Tuberculosis treatment without rifampin in kidney/kidney-pancreas transplantation: A case series report.

BACKGROUND: The best approach to tuberculosis (TB) treatment in transplanted patients is still unknown. Current guidelines are based on evidence either extrapolated from other populations or observational. Rifampin-containing regimens have strong pharmacokinetic interactions with immunosuppressive regimens, with high rates of organ dysfunction and ∼20% mortality. This report describes the results obtained using non-rifampin-containing regimens to treat confirmed TB in adult patients with kidney/kidney-pancreas transplantation. METHODS: Retrospective data analysis from confirmed TB cases in adult kidney/kidney-pancreas transplant recipients (2006-2019), treated "de novo" with non-rifampin-containing regimens. RESULTS: Fifty-seven patients had confirmed TB. Thirty patients were treated "de novo" with non-rifampin-containing regimens. These patients' mean age was 49.24 (±11.50) years. Induction immunosuppression was used in 22 patients. Maintenance immunosuppression was tacrolimus-mycophenolate-steroids in 13 (43%), sirolimus-mycophenolate-steroids in 6 (20%), and other immunosuppressive regimens in 11 (36%). Belatacept was used in four patients. TB localizations: pulmonary 43%; disseminated 23%; extrapulmonary 33%. Twenty-seven (90%) patients completed treatment with isoniazid, ethambutol, and levofloxacin (12 months, 23; 9 months, 3; 6 months, 1); 12 of these patients also received pyrazinamide for the first 2 months and were cured with functioning grafts. One patient (3%) lost the graft while on treatment. Two patients (7%) died while on TB treatment. Median (range) follow-up after completion of TB treatment was 32 (8-150) months. No TB relapses were observed. CONCLUSIONS: Results with non-rifampin-containing TB treatments in this case series were better (in terms of mortality and graft dysfunction) than those previously described with rifampin-containing regimens in transplanted patients.

UV and NIR-Responsive Layer-by-Layer Films Containing 6-Bromo-7-hydroxycoumarin Photolabile Groups.

This paper describes polyelectrolyte multilayer films prepared by the layer-by-layer (LbL) technique capable of undergoing dissolution upon exposure to either ultraviolet or near-infrared light. Film dissolution is driven by photochemical deprotection of a random methacrylic copolymer with two types of side chains: (i) 6-bromo-7-hydroxycoumarinyl esters, photocleavable groups that are known to have substantial two-photon photolysis cross sections, and (ii) cationic residues from the commercially available monomer N,N-dimethylaminoethyl methacrylate (DMAEMA). In addition, the dependence of stability of both unirradiated and irradiated films on pH provides experimental evidence for the necessity of disrupting both ion-pairing and hydrophobic interactions between polyelectrolytes to realize film dissolution. This work therefore provides both new fundamental insight regarding photolabile LbL films and expands their applied capabilities to nonlinear photochemical processes.

[Clinical manifestations of organizing pneumonia]. / Manifestaciones clínicas de la neumonía en organización.

Organizing pneumonia is a clinical entity asociated with nonspecific symptoms and radiological findings and abnormalities in pulmonary function tests. It is defined by the characteristic histopathological pattern: filling of alveoli and respiratory bronchioles by plugs of granulation tissue. It can be idiopathic (COP) or secondary to other causes (SOP). It is an unusual finding and the clinical and radiographic findings are nonspecific. For specific diagnosis an invasive procedure has to be done, but often empirical treatment is started when there's a clinical suspicion. We describe the clinical characteristics of 13 patients with histological diagnosis of organizing pneumonia. Data was obtained from their medical records. The median age was 76 years and the median time to diagnosis from the onset of symptoms was 31 days. In 10 cases the diagnosis was made by transbronchial biopsy. 8 patients required hospitalization, 4 of them received high doses of steroids and 3 required ventilatory support. One patient died from a cause attributable to this entity and 5 relapsed. Dyspnea, cough and fever were the most frequent symptoms. Most patients had more than one tomographic pattern being the most common ground glass opacities and alveolar consolidation. Nine patients were diagnosed with COP and 4 with SOP. The most frequent underlying cause of SOP was drug toxicity. The clinical characteristics of the reported cases are consistent with previously published series. As an interesting feature, there was a group of patients that needed high doses of steroids and ventilatory support.

