Embracing multiple infection models to tackle Q fever: A review of in vitro, in vivo, and lung ex vivo models.

Multiple animal and cell culture models are employed to study pathogenesis of Coxiella burnetii, the causative agent of acute and chronic human Q fever. C. burnetii is a lung pathogen that is aerosolized in contaminated products and inhaled by humans to cause acute disease that can disseminate to other organs and establish chronic infection. Cellular models of Q fever include a variety of tissue-derived cell lines from mice and humans such as lung alveolar ex vivo cells. These models have the advantage of being cost-effective and reproducible. Similarly, animal models including mice and guinea pigs are cost-effective, although only immunocompromised SCID mice display a severe disease phenotype in response to Nine Mile I and Nine Mile II isolates of C. burnetii while immunocompetent guinea pigs display human-like symptoms and robust immune responses. Non-human primates such as macaques and marmosets are the closest model of human disease but are costly and largely used for adaptive immune response studies. All animal models are used for vaccine development but many differences exist in the pathogen's ability to establish lung infection when considering infection routes, bacterial isolates, and host genetic background. Similarly, while cellular models are useful for characterization of host-pathogen mechanisms, future developments should include use of a lung infection platform to draw appropriate conclusions. Here, we summarize the current state of the C. burnetii lung pathogenesis field by discussing the contribution of different animal and cell culture models and include suggestions for continuing to move the field forward.

TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Validation of an inhibition enzyme-linked immunosorbent assay system for the diagnosis of Toxoplasma gondii infection in buffaloes (Bubalus bubalis). / Validación de un sistema inmunoenzimático de inhibición de un anticuerpo para el diagnóstico de infección por Toxoplasma gondii en búfalos (Bubalus bubalis).

Toxoplasmosis is one of the most widespread zoonoses in the world, due to the existence of a wide variety of Toxoplasma gondii hosts, which include several domestic animal species. In Cuba, there is sustained production of the Bubalus species, which is highly adaptable and disease resistant, although it has been identified as a reservoir for a range of aetiological agents. Several countries have reported buffaloes as the intermediate host of T. gondii, noting the need to carry out epidemiological studies and confirm the possible presence of this parasitic infection in the Bubalus species. The current study was conducted to validate an inhibition enzyme-linked immunosorbent assay (i/ELISA) system for the diagnosis of T. gondii infection in buffaloes (Bubalus bubalis). This involved evaluating its performance in relation to that of a latex agglutination test. With buffalo sera, the i/ELISA assay showed a sensitivity of 100%, a specificity of 99.5%,and a concordance of 0.99 (considered very good) with respect to the reference diagnostic method. The conclusion is that i/ELISA performs extremely well as a serological test for the diagnosis of T. gondii in buffaloes.

La toxoplasmose est l'une des zoonoses les plus répandues dans le monde, ce qui s'explique par le très large spectre d'hôtes de Toxoplasma gondii, dont plusieurs espèces d'animaux domestiques. À Cuba, les buffles font l'objet d'un élevage durable et présentent de bonnes aptitudes d'adaptation et de résistance aux maladies, bien que cette espèce joue un rôle avéré de réservoir pour un certain nombre d'agents pathogènes. Des rapports émanant de plusieurs pays ont fait état du rôle joué par les buffles en tant qu'hôtes intermédiaires de T. gondii, d'où la nécessité d'effectuer des études épidémiologiques afin de confirmer la présence éventuelle de cette parasitose chez cette espèce. Les auteurs présentent des résultats d'une étude de validation d'une méthode immuno-enzymatique d'inhibition des anticorps pour le diagnostic de T. gondii chez le buffle (Bubalusbubalis). Pour ce faire, les performances de cette méthode ont été évaluées par rapport à celles du test d'agglutination au latex. La comparaison à partir de sérums de buffles a montré que la sensibilité de l'épreuve immuno-enzymatique était de 100 % et sa spécificité de 99,5%, avec une concordance par rapport à la méthode de référence de 0,99, ce qui est considéré un très bon résultat. Cette étude démontre l'aptitude de l'ELISA d'inhibition pour le diagnostic sérologique de T. gondii chez le buffle et conclut à son excellente performance diagnostique.

