The best Receiver Operating Characteristic (ROC) analysis results for confirmed and suspected glaucoma were obtained with the combination of GDF and TCV (AUC: 0.995 and 0.935, respectively. Sensitivities: 94.5% and 45.9%, respectively, for 99% specificity). The best combination of OCT and perimetry was obtained with the vertical cup/disc ratio and PSD (AUC: 0.988 and 0.847, respectively. Sensitivities: 84.7% and 18.4%, respectively, for 99% specificity). CONCLUSION: Using Laguna ONhE, morphology, perfusion, and function can be mutually enhanced with the methods described for the purpose of glaucoma assessment, providing early sensitivity.