Donor side effects experienced under minimal controlled ovarian stimulation with in vitro maturation vs. conventional controlled ovarian stimulation for in vitro fertilization treatment.

OBJECTIVE: To evaluate oocyte retrieval experiences and side effects under minimally controlled ovarian stimulation (COS) treatment for in vitro maturation (IVM) of oocytes compared with conventional COS treatment. DESIGN: A retrospective survey study. SETTING: Clinical in vitro fertilization treatment center. PATIENT(S): Data were collected from subjects undergoing minimal COS treatment (n = 110; 600-800 IU follicle-stimulating hormone) for IVM of oocytes and conventional COS treatment for egg donation (n = 48; 1,800-2,600 IU follicle-stimulating hormone) from April 2022 to November 2023. INTERVENTION(S): Minimal and conventional COS treatments. MAIN OUTCOME MEASURE(S): The most common side effects experienced during ovarian stimulation and after oocyte pick-up, satisfaction level, and the likelihood of recommending or repeating minimal or conventional COS. Statistical analysis included Mann-Whitney U test and χ2 tests, with a significance level. RESULT(S): During minimal COS treatment, most subjects did not experience breast swelling (86%), pelvic or abdominal pain (76%), nausea or vomiting (96%), and bleeding (96%). After oocyte pick-up, the majority (75%) reported no pelvic or abdominal pain. The most common side effect was abdominal swelling (52%). Compared with conventional COS cycles, minimal COS subjects reported significantly less postretrieval pain, with 33% experiencing no pain (vs. 6%) and with a reduced severe level of pain (5% vs. 19%), leading to fewer subjects requiring pain medication (25% vs. 54%). Additionally, 85% of women were very satisfied with minimal stimulation treatment and would recommend or repeat the treatment. CONCLUSION(S): Reducing the hormonal dose for ovarian stimulation has a beneficial effect on subjects, suggesting the combination of minimal COS treatment with IVM techniques is a well-tolerated alternative for women who cannot or do not wish to undergo conventionally controlled ovarian hyperstimulation treatment.

Rescue in vitro maturation using ovarian support cells of human oocytes from conventional stimulation cycles yields oocytes with improved nuclear maturation and transcriptomic resemblance to in vivo matured oocytes.

PURPOSE: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM). METHODS: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls. RESULTS: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM. CONCLUSION: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

STUDY QUESTION: Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem cells (hiPSCs)? SUMMARY ANSWER: OSC-IVM significantly improves the rates of metaphase II (MII) formation and euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system. WHAT IS KNOWN ALREADY: IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity, while limited studies have shown a positive benefit of primary granulosa cell co-culture for IVM. We recently reported the development of OSCs generated from hiPSCs that recapitulate dynamic ovarian function in vitro. STUDY DESIGN, SIZE, DURATION: The study was designed as a basic science study, using randomized sibling oocyte specimen allocation. Using pilot study data, a prospective sample size of 20 donors or at least 65 oocytes per condition were used for subsequent experiments. A total of 67 oocyte donors were recruited to undergo abbreviated gonadotropin stimulation with or without hCG triggers and retrieved cumulus-oocyte complexes (COCs) were allocated between the OSC-IVM or control conditions (fetal-like OSC (FOSC)-IVM or media-only IVM) in three independent experimental design formats. The total study duration was 1 April 2022 to 1 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte donors between the ages of 19 and 37 years were recruited for retrieval after informed consent, with assessment of anti-Mullerian hormone, antral follicle count, age, BMI and ovarian pathology used for inclusion and exclusion criteria. In experiment 1, 27 oocyte donors were recruited, in experiment 2, 23 oocyte donors were recruited, and in experiment 3, 17 oocyte donors and 3 sperm donors were recruited. The OSC-IVM culture condition was composed of 100 000 OSCs in suspension culture with hCG, recombinant FSH, androstenedione, and doxycycline supplementation. IVM controls lacked OSCs and contained either the same supplementation, FSH and hCG only (a commercial IVM control), or FOSCs with the same supplementation (Media control). Experiment 1 compared OSC-IVM, FOSC-IVM, and a Media control, while experiments 2 and 3 compared OSC-IVM and a commercial IVM control. Primary endpoints in the first two experiments were the MII formation (i.e. maturation) rate and morphological quality assessment. In the third experiment, the fertilization and embryo formation rates were assessed with genetic testing for aneuploidy and epigenetic quality in blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a statistically significant improvement (∼1.5×) in maturation outcomes for oocytes that underwent IVM with OSCs compared to control Media-IVM and FOSC-IVM in experiment 1. More specifically, the OSC-IVM group yielded a MII formation rate of 68% ± 6.83% SEM versus 46% ± 8.51% SEM in the Media control (P = 0.02592, unpaired t-test). FOSC-IVM yielded a 51% ± 9.23% SEM MII formation rate which did not significantly differ from the media control (P = 0.77 unpaired t-test). Additionally, OSC-IVM yielded a statistically significant ∼1.6× higher average MII formation rate at 68% ± 6.74% when compared to 43% ± 7.90% in the commercially available IVM control condition (P = 0.0349, paired t-test) in experiment 2. Oocyte morphological quality between OSC-IVM and the controls did not significantly differ. In experiment 3, OSC-IVM oocytes demonstrated a statistically significant improvement in Day 5 or 6 euploid blastocyst formation per COC compared to the commercial IVM control (25% ± 7.47% vs 11% ± 3.82%, P = 0.0349 logistic regression). Also in experiment 3, the OSC-treated oocytes generated blastocysts with similar global and germline differentially methylated region epigenetic profiles compared commercial IVM controls or blastocysts after either conventional ovarian stimulation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: While the findings of this study are compelling, the cohort size remains limited and was powered on preliminary pilot studies, and the basic research nature of the study limits generalizability compared to randomized control trials. Additionally, use of hCG-triggered cycles results in a heterogenous oocyte cohort, and potential differences in the underlying maturation state of oocytes pre-IVM may limit or bias findings. Further research is needed to clarify and characterize the precise mechanism of action of the OSC-IVM system. Further research is also needed to establish whether these embryos are capable of implantation and further development, a key indication of their clinical utility. WIDER IMPLICATIONS OF THE FINDINGS: Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. The controls used in this study are in line with and have produced similar to findings to those in the literature, and the outcome of this study supports findings from previous co-culture studies that found benefits of primary granulosa cells on IVM outcomes. The OSC-IVM system shows promise as a highly flexible IVM approach that can complement a broad range of stimulation styles and patient populations. Particularly for patients who cannot or prefer not to undergo conventional gonadotropin stimulation, OSC-IVM may present a viable path for obtaining developmentally competent, mature oocytes. STUDY FUNDING/COMPETING INTEREST(S): A.D.N., A.B.F., A.G., B.P., C.A., C.C.K., F.B., G.R., K.S.P., K.W., M.M., P.C., S.P., and M.-J.F.-G. are shareholders in the for-profit biotechnology company Gameto Inc. P.R.J.F. declares paid consultancy for Gameto Inc. P.C. also declares paid consultancy for the Scientific Advisory Board for Gameto Inc. D.H.M. has received consulting services from Granata Bio, Sanford Fertility and Reproductive Medicine, Gameto, and Buffalo IVF, and travel support from the Upper Egypt Assisted Reproduction Society. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., and A.D.N. are listed on a patent covering the use of OSCs for IVM: U.S. Provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on three patents covering the use of OSCs for IVM: U.S. Patent Application No. 17/846,725, U.S Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K., M.P.S., and P.C. additionally are listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, U.S. Provisional Application No. 63/326,640, and U.S. Provisional Application No. 63/444,108. The remaining authors have no conflicts of interest to declare.