Noninvasive assessment of mitochondrial organization in three-dimensional tissues reveals changes associated with cancer development.

Mitochondrial organization is often altered to accommodate cellular bioenergetic and biosynthetic demands. Changes in metabolism are a hallmark of a number of diseases, including cancer; however, the interdependence between mitochondrial metabolic function and organization is not well understood. Here, we present a noninvasive, automated and quantitative method to assess mitochondrial organization in three-dimensional (3D) tissues using exclusively endogenous two-photon excited fluorescence (TPEF) and show that mitochondrial organization reflects alterations in metabolic activities. Specifically, we examine the organization of mitochondria within live, engineered epithelial tissue equivalents that mimic normal and precancerous human squamous epithelial tissues. We identify unique patterns of mitochondrial organization in the different tissue models we examine, and we attribute these to differences in the metabolic profiles of these tissues. We find that mitochondria are clustered in tissues with high levels of glycolysis and are more highly networked in tissues where oxidative phosphorylation is more dominant. The most highly networked organization is observed within cells with high levels of glutamine consumption. Furthermore, we demonstrate that mitochondrial organization provides complementary information to traditional morphological hallmarks of cancer development, including variations in nuclear size. Finally, we present evidence that this automated quantitative analysis of endogenous TPEF images can identify differences in the mitochondrial organization of freshly excised normal and pre-cancerous human cervical tissue specimens. Thus, this method could be a promising new modality to assess the role of mitochondrial organization in the metabolic activity of 3D tissues and could be further developed to serve as an early cancer clinical diagnostic biomarker.

[Inflammatory myopathy with initial respiratory muscles involvement and rheumatoid arthritis]. / Miopatía inflamatoria con compromiso inicial de músculos respiratorios y artritis reumatoidea.

Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.

Autocorrelation method for fractal analysis in nonrectangular image domains.

We report an autocorrelation-based approach that accurately measures fractal organization within arbitrarily shaped (nonrectangular) regions of interest of gray-scale images. It extends fractal analysis beyond what is possible using fast Fourier transforms and improves on a previous autocorrelation algorithm. We illustrate its use in detecting subtle changes in mitochondrial organization within murine fibroblasts expressing the human papillomavirus E7 oncogene.

Evaluation of a polarization-enhanced laparoscopy prototype for improved intra-operative visualization of peritoneal metastases.

Despite careful staging, the accuracy for preoperative detection of small distant metastases remains poor, creating a clinical need for enhanced operative staging to detect occult peritoneal metastases. This study evaluates a polarization-enhanced laparoscopy (PEL) prototype and assesses its potential for label-free contrast enhancement of peritoneal metastases. This is a first-in-human feasibility study, including 10 adult patients who underwent standard staging laparoscopy (SSL) for gastrointestinal malignancy along with PEL. Image frames of all detectable peritoneal lesions underwent analysis. Using Monte Carlo simulations, contrast enhancement based on the color dependence of PEL (mPEL) was assessed. The prototype performed safely, yet with limitations in illumination, fogging of the distal window, and image co-registration. Sixty-five lesions (56 presumed benign and 9 presumed malignant) from 3 patients represented the study sample. While most lesions were visible under human examination of both SSL and PEL videos, more lesions were apparent using SSL. However, this was likely due to reduced illumination under PEL. When controlling for such effects through direct comparisons of integrated (WLL) vs differential (PEL) polarization laparoscopy images, we found that PEL imaging yielded an over twofold Weber contrast enhancement over WLL. Further, enhancements in the discrimination between malignant and benign lesions were achieved by exploiting the PEL color contrast to enhance sensitivity to tissue scattering, influenced primarily by collagen. In conclusion, PEL appears safe and easy to integrate into the operating room. When controlling for the degree of illumination, image analysis suggested a potential for mPEL to provide improved visualization of metastases.

