Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKÆ´ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.

Insights into estrogen impact in oral health & microbiome in COVID-19.

BACKGROUND: COVID-19 emerged in late 2019 and has occasioned more than 765 millions cumulative cases and 6.9 millions of deaths globally. Notably, around 70% of patients with severe COVID-19 are men. Therefore, it is to be presumed that women have a hormonal protector factor in inflammation and ACE2 expression. On the other hand, oral health status, and local microbiome can be key factors to respiratory viral infections control. Nevertheless, it has been poorly investigated. In our study 20 premenopausal, 18 postmenopausal and 22 men with COVID-19 were included. Oral health status, viral load, lingual ACE2 expression, as well as microbiome, estrogens and cytokines in saliva were analyzed. RESULTS: Our results showed a lower expression of ACE2 in tongue cells of postmenopausal compared with premenopausal (p = 0.05), and a strong negative correlation between saliva estrogen and viral load (r = -0.76; p = 0.001). Respect to IFN-γ (p = 0.05), IL-1ß, TNF-α, IL-18, and IL-23 levels were increased in postmenopausal. Oral microbiome signature of premenopausal was characterized by Prevotella melaninogenica (Log2 = 26.68; p = 1.34e-10), Haemophilus (Log2 = 23.99; p = 2.96e-9), and Alloprevotella (Log2 = 7.92; p = 0.0001). On the other hand, Leptotrichia (Log2 = -18.74; p = 0.001), Tanerella (Log2 = -17.08; p = 0.004), and Clostridiales (Log2 = -2.88; p = 0.04) represented the poor oral health group compared with the adequate group which was enriched with the commensal microorganism Neisseria perflava (Log2 = 26.70; p = 1.74e-7). Furthermore, the high viral load group was characterized by Prevotella nanceiensis (Log2 = 19.60; p = 6.06e-8), Prevotella melaninogenica (Log2 = 21.45; p = 9.59e-6), Alloprevotella (Log2 = 23.50; p = 2.70e-7) and bacteria from the red complex Porphyromonas endodentalis (Log2 = 21.97; p = 1.38e-7). CONCLUSIONS: Postmenopausal and men have a poor oral health status which could be related to a detrimental progression of COVID-19 also linked to a lower expression of ACE2, lower saliva estrogen levels and oral dysbiosis. Nevertheless, functional studies are required for a deeper knowledge.

Categorization of the amyotrophic lateral sclerosis population via the clinical determinant of post-onset ΔFS for study design and medical practice.

The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) has become the most widely utilized measure of disease severity in patients with ALS, with change in ALSFRS-R from baseline being a trusted primary outcome measure in ALS clinical trials. This is despite the scale having several established limitations, and although alternative scales have been proposed, it is unlikely that these will displace ALSFRS-R in the foreseeable future. Here, we discuss the merits of delta FS (ΔFS), the slope or rate of ALSFRS-R decline over time, as a relevant tool for innovative ALS study design, with an as yet untapped potential for optimization of drug effectiveness and patient management. In our view, categorization of the ALS population via the clinical determinant of post-onset ΔFS is an important study design consideration. It serves not only as a critical stratification factor and basis for patient enrichment but also as a tool to explore differences in treatment response across the overall population; thereby, facilitating identification of responder subgroups. Moreover, because post-onset ΔFS is derived from information routinely collected as part of standard patient care and monitoring, it provides a suitable patient selection tool for treating physicians. Overall, post-onset ΔFS is a very attractive enrichment tool that is, can and should be regularly incorporated into ALS trial design.

European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).

BACKGROUND: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS). METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available. RESULTS: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management. CONCLUSIONS: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.

Beyond diagnosis: exploring the significance of IgG4+ plasma cell count through immunostaining in IgG4-related disease.

