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PURPOSE: Performing intracorporeal anastomoses in minimally invasive colon surgery appears to provide better short-term outcomes for patients with colon cancer. The aim of the study is to compare surgical aspects and short-term outcomes between intracorporeal and extracorporeal techniques in left colectomies with both laparoscopic and robotic approaches and evaluate advantages and disadvantages of intracorporeal anastomosis according to IDEAL framework (Exploration, stage 2b). METHODS: This is a single center, ambispective cohort study comparing total intracorporeal anastomosis (TIA) and standard surgery with extracorporeal anastomosis (EA). Patients with colon cancer treated by left colectomy, sigmoidectomy and high anterior resection by total intracorporeal anastomosis between May 2020 and January 2023 without exclusion criteria were prospectively included in a standardized database. Short-term outcomes in the group undergoing TIA were compared with a historical EA cohort. The main assessment outcomes were intraoperative complications, postoperative morbidity according to the Clavien-Dindo scale and the comparison of pathological. We conducted a preliminary comparative study within the TIA group between approaches, a primary analysis between the two anastomotic techniques, and a propensity score matched analysis including only the laparoscopic approach, between both anastomotic techniques. RESULTS: Two hundred and forty-six patients were included: 103 who underwent TIA, 35 of them with laparoscopic approach and 68 with robotic approach, and a comparison group comprising another 103 eligible consecutive patients who underwent laparoscopic EA. There were no statistically significant differences between the two groups in terms of demographic variables. No statistically significant differences were observed in anastomotic dehiscence. Intraoperative complications are fewer in the TIA group, with a higher C-Reactive Protein levels. Relevant anastomotic bleeding and the number of retrieved lymph nodes were higher in EA group. Nevertheless, no differences were observed in terms of overall morbidity. CONCLUSION: Minimally invasive left colectomy with intracorporeal resection and anastomosis is technically feasible and safe suing either a laparoscopic or a robotic approach. Clinical data from this cohort demonstrate outcomes comparable to those achieved through the conventional EA procedure in relation to postoperative morbidity and oncological efficacy, with indications suggesting that the utilization of robotic-assisted techniques may play a contributing role in enhancing overall treatment outcomes.
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Anastomosis Quirúrgica , Colectomía , Neoplasias del Colon , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Humanos , Colectomía/métodos , Masculino , Femenino , Anastomosis Quirúrgica/métodos , Persona de Mediana Edad , Anciano , Laparoscopía/métodos , Neoplasias del Colon/cirugía , Neoplasias del Colon/patología , Procedimientos Quirúrgicos Robotizados/métodos , Estudios de Cohortes , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Spinocerebellar ataxia type 8 (SCA8) is a dominantly inherited expansion disorder with highly variable penetrance. ATXN8OS/ATXN8 expanded alleles have been identified in association with other types of hereditary ataxias, pointing to a possible genetic synergism. OBJECTIVES: We aimed to further investigate the molecular background of patients with SCA8 diagnosis. METHODS: Patients were selected from our cohort of 346 families. A total of 14 probands with SCA8 underwent additional investigation through exome sequencing. RESULTS: Pathogenic heterozygous STUB1 variants were found in 21.4% of SCA8 patients (3 of 14) compared to only 0.5% in the non-SCA8 group (1 of 222), indicating a statistically significant association (P < 0.05). CONCLUSIONS: The findings reported in this study might suggest a genetic synergism between STUB1 and ATXN8OS/ATXN8 expanded alleles. Further studies are needed to validate this observation and better define the clinical impact of this genetic interaction. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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PURPOSE: Meniscal wrapping is a fully arthroscopic technique that involves enhanced meniscal repair with a tissue-engineered collagen matrix wrapping. This study aims to investigate the feasibility of using the meniscal wrapping technique for the treatment of chronic or complex meniscal tears. The primary objective is to assess its failure rate. The secondary objectives are to analyse complication rate, functional outcomes and overall patient satisfaction. METHODS: This retrospective case series study included patients who sustained chronic and complex tears undergoing meniscal wrapping with autologous liquid bone marrow injection. Failure rate was considered if the patient underwent partial or complete meniscectomy or knee replacement during the follow-up, while other unexpected knee reoperations were considered as complications. Clinical outcomes were evaluated through the IKDC score, Tegner Activity Score and Short Assessment of Patient Satisfaction. RESULTS: Twenty-one patients were included (15 non-acute bucket-handle tears, three non-acute horizontal tears and three non-acute complex injuries). The failure rate was 9.5% at 33 months. The rate of other unplanned reoperations was 14.3%, but none of these complications were apparently directly related to the wrapping technique. The average postoperative IKDC was 73.3/100. No statistically significant difference was encountered between preinjury and postoperative Tegner Activity Score. The mean overall patient satisfaction was 88.3/100. CONCLUSIONS: Meniscal wrapping can be safely used as an adjunctive technique to meniscal repair in such difficult-to-treat cases to preserve the meniscus. The technique achieves a low failure rate and promising results of knee function, and patient satisfaction.
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BACKGROUND: Secondary pseudohypoaldosteronism (S-PHA) is a rare condition resulting from renal tubular resistance to aldosterone in children with urinary tract infection (UTI) and/or nephrourological malformations. It is characterized by nonspecific symptoms but with the potential for life-threatening complications. We aim to evaluate the clinical manifestations, diagnostic approach, and therapeutic interventions in children with S-PHA, along with a review of recent publications. METHODS: A retrospective observational descriptive study was conducted on S-PHA cases diagnosed over the last 15 years at a tertiary pediatric nephrology unit. The literature for the last 10 years was reviewed. RESULTS: Twelve patients (10 males, 6 days to 6 months) were identified. Weight loss was the main reason for consultation (50%). Ninety-two percent of patients had an underlying nephrourological pathology and 62% concomitant confirmed UTI. Seven out of 12 children were admitted to the PICU. A subsequent extrapontine myelinolysis was observed in one patient as neurological sequelae. Twenty-one articles related to S-PHA have been identified on PubMed and Embase. CONCLUSIONS: S-PHA should be considered in infants under 6 months of age with UTI and/or CAKUT. Obstructive anomalies and vesicoureteral reflux can be found, affecting both unilateral and bilateral systems. Early medical and surgical interventions are crucial and require close monitoring to avoid iatrogenic complications.
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Communities neighboring monoculture plantations are vulnerable to different forms of pollution associated with agro-industrial operations. Herein, we examine the case of El Tiple, a rural Afro descendant community embedded within one of the largest sugarcane plantations in the Americas. We implemented a participatory approach to assess water pollution, exposure via water ingestion, and non-carcinogenic health risks associated with the use of local water sources available to the community. We conducted household surveys to unveil demographic characteristics and family dynamics linked to water consumption. Additionally, we measured water quality parameters and assessed the concentration glyphosate, its major metabolite (aminomethylphosphonic acid) and metals and metalloids. Drinking water El Tiple households is sourced from three primary sources: the local aqueduct system, water delivery trucks, and private deep wells. Tests on water samples from both the local aqueduct and delivery trucks showed no traces of pesticides, metals, or metalloids surpassing regulatory limits set by Colombian or EPA standards. However, we found concentration of contaminants of primary concern, including mercury (up to 0.0052 ppm) and lead (up to 0.0375 ppm) that exceed the permissible regulatory thresholds in water from groundwater wells. Residents of the peripheric subdivisions of El Tiple are four times more reliant on well water extraction than residents of the central area of the town due to lack of access to public drinking water and sanitation infrastructure. Finally, adult women and school-age children have a higher health risk associated with exposure to local pollutants than adult men due to their constant presence in the town. We conclude that expanding the coverage of clean water and sanitation infrastructure to include all households of the community would be the most recommended measure to minimize exposure and risk via ingestion of water pollutants.