Improved Fourier-based characterization of intracellular fractal features.

A novel Fourier-based image analysis method for measuring fractal features is presented which can significantly reduce artifacts due to non-fractal edge effects. The technique is broadly applicable to the quantitative characterization of internal morphology (texture) of image features with well-defined borders. In this study, we explore the capacity of this method for quantitative assessment of intracellular fractal morphology of mitochondrial networks in images of normal and diseased (precancerous) epithelial tissues. Using a combination of simulated fractal images and endogenous two-photon excited fluorescence (TPEF) microscopy, our method is shown to more accurately characterize the exponent of the high-frequency power spectral density (PSD) of these images in the presence of artifacts that arise due to cellular and nuclear borders.

Assessing the contribution of cell body and intracellular organelles to the backward light scattering.

We report a method of assessing the contribution of whole cell body and its nucleus to the clinically most relevant backward light scattering. We first construct an experimental system that can measure forward scattering and use the system to precisely extract the optical properties of a specimen such as the refractive index contrast, size distribution, and their density. A system that can simultaneously detect the backscattered light is installed to collect the backscattering for the same specimen. By comparing the measured backscattering spectrum with that estimated from the parameters determined by the forward scattering experiment, the contribution of cell body and nucleus to the backward light scattering is quantitatively assessed. For the HeLa cells in suspension, we found that the cell body contributes less than 10% and cell nucleus on the order of 0.1% to the total backscattering signal. Quantitative determination of the origin of backscattered light may help design a system that aims for detecting particular structure of biological tissues.

Echocardiographic findings in patients under mechanical ventilation with COVID-19 acute respiratory distress syndrome.

Coronavirus disease 2019 (COVID-19) produces a significant burden to severely ill patients affected by acute respiratory failure. The aim of this study was to describe echocardiographic findings in a series of mechanically ventilated patients with moderate and severe acute respiratory distress syndrome (ARDS) due to COVID-19. This was a single center, descriptive and cros s-sectional study of prospectively collected data. Patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate or severe ARDS. Initial echocardiogram was performed within 7 days of intensive care unit admission and every 15 days until mechanical ventilation ended, 28 days or death. Time spent by the physician for each study was measured. Multiple echographic measurements were acquired; 33 patients were analyzed. Total number of echocardiograms performed was 76. The median imaging time required to complete a standard study was 13 [10-15] minutes. Chronic structural abnormalities were present in 16 patients (48%), being LV hypertrophy the main finding in 11 patients (33%). The most frequent acute or dynamic finding was RV enlargement (43%) when considering all echocardiograms performed from admission to day 28 of follow-up. Other findings were: pulmonary hypertension (15%), new or dynamic left ventricle (LV) regional wall motion abnormalities (15%), new or dynamic LV global contractility deterioration (6%) and hypercontractility (12%).

La enfermedad por coronavirus 2019 (COVID-19) produce una carga significativa para los pacientes gravemente enfermos afectados por insuficiencia respiratoria aguda. El objetivo de este estudio fue describir los hallazgos ecocardiográficos en una serie de pacientes ventilados mecánicamente con síndrome de dificultad respiratoria aguda (SDRA) moderado y grave debido a COVID-19. Se trata de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Los pacientes tenían una infección por el coronavirus SARS-Cov-2 y SDRA moderado o grave. El ecocardiograma inicial se realizó dentro de los 7 días del ingreso en la unidad de cuidados intensivos y luego cada 15 días hasta finalizar la ventilación mecánica, 28 días o fallecimiento. Se midió el tiempo empleado por el operador en cada estudio. Se adquirieron múltiples medidas ecográficas. Se analizaron 33 pacientes. El número total de ecocardiogramas realizados fue de 76. El tiempo necesario (mediana [RIQ]) para la obtención de las imágenes de un estudio estándar fue de 13 [10-15] minutos. Las anomalías estructurales crónicas estuvieron presentes en 16 pacientes (48%), siendo la hipertrofia ventricular izquierda la principal (11 pacientes, 33%). El hallazgo agudo o dinámico más frecuente fue el agrandamiento del ventríc ulo derecho (VD) (43%) al considerar todos los ecocardiogramas realizados desde el ingreso hasta el día 28 de seguimiento. Otros hallazgos fueron: hipertensión pulmonar (15%), anomalías del movimiento de la pared regional del VI nuevas o dinámicas (15%), deterioro de la contractilidad global del ventrículo izquierdo, nuevo o dinámico (6%), e hipercontractilidad (12%).