OBJECTIVES: To evaluate whether the grade of IgG4+ plasma cell infiltration in biopsies is associated with clinical or serologic outcomes in IgG4-RD. METHODS: We included 57 patients with biopsy proven IgG4-RD according to the Comprehensive Diagnostic Criteria and/or the 2019 ACR/EULAR Classification Criteria. We collected histological, clinical (disease duration, phenotype, remission and relapses) and serological variables. RESULTS: 29 (50.9%) patients were men, mean age 49.9 years, with a median disease duration of 22 months. The distribution among clinical phenotypes were 14% pancreato-hepato-biliary, 12.3% retroperitoneal/aortic, 29.8% head and neck-limited, 29.8% Mikulicz/systemic and 14% undefined. Thirty-nine patients had a proliferative and 18 a fibrotic phenotype. Most biopsies were from lacrimal gland, lymph node, pancreas, orbit, kidney, retroperitoneum and thyroid gland. Thirty-nine (68.4%) patients had <100 IgG4+ plasma cells/HPF and 18 (31.6%) ≥100 IgG4+ plasma cells/HPF. Patients with ≥100 IgG4+ plasma cells/HPF were more likely to belong to the pancreato-hepato-biliary and the proliferative phenotypes, had fewer relapses and a higher remission rate. On multivariate analysis, the OR for remission at last follow-up was 6.7, 95% CI 1.1-4.42, p=0.03. The log-rank test showed a difference in relapse-free survival between the two groups (HR 2.6, 95% CI 1.2-5.6, p=0.01). According to the ROC analysis, patients with more than 61 IgG4+ plasma cells were less likely to relapse. CONCLUSIONS: A count of ≥100 IgG4+ plasma cells/HPF may identify patients with a proliferative phenotype, fewer relapses and a higher remission rate.

Total lockdown and fairness towards the sufferer: an egalitarian response to Savulescu and Cameron.

Savulescu and Cameron supported selectively locking down the elderly during the COVID-19 pandemic on two grounds: first, that preserving total lockdown would entail levelling down and, second, that levelling down is wrong. Their first assumption has been thoroughly addressed, but more can be said about their wider antiegalitarian point that levelling down is simply wrong. Egalitarians are not defenceless against the levelling-down objection. Even though some consider it the most serious challenge to supporters of equality, egalitarianism possesses sound reasons to assert, not only that something valuable is preserved when we level down, but also that preserving it may be, in certain circumstances, preferable to pursuing other fundamental moral goals. Although troublesome from a well-being maximising standpoint, levelling down ensures that healthcare policy reflects a commitment with the idea that people are equal in moral worth. That commitment is important enough to trump certain improvements in individual well-being. In the case of pandemic lockdowns, not all the interests protected by free movement are as fundamental as to pursue them at the cost of equality. Savulescu and Cameron's framework is so reliant on the view that levelling down is wrong that it fails to account for the valuable loss that having the elderly suffer alone represents.

Performance of the 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease in a Latin American Cohort.

BACKGROUND/OBJECTIVE: The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria (2019 AECC) for IgG4-related disease (IgG4-RD) is considered a significant advancement in the study of this condition. Most studies evaluating their performance have focused on White and Asian patients, leaving a knowledge gap regarding Latin American populations. Therefore, this study aimed to assess the performance of the 2019 AECC for IgG4-RD in a cohort of Latin American patients. METHODS: A multicenter medical records review study was conducted, involving centers from Argentina, Chile, Mexico, Peru, and Uruguay. Data on IgG4-RD patients and mimicker conditions were collected through a standardized online form. The criterion standard for diagnosing IgG4-RD was based on the fulfillment of the Comprehensive Diagnostic Criteria for IgG4-RD and/or the Consensus Statement on Pathology. The 2019 AECC was retrospectively applied. RESULTS: We included 300 patients, with 180 (60%) having IgG4-RD and 120 (40%) having mimicker conditions. The 2019 AECC had a sensitivity of 66.7% and a specificity of 100%. Sensitivity increased to 73.3% when disease-specific autoantibody items were removed, without affecting specificity. The true-positive cases had more involved organs, a higher availability of biopsy results, and were more likely to belong to the Mikulicz/systemic and proliferative phenotypes. CONCLUSIONS: The use of the 2019 AECC for IgG4-RD in a Latin American population confirms its high specificity in excluding those without the disease. The presence of concomitant autoimmune diseases and clinically nonsignificant disease-specific autoantibodies excludes a significant number of patients from fulfilling the criteria.

Is iron overload associated with worse outcomes in patients with chronic liver disease undergoing liver transplantation?