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Saccharum , Contaminantes Químicos del Agua , Colombia , Contaminantes Químicos del Agua/análisis , Humanos , Medición de Riesgo , Agricultura , Agua Potable/química , Monitoreo del Ambiente , Contaminación del Agua/estadística & datos numéricos , Contaminación del Agua/análisis , Glicina/análogos & derivados , Glicina/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición a Riesgos Ambientales/análisis , Abastecimiento de Agua , GlifosatoRESUMEN
IMPORTANCE: The field of meniscal root preservation has undergone significant advancement over the past decades; however, the challenge remains to fully understand whether meniscal root repair can ultimately arrest or delay osteoarthritic changes. OBJECTIVE: To assess longitudinal changes in articular cartilage, subchondral bone, and progression to meniscal extrusion (ME) using high-resolution magnetic resonance imaging (MRI). METHODS: Medial meniscus posterior root tear was surgically induced in 39 New Zealand white rabbits. Animals were randomly assigned into three experimental groups: partial meniscectomy after root tear (PM, n â= â13); root tear left in situ (CT, n â= â13); and transtibial root repair (RR, n â= â13). Contralateral limbs were used as healthy controls. High resolution 4.7 Tesla MRI of the knee joint was performed at baseline, after 2-, and 4-months of post-surgery. Cartilage thickness was calculated in medial and lateral compartments. In addition, the evaluation of ME, subchondral bone edema and healing potential after root repair were assessed too. RESULTS: Progressive cartilage thinning, ME, and subchondral bone edema were evident in all 3 study groups after 4-months of follow-up. The mean cartilage thickness in the PM group was 0.53 âmm (±0.050), 0.57 âmm (±0.05) in the CT group, and 0.60 âmm (±0.08) in the RR group. The PM group exhibited significantly higher cartilage loss when compared to the CT and RR groups (p â< â0.001). Moreover, progressive ME and subchondral bone edema were associated with a more severe cartilage loss at the final follow-up. CONCLUSION: Meniscal root repair did not halt but rather reduced the progression of osteoarthritis (OA). Degenerative changes worsened at a rapid rate in the PM group compared to the RR and CT groups. Early cartilage swelling, persistent subchondral edema, and progressive ME predicted a more severe progression to knee OA in the CT and RR groups. LEVEL OF EVIDENCE: II.
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Cartílago Articular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Imagen por Resonancia Magnética , Meniscos Tibiales , Lesiones de Menisco Tibial , Animales , Conejos , Imagen por Resonancia Magnética/métodos , Lesiones de Menisco Tibial/cirugía , Lesiones de Menisco Tibial/diagnóstico por imagen , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Meniscos Tibiales/cirugía , Meniscos Tibiales/diagnóstico por imagen , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Meniscectomía/métodos , Distribución Aleatoria , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/patología , Valor Predictivo de las Pruebas , Traumatismos de la Rodilla/diagnóstico por imagen , Traumatismos de la Rodilla/cirugíaRESUMEN
The historical and contemporary alignment of medical and health journals with colonial practices needs elucidation. Colonialism, which sought to exploit colonised people and places, was justified by the prejudice that colonised people's ways of knowing and being are inferior to those of the colonisers. Institutions for knowledge production and dissemination, including academic journals, were therefore central to sustaining colonialism and its legacies today. This invited Viewpoint focuses on The Lancet, following its 200th anniversary, and is especially important given the extent of The Lancet's global influence. We illuminate links between The Lancet and colonialism, with examples from the past and present, showing how the journal legitimised and continues to promote specific types of knowers, knowledge, perspectives, and interpretations in health and medicine. The Lancet's role in colonialism is not unique; other institutions and publications across the British empire cooperated with empire-building through colonisation. We therefore propose investigations and raise questions to encourage broader contestation on the practices, audience, positionality, and ownership of journals claiming leadership in global knowledge production.
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Colonialismo , Prejuicio , Humanos , Colonialismo/historia , Liderazgo , ConocimientoRESUMEN
Corporate influence in policy and decision-making is an important public health concern. This Health Policy paper reviews Ecuador's child malnutrition strategy instruments, approved between 2020 and 2023, to identify how private interests are becoming legally integrated into the public sector. Evidence indicates that recent changes are enabling corporations to promote their brands, gain tax deductions, oversee public policy and set priorities, allocate resources, and decide on implementation of the country's child malnutrition strategy. Further, corporate representatives are active members of an advisory council, free from scrutiny or accountability, while being privy to undisclosed government information. Moreover, a UN agency (the World Food Program) engaged in corporate promotion of highly processed foods, illustrating the breadth of Ecuador's corporate influence scheme. Improved regulations should set clear limits to the influence of food and beverage industries in national nutrition policy, while following transparency laws in the composition and operation of Ecuador's child malnutrition strategy and related efforts.
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Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical responses to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (five responders and five non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signaling pathways. These DEGs were predominantly immune related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). The S1P, NF-kB and TCR signaling pathways were differentially modulated in responder and non-responder patients. These transcriptomic differences offer the potential of being exploited as biomarkers of a clinical response to fingolimod.
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Lisofosfolípidos , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Esfingosina/análogos & derivados , Humanos , Clorhidrato de Fingolimod/farmacología , Clorhidrato de Fingolimod/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/genética , Inmunosupresores/efectos adversos , Leucocitos Mononucleares , FN-kappa B , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/genética , Perfilación de la Expresión Génica , BiomarcadoresRESUMEN
BACKGROUND: The real degree of constraint of rotating hinge knee and condylar constrained prostheses is a matter of discussion in revision knee arthroplasty. The objective of this study is to compare the tibial rotation between implants in the clinical settings. METHODS: An investigator blinded experimental study was designed including 20 patients: in 10 of them a rotating hinge knee prosthesis (Endomodel®, LINK) was implanted and in the remaining 10 a constrained condylar knee prosthesis (LCCK®, Zimmer) was used. A medial parapatellar approach was performed and implantation was performed according to conventional surgical technique. Tibial rotation was measured with two accelerometers in full extension and at 30°, 60° and 90° of flexion. Pre and postoperative Knee Injury and Osteoarthritis Outcome Score was recorded. FINDINGS: Both groups were homogenous in age (73.4 years in rotating hinge knee prosthesis vs 74 years in constrained condylar knee group), sex, laterality and preoperative Knee Injury and Osteoarthritis Outcome Score (p > 0.05). The postoperative Knee Injury and Osteoarthritis Outcome Score was significantly higher in the rotating hinge knee prosthesis group (80.98 vs 76.28). The degrees of tibial rotation measured by inertial sensors in the rotating hinge knee prosthesis group were also significantly higher than those measured in the constrained condylar knee group (5.66° vs 2.1°) with p = 0.001. INTERPRETATION: Rotating hinge knee prosthesis appears to represent a lower rotational constraint degree than constrained condylar knee systems in clinical practice and it may increase the clinical satisfaction. The clinical significance: Rotating hinge knee prosthesis appears to represent a lower constraint degree than constrained condylar knee systems in clinical practice.
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Traumatismos de la Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Humanos , Anciano , Diseño de Prótesis , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Reoperación , Traumatismos de la Rodilla/cirugía , Resultado del Tratamiento , Falla de Prótesis , Estudios RetrospectivosRESUMEN
PURPOSE: To describe our institutional experience and results in the surgical management of multiligament knee injuries (MLKI). MATERIALS AND METHODS: Retrospective series of MLKI consecutively operated on at a single, level I Trauma Center. Data on patients' baseline characteristics, injuries, treatments, and outcomes were recorded up to one-year follow-up. Recorded outcomes included the Tegner-Lysholm Knee Scoring Scale (TLKSS), return to work, and patient satisfaction. RESULTS: MLKI incidence was 0.03% among 9897 orthopedic trauma admissions. Twenty-four patients of mean age 43.6 years were included in analysis. The mean Injury Severity Score was 12.6. Five patients presented with knee dislocations and six had fracture-dislocations, two of them open fractures. There was one popliteal artery injury requiring a bypass and four common peroneal nerve palsies. Staged ligamental reconstruction was performed in all cases. There were seven postoperative complications. The median TLKSS was 80 and, though patient satisfaction was high, and dissatisfaction was largely restricted to recreational activities (only 58.3% satisfied). Seventeen patients returned to their previous employment. CONCLUSIONS: We found a high aggregation of fracture-dislocations secondary to road traffic accidents. One in four patients experienced complications, particularly stiffness. Complications were more common in cases involving knee dislocation. Most patients had good functional results, but 25% were unable to return to their previous work, which demonstrates the long-lasting sequelae of this injury.