Polarization enhanced laparoscope for improved visualization of tissue structural changes associated with peritoneal cancer metastasis.

A polarization enhanced laparoscopy (PEL) imaging system was developed to examine the feasibility of utilizing PEL to augment conventional white light laparoscopy (WLL) in the visualization of peritoneal cancer metastases. The system includes a modified tip to illuminate tissue with linearly polarized light and elements in the detection path enabling recording of corresponding images linearly co- and cross-polarized relative to the incident light. WLL and PEL images from optical tissue phantoms with features of distinct scattering cross-section confirm the enhanced sensitivity of PEL to such characteristics. Additional comparisons based on images acquired from collagen gels with different levels of fiber alignment highlight another source of PEL contrast. Finally, PEL and WLL images of ex vivo human tissue illustrate the potential of PEL to improve visualization of cancerous tissue surrounded by healthy peritoneum. Given the simplicity of the approach and its potential for seamless integration with current clinical practice, our results provide motivation for clinical translation.

[Deep venous thrombosis incidence in patients with COVID-19 acute respiratory distress syndrome, under intermediate dose of chemical thromboprophylaxis]. / Incidencia de trombosis venosa profunda en pacientes con síndrome de distrés respiratorio agudo secundario a COVID-19, bajo tromboprofilaxis con dosis intermedia de heparina de bajo peso molecular.

Despite standard thromboprophylaxis, venous thrombosis is common in critically ill patients with COVID-19. The objective of this study was to evaluate deep venous thrombosis (DVT) incidence in patients with severe COVID-19 pneumonia with mechanical ventilation requirements under intermediate dose of chemical thromboprophylaxis (1 mg/kg/day of enoxaparin). This was a single-center, descriptive, cross-sectional study of prospectively collected data. An active and systematic protocol with venous doppler was carried out for DVT diagnosis in lower limbs (or in jugulo-subclavian venous confluence) every 7 days. Weekly doppler evaluation was continued until the end of mechanical ventilation, up to 28 days of intensive care unit admission, until death or until the thromboprophylaxis suspension for any cause. Forty-six patients were included. DVT was diagnosed in 5 (3 in lower limbs and 2 in jugulo-subclavian confluent). In 3 cases, DVT was catheter-related (2 in lower limbs and 1 in jugulo-subclavian confluent), 2 died during follow-up due to acute respiratory distress syndrome (ARDS) complications without thrombotic events or major bleeding. All thrombotic events were asymptomatic. In our series of patients with moderate/severe COVID-19 ARDS, DVT incidence was 10.9% under thromboprophylaxis with intermediate dose (1 mg/kg/ day) of enoxaparin.