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Exploring the Influence of Spacers in EDTA-ß-Cyclodextrin Dendrimers: Physicochemical Properties and In Vitro Biological Behavior.

The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four ß-cyclodextrin (ßCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d6 and the self-inclusion process was studied in D2O by 1H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the ßCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-ßCD platforms and the classical PAMAM-ßCD dendrimer. Finally, we determined the toxicity for all EDTA-ßCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-ßCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery.

A tool for early estimation of influenza vaccination coverage in Spanish general population and healthcare workers in the 2018-19 season: the Gripómetro.

ASBTRACT: BACKGROUND: Electronic vaccine registries are not yet widely established. There is a need to real-time monitor influenza vaccine coverage, which may raise awareness to risk groups and professionals, and eventually allow to adopt tailored measures during the vaccination campaign. To evaluate the utility of the "Gripómetro", a demographic study designed to monitor national and regional influenza vaccine coverage on a weekly basis in Spain. METHODS: Quantitative study based on surveys of the Spanish population between 18-80 years and a sample of primary care doctors and nurses randomly selected. Pre-proportional fixation has been established by Autonomous Communities and age group to guarantee the representativeness of all the autonomies. RESULTS: Interviews were conducted in 3400 households of general population and 807 respondents among health care professionals. We found that the results of influenza vaccination coverage in the population ≥ 65 years obtained by the Gripómetro for 2018-2019 season were mostly comparable with the official data presented by the Ministry of Health after the end of the vaccination campaign. CONCLUSIONS: The Gripómetro is a robust research method that provides real-time data and trends for influenza vaccine coverage along with other useful information related to vaccination such as intention to vaccinate, motivation and barriers to vaccination.

The Role of Postmastectomy Radiotherapy in Locally Advanced Breast Cancer After Pathological Complete Response to Neoadjuvant Chemotherapy.

The Case A previously healthy woman, aged 32 years, presented to the oncology clinic with a 6-month history of left-breast tumor, mastalgia, and swollen axillary nodes. Physical examination was relevant for a 6-cm palpable mass in the upper outer quadrant of the left breast and an ipsilateral 2-cm, nonfixed axillary lymph node. Mammography showed a 1-cm mass in the upper outer quadrant, a 5.2-cm mass in the lower outer quadrant, and enlarged pathologic lymph nodes (BI-RADS category 5 disease). Breast ultrasound revealed 3 axillary lymph nodes with cortical thickening and loss of normal morphology (the largest with a 2.6-cm length in the long axis) (Figure 1A-B). The breast´s core biopsy revealed a grade 3 apocrine invasive carcinoma with lymphovascular invasion; immunohistochemistry testing showed HER2-negative, hormone receptor-negative disease (estrogen receptor, 0%; progesterone receptor, 0%; HER2-negative, Ki67, 50%) (Figure 2A-B). A fine-needle aspiration biopsy of the axillary lymph nodes showed invasive breast carcinoma as well. Bone scintigraphy and a chest/abdomen CT scan ruled out metastatic disease. Upon initial diagnosis, clinical stage was deemed as cT3N1M0 (American Joint Committee on Cancer 8th edition: anatomic stage IIIA, clinical prognostic stage IIIC). After a multidisciplinary tumor board discussion, the patient underwent neoadjuvant chemotherapy with weekly paclitaxel, followed by 4 cycles of dose-dense doxorubicin plus cyclophosphamide. After completing neoadjuvant treatment, clinical examination was relevant for a residual 1-cm palpable left breast mass and no palpable axillary nodes. Mammography and breast ultrasound showed a 77% partial response in the primary tumors, and axillary nodes with normal morphology and size (Figure 1C-D). Due to multicentric tumor disease, breast-conserving surgery would not confer satisfactory cosmetic results on her, and a modified radical mastectomy with intraoperative sentinel lymph node biopsy (and second-stage breast reconstruction) was planned. However, during surgery, the surgeons failed to identify the mapped lymph node, and level I-III axillary lymph node dissection was performed. The pathology report described complete pathological response: Miller and Payne criteria grade 5 response with the absence of malignant cells within the mastectomy specimen and in 24 lymph nodes (Figure 2C-E). Pathological staging after neoadjuvant treatment concluded ypT0N0M0 disease. Subsequent treatment for this patient was discussed in another tumor board.