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Luxación de la Rodilla , Traumatismos de la Rodilla , Humanos , Adulto , Estudios Retrospectivos , Centros Traumatológicos , Universidades , Traumatismos de la Rodilla/epidemiología , Traumatismos de la Rodilla/cirugía , Traumatismos de la Rodilla/complicaciones , Luxación de la Rodilla/cirugía , Luxación de la Rodilla/complicaciones , Articulación de la RodillaRESUMEN
BACKGROUND: The optimal treatment option for meniscus root tears is still challenging, and whether the meniscus root repair ultimately can arrest or delay osteoarthritic changes is still a concern. PURPOSE/HYPOTHESIS: The purpose of this study was 2-fold: (1) to describe and compare histopathologic findings of 3 different therapeutic options for medial meniscus posterior root tear: nonoperative management, partial meniscectomy, and meniscus root repair; and (2) to test the hypothesis that meniscus root tears treated nonoperatively predispose to a lower risk of osteoarthritic progression compared with partial meniscectomy. STUDY DESIGN: Controlled laboratory study. METHODS: Posteromedial meniscus root tears were carried out in 39 New Zealand White rabbits. Animals were randomly assigned into 3 experimental groups: partial meniscectomy after root tear (PM; n = 13), root tears treated conservatively (CT; n = 13), and transtibial root repair (RR; n = 13). Contralateral limbs were used as healthy controls. The animals were euthanized at 16 weeks postoperatively; tissue samples of femoral and tibial articular cartilage were collected and processed for macro- and microscopic assessment to detect signs of early osteoarthritis (OA). Each sample was histopathologically assessed using the Osteoarthritis Research Society International grading and staging system. RESULTS: Osteoarthritic changes were the hallmark in all 3 experimental groups. The RR group had the lowest scores for cartilage damage (mean, 2.5; range, 2-3), and the PM group exhibited higher and more severe signs of OA (mean, 16; range, 9-16) compared with the CT group (mean, 5; range, 4-6). The between-group comparison revealed significant differences, as the PM group showed a significantly higher rate of macro- and microscopic osteoarthritic changes compared with the RR (P < .001) and CT (P < .001) groups. The weightbearing area of the medial femoral condyle was the most severely affected, and tidemark disruption was evident in all tissue samples. CONCLUSION: Meniscus root repair cannot completely arrest the histopathologic progression of knee OA but leads to significantly less severe degenerative changes than partial meniscectomy and nonoperative treatment. Partial meniscectomy leads to the most severe osteoarthritic progression, while stable radial tears left in situ have lower progression compared with partial meniscectomy. CLINICAL RELEVANCE: Histologic assessment is an essential tool and metric for guiding and understanding osteoarthritic features, providing insight into the disease development and progression. This study provides histopathologic evidence on osteoarthritic progression after medial meniscus posterior root repair. This knowledge can help to set more realistic expectations and can lead to the future development of augmented techniques.
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Artroplastia de Reemplazo de Rodilla , Laceraciones , Osteoartritis de la Rodilla , Animales , Conejos , Meniscectomía , Meniscos Tibiales/cirugía , TibiaRESUMEN
Venezuela's ongoing economic and political crisis has forced >6 million people to emigrate from the country since 2014. In the Andean region, Ecuador is one of the main host countries for Venezuelan migrants and refugees. During the coronavirus disease 2019 (COVID-19) pandemic, specific measures were implemented in the country to control the spread of the disease and its associated impacts. In this context, we conducted a scoping review to understand how policies implemented by the Ecuadorian government during the pandemic impacted Venezuelan migrants' right to health. The literature search focused on scientific and grey publications between 2018 and 2022 in electronic databases and institutional websites, complemented by snowball sampling and expert advice. Our thematic analysis revealed discrepancies between the rights granted to migrants in Ecuador's legal framework and their practical implementation during the pandemic, with several instances of policy and programmatic infringement. The disruption of services further complicated migrant's options for regularization. Some measures, like border closures, negatively impacted migrants' health, including increased exposure to abuse and violence. While migrants were included in the country's COVID-19 vaccination plan, they were excluded from other national aid programmes. There are indications of an increase in xenophobia and discrimination stigmatizing migrants as 'disease carriers' and 'resource takers', resulting in a prioritization of services for the Ecuadorian population. We found limited research on the emergent topic of migrants' vulnerability and related health system challenges. Future research should include working in border zones, consider socioeconomic factors and further explore the poor implementation of Ecuador's legal framework towards upholding migrants' right to health.