La toxoplasmosis es una de las zoonosis más difundidas en el mundo debido a que existe una amplia variedad de hospedadores de Toxoplasma gondii, entre los que se encuentran varias de las especies de animales domésticos. En Cuba, la especie bufalina se produce de manera sostenida con buena adaptabilidad y resistencia a las enfermedades, aunque se ha identificado como reservorio de diversos agentes etiológicos. En varios países se ha informado que los búfalos son hospedadores intermediarios de T. gondii y se ha indicado la necesidad derealizar estudios epidemiológicos y de comprobar la posible presencia de dicha parasitosis en esta especie. Este trabajo se realizó para validar un sistema inmunoenzimático de inhibición de un anticuerpo (ELISA/i) para el diagnósticode infección por T. gondii en búfalos (Bubalus bubalis). Para ello, se evaluó su rendimiento respecto a una prueba de aglutinación por látex. Frente a sueros de búfalo, el sistema inmunoenzimático demostró tener una sensibilidad del 100%, una especificidad del 99,5% y una concordancia de 0,99, considerada muy buena, respecto al método de diagnóstico de referencia. Se concluye que el ELISA/i permite el diagnóstico serológico de T. gondii en búfalos con un excelente rendimiento diagnóstico.

1 GHz InP on-chip monolithic extended cavity colliding-pulse mode-locked laser.

A record low-repetition rate from an on-chip monolithic InP extended cavity colliding-pulse mode-locked laser is experimentally reported. The device, fabricated in generic InP-based active-passive integration technology, makes use of integrated mirrors to enable its use as a building block within a photonic integrated circuit. This structure allows us to generate an electrical frequency comb with mode spacing of 1 GHz, determined by the 40.5 mm long resonator. Passive and hybrid mode-locking regime conditions are experimentally demonstrated. In the passive regime, an electrical beat tone at the fundamental repetition rate with an electrical linewidth (LW) of 398 kHz and a signal-to-noise ratio (SNR) >30 dB is measured. In the hybrid regime, the optical comb is locked to a continuous wave signal source, improving the LW of the generated signal and the SNR>40 dB.

Schistosomus Reflexus Syndrome in Olive Ridley Sea Turtles ( Lepidochelys olivacea).

The olive ridley sea turtle ( Lepidochelys olivacea), considered the most abundant sea turtle species, is listed as vulnerable on the International Union for Conservation of Nature Red List. The most important nesting areas are located in the Eastern Pacific, and congenital malformations have been previously reported in this species. The present study was conducted in a single population at El Verde beach, one of the most important nesting beaches for the species in the northwestern Mexican Pacific. The study was based on embryos that had been incubated in a controlled environment. Schistosomus reflexus syndrome (SRS) was observed in 124 of 20 257 olive ridley embryos (0.6%), comprising 124 of 400 (31%) cases of congenital malformations over a 7-month period. Affected embryos had malformations of the carapace, bridge, or plastron, resulting in exposure of the abdominal or thoracic viscera, as well as spinal malformation and abnormal positioning of limbs adjacent to the head with subsequent ankylosis. SRS phenotypes (although lethal) varied from mild to severe, although most cases were severe. SRS was mostly associated with congenital malformations in the neck (short neck, 80%), tail (anury, 38%), and flippers (different types of dysmelias, 53%). In most cases of severe SRS, ankyloses were present. Documenting these findings could be important to identify the cause of the developmental defects, and identification of the cause of the defects may be of significance to the population and to our efforts to manage this and other populations at risk.

Millimeter-wave signal generation for a wireless transmission system based on on-chip photonic integrated circuit structures.

We demonstrate and compare two different photonic-based signal sources for generating the carrier wave in a wireless communication link operating in the millimeter-wave range. The first signal source uses the optical heterodyne technique to generate a 113 GHz carrier wave frequency, while the second employs a different technique based on a pulsed mode-locked source with 100 GHz repetition rate frequency. The two optical sources were fabricated in a multi-project wafer run from an active/passive generic integration platform process using standardized building blocks, including multimode interference reflectors which allow us to define the structures on chip, without the need for cleaved facet mirrors. We highlight the superior performance of the mode-locked sources over an optical heterodyne technique. Error-free transmission was achieved in this experiment.

Optical frequency comb generator based on a monolithically integrated passive mode-locked ring laser with a Mach-Zehnder interferometer.