Deciphering reproductive aging in women using a NOD/SCID mouse model for distinct physiological ovarian phenotypes.

Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. Thus, we aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life. NOD/SCID mice of different ages (8-, 28-, and 36-40-week-old) were employed to mimic ovarian phenotypes of young, Advanced Maternal Age (AMA), and old women (~18-20-, ~36-38-, and >45-years-old, respectively). Mice were stimulated, mated, and sacrificed to recover oocytes and embryos. Then, ovarian reserve, follicular growth, ovarian stroma, mitochondrial dysfunction, and proteomic profiles were assessed. Age-matched C57BL/6 mice were employed to cross-validate the reproductive outcomes. The quantity and quality of oocytes were decreased in AMA and Old mice. These age-related effects associated spindle and chromosome abnormalities, along with decreased developmental competence to blastocyst stage. Old mice had less follicles, impaired follicle activation and growth, an ovarian stroma inconducive to growth, and increased mitochondrial dysfunctions. Proteomic analysis corroborated these histological findings. Based on that, NOD/SCID mice can be used to model different ovarian aging phenotypes and potentially test human anti-aging treatments.

Brote de histoplasmosis en el contexto de la pandemia por COVID-19 / Histoplasmosis outbreak in the context of the COVID-19 pandemic

La histoplasmosis es una micosis profunda de distribución mundial causada por el Histoplasma capsulatum var. capsulatum. Se caracteriza por una variabilidad clínica que depende principalmente de la carga fúngica, del estado inmunológico del paciente y de la virulencia del germen. Se describe un brote de histoplasmosis pulmonar aguda en militares, producido en el contexto epidemiológico de la COVID-19. El episodio tuvo lugar a partir de actividad laboral en cuevas donde participaron cuatro militares, tres de los cuales desarrollaron síntomas y fueron admitidos en el Hospital Dr. Gustavo Aldereguía Lima de Cienfuegos en enero de 2022. La información fue obtenida a través de la entrevista médica y la historia clínica. Se evidenció que en el contexto epidemiológico de la pandemia por COVID-19 no se debe subestimar el diagnóstico de otras enfermedades respiratorias, incluidas las micosis endémicas(AU)

Histoplasmosis is a deep mycotic infection of worldwide distribution caused by Histoplasma capsulatum var. capsulatum. It is characterized by clinical variability that depends mainly on the fungal load, the patient's immune status and the virulence of the germ. We describe an outbreak of acute pulmonary histoplasmosis among military officers, which occurred in the epidemiological context of COVID-19. The episode occurred during work activities in caves in which four soldiers participated, three of whom developed symptoms and were admitted to the "Dr. Gustavo Aldereguía Lima" Hospital in Cienfuegos in January 2022. The information was obtained through medical interviews and clinical records. It was evidenced that in the epidemiological context of the COVID-19 pandemic, the diagnosis of other respiratory diseases, including endemic mycoses, should not be underestimated(AU)

Single intraovarian dose of stem cell- and platelet-secreted factors mitigates age-related ovarian infertility in a murine model.

BACKGROUND: Systemic administration of soluble factors from bone marrow-derived stem cells combined with activated platelet-rich plasma (SC-PRP) restored ovarian function, mediated through paracrine signaling, in murine models of chemotherapy-induced ovarian damage and human tissue from poor responder patients. However, the effects against age-related infertility and the efficacy of local administration have not been evaluated yet. OBJECTIVE: This study aimed to assess whether a single intraovarian dose of stem cells combined with activated platelet-rich plasma can recover ovarian function, oocyte quality, and developmental competence in older mice. STUDY DESIGN: The effects of stem cells combined with activated platelet-rich plasma against age-related infertility were assessed following controlled ovarian stimulation in an aging murine model reproducing 3 physiological stages of women's reproductive life, namely young, advanced maternal age, and menopausal (n=12 animals per group). Female mice were randomized to receive a single intraovarian injection (10 µL/ovary) of either saline, activated platelet-rich plasma, or stem cells combined with activated platelet-rich plasma. Seven days later, the mice were stimulated, naturally mated, and sacrificed to harvest their ovaries for histologic assessment and molecular analysis and their oviducts to evaluate oocyte maturation and to assess early embryo development. RESULTS: A single intraovarian injection of stem cells combined with activated platelet-rich plasma promoted follicle activation and development in young, advanced maternal age, and old mice. Furthermore, stem cells combined with activated platelet-rich plasma rescued fertility in older mice by enhancing the quantity and quality of ovulated mature oocytes and supporting early embryo development to the blastocyst stage in all the evaluated ages. These fertility outcomes were positively associated with mitochondrial quality, treatment-increased mitochondrial DNA copy numbers, and reduced oxidative damage and apoptosis. Finally, the effects observed by histologic analysis were supported at the proteomic level. Functional proteomic analyses revealed molecular mechanisms involved in oocyte maturation and quality, mitochondrial function, and recovery of the ovarian stroma. CONCLUSION: Bone marrow-derived stem cells combined with activated platelet-rich plasma is a promising treatment with the potential to improve the reproductive outcomes of women with age-related infertility, exceeding the restorative effects of platelet-rich plasma alone. Although further research in human ovarian samples is still required, the autologous nature of stem cell factors collected by noninvasive mobilization, their combination with platelet-rich plasma, and the local administration route suggest that stem cells combined with activated platelet-rich plasma treatment could be a potentially effective and safe application for future clinical practice.

Comportamiento de características seleccionadas en pacientes hospitalizados por neumonía adquirida en la comunidad y algunas asociaciones de interés práctico / Behavior of selected characteristics in patients hospitalized for community-acquired pneumonia and some associations of practical interest

La neumonía adquirida en la comunidad constituye una de las afecciones respiratorias que provoca más demanda de asistencia médica, y es responsable del mayor número de fallecidos por enfermedades infecciosas en Cuba. El objetivo del estudio ha sido determinar el comportamiento de características seleccionadas en pacientes hospitalizados por neumonía y precisar la existencia de asociaciones entre algunas de estas características.Se realizó un estudio observacional, con diseño descriptivo, que incluyó 1,809 pacientes hospitalizados por neumonía entre enero de 2012 y febrero de 2020. Fueron analizadas características relacionadas con las condiciones de base, clínico-radiológicas, y relativas al manejo y la evolución, mediante análisis bivariante y multivariante (regresión logística). La serie estuvo constituida fundamentalmente por pacientes ancianos (79%), mientras que el 20% presentaba la condición de encamamiento. Esta condición se asoció significativamente con el estado de demencia avanzada (OR 7,6[5,5;10,4]), y fue determinante en la presentación "solapada" del proceso (OR 1,5[1,09;2]). La presentación "solapada" de la neumonía estuvo significativamente asociada al ingreso tardío (OR 1,6[1,2;2,2]). Como conclusiones se ratifica el lugar que ocupan varios elementos en las características de la morbilidad por neumonía: edad avanzada, presencia de comorbilidades, y presentación no clásica del proceso. Fueron constatadas interrelaciones de importancia práctica entre la presencia de comorbilidades particulares, las formas clínicas de presentación, el momento del ingreso, y la utilización de antimicrobianos durante la atención prehospitalaria del paciente. Se destaca el papel del encamamiento en la extensión radiológica del proceso neumónico y en la presencia de derrame pleural de mediana o gran cuantía al momento del ingreso.

Community-acquired pneumonia is one of the respiratory conditions that causes the greatest demand for medical care, and is responsible for the largest number of deaths from infectious diseases in Cuba. The objective of the study was to determine the behavior of selected characteristics in patients hospitalized for pneumonia and to specify the existence of associations between some of these characteristics. An observational study, with a descriptive design, was carried out, which included 1,809 patients hospitalized for pneumonia between January 2012 and February 2020. Characteristics related to the basic, clinical-radiological conditions, and relative to management and evolution were analyzed, through analysis bivariate and multivariate (logistic regression). The series consisted mainly of elderly patients (79%), while 20% were bedridden. This condition was significantly associated with the state of advanced dementia (OR 7.6[5.5;10.4]) and was decisive in the "overlapping" presentation of the process (OR 1.5[1.09;2]). The "overlapping" presentation of pneumonia was significantly associated with late admission (OR 1.6[1.2;2.2]). As conclusions, the place occupied by several elements in the characteristics of pneumonia morbidity is ratified: advanced age, presence of comorbidities, and non-classical presentation of the process. Interrelationships of practical importance were found between the presence of comorbidities, the clinical forms of presentation, the time of admission, and the use of antimicrobials during the patient's prehospital care. The role of bed rest in the radiological extension of the pneumonic process and in the presence of medium or large pleural effusion at the time of admission is highlighted.

Instrumento para la estratificación de pacientes con neumonía adquirida en la comunidad en el Departamento de Urgencias: su utilidad en la valoración pronóstica al ingreso / Instrument for the Stratification of Patients with Community-Acquired Pneumonia in the Emergency Department: its Usefulness in the Prognostic Assessment on Admission

Introducción: La estratificación de riesgo del paciente con neumonía adquirida en la comunidad constituye una acción médica de mucho valor en la evaluación integral del enfermo. Objetivo: Determinar la utilidad de un instrumento para la estratificación de pacientes con neumonía en la valoración pronóstica al momento del ingreso. Material y métodos: Investigación descriptiva, que abarcó 2203 pacientes con diagnóstico de neumonía comunitaria, divididos en cinco series entre los años 2009 y 2020; se calculó la letali dad por clase y por categoría de estratificación. En el análisis estadístico, se utilizó la razón de productos cruzados (Odds Ratio) con su intervalo de confianza de 95%. Resultados: Se observó un incremento progresivo de la letalidad desde la clase ligera hasta la grave, tanto para el total de casos (ligera: 5%; moderada: 17%; grave: 59%), como en cada una de las series. Hubo significación estadística en las diferencias en la letalidad entre la neumonía grave y la neumonía moderada (OR 7[5,6;8,6]). En los pacientes con neumonía moderada y en los pacientes con neumonía grave al ingreso, la letalidad fue mayor en la categoría B que en la A (neumonía moderada: 18% vs. 11%, OR 1,7[1;2,7]; neumonía grave: 68% vs. 29%, OR 5,2[3,4;8]). Conclusiones: Se demostró la utilidad del instrumento empleado en la predicción del curso evolutivo del paciente con neumonía, además de su valor orientador para la toma de decisiones. El comportamiento de la letalidad en los diferentes estratos del instrumento avala la manera en que ha sido concebido.

Background: Risk stratification of patients with community-acquired pneumonia is a very important process for the comprehensive evaluation of the patient. Objective: To determine the usefulness of a tool that was created for the stratifica tion of patients with pneumonia in the prognostic assessment on admission. Materials and Methods: Descriptive research including 2,203 patients diagnosed with community pneumonia, divided in five series between 2009 and 2020; the mortality rate was calcu lated according to the stratification class and category. For the statistical analysis, we used the cross-product ratio (Odds Ratio) with its 95% confidence interval. Results: We observed a progressive increase in mortality from mild to severe class, both in the total number of cases (mild: 5%; moderate: 17%; severe: 59%) and in each one of the series. There was statistical significance in the mortality differences between severe and moderate pneumonia (OR 7[5.6;8.6]). In patients who had moderate and severe pneumonia on admission, the mortality in category B was higher than in cat egory A (moderate pneumonia: 18% vs. 11%, OR 1.7[1;2.7]; severe pneumonia: 68% vs. 29%, OR 5.2[3.4;8]). Conclusions: We have proven the usefulness of the tool in predicting the progression of patients with pneumonia and its importance in guiding the decision-making process. The behavior of the mortality rate in the different strata of the tool supports the purpose envisioned for it.

Instrument for the Stratification of Patients with Community- Acquired Pneumonia in the Emergency Department: its Usefulness in the Prognostic Assessment on Admission / Instrumento para la estratificación de pacientes con neumonía adquirida en la comunidad en el Departamento de Urgencias: su utilidad en la valoración pronóstica al ingreso

ABSTRACT Background: Risk stratification of patients with community-acquired pneumonia is a very important process for the comprehensive evaluation of the patient. Objective: To determine the usefulness of a tool that was created for the stratifica tion of patients with pneumonia in the prognostic assessment on admission. Materials and Methods: Descriptive research including 2,203 patients diagnosed with community pneumonia, divided in five series between 2009 and 2020; the mortality rate was calcu lated according to the stratification class and category. For the statistical analysis, we used the cross-product ratio (Odds Ratio) with its 95% confidence interval. Results: We observed a progressive increase in mortality from mild to severe class, both in the total number of cases (mild: 5%; moderate: 17%; severe: 59%) and in each one of the series. There was statistical significance in the mortality differences between severe and moderate pneumonia (OR 7[5.6;8.6]). In patients who had moderate and severe pneumonia on admission, the mortality in category B was higher than in cat egory A (moderate pneumonia: 18% vs. 11%, OR 1.7[1;2.7]; severe pneumonia: 68% vs. 29%, OR 5.2[3.4;8]). Conclusions: We have proven the usefulness of the tool in predicting the progression of patients with pneumonia and its importance in guiding the decision-making process. The behavior of the mortality rate in the different strata of the tool supports the purpose envisioned for it.