Performance evaluation of a lateral flow assay for nasopharyngeal antigen detection for SARS-CoV-2 diagnosis.

BACKGROUND: SARS-CoV-2 has become a global pandemic due to its capacity for rapid transmission. In this context, an early and rapid diagnosis of infected patients that do not require expensive equipment or highly trained personnel is crucial in order to reduce the contagious rate. The aim of this study was to evaluate a chromatographic immunoassay's performance for the rapid diagnosis of SARS-CoV-antigen. METHODS: A cross-sectional study included 369 adults from Western México with diagnosis or suspicion of SARS-CoV-2 infection. Two samples were collected; a naso-oropharyngeal was used for a molecular determination of SARS-CoV-2 RNA. The molecular analysis was carried out using DeCoV19 Kit Triplex (Genes2life S.A.P.I.) based on the CDC diagnostic panel for N1, N2, and N3 regions. The second sample was retrieved from a nasopharyngeal rub and used for the rapid diagnosis of SARS-CoV-2 antigen employing the commercial STANDARD™ Q COVID-19 Ag Test (SD BIOSENSOR). RESULTS: Overall, in 28.2% of the patients was detected the SARS-CoV-2 RNA, and 21.4% were positive for antigen detection. The rapid antigen test showed a sensitivity and specificity of 75.9% and 100%, respectively, with a positive predictive and negative values of 100% and 91%. Symptoms as anosmia presented a high OR for the positive diagnosis for both test, reverse transcription-polymerase chain reaction (RT-PCR), and the rapid antigen test of 8.86 (CI = 4.91-16) and 6.09 (CI = 3.42-10.85), respectively. CONCLUSION: SD BIOSENSOR is a useful assay, but some caveats must be considered before the general implementation.

Clinical features of patients with Rocky Mountain spotted fever, dengue and chikungunya infection.

INTRODUCTION: Clinical distinction between arbovirus infections and those caused by rickettsia is crucial to initiate appropriate medical treatment. OBJECTIVE: To compare the differences between Rocky Mountain spotted fever (RMSF) and other vector-borne diseases (dengue and chikungunya) with similar clinical presentation, and to identify data that could aid rapid diagnosis of these diseases. METHODS: We evaluated sociodemographic, clinical and laboratory data of 399 patients from five hospitals and clinics of Sonora, Mexico, between 2004 and 2016, with laboratory-confirmed diagnosis of RMSF, dengue, or chikungunya. RESULTS: The RMSF group had the highest lethality (49/63 deaths, 77.8 %), followed by the chikungunya group (3/161, 1.9 %) and the dengue group (3/161, 1.9 %). Clinical differences included the presence of rash, edema, and pruritus; in addition, differences in multiple biomarkers such as platelets, hemoglobin, indirect bilirubin, and serum sodium levels were documented. CONCLUSION: Rash on the palms and soles, edema and absence of pruritus, together with high levels of direct bilirubin and severe thrombocytopenia could be useful indicators to differentiate patients at RMSF advanced stages from those with dengue and chikungunya.

INTRODUCCIÓN: La distinción clínica entre infecciones arbovirales y las provocadas por rickettsias es crucial para iniciar el tratamiento médico apropiado. OBJETIVO: Comparar las diferencias entre fiebre manchada de las montañas rocosas (FMMR) y otras enfermedades transmitidas por vector (dengue y chikungunya) con presentación clínica similar e identificar los datos que pudieran ayudar al diagnóstico rápido de esas enfermedades. MÉTODOS: Se evaluaron datos sociodemográficos, clínicos y de laboratorio de 399 pacientes de cinco hospitales y clínicas en Sonora, México, entre 2004 y 2016, con el diagnóstico confirmado por laboratorio de FMMR, dengue o chikungunya. RESULTADOS: El grupo con FMMR presentó la mayor letalidad (49/63 muertes, 77.8 %), seguido por el de chikungunya (3/161, 1.9 %) y el de dengue (3/161, 1.9 %). Las diferencias clínicas consistieron en la presencia de exantema, edema y prurito; además, se documentaron diferencias en múltiples biomarcadores como plaquetas, hemoglobina, bilirrubina indirecta y niveles de sodio sérico. CONCLUSIÓN: El exantema en palmas y plantas, edema y ausencia de prurito, aunados a niveles altos de bilirrubina directa y trombocitopenia severa pudieran ser indicadores útiles para diferenciar a pacientes con FMMR en etapas avanzadas de aquellos con dengue y chikungunya.