We report the demonstration of an optical-frequency comb generator based on a monolithically integrated ring laser fabricated in a multiproject wafer run in an active/passive integration process in a generic foundry using standardized building blocks. The device is based on a passive mode-locked ring laser architecture, which includes a Mach-Zehnder interferometer to flatten the spectral shape of the comb output. This structure allows monolithic integration with other optical components, such as optical filters for wavelength selection, or dual wavelength lasers for their stabilization. The results show a -10 dB span of the optical comb of 8.7 nm (1.08 THz), with comb spacing of 10.16 GHz. We also obtain a flatness of 44 lines within a 1.8 dB power variation.

Proteomic profile of circulating immune complexes in chronic Chagas disease.

Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease.

Digesting pythons quickly oxidize the proteins in their meals and save the lipids for later.

Pythons digesting rodent meals exhibit up to 10-fold increases in their resting metabolic rate (RMR); this increase in RMR is termed specific dynamic action (SDA). Studies have shown that SDA is partially fueled by oxidizing dietary nutrients, yet it remains unclear whether the proteins and the lipids in their meals contribute equally to this energy demand. We raised two populations of mice on diets labeled with either [(13)C]leucine or [(13)C]palmitic acid to intrinsically enrich the proteins and lipids in their bodies, respectively. Ball pythons (Python regius) were fed whole mice (and pureed mice 3 weeks later), after which we measured their metabolic rates and the δ(13)C in the breath. The δ(13)C values in the whole bodies of the protein- and lipid-labeled mice were generally similar (i.e. 5.7±4.7‰ and 2.8±5.4‰, respectively) but the oxidative kinetics of these two macronutrient pools were quite different. We found that the snakes oxidized 5% of the protein and only 0.24% of the lipids in their meals within 14 days. Oxidation of the dietary proteins peaked 24 h after ingestion, at which point these proteins provided ∼90% of the metabolic requirement of the snakes, and by 14 days the oxidation of these proteins decreased to nearly zero. The oxidation of the dietary lipids peaked 1 day later, at which point these lipids supplied ∼25% of the energy demand. Fourteen days after ingestion, these lipids were still being oxidized and continued to account for ∼25% of the metabolic rate. Pureeing the mice reduced the cost of gastric digestion and decreased SDA by 24%. Pureeing also reduced the oxidation of dietary proteins by 43%, but it had no effect on the rates of dietary lipid oxidation. Collectively, these results demonstrate that pythons are able to effectively partition the two primary metabolic fuels in their meals. This approach of uniquely labeling the different components of the diet will allow researchers to examine new questions about how and when animals use the nutrients in their meals.

Multibacillary leprosy mimicking systemic lupus erythematosus: case report and literature review.

Leprosy is an infectious chronic disease with a wide range of clinical and serological manifestations. We report a case of a woman presenting with a malar rash, painless oral ulcers, photosensitivity, arthritis, positive antinuclear antibodies test and leuko-lymphopenia. Our case illustrates an unusual presentation of leprosy initially diagnosed as systemic lupus erythematosus (SLE). After the confirmation of multibacillary leprosy and multidrug therapy recommended by the World Health Organization, a good clinical response was observed. Recognition of rheumatic manifestations in leprosy is important as they may be confused with SLE. A literature review is presented to encourage clinicians to consider leprosy as a differential diagnosis. Specifically in patients with unusual rheumatic manifestations and persistent skin lesions, and when neurological symptoms are present. Leprosy has not been eradicated, so misdiagnosis can be frequent. It is necessary to increase medical practitioner awareness in order start proper treatment.

Polyradical character and spin frustration in fullerene molecules: an ab initio non-collinear Hartree-Fock study.

Most ab initio calculations on fullerene molecules have been carried out on the basis of the paradigm of the Hückel model. This is consistent with the restricted nature of the independent-particle model underlying such calculations, even in single-reference-based correlated approaches. Notwithstanding, previous works on some of these molecules using model Hamiltonians have clearly indicated the importance of short-range interatomic spin-spin correlations. In this work, we consider ab initio non-collinear Hartree-Fock (HF) solutions for representative fullerene systems: the bowl, cage, ring, and pentagon isomers of C20, and the larger C30, C36, C60, C70, and C84 fullerene cages. In all cases but the ring we find that the HF minimum corresponds to a truly non-collinear solution with a torsional spin density wave. Optimized geometries at the generalized HF (GHF) level lead to fully symmetric structures, even in those cases where Jahn-Teller distortions have been previously considered. The nature of the GHF solutions is consistent with the π-electron space becoming polyradical in nature: each p-orbital remains effectively singly occupied. The spin frustration, induced by the presence of pentagon rings on an otherwise antiferromagnetic background, is minimized at the HF level by aligning the spins with non-collinear arrangements. The long-range magnetic ordering observed is reminiscent of the character of broken symmetry HF solutions in polyacene systems.