RESUMEN Introducción: La estratificación de riesgo del paciente con neumonía adquirida en la comunidad constituye una acción médica de mucho valor en la evaluación integral del enfermo. Objetivo: Determinar la utilidad de un instrumento para la estratificación de pacientes con neumonía en la valoración pronóstica al momento del ingreso. Material y métodos: Investigación descriptiva, que abarcó 2203 pacientes con diagnóstico de neumonía comunitaria, divididos en cinco series entre los años 2009 y 2020; se calculó la letali dad por clase y por categoría de estratificación. En el análisis estadístico, se utilizó la razón de productos cruzados (Odds Ratio) con su intervalo de confianza de 95%. Resultados: Se observó un incremento progresivo de la letalidad desde la clase ligera hasta la grave, tanto para el total de casos (ligera: 5%; moderada: 17%; grave: 59%), como en cada una de las series. Hubo significación estadística en las diferencias en la letalidad entre la neumonía grave y la neumonía moderada (OR 7[5,6;8,6]). En los pacientes con neumonía moderada y en los pacientes con neumonía grave al ingreso, la letalidad fue mayor en la categoría B que en la A (neumonía moderada: 18% vs. 11%, OR 1,7[1;2,7]; neumonía grave: 68% vs. 29%, OR 5,2[3,4;8]). Conclusiones: Se demostró la utilidad del instrumento empleado en la predicción del curso evolutivo del paciente con neumonía, además de su valor orientador para la toma de decisiones. El comportamiento de la letalidad en los diferentes estratos del instrumento avala la manera en que ha sido concebido.

Behavior of clinical and humoral variables on admission as predictors of death in patients with community-acquired pneumonia. Comparative study between adults and older adults. / Comportamiento de variables clínicas y humorales al ingreso, como predictores de fallecimiento en pacientes con neumonía adquirida en la comunidad. Estudio comparativo entre adultos y adultos mayores

Community-acquired pneumonia is recognized as one of the main infectious health problems worldwide. The objective was to determine the condition of predictors of death for a group of selected clinical conditions, and for laboratory variables frequently used in practice. Study with descriptive design, which included 967 patients with pneumonia hospitalized between 2016 and 2019, and whose information was obtained from clinical records. Statistical treatment included bivariate and multivariate analysis (logistic regression); it was used the ratio of crossed products (odds ratio) and its 95% confidence interval. Several manifestations were significantly more frequent in older adults: dyspnea (OR 1.5[1.07,2.1]), absence of productive cough (OR 1.7 [1.3, 2.4]), neuropsychological manifestations (OR 2 [1.4,2.8]), tachypnea (OR 1.5 [1.1,2.1]), arterial hypotension (OR 2.1 [1.2,3.6]), anemia (OR 1.6[1.2,2.2]), elevated creatinine (OR 1.6[1.2,2.3]) and hypoproteinemia (OR 3.3[1.9,5.7]); showed a significant association with death: absence of productive cough, neuropsychological manifestations, temperature below 36 degrees Celsius, blood pressure below 110/70 mmHg, respiratory rate above 20 per minute, hemoglobin below 100 g/L, erythrosedimentation greater than 20 mm/L, leukopenia less than 5 x 109/L and serum creatinine above 130 micromol/L. As conclusions certain clinical and laboratory conditions present in the patient at the time of hospital admission, of routine exploration in the comprehensive assessment of the patient, were predictors of death. Additionally, the existence of evident differences in the number of conditions with a predictive nature of death between the population with pneumonia under 60 years of age and the elderly, as well as in the frequency of these conditions in both subgroups, is verified.

La neumonía adquirida en la comunidad está reconocida como uno de los principales problemas de salud de tipo infeccioso al nivel mundial. La investigación tuvo como objetivo determinar el carácter de predictores de fallecimiento de un grupo de condiciones clínicas seleccionadas, y de variables de laboratorio de uso frecuente en la práctica. Se realizó un estudio con diseño descriptivo, que incluyó a 967 pacientes con neumonía hospitalizados entre 2016 y 2019, y cuya información se obtuvo de los expedientes clínicos. El tratamiento estadístico incluyó análisis bivariante y multivariado (regresión logística); como estadígrafo se utilizó la razón de productos cruzados (odds ratio) y su intervalo de confianza de 95%. Entre los resultados se destacan los siguientes: varias manifestaciones fueron significativamente más frecuentes en los adultos mayores: disnea (OR 1,5[1,07;2,1]), ausencia de tos productiva (OR 1,7[1,3;2,4]), manifestaciones neuropsicológicas (OR 2[1,4;2,8]), taquipnea (OR 1,5[1,1;2,1]), hipotensión arterial (OR 2,1[1,2;3,6]), anemia (OR 1,6[1,2;2,2]), creatinina elevada (OR 1,6[1,2;2,3]) e hipoproteinemia (OR 3,3[1,9;5,7]); mostraron asociación significativa con el fallecimiento: ausencia de tos productiva, manifestaciones neuropsicológicas, temperatura por debajo de 36 grados Celsius, tensión arterial inferior a 110/70 mmHg, frecuencia respiratoria por encima de 20 por minuto, hemoglobina inferior a 100 g/L, velocidad de sedimentación eritrocitaria superior a 20 mm/L, leucopenia inferior a 5 x 109/L y creatinina sérica por encima de 130 micromol/L. Se concluye que ciertas condiciones clínicas y de laboratorio presentes en el paciente al momento del ingreso hospitalario, de exploración habitual en la valoración integral del enfermo, constituyeron predictores de fallecimiento. Adicionalmente, se comprueba la existencia de evidentes diferencias en el número de condiciones con carácter predictor de muerte entre la población con neumonía menor de 60 años y los adultos mayores, así como en la frecuencia de estas condiciones en ambos subgrupos.

Ubicación intrahospitalaria y tratamiento antimicrobiano inicial en pacientes con neumonía adquirida en la comunidad y su relación con la frecuencia y calidad del proceso de estratificación / Intrahospitalary location and antimicrobial initial treatment in patients with acquired pneumonia in the community and their relationship with the frequency and quality of the stratification process

La importancia de la evaluación inicial de la gravedad del paciente con neumonía es una acción diagnóstica de importancia bien establecida. El objetivo del trabajo fue evaluar la relación entre la frecuencia y calidad del proceso de estratificación de pacientes con neumonía, y el cumplimiento de las sugerencias de ubicación intrahospitalaria y de tratamiento antimicrobiano inicial de un instrumento de estratificación. Se realizó un estudio descriptivo sobre una población de 1,809 pacientes hospitalizados durante 10 años. Se analizó el comportamiento de los índices de ubicación intrahospitalaria y tratamiento antimicrobiano inicial acorde a la sugerencia de un instrumento de estratificación utilizado; en el análisis estadístico se utilizó el Odds ratio y el estadígrafo X2, con un nivel de significación de 95%. En los resultados se destacan que la ubicación intrahospitalaria estuvo acorde a la sugerencia del instrumento en el 96%, con el valor más bajo en los pacientes con neumonía grave y altas probabilidades de recuperación (82%, p<,05). Se constató mayor frecuencia de ubicación intrahospitalaria acorde a la sugerencia del instrumento en los pacientes bien estratificados (p<,05), fundamentalmente en los pacientes con neumonía grave y altas probabilidades de recuperación. La correspondencia del tratamiento antimicrobiano inicial con la propuesta del instrumento fue del 61%; el estrato IIIA mostró el valor más elevado (80%, p<,05). Como conclusiones del estudio se constató un elevado desempeño en el cumplimiento de la sugerencia de ubicación intrahospitalaria del instrumento de estratificación, no así en el cumplimiento de la sugerencia de tratamiento antimicrobiano inicial. Se demostró la existencia de una relación entre el proceso de estratificación y el cumplimiento de la ubicación intrahospitalaria sugerida por el instrumento empleado.

The initial evaluation of the patient's condition with pneumonia is a very important assistance action. The objective was evaluate the relationship between the frequency and quality of the stratification process of the patient with pneumonia, and the execution of suggestions of intrahospitalary location and the initial antimicrobial treatment of stratification instrument. A descriptive study was done on a population of 1,809 patients hospitalized during 10 years. The indexes of intrahospitalary location and of antimicrobian initial treatment were analized according to the suggestions of the instrument; in the statistical analysis it was used the odds ratio and the statistician X2, with a significant level of 95%. The intrahospitalary location was in agreement with the suggestion of the instrument in 96% of the cases, with the lowest value in patients with serious pneumonia and high recovery probabilities (82%, p <,05). The frequency of intrahospitalary location was bigger and veryfied with the suggestion of the instrument in the termed well stratified patients (p <,05), fundamentally in the patients with serious pneumonia and high recovery probabilities. The correspondence of the initial antimicrobial treatment with the proposal of the instrument was of 61%; the stratum IIIA showed the highest value (80%, p <,05). As conclusions, a high performance in the execution of the suggestion of the intrahospitalary location has been one of the characteristics of the process, although as a negative element it stands out the frequent non-fulfillment of the suggestion of the initial antimicrobial treatment. There was a relationship between the stratification process and the execution of the suggestion of the intrahospitalary location.

Evaluación del proceso de estratificación en pacientes hospitalizados con neumonía adquirida en la comunidad / Evaluation of stratification process in hospitalized patients with community-acquired pneumonia

Introducción: Un instrumento ha sido utilizado para la estratificación de pacientes con neumonía adquirida en la comunidad en el Departamento de urgencias desde 2006. Objetivo: Evaluar el proceso de estratificación de pacientes con neumonía adquirida en la comunidad de pacientes hospitalizados. Métodos: Estudio descriptivo que incluyó 1 809 pacientes hospitalizados en el Departamento de urgencias entre los años 2009 y 2019. Para la evaluación del proceso se realizó una estratificación de control que permitió determinar la frecuencia y calidad de la estratificación inicial, así como la coincidencia entre esta y la estratificación real. En el análisis estadístico se utilizó la razón de productos cruzados (Odds Ratio) y el estadígrafo X2 para diferencias de proporciones; se aceptó un nivel de significación de 95 por ciento. Resultados: El índice de estratificación de la serie fue de 86 por ciento, y el índice de estratificación adecuada fue de 80 por ciento. Predominaron los pacientes con neumonía moderada y altas probabilidades de evolución desfavorable. La menor estratificación se comprobó en los pacientes con neumonía grave y altas probabilidades de recuperación (p<,05). Hubo diferencias en la calidad de la estratificación entre las agrupaciones de los estratos IA-IB-IIA y IIB-IIIA-IIIB (p<,05). Estos tres últimos estratos presentaron las cifras más altas del valor predictivo positivo de la estratificación inicial (p<,05). Conclusiones: El proceso de estratificación de pacientes con neumonía adquirida en la comunidad hospitalizados se caracterizó por una elevada frecuencia de estratificación y una adecuada calidad. No obstante, fueron identificados grupos de pacientes y situaciones específicas que se consideran áreas de superación de importancia para el mejoramiento de la calidad asistencia(AU)

Introduction: An instrument has been used for stratifying patients with community-acquired pneumonia in the emergency department since 2006. Objective: To evaluate the stratifying process of patients with community-acquired pneumonia in hospitalized patients. Methods: A descriptive study that included 1 809 patients hospitalized in the emergency department from 2009 to 2019 was carried out. A control stratification evaluated the process, which allowed determining the frequency and quality of the initial stratification, as well as the coincidence between this and the actual stratification. In the statistical analysis, the ratio of crossed products (Odds Ratio) and X2 statistic were used for differences in proportions; a significance level of 95 percent was accepted. Results: The stratification index of the series was 86 percent, and the adequate stratification index was 80 percent. Patients with moderate pneumonia and high probabilities of unfavorable evolution predominated. The lowest stratification was found in patients with severe pneumonia and high probability of recovery (p <.05). There were differences in the quality of stratification between the groupings of strata IA-IB-IIA and IIB-IIIA-IIIB (p <.05); these last three strata sowed the highest figures of the positive predictive value of the initial stratification (p <.05). Conclusions: The stratification process of hospitalized community-acquired pneumonia patients was characterized by high stratification frequency and adequate quality. However, this study identified groups of patients and specific situations that were considered as areas of improvement, important for improving the quality of care(AU)

Stem cell-secreted factor therapy regenerates the ovarian niche and rescues follicles.

BACKGROUND: Ovarian senescence is a normal age-associated phenomenon, but increasingly younger women are affected by diminished ovarian reserves or premature ovarian insufficiency. There is an urgent need for developing therapies to improve ovarian function in these patients. In this context, previous studies suggest that stem cell-secreted factors could have regenerative properties in the ovaries. OBJECTIVE: This study aimed to test the ability of various human plasma sources, enriched in stem cell-secreted factors, and the mechanisms behind their regenerative properties, to repair ovarian damage and to promote follicular development. STUDY DESIGN: In the first phase, the effects of human plasma enriched in bone marrow stem cell soluble factors by granulocyte colony-stimulating factor mobilization, umbilical cord blood plasma, and their activated forms on ovarian niche, follicle development, and breeding performance were assessed in mouse models of chemotherapy-induced ovarian damage (n=7 per group). In addition, the proteomic profile of each plasma was analyzed to find putative proteins and mechanism involved in their regenerative properties in ovarian tissue. In the second phase, the most effective plasma treatment was validated in human ovarian cortex xenografted in immunodeficient mice (n=4 per group). RESULTS: Infusion of human plasma enriched bone marrow stem cell soluble factors by granulocyte colony-stimulating factor mobilization or of umbilical cord blood plasma-induced varying degrees of microvessel formation and cell proliferation and reduced apoptosis in ovarian tissue to rescue follicular development and fertility in mouse models of ovarian damage. Plasma activation enhanced these effects. Activated granulocyte colony-stimulating factor plasma was the most potent inducing ovarian rescue in both mice and human ovaries, and proteomic analysis indicated that its effects may be mediated by soluble factors related to cell cycle and apoptosis, gene expression, signal transduction, cell communication, response to stress, and DNA repair of double-strand breaks, the most common form of age-induced damage in oocytes. CONCLUSION: Our findings suggested that stem cell-secreted factors present in both granulocyte colony-stimulating factor-mobilized and umbilical cord blood plasma could be an effective treatment for increasing the reproductive outcomes in women with impaired ovarian function owing to several causes. The activated granulocyte colony-stimulating factor plasma, which is already enriched in both stem cell-secreted factors and platelet-enclosed growth factors, seems to be the most promising treatment because of its most potent restorative effects on the ovary together with the autologous source.

Factores relacionados con la letalidad en pacientes con neumonía adquirida en la comunidad hospitalizados / Factors related to lethality of admitted patients with pneumonia acquired in the community

RESUMEN Fundamento: la neumonía adquirida en la comunidad constituye un importante problema de salud en muchos países, incluyendo Cuba. Objetivo: determinar los principales factores relacionados con la letalidad, en pacientes con neumonía adquirida en la comunidad hospitalizados. Métodos: estudio de serie de casos, con diseño descriptivo-correlacional, con carácter prospectivo; fueron estudiados 521 pacientes con neumonía hospitalizados entre el primero de abril de 2016 y el 31 de marzo de 2018. La información fue obtenida de los expedientes clínicos, agrupada en cuatro categorías de variables: relativas a condiciones del paciente, al proceso patológico, analíticas y relativas a la intervención terapéutica. En el análisis estadístico fue utilizado el odds ratio (OR) y su intervalo de confianza. Resultados: la letalidad más elevada fue observada en los de 75 años y más (40 %); en los pacientes previamente encamados (47 % vs 22 %), en los casos con enfermedades crónicas presentes (31 % vs 18 %), y en los que tenían antecedentes de cardioesclerosis (35 % vs 24 %) y demencia (50 % vs 26 %). También mostraron asociación con la letalidad la gravedad de la afección al momento del ingreso, la extensión de las lesiones en la radiografía de tórax más allá de los límites de un lóbulo, y el encamamiento durante el ingreso. Conclusiones: se ratifica la importancia de un grupo de factores relacionados con las condiciones del paciente, el proceso morboso en sí, con los exámenes complementarios y la intervención terapéutica, en la evolución final del paciente con neumonía adquirida en la comunidad.

ABSTRACT Foundation: acquired pneumonia is an important health problem in many countries including Cuba. Objective: to determine the main factors related to lethality, in admitted patients with pneumonia acquired in the community. Method: prospective study of case series, with correlational descriptive design; a number of 521 admitted patients were studied between April the 1st 2016 and March 31st 2018. The information was obtained from clinical records, grouped in four variable categories: those related to patient´s conditions, to pathological process, analytic and therapeutic intervention. For the statistical analysis it was used odds ratio (OR) and confidence interval. Results: lethality was higher in patients older than 75 years (40 %); in patients previously laid in bed (47 % vs 22 %), in cases with chronic diseases (31 % vs 18 %), and those with history of cardio-sclerosis (35 % vs 24 %) and dementia (50 % vs 26 %). In addition, there was an association between lethality and severity of the disease on admission, extension of the lesions on thoracic x-ray over a lobule limit and lying in bed during admission. Conclusion: the importance of factors related to the patient´s conditions is confirmed, the morbid process itself with lab tests and therapeutic intervention, in the final evolution of the patient with community acquired pneumonia.

Diminished Ovarian Reserve Chemotherapy-Induced Mouse Model: A Tool for the Preclinical Assessment of New Therapies for Ovarian Damage.

Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Twenty-one Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were allocated to 3 groups (n = 7/group): control, single dose of vehicle (Dimethyl Sulfoxide [DMSO]); DOR, single reduced chemotherapy dose; and POI, single standard chemotherapy dose. After 21 days, mice underwent ovarian hyperstimulation and mating. Part of the animals were harvested to analyze ovarian reserve, ovulation and fertilization rates, and morphology, apoptosis, and vascularization of the ovarian stroma. The remaining mice underwent multiple matings to assess pregnancy rates and litter sizes. The DOR and POI mice showed an impaired estrous cyclicity and a decrease in ovarian mass, number of follicles, Metaphase II (MII) oocytes, and embryos as well as in ovarian stroma vascularization. Mice in both models showed also an increase in the percentage of morphologically abnormal follicles, stromal degeneration, and apoptosis. Similar to that observed in DOR and POI patients, these impairments were less severe in DOR than in POI mice. None of the POI females were able to achieve a pregnancy. Meanwhile, DOR females achieved several consecutive pregnancies, although litter size was decreased when compared to controls. In conclusion, a mouse model which displayed most of the ovarian characteristics and fertility outcomes of women with DOR has been established using a single dose of chemotherapy.

Diminished Ovarian Reserve Chemotherapy-Induced Mouse Model: A Tool for the Preclinical Assessment of New Therapies for Ovarian Damage.

Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Twenty-one Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were allocated to 3 groups (n = 7/group): control, single dose of vehicle (Dimethyl Sulfoxide [DMSO]); DOR, single reduced chemotherapy dose; and POI, single standard chemotherapy dose. After 21 days, mice underwent ovarian hyperstimulation and mating. Part of the animals were harvested to analyze ovarian reserve, ovulation and fertilization rates, and morphology, apoptosis, and vascularization of the ovarian stroma. The remaining mice underwent multiple matings to assess pregnancy rates and litter sizes. The DOR and POI mice showed an impaired estrous cyclicity and a decrease in ovarian mass, number of follicles, Metaphase II (MII) oocytes, and embryos as well as in ovarian stroma vascularization. Mice in both models showed also an increase in the percentage of morphologically abnormal follicles, stromal degeneration, and apoptosis. Similar to that observed in DOR and POI patients, these impairments were less severe in DOR than in POI mice. None of the POI females were able to achieve a pregnancy. Meanwhile, DOR females achieved several consecutive pregnancies, although litter size was decreased when compared to controls. In conclusion, a mouse model which displayed most of the ovarian characteristics and fertility outcomes of women with DOR has been established using a single dose of chemotherapy.

Thorax Trauma Severity Score: Is it reliable for Patient's Evaluation in a Secondary Level Hospital?

OBJECTIVE: To determine the predictive and diagnostic value of thorax trauma severity score (TTSS) in a population of thoracic trauma patients admitted to a secondary level trauma center. METHODS: A Retrospective analysis of patients admitted over a period of two years with IDC-9 codes related to thoracic trauma was undertaken. The association of TTSS with complications and mortality was evaluated. We also determined the predictive value of TTSS using receiver operating characteristic curve (ROC). RESULTS: 238 patients with thoracic trauma, mostly middle-aged (62.2 ± 15 years), were included. The main mechanisms of injury were falls and traffic accidents. Thirty-three patients had important extra-thoracic injuries, but only 9 presented an ISS> 15. The average ISS was 3 ± 5; Morbidity was 2.5% and mortality was 2.1% as a result of thoracic injury and these patients had significantly higher TTSS values. Each score component was analyzed separately, showing significant association with complications and mortality. The area under the curve for TTSS was significant for predicting complications (0.848) and mortality (0.856) values. TTSS with a cut off value of 8 points had a sensitivity of 66% and specificity of 94% to predict complications and 80% sensitivity and 94% specificity for predicting mortality. CONCLUSIONS: The TTSS is an appropriate and feasible tool to predict the development of complications or mortality in a population of mostly mild thoracic trauma.