A pesar de la tromboprofilaxis estándar, el diagnóstico de tromb osis es común en pacientes críticos con COVID-19. El objetivo del presente estudio fue evaluar la incidencia de trombosis venosa profunda (TVP) en pacientes con neumonía grave por COVID-19 con requerimientos de asistencia respiratoria mecánica, bajo tromboprofilaxis química con dosis intermedia (1 mg/kg/día) de heparina de bajo peso molecular (enoxaparina). Se trató de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Se realizó búsqueda activa y sistemática de TVP en miembros inferiores (o en confluente yúgulosubclavio en su defecto) mediante doppler venoso cada 7 días. Se continuó con la evaluación por doppler semanal hasta la finalización de la ventilación mecánica, el cum plimiento de los 28 días de internación en unidad de cuidados intensivos, el fallecimiento o la suspensión de la tromboprofilaxis con enoxaparina por cualquier causa. Se incluyeron 46 pacientes. Se realizó diagnóstico de TVP en 5 (3 en miembros inferiores y 2 en confluente yúgulosubclavio). Tres diagnósticos de TVP fueron asociados a la presencia de catéter venoso central (2 en miembros inferiores y 1 en el confluente yúgulosubclavio), dos fallecieron durante el seguimiento por causas vinculadas al síndrome de distrés respiratorio agudo (SDRA) pero no por eventos trombóticos o de sangrado mayor. En todos los casos, los eventos trombóticos fueron asintomáticos. En nuestra serie de pacientes con SDRA moderado/grave secundario a neumonía por COVID-19, la incidencia de TVP fue del 10.9% en aquellos bajo tromboprofilaxis con dosis intermedia (1 mg/kg/día) de enoxaparina.

Confocal backscattering spectroscopy for leukemic and normal blood cell discrimination.

Leukemia is the most common pediatric cancer and leading cause of cancer related deaths in children. Improvements in the assessment of leukemic cells have the potential to influence not only the diagnosis of leukemia, but also the risk assessment of patients during the course of the treatment, both of which are important for improving the cure rate for this disease. In this study, we report on the design and performance of a confocal laser based system built to collect backscattered light over a range of 26° at 405, 488, and 633 nm to discriminate leukemic cells from normal red blood cells (RBC) and white blood cells (WBC). The design of the system is based on the spectral differences observed from spectroscopy measurements with a similar system designed with a white light source. Significant differences are observed in the intensity and wavelength dependence of leukemic cells from normal RBC and WBC. Specifically, the distinct light scattering of RBC is due to hemoglobin absorption, allowing for its discrimination from leukemic cells, mononuclear, and polymorphonuclear WBC particularly at certain wavelengths. Meanwhile, the high scattering intensities of polymorphonuclear WBC reflect the intracellular complexity of these cells in comparison to the leukemic or normal lymphocytes. Additionally, the detected light scattering spectra for leukemic cells are consistently steeper in comparison to normal WBC, which we attributed to differences in the fractal organization of intracellular scatterers. Based on our findings, the system has potential applications in the detection and quantification of leukemic cells in blood either in vivo or in vitro, using microfluidic-based systems, for disease monitoring.

Confocal backscattering-based detection of leukemic cells in flowing blood samples.

The prognostic value of assessing minimal residual disease (MRD) in leukemia has been established with advancements in flow cytometry and PCR. Nonetheless, these techniques are limited by high equipment costs, complex, and costly cell processing and the need for highly trained personnel. Here, we demonstrate the potential of exploiting differences in the relative intensities of backscattered light at three wavelengths to detect the presence of leukemic cells in samples containing varying mixtures of white blood cells (WBCs) and leukemic cells flowing through microfluidic channels. Using 405, 488, and 633 nm illumination, we identify distinct light scattering intensity distributions for Nalm-6 leukemic cells, normal mononuclear (PBMC) and polymorphonuclear (PMN) white blood cells and red blood cells. We exploit these differences to develop cell classification algorithms, whose performance is evaluated based on simultaneous acquisition of light scattering and fluorescence flow cytometry data. When this algorithm is used prospectively for the analysis of samples consisting of mixtures of PBMCs and leukemic cells, we achieve an average specificity and sensitivity of leukemic cell detection of 99.6 and 45.2%, respectively. When we consider samples that include leukemic cells along with PMNs and PBMCs, which can be acquired using a simple red blood cell lysis step following venipuncture, the specificity and sensitivity of the approach decreases to 91.6 and 39.5%, respectively. On the basis of the performance of these algorithms, we estimate that 42 or 71 µL of blood would be adequate to confirm the presence of leukemia at an 80% power level in samples containing 0.01% leukemia to either PBMCs or PBMCs and PMNs, respectively. Therefore, light scattering-based flow cytometry in a microfluidic platform could provide a low cost, highly portable, minimally invasive approach for detection and monitoring of leukemic patients. This could offer significant improvements especially for pediatric patients and for patients in developing countries.