Stem cells for brain repair in neonatal hypoxia-ischemia.

Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

Nanoscale strain-induced pair suppression as a vortex-pinning mechanism in high-temperature superconductors.

Boosting large-scale superconductor applications require nanostructured conductors with artificial pinning centres immobilizing quantized vortices at high temperature and magnetic fields. Here we demonstrate a highly effective mechanism of artificial pinning centres in solution-derived high-temperature superconductor nanocomposites through generation of nanostrained regions where Cooper pair formation is suppressed. The nanostrained regions identified from transmission electron microscopy devise a very high concentration of partial dislocations associated with intergrowths generated between the randomly oriented nanodots and the epitaxial YBa(2)Cu(3)O(7) matrix. Consequently, an outstanding vortex-pinning enhancement correlated to the nanostrain is demonstrated for four types of randomly oriented nanodot, and a unique evolution towards an isotropic vortex-pinning behaviour, even in the effective anisotropy, is achieved as the nanostrain turns isotropic. We suggest a new vortex-pinning mechanism based on the bond-contraction pairing model, where pair formation is quenched under tensile strain, forming new and effective core-pinning regions.

Excited electronic states from a variational approach based on symmetry-projected Hartree-Fock configurations.

Recent work from our research group has demonstrated that symmetry-projected Hartree-Fock (HF) methods provide a compact representation of molecular ground state wavefunctions based on a superposition of non-orthogonal Slater determinants. The symmetry-projected ansatz can account for static correlations in a computationally efficient way. Here we present a variational extension of this methodology applicable to excited states of the same symmetry as the ground state. Benchmark calculations on the C2 dimer with a modest basis set, which allows comparison with full configuration interaction results, indicate that this extension provides a high quality description of the low-lying spectrum for the entire dissociation profile. We apply the same methodology to obtain the full low-lying vertical excitation spectrum of formaldehyde, in good agreement with available theoretical and experimental data, as well as to a challenging model C2v insertion pathway for BeH2. The variational excited state methodology developed in this work has two remarkable traits: it is fully black-box and will be applicable to fairly large systems thanks to its mean-field computational cost.

Multi-component symmetry-projected approach for molecular ground state correlations.

The symmetry-projected Hartree-Fock ansatz for the electronic structure problem can efficiently account for static correlation in molecules, yet it is often unable to describe dynamic correlation in a balanced manner. Here, we consider a multi-component, systematically improvable approach, that accounts for all ground state correlations. Our approach is based on linear combinations of symmetry-projected configurations built out of a set of non-orthogonal, variationally optimized determinants. The resulting wavefunction preserves the symmetries of the original Hamiltonian even though it is written as a superposition of deformed (broken-symmetry) determinants. We show how short expansions of this kind can provide a very accurate description of the electronic structure of simple chemical systems such as the nitrogen and the water molecules, along the entire dissociation profile. In addition, we apply this multi-component symmetry-projected approach to provide an accurate interconversion profile among the peroxo and bis(µ-oxo) forms of [Cu2O2](2+), comparable to other state-of-the-art quantum chemical methods.

Development of a model to investigate the effects of prolonged ischaemia on the muscles of mastication of male Sprague Dawley rats.

OBJECTIVE: The aims of this study were to develop a novel rodent model of masticatory muscle ischaemia via unilateral ligation of the external carotid artery (ECA), and to undertake a preliminary investigation to characterize its downstream effects on mechanosensitivity and cellular features of the masseter and temporalis muscles. DESIGN: The right ECA of 18 male Sprague-Dawley rats was ligated under general anaesthesia. Mechanical detection thresholds (MDTs) at the masseter and temporalis bilaterally were measured immediately before ECA ligation and after euthanasia at 10-, 20-, and 35-days (n = 6 rats/timepoint). Tissue samples from both muscles and sides were harvested for histological analyses and for assessing changes in the expression of markers of hypoxia and muscle degeneration (Hif-1α, VegfA, and Fbxo32) via real time PCR. Data were analyzed using mixed effect models and non-parametric tests. Statistical significance was set at p < 0.05. RESULTS: MDTs were higher in the right than left hemiface (p = 0.009) after 20 days. Histological changes indicative of muscle degeneration and fibrosis were observed in the right muscles. Hif-1α, VegfA, and Fbxo32 were more highly expressed in the masseter than temporalis muscles (all p < 0.05). Hif-1α and, VegfA did not change significantly with time in all muscles (all p > 0.05). Fbxo32 expression gradually increased in the right masseter (p = 0.024) and left temporalis (p = 0.05). CONCLUSIONS: ECA ligation in rats induced hyposensitivity in the homolateral hemiface after 20 days accompanied by tissue degenerative changes. Our findings support the use of this model to study pathophysiologic mechanisms of masticatory muscle ischaemia in larger investigations.