In vitro release of new designs of modified-release tramadol hydrochloride included in a polymer matrix.

Tramadol reaches therapeutic plasma concentrations in a time interval of 0.5 to 1.7 hours, so it is necessary to dose 4 times/day, which reduces compliance with the dose and the effectiveness of the treatment. Design formulations of tramadol that allow the release time to be prolonged, surpassing those obtained with the commercial product and tramadol without excipients. Several formulations of 5% tramadol hydrochloride were designed in a matrix system based on poloxamer 407 at different concentrations (10%, 14%, 17%, and 20%). In vitro release studies were performed, using a spectrophotometer at a wavelength of 273.15 nm; were compared the results with tramadol without polymeric supplements and with the commercial formulation samples were taken in a period of time from 0.25 to 72 hours, and also compared the use or absence of dialysis membrane with a porosity of 50 kilodaltons was. With the use of the membrane, the designed formulations had a release of 98%, 50%, 23%, 16% at 72 hours, respectively, different from the commercial product and the tramadol formulation without excipients released the 24 hours. Without using dialysis membranes, a 90-100% release was achieved in the 10% and 14% formulation at 36 hours. The 17% and 20% formulation at 48 hours and the commercial formulation and tramadol without excipient were released within 2 hours. Modified release formulations were obtained, which retain and prolong the release of tramadol compared to the commercial product. Therefore, we propose to conduct further in vivo model experiments to confirm our conclusion.

Reproductive incompatibility between Amblyomma maculatum (Acari: Ixodidae) group ticks from two disjunct geographical regions within the USA.

The Amblyomma maculatum Koch group of ixodid ticks consists of three species: A. maculatum, A. triste, and A. tigrinum. However, since Koch described this group in 1844, the systematics of its members has been the subject of ongoing debate. This is especially true of A. maculatum and A. triste; recent molecular analyses reveal insufficient genetic divergence to separate these as distinct species. Further confounding this issue is the discovery in 2014 of A. maculatum group ticks in southern Arizona (AZ), USA, that share morphological characteristics with both A. triste and A. maculatum. To biologically evaluate the identity of A. maculatum group ticks from southern Arizona, we analyzed the reproductive compatibility between specimens of A. maculatum group ticks collected from Georgia (GA), USA, and southern Arizona. Female ticks from both Arizona and Georgia were mated with males from both the Georgia and Arizona Amblyomma populations, creating two homologous and two heterologous F1 cohorts of ticks: GA ♀/GA ♂, AZ ♀/AZ ♂, GA ♀/AZ ♂, and AZ ♀/GA ♂. Each cohort was maintained separately into the F2 generation with F1 females mating only with F1 males from their same cohort. Survival and fecundity parameters were measured for all developmental stages. The observed survival parameters for heterologous cohorts were comparable to those of the homologous cohorts through the F1 generation. However, the F1 heterologous females produced F2 egg clutches that did not hatch, thus indicating that the Arizona and Georgia populations of A. maculatum group ticks tested here represent different biological species.

Rickettsia parkeri and Candidatus Rickettsia andeanae in Tick of the Amblyomma maculatum Group, Mexico.

We report Rickettsia parkeri and Candidatus Rickettsia andeanae in ticks of the Amblyomma maculatum group collected from dogs in Sonora, Mexico. Molecular characterization of these bacteria was accomplished by DNA amplification and sequence analysis of portions of the rickettsial genes gltA, htrA, ompA, and ompB.

Molecular Confirmation of Rickettsia parkeri in Amblyomma ovale Ticks, Veracruz, Mexico.

We found Rickettsia parkeri in Amblyomma ovale ticks collected in Veracruz, Mexico, in 2018. We sequenced gene segments of gltA, htrA, sca0, and sca5; phylogenetic reconstruction revealed near-complete identity with R. parkeri strain Atlantic Rainforest. Enhanced surveillance is needed in Mexico to determine the public health relevance of this bacterium.

Enfermedad granulomatosa hepática.

Granulomas are circumscribed lesions mainly composed of mononuclear cells that arise in response to poorly degradable antigenic stimuli. They are found in 2-15 % of liver biopsies and the meaning of their finding can range from an incidental phenomenon to the manifestation of a systemic disease of infectious, autoimmune or neoplastic origin. Clinical presentation usually points at the underlying pathology; however, the list of associated conditions is extensive, and differs based on patient epidemiological history and baseline characteristics. The most useful element for their study is a thorough medical history, with an emphasis on recent trips, exposures and consumption of drugs or raw or exotic foods. Detailed histopathological analysis may help identify the etiology. For example, the presence of epithelioid granulomas with caseous necrosis indicates tuberculosis and, its absence, sarcoidosis; eosinophil abundance can be associated with drug reactions or parasitic infections; and the presence of foreign bodies can be the cause of granulomatous liver disease (GLD). In this article, we describe the basic clinical-pathological aspects of GLD, and provide a brief summary of the most common etiologies, with an emphasis on the Latin-American region.

Los granulomas son lesiones circunscritas compuestas principalmente por células mononucleares que surgen en respuesta a estímulos antigénicos pobremente degradables. Se encuentran en 2 a 15 % de las biopsias hepáticas; su hallazgo puede significar desde un fenómeno incidental, hasta la manifestación de una enfermedad sistémica de origen infeccioso, autoinmune o neoplásico. El cuadro clínico suele apuntar a la patología subyacente, sin embargo, la lista de condiciones asociadas es amplia y difiere con base en los antecedentes epidemiológicos y a las características basales del paciente. El elemento de mayor utilidad para su estudio es la historia clínica exhaustiva, con énfasis en viajes recientes, exposición de riesgo y consumo de fármacos o alimentos crudos o exóticos. El análisis histopatológico detallado puede auxiliar en la identificación de la etiología, por ejemplo, la presencia de granulomas epitelioides con necrosis caseosa indica tuberculosis y su ausencia, sarcoidosis; la abundancia de eosinófilos es señal de reacciones farmacológicas o infecciones parasitarias; la presencia de cuerpos extraños puede ser la causa de la enfermedad granulomatosa hepática. En este artículo describimos los aspectos clínico-patológicos básicos de esta enfermedad y proveemos un breve resumen de las etiologías más comunes, principalmente en la región de Latinoamérica.

Rickettsia parkeri in Dermacentor parumapertus Ticks, Mexico.

During a study to identify zoonotic pathogens in northwestern Mexico, we detected the presence of a rickettsial agent in Dermacentor parumapertus ticks from black-tailed jackrabbits (Lepus californicus). Comparison of 4 gene sequences (gltA, htrA, ompA, and ompB) of this agent showed 99%-100% identity with sequences of Rickettsia parkeri.

Delayed surgery in hip fracture patients. Can we afford it?

The aim is to analyze whether time to surgery (TtoS) in hip fracture patients is associated with longer than expected length of stay (LofS) and whether there is any particular group in which this is especially relevant. We developed an observational study in Madrid, Spain. From 771 patients admitted to the orthopedic ward, we selected 723 with surgical delay ≤7 days. Age was characterized as younger (<81), elderly (81-90), very elderly (>90). Modified Barthel Index was classified as very dependent (<41), moderately dependent (41-80), independent (>80). RESULTS: Median (IQR) TtoS was 3 (1-4) days; LofS 12 (7-15). Mean age was 84.3 years, 78.4% were women. TtoS was associated with LofS, which increased by 1.80 days (95% CI, 1.50-2.10) per delayed day (p<0.001). After adjustment for age, sex, functional status, we found an increase of 1.75 days (1.46-2.04) per day (p<0.001). We did not find effect of age or sex. Functional status had a higher effect in moderately dependent patients 2.25 days (1.78-2.72) than in very dependent or independent patients, 1.33 (0.37-2.30) and 1.50 days (1.09-1.91) respectively (p 0.012). As conclusion we could affirm that increasing TtoS leads to longer than expected LofS in hip fracture patients, particularly moderately dependent patients. Copyright © 2016 John Wiley & Sons, Ltd.