Decellularized extracellular matrix scaffolds identify full-length collagen VI as a driver of breast cancer cell invasion in obesity and metastasis.

The extracellular matrix (ECM), a major component of the tumor microenvironment, promotes local invasion to drive metastasis. Here, we describe a method to study whole-tissue ECM effects from disease states associated with metastasis on tumor cell phenotypes and identify the individual ECM proteins and signaling pathways that are driving these effects. We show that decellularized ECM from tumor-bearing and obese mammary glands drives TNBC cell invasion. Proteomics of the ECM from the obese mammary gland led us to identify full-length collagen VI as a novel driver of TNBC cell invasion whose abundance in tumor stroma increases with body mass index in human TNBC patients. Last, we describe the mechanism by which collagen VI contributes to TNBC cell invasion via NG2-EGFR cross-talk and MAPK signaling. Overall, these studies demonstrate the value of decellularized ECM scaffolds obtained from tissues to identify novel functions of the ECM.

Cancer cells with defective oxidative phosphorylation require endoplasmic reticulum-to-mitochondria Ca2+ transfer for survival.

Spontaneous Ca2+ signaling from the InsP3R intracellular Ca2+ release channel to mitochondria is essential for optimal oxidative phosphorylation (OXPHOS) and ATP production. In cells with defective OXPHOS, reductive carboxylation replaces oxidative metabolism to maintain amounts of reducing equivalents and metabolic precursors. To investigate the role of mitochondrial Ca2+ uptake in regulating bioenergetics in these cells, we used OXPHOS-competent and OXPHOS-defective cells. Inhibition of InsP3R activity or mitochondrial Ca2+ uptake increased α-ketoglutarate (αKG) abundance and the NAD+/NADH ratio, indicating that constitutive endoplasmic reticulum (ER)-to-mitochondria Ca2+ transfer promoted optimal αKG dehydrogenase (αKGDH) activity. Reducing mitochondrial Ca2+ inhibited αKGDH activity and increased NAD+, which induced SIRT1-dependent autophagy in both OXPHOS-competent and OXPHOS-defective cells. Whereas autophagic flux in OXPHOS-competent cells promoted cell survival, it was impaired in OXPHOS-defective cells because of inhibition of autophagosome-lysosome fusion. Inhibition of αKGDH and impaired autophagic flux in OXPHOS-defective cells resulted in pronounced cell death in response to interruption of constitutive flux of Ca2+ from ER to mitochondria. These results demonstrate that mitochondria play a fundamental role in maintaining bioenergetic homeostasis of both OXPHOS-competent and OXPHOS-defective cells, with Ca2+ regulation of αKGDH activity playing a pivotal role. Inhibition of ER-to-mitochondria Ca2+ transfer may represent a general therapeutic strategy against cancer cells regardless of their OXPHOS status.

Confocal light scattering spectroscopic imaging system for in situ tissue characterization.

We report on the design and construction of a confocal light scattering spectroscopic imaging system aimed ultimately to conduct depth-resolved characterization of biological tissues. The confocal sectioning ability of the system is demonstrated using a two-layer sample consisting of a 200 microm thick cancer cell layer on top of a scattering layer doped with a green absorber. The measurement results demonstrate that distinct light scattering signals can be isolated from each layer with an axial and a lateral resolution of 30 and 27 microm, respectively. Such a system is expected to have significant applications in the areas of tissue engineering and disease diagnostics and monitoring.

Optical characterization of the nanoscale organization of mineral deposits on silk films.