Patient-reported outcomes in RA patients treated with tofacitinib or bDMARDs in real-life conditions in two Latin American countries.

OBJECTIVE: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. METHODS: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). RESULTS: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients' mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (-2.55[.30] vs. -2.52[.26]), HAQ-DI score (-.56[.07] vs. -.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (-2.37[.22] vs. -2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported. CONCLUSION: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs. CLINICAL TRIAL NUMBER: NCT03073109.

[Clinicopathologic characteristics of 127 cases of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) studied in an oncology hospital]. / Características clínico-patológicas de 127 casos de neoplasias neuroendocrinas del aparato gastrointestinal y páncreas (NNE-GEP) estudiadas en un hospital de oncología.

BACKGROUND: Neuroendocrine tumors (NETs) present all along the length of the gastrointestinal (GI) tract, from the esophagus to the anus, and they also present in the pancreas. AIMS: To classify NETs according to the WHO 2010 criteria and to evaluate their anatomic distribution and clinicopathologic characteristics. MATERIAL AND METHODS: A search was carried out in the hospital pathology archives of all the cases diagnosed with carcinoid tumor and neuroendocrine carcinoma of the GI tract and pancreas studied over a period of 11 years (1999-2010). The cases were reclassified according to the WHO 2010 criteria. The clinical case records of each patient were reviewed. RESULTS: The study group was made up of 127 cases (68 men; 59 women). Age ranged from 24 to 85 years with a median of 52 years. A total of 113 (89.00%) tumors occurred in the GI tract and 14 (11.00%) in the pancreas. Tumor size varied from 0.4cm to 9cm (median: 2.5cm). GI tumor histologic grades were: 54.00% grade 1; 31.00% grade 2; and 15.00% grade 3. Pancreatic tumor histologic grades were: 43.00% grade 1; 36.00% grade 2; and 21.00% grade 3. Ki-67 overexpression was correlated with tumor grade (22.00% grade 3 vs 2.50% grade 1). CONCLUSIONS: Histologic grade of the gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is one of the most important prognostic factors. The term carcinoid should be eliminated because it does not reflect the biological behavior of these tumors.

Work productivity in rheumatoid arthritis patients from two Latin American countries treated with tofacitinib or biological DMARDs.

OBJECTIVE: To evaluate work productivity of adult Latin American patients with rheumatoid arthritis (RA) treated with tofacitinib and biological disease-modifying anti-rheumatic drugs (bDMARDs) measured by the Work Productivity and Activity Impairment (WPAI) in RA questionnaire at 0- and 6-month follow-up. METHODS: This non-interventional study was performed in Colombia and Peru. Evaluated the effects of tofacitinib and bDMARDs in patients with RA after failure of conventional DMARDs. The WPAI-RA questionnaire was administered at baseline and at the 6-month (±1 month) follow-up. The results are expressed as least squares means (LSMs), and standard errors (SEs). RESULTS: One hundred patients treated with tofacitinib and 70 patients treated with bDMARDs were recruited. Twenty-eight percent of patients from the tofacitinib group and 40.0% from the bDMARDs group were working for pay at baseline. At month 6, the changes in absenteeism, presenteeism, and work impairment due to health were -18.3% (SE 7.7), -34.8% (SE 5.9), and -11.0% (SE 16.5), respectively, in the tofacitinib group and -19.4% (SE 8.0), -34.8% (SE 6.2), and -15.9% (SE 15.0), for the bDMARD group. CONCLUSION: For patients who reported working, there were improvements in presenteeism, absenteeism, and work impairment due to health in both groups. TRIAL REGISTRATION: NCT03073109.