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The Cervidae family has a wide distribution due to its adaptation to numerous ecological environments, which allows it to develop a diverse microbial community in its digestive tract. Recently, research has focused on the taxonomic composition and functionality of the intestinal and faecal microbiota of different cervid species worldwide, as well as their microbial diversity and variation under different associated factors such as age, sex, diet, distribution, and seasonal variation. In addition, there is special interest in knowing how cervids act as reservoirs of zoonotic pathogenic microorganisms, which represent a threat to public health. This review provides a synthesis of the growing field of microbiota determination in cervids worldwide, focusing on intestinal and faecal samples using 16S next-generation sequencing. It also documents factors influencing microbial diversity and composition, the microorganisms reported as pathogenic/zoonotic, and the perspectives regarding the conservation of these species. Knowing the interactions between bacteria and cervid health can drive management and conservation strategies for these species and help develop an understanding of their evolutionary history and the interaction with emerging disease-causing microorganisms.
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Background and objective: Dimethyl fumarate (DMF) is an immunomodulatory drug approved for the therapy of multiple sclerosis (MS). The identification of response biomarkers to DMF is a necessity in the clinical practice. With this aim, we studied the immunophenotypic and transcriptomic changes produced by DMF in peripheral blood mononuclear cells (PBMCs) and its association with clinical response. Material and methods: PBMCs were obtained from 22 RRMS patients at baseline and 12 months of DMF treatment. Lymphocyte and monocyte subsets, and gene expression were assessed by flow cytometry and next-generation RNA sequencing, respectively. Clinical response was evaluated using the composite measure "no evidence of disease activity" NEDA-3 or "evidence of disease activity" EDA-3 at 2 years, classifying patients into responders (n=15) or non-responders (n=7), respectively. Results: In the whole cohort, DMF produced a decrease in effector (TEM) and central (TCM) memory T cells in both the CD4+ and CD8+ compartments, followed by an increase in CD4+ naïve T cells. Responder patients presented a greater decrease in TEM lymphocytes. In addition, responder patients showed an increase in NK cells and were resistant to the decrease in the intermediate monocytes shown by non-responders. Responder patients also presented differences in 3 subpopulations (NK bright, NK dim and CD8 TCM) at baseline and 4 subpopulations (intermediate monocytes, regulatory T cells, CD4 TCM and CD4 TEMRA) at 12 months. DMF induced a mild transcriptional effect, with only 328 differentially expressed genes (DEGs) after 12 months of treatment. The overall effect was a downregulation of pro-inflammatory genes, chemokines, and activators of the NF-kB pathway. At baseline, no DEGs were found between responders and non-responders. During DMF treatment a differential transcriptomic response was observed, with responders presenting a higher number of DEGs (902 genes) compared to non-responders (189 genes). Conclusions: Responder patients to DMF exhibit differences in monocyte and lymphocyte subpopulations and a distinguishable transcriptomic response compared to non-responders that should be further studied for the validation of biomarkers of treatment response to DMF.
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Dimetilfumarato , Esclerosis Múltiple , Humanos , Dimetilfumarato/uso terapéutico , Inmunosupresores/uso terapéutico , Leucocitos Mononucleares , Células Asesinas Naturales , BiomarcadoresRESUMEN
Primary health care is at the core of health systems that aim to ensure equitable health outcomes. With an estimated 36% of rural population, Ecuador has a service year programme (created in 1970) for recently graduated doctors to provide primary care services in rural and remote communities. However, little has been done to monitor or evaluate the programme since its inception. The aim of this study was to assess Ecuador's rural medical service implementation with a focus on equitable distribution of doctors across the country. For this purpose, we analysed the distribution of all doctors, including rural service doctors, in health-care facilities across rural and remote areas of Ecuador in the public sector at the canton level for 2015 and 2019, by level of care (primary, secondary and tertiary). We used publicly available data from the Ministry of Public Health, the Ecuadorian Institute of Social Security and the Peasant Social Security. Our analyses show that two of every three rural service doctors are concentrated at the secondary level, while almost one in five rural service doctors, at the tertiary level. Moreover, cantons concentrating most rural service doctors were in the country's major urban centres (Quito, Guayaquil, Cuenca). To our knowledge, this is the first quantitative assessment of the mandatory rural service year in Ecuador in its five-decade existence. We provide evidence of gaps and inequities impacting rural communities and present decision makers with a methodology for placement, monitoring and support of the rural service doctors programme, provided that legal and programmatic reforms come into place. Changing the programme's approach would be more likely to fulfill the intended goals of rural service and contribute to strengthening primary health care.