The alignment of deposited minerals in tissues such as bone and teeth plays a critical role in the mechanical properties of these tissues. Therefore, assessment of features that are characteristic of aligned biominerals could aid in the development of novel biomaterials and engineered tissues that can be used to replace damaged or defective human tissues. In this study, we demonstrate that light scattering spectroscopy can serve as a useful tool for the noninvasive characterization of mineralization on aligned organic substrates. Specifically, we used silk films with oriented and nonoriented secondary structures as a protein matrix for control of mineralization. The mineral deposits displayed self-affine fractal morphologies with the oriented films yielding a significantly higher Hurst parameter, which in turn suggests higher levels of fractal organization. In addition, the value of the upper bound of fractal correlation lengths was significantly smaller for the oriented than for the nonoriented films and correlated well with the size of the corresponding nanocrystalline mineral beads identified by scanning electron microscope imaging.

[Strongyloides hyperinfection in patient from Patagonia with HTLV-1 co-infection]. / Hiperinfección por Strongyloides en paciente de la Patagonia con co-infección por HTLV-1.

Strongylodiasis is an unattended condition caused by the parasite Strongyloides stercoralis. The Strongyloides hyperinfection syndrome can develop in immunosuppressed hosts, mainly in those with depression of cellular immunity. Co-infection with human T-cell lymphotropic virus (HTLV) is a risk factor for the development of severe forms of strongyloidiasis. We present the case of a 50-year-old man with Strongyloides hyperinfection and coinfection with HTLV. The diagnosis was delayed owing to its unusual epidemiology and an initial suspicion of inflammatory bowel disease. Identification of the parasite in bronchioalveolar lavage and duodenal and colonic mucosa biopsies confirmed the diagnosis. Subcutaneous ivermectin was used as an anthelmintic treatment with an adequate therapeutic response.

La estrongiloidiasis es una afección desatendida causada por el parásito Strongyloides stercoralis. En los individuos inmunosuprimidos, fundamentalmente en los que tienen depresión de la inmunidad celular, puede desarrollarse el síndrome de hiperinfección por Strongyloides. La coinfección con virus linfotrópico de células T humanas (HTLV) es un factor de riesgo para el desarrollo de formas graves de estrongiloidiasis. Presentamos el caso de un hombre de 50 años con hiperinfección por Strongyloides y coinfección con HTLV. Se demoró el diagnóstico debido a su epidemiología inusual y a la sospecha inicial de enfermedad inflamatoria intestinal. El diagnóstico se confirmó mediante la identificación del parásito en muestras de lavado bronquio-alveolar y biopsias de mucosa duodenal y colónica. Se utilizó ivermectina subcutánea como tratamiento antihelmíntico con adecuada respuesta terapéutica.

Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells.

Cellular transformation is associated with a number of phenotypic, cell biological, biochemical and metabolic alterations. The detection and classification of morphological cellular abnormalities represents the foundation of classical histopathology and remains an important mainstay in the clinic. More recently, significant effort is being expended towards the development of noninvasive modalities for the detection of cancer at an early stage, when therapeutic interventions are highly successful. Methods that rely on the detection of optical signatures represent one class of such approaches that have yielded promising results. In our study, we have applied two spectroscopic imaging approaches to systematically identify in a quantitative manner the fluorescence and light scattering signatures of subcellular abnormalities that are associated with cellular transformation. Notably, we find that tryptophan images reveal not only intensity but also localization differences between normal and human papillomavirus immortalized cells, possibly originating from changes in the expression, 3D packing and organization of proteins and protein-rich subcellular organelles. Additionally, we detect alterations in cellular metabolism through quantitative evaluation of the NADH, FAD fluorescence and the corresponding redox ratio. Finally, we use light scattering spectroscopy to identify differences in nuclear morphology and subcellular organization that occur from the nanometer to the micrometer scale. Thus, these optical approaches provide complementary biomarkers based on endogenous fluorescence and scattering cellular changes that occur at the molecular, biochemical and morphological level. Since they obviate the need for staining and tissue removal and can be easily combined, they provide desirable options for further clinical development and assessment.