Use Of Replacement Therapy Research Articles

A hypothesis on treatment strategy of severe multicentric Castleman disease with continuous renal replacement therapy.

Castleman disease (CD) is a rare lymphoproliferative disorder, with non-specific clinical manifestations, often delayed diagnosis and treatment, which pose a significant challenge in the present times. Patients diagnosed with this disease have poor prognosis due to the limited treatment options. Multicentric CD occurs at multiple lymph node stations and is associated with a proinflammatory response that leads to the development of the so-called 'B symptoms'. IL-6 seems to be a key cytokine involved in various manifestations such as lymphadenopathies, hepatosplenomegaly, and polyclonal hypergammaglobulinemia. Its levels correlate with the activity of the disease. Other consequences of MCD include increased fibrinogen levels leading to deep vein thrombosis and thromboembolic disorders, high hepcidin levels causing anaemia, elevated VEGF levels promoting angiogenesis and vascular permeability, which, along with hypoalbuminemia, induce oedema, ascites, pleural and pericardial effusions, and in severe cases, generalized anasarca. In extreme cases multiple organ failure can occur, often resulting in death. We propose the use of continuous renal replacement therapy (CRRT) in managing severe multicentric CD. Our arguments are based on the principles that CRRT is able to remove IL-6 from circulation thus attenuating the cytokine storm, can influence hepcidin levels, and reduction in oedema, and is often used in multiple organ failure to regain homeostasis control. Therefore, it could be used as a therapy or bridge therapy in severe cases. To sustain our hypothesis with evidence, we have gathered several studies from the literature confirming the successful removal of cytokines, especially IL-6 from circulation, which can be used as a starting point.

Obesity and 1-year all-cause survival of adult intensive care patients with heart failure: data from the MIMIC-IV.

BackgroundHeart failure is a disease that threatens global public safety. In recent years, the obesity paradox has been studied in cardiovascular disease and other fields. With the progress of aging, metabolic changes and regulation of fat function, it also provides many bridges for the dialogue between disease and molecular metabolism. The purpose of this study is to investigate the effect of obesity on the outcome of adult intensive care patients with heart failure combined with age factors.MethodData were derived from the fourth-generation Medical Information Marketplace for Intensive Care (MIMIC-IV version2.1) using structured query language on the Navicat (12.0.11) platform. People were divided into two groups based on the body mass index (BMI), one group with BMI ≥ 30 kg/m² and another group with BMI < 30 kg/m². Afterwards, the patients were divided into two subgroups based on their ages. One group included patients aged<60, and the other included patients aged ≥ 60. The extracted information includes demographic characteristics, laboratory findings, comorbidities, scores. Main results included in-hospital mortality, ICU mortality, and 1-year mortality. Secondary outcomes included hospital interval and ICU interval, use of renal replacement therapy, and rates of noninvasive and invasive ventilation support.ResultIn this cohort study, 3390 people were in the BMI<30 group, 2301 people were in the BMI ≥ 30 group, 960 people were in the age<60 group, and 4731 people were in the age ≥ 60 group, including 3557 patients after propensity score matching in high age group. Among patients aged ≥ 60, BMI ≥ 30 group vs. BMI<30 group showed significantly lower in-hospital mortality (13% vs. 16%) and one-year mortality (41% vs. 55%), respectively. Neither primary nor secondary outcomes were significantly described in the competition among patients aged under 60. Restricted cubic spline reveals a J-shaped nonlinear association between BMI and clinical endpoints within the entire cohort. Kaplan-Meier curves revealed a survival advantage in BMI ≥ 30 group (p < 0.001). Following age stratification, a beneficial effect of BMI categories on one-year mortality risk was observed in heart failure patients aged ≥ 60 (Univariable HR, 0.71, 95% CI, 0.65–0.78, p < 0.001; Multivariable HR, 0.74, 95% CI, 0.67–0.81, p < 0.001), but not in those under 60 years old.OutcomeIn ICU patients with heart failure, obesity offers a survival benefit to those aged ≥ 60. No obesity paradox was observed in patients younger than 60 years old. The obesity paradox applies to patients aged ≥ 60 with heart failure.

Anemia of chronic diseases

Anemia of chronic diseases (ACD) is a pathological process that develops in patients with systemic inflammation in a wide range of diseases of both infectious and non-infectious origin. ACD is the second most common disease in the world after iron deficiency anemia (IDA) and is a factor that aggravates the course of the underlying disease and increases mortality. Pathophysiologically, ACD is a complex multifactorial process and includes 3 main development mechanisms: an increase in the production of hepcidin, a decrease in the formation of erythropoietin and inhibition of normal erythropoiesis in the bone marrow. These processes are triggered by pro-inflammatory cytokines. Special attention in the article is paid to the universal humoral regulator of iron metabolism – hepcidin. For a doctor of any specialty it is important to identify ACD, conduct a differential diagnosis that allows one to distinguish ACD from other types of anemia (including iron deficiency), establish a possible combination of IDA and ACD, since different types of anemia require their own therapeutic approaches. The patient’s prognosis will depend on the correct treatment. In order to verify ACD a thorough search for the underlying disease is carried out, СBC indicators and iron metabolism indicators are assessed. The basis of the therapeutic approach to the treatment of ACD is the treatment of the underlying disease. Therapy for this type of anemia includes the use of iron preparations, erythropoietin and replacement therapy with blood components.

The effects and safety of testosterone replacement therapy for men with hypogonadism: the TestES evidence synthesis and economic evaluation.

Low levels of testosterone cause male hypogonadism, which is associated with sexual dysfunction, tiredness and reduced muscle strength and quality of life. Testosterone replacement therapy is commonly used for ameliorating symptoms of male hypogonadism, but there is uncertainty about the magnitude of its effects and its cardiovascular and cerebrovascular safety. The primary aim was to evaluate the safety of testosterone replacement therapy. We also assessed the clinical and cost-effectiveness of testosterone replacement therapy for men with male hypogonadism, and the existing qualitative evidence on men's experience and acceptability of testosterone replacement therapy. Evidence synthesis and individual participant data meta-analysis of effectiveness and safety, qualitative evidence synthesis and model-based cost-utility analysis. Major electronic databases were searched from 1992 to February 2021 and were restricted to English-language publications. We conducted a systematic review with meta-analysis of individual participant data according to current methodological standards. Evidence was considered from placebo-controlled randomised controlled trials assessing the effects of any formulation of testosterone replacement therapy in men with male hypogonadism. Primary outcomes were mortality and cardiovascular and cerebrovascular events. Data were extracted by one reviewer and cross-checked by a second reviewer. The risk of bias was assessed using the Cochrane Risk of Bias tool. We performed one-stage meta-analyses using the acquired individual participant data and two-stage meta-analyses to integrate the individual participant data with data extracted from eligible studies that did not provide individual participant data. A decision-analytic Markov model was developed to evaluate the cost per quality-adjusted life-years of the use of testosterone replacement therapy in cohorts of patients of different starting ages. We identified 35 trials (5601 randomised participants). Of these, 17 trials (3431 participants) provided individual participant data. There were too few deaths to assess mortality. There was no difference between the testosterone replacement therapy group (120/1601, 7.5%) and placebo group (110/1519, 7.2%) in the incidence of cardiovascular and/or cerebrovascular events (13 studies, odds ratio 1.07, 95% confidence interval 0.81 to 1.42; p = 0.62). Testosterone replacement therapy improved quality of life and sexual function in almost all patient subgroups. In the testosterone replacement therapy group, serum testosterone was higher while serum cholesterol, triglycerides, haemoglobin and haematocrit were all lower. We identified several themes from five qualitative studies showing how symptoms of low testosterone affect men's lives and their experience of treatment. The cost-effectiveness of testosterone replacement therapy was dependent on whether uncertain effects on all-cause mortality were included in the model, and on the approach used to estimate the health state utility increment associated with testosterone replacement therapy, which might have been driven by improvements in symptoms such as sexual dysfunction and low mood. A meaningful evaluation of mortality was hampered by the limited number of defined events. Definition and reporting of cardiovascular and cerebrovascular events and methods for testosterone measurement varied across trials. Our findings do not support a relationship between testosterone replacement therapy and cardiovascular/cerebrovascular events in the short-to-medium term. Testosterone replacement therapy improves sexual function and quality of life without adverse effects on blood pressure, serum lipids or glycaemic markers. Rigorous long-term evidence assessing the safety of testosterone replacement therapy and subgroups most benefiting from treatment is needed. The study is registered as PROSPERO CRD42018111005. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/68/01) and is published in full in Health Technology Assessment; Vol. 28, No. 43. See the NIHR Funding and Awards website for further award information.

Disease Activity and Bone Microarchitectural Phenotype in Patients With Axial Spondyloarthritis

Background: Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease characterized by spine inflammation, abnormal bone growth, and paradoxically osteoporosis and vertebral fractures. The pathogenesis of skeletal deficits in this disease is poorly understood. Purpose: We sought to evaluate volumetric bone mineral density (vBMD) and bone microarchitecture in patients with AxSpA and to identify disease-related factors associated with skeletal abnormalities. Methods: We enrolled patients between 2018 and 2021 as part of a 2-year prospective study at a single institution investigating skeletal health and the skeletal effects of interleukin-17 (IL-17) treatment. Patients with AxSpA who met Assessment in SpondyloArthritis International Society (ASAS) classification criteria by X-ray or had evidence of active inflammation on magnetic resonance imaging suggestive of sacroiliitis were referred to the study by their rheumatologists. We excluded those with a history of fragility fracture, multiple myeloma, Cushing’s disease, primary hyperparathyroidism, osteomalacia, untreated vitamin D deficiency, secondary osteoporosis, or other systemic rheumatic diseases, as well as use of oral steroids for 2 or more weeks in the 6 months prior or current use of hormone replacement therapy, current oral bisphosphonate, past or current intravenous bisphosphonate, teriparatide, or denosumab therapies. A total of 1606 patients were screened for eligibility. Of these, 30 participants were enrolled (mean age 43 years, 50% male). Patients with AxSpA had dual-energy X-ray absorptiometry (DXA) measurements of areal BMD (aBMD) and high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of vBMD microarchitecture and failure load by finite element analysis. Standardized disease assessment tools used included the Bath Ankylosing Spondylitis Disease Activity (BASDAI), Metrology Index (BASMI), and Functional Index (BASFI). Results: In the 30 included patients, mean DXA and HR-pQCT Z-scores were within 1 standard deviation (SD) of normal for all indices, except for total vBMD in males (–1.2 SD below mean). Mean symptom duration was 11.7 years and mean scores for BASDAI, BASFI, and BASMI were 4.6, 3.6, and 2.7, respectively (range 1–10, 10 = severe limitation). Longer disease duration was associated with more severe skeletal deficits at the hip and tibia—specifically, lower hip aBMD, lower meta- and inner-trabecular vBMD, lower trabecular number, and higher trabecular separation and heterogeneity. Conclusion: This study of 30 patients with AxSpA found that abnormalities in bone density and microarchitecture at weightbearing sites were associated with longer disease duration. Because of its small sample size, larger studies are needed to better characterize the pathogenic disease factors that govern skeletal damage in AxSpA.

Diagnosis, treatment and management of lipodystrophy: the physician perspective on the patient journey

BackgroundLipodystrophy syndromes are a heterogeneous group of rare, life-limiting diseases characterized by a selective loss of adipose tissue and severe metabolic complications. There is a paucity of information describing the experiences and challenges faced by physicians who have seen and treated patients with lipodystrophy. This study aimed to provide a better understanding of the physician’s perspective regarding the patient journey in lipodystrophy, including diagnosis, the burden of disease, and treatment approaches.MethodsThirty-three physicians from six countries who had seen or treated patients with lipodystrophy were interviewed using a semi-structured questionnaire. Interviews were transcribed, anonymized, and analyzed for themes and trends. Four main themes were developed: (1) the diagnostic journey in lipodystrophy including the disease features or ‘triggers’ that result in the onward referral of patients to specialist medical centers with experience in managing lipodystrophy; (2) the impact of lipodystrophy on patient quality of life (QoL); (3) the use of standard therapies and leptin replacement therapy (metreleptin) in lipodystrophy, and (4) barriers to metreleptin use.ResultsParticipants reported that, due to their rarity and phenotypic heterogeneity, lipodystrophy cases are frequently unrecognized, leading to delays in diagnosis and medical intervention. Early consultation with multidisciplinary specialist medical teams was recommended for suspected lipodystrophy cases. The development and progression of metabolic complications were identified as key triggers for the referral of patients to specialist centers for follow-up care. Participants emphasized the impact of lipodystrophy on patient QoL, including effects on mental health and self-image. Although participants routinely used standard medical therapies to treat specific metabolic complications associated with lipodystrophy, it was acknowledged that metreleptin was typically required in patients with congenital generalized lipodystrophy and in some acquired generalized and partial lipodystrophy cases. A lack of experience among some participants and restrictions to access remained as barriers to metreleptin use.ConclusionsTo our knowledge, this is one of the first studies describing the qualitative experiences of physicians regarding the diagnosis and management of lipodystrophy. Other physician-centered studies may help increase the awareness of lipodystrophy among the wider medical community and support clinical approaches to this rare disease.

Premenopausal bilateral oophorectomy and brain white matter brain integrity in later-life.

Premenopausal bilateral oophorectomy (PBO) is associated with later-life cognition, but the underlying brain changes remain unclear. We assessed the impact of PBO and PBO age on white matter integrity. Female participants with regional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity (MD) were included (22 with PBO<40 years; 43 with PBO 40-45 years; 39 with PBO 46-49 years; 907 referents without PBO<50 years). Linear regression models adjusted for age and apolipoprotein E (APOE) genotype. Females with PBO<40 years, compared to referents, had lower FA and higher MD in the anterior corona radiata, genu of the corpus collosum, inferior fronto-occipital fasciculus, superior occipital, and superior temporal white matter. Females who underwent PBO between 45 and 49 also had some changes in white matter integrity. Females who underwent PBO<40 years had reduced white matter integrity across multiple regions in later-life. These results are important for females considering PBO for noncancerous conditions. Females with premenopausal bilateral oophorectomy (PBO)<40 years had lower FA versus referents. Females with PBO<40 years had higher MD in many regions versus referents. Adjusting for estrogen replacement therapy use did not attenuate results. Females with PBO 45-49 years also had some white matter changes versus referents.

Management of male obesity-related secondary hypogonadism: A clinical update.

The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism (MOSH) with emerging evidence on the role of testosterone therapy. We aim to provide an updated and practical approach towards its management. We did a comprehensive literature search across MEDLINE (via PubMed), Scopus, and Google Scholar databases using the keywords "MOSH" OR "Obesity-related hypogonadism" OR "Testosterone replacement therapy" OR "Selective estrogen receptor modulator" OR "SERM" OR "Guidelines on male hypogonadism" as well as a manual search of references within the articles. A narrative review based on available evidence, recommendations and their practical implications was done. Although weight loss is the ideal therapeutic strategy for patients with MOSH, achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world practice. Therefore, androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to obesity. However, there is conflicting evidence for the appropriate use of testosterone replacement therapy (TRT), and it can also be associated with complications. This evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with MOSH. Before starting testosterone replacement in functional hypogonadism of obesity, it would be desirable to initiate lifestyle modification to ensure weight reduction. TRT should be coupled with the management of other comorbidities related to obesity in MOSH patients. Balancing the risks and benefits of TRT should be considered in every patient before and during long-term management.

Clinical Characteristics and Prognosis of Older Patients with Coronavirus Disease 2019 Requiring Mechanical Ventilation.

An older age is associated with severe progression and poor prognosis in coronavirus disease 2019 (COVID-19), and mechanical ventilation is often required. The specific characteristics of older patients undergoing mechanical ventilation and their prognostic factors are largely unknown. We aimed to identify potential prognostic factors in this group to inform treatment decisions. This retrospective cohort study collected data from patients with COVID-19 at 22 medical centers. Univariate and multivariate Cox regression analyses were performed to assess factors that influence mortality. We allocated 434 patients in geriatric (≥80 years) and elderly (65-79 years) groups. The former group scored significantly higher than the elderly group in the clinical frailty scale and sequential organ failure assessment, indicating more severe organ dysfunction. Significantly lower administration rates of tocilizumab and extracorporeal membrane oxygenation and higher intensive care unit (ICU) and in-hospital mortality were noted in the geriatric group. The factors associated with ICU and in-hospital mortality included high creatinine levels, the use of continuous renal replacement therapy, prone positioning, and the administration of life-sustaining treatments. These results highlight significant age-related differences in the management and prognosis of critically ill older patients with COVID-19. Increased mortality rates and organ dysfunction in geriatric patients undergoing mechanical ventilation necessitate age-appropriate treatment strategies to improve their prognoses.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant.

With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed. Exclusion criteria included patients who were not solid organ donors, patients who were not declared brain dead (donation after circulatory death), and patients who did not receive steroids in their hospital course. Levothyroxine and steroid administration, the number of organs donated, the types of organs donated, and demographic information were recorded. Univariate analyses were performed with P < 0.05 considered to be statistically significant. A total of 88 patients met inclusion criteria, 69 (78%) of whom received levothyroxine and steroids (ST/LT group) vs 19 (22%) receiving steroids without levothyroxine (ST group). No differences were observed between the groups for gender, race, pertinent injury factors, age, or other hormone therapies used (P > 0.05). In the ST/LT group, 68.1% (n = 47) donated a high yield (3-5) of organ types per donor compared to 42.1% (n = 8) in the ST group (P = 0.038). There was no difference in the total number of organ types donated between the groups (P = 0.068). This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population. Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria. This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Hormone replacement therapy and myocardial infarction and stroke in postmenopausal Korean women

Objective This study aimed to investigate the association of hormone replacement therapy (HRT) use, type, duration and age of commencement with myocardial infarction (MI) and stroke in postmenopausal Korean women. Methods This nested case–control study used data from the National Health Insurance Service database to analyze 2017 data from women aged ≥50 years and diagnosed with natural menopause between 2004 and 2007. Among 356,160 eligible women, 36,446 used HRT for ≥1 year and 319,714 did not (controls). These two groups were matched 1:1 for statistical analysis. Type and duration were categorized into three categories. Results Women who started estrogen–progestogen therapy (EPT) or estrogen therapy (ET) in their 50s, or EPT or tibolone in their ≥60s exhibited a lower stroke risk than controls. MI risk was lower among women who used tibolone – regardless of duration – or EPT or ET for 1–3 years than among controls. Stroke risk was lower with tibolone use for ≥5 years or with EPT or ET use for 1–3 years or ≥5 years than non-users. Conclusion Our study may support the beneficial effect of HRT by showing that Korean postmenopausal women who used HRT at a relatively younger and healthier age had a relative benefit for MI and stroke.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction

ImportanceSodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown.ObjectiveTo determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023.InterventionParticipants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first.Main Outcomes and MeasuresThe primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support–free days, ICU, and hospital stay, assessed using bayesian regression models.ResultsAmong 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group.Conclusion and RelevanceThe addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin.Trial RegistrationClinicalTrials.gov Identifier: NCT05558098

Management of menopause in women with a history of endometriosis.

Due to increasing life expectancy, women spend a significant part of their lives in menopause. Women with a history of endometriosis are more likely to become menopausal at an early age due to bilateral oophorectomy or repeated ovarian surgery. In addition, some medical therapies used for endometriosis, such as gonadotropin releasing hormone agonists or progestins reduce bone mineral density. Furthermore, women with endometriosis have a higher background risk of cardiovascular disorders and hypercholesterolemia. Hence, it is important to recommend the use of hormone replacement therapy (HRT) to these women when they become menopausal, at least until the age of natural menopause. Although based on limited data, there is a possibility of reactivation of symptoms of endometriosis or its lesions, and a theoretical possibility of malignant transformation, although this remains unproven. Therefore, women should be advised in the light of this information before starting HRT after the age of natural menopause and are asked to seek help if they experience symptoms that may indicate these changes. Estrogen only HRT should be avoided and combined HRT preparations should be recommended, even after a hysterectomy.

Foramen magnum stenosis in patients with mucopolysaccharidoses: diagnosis and surgical treatment. Review of literature

Cervico-medullary compression and atlantoaxial dislocation syndromes are the dominant clinical manifestations of mucopolysaccharidoses at the craniovertebral level. The review provides an analysis of international literary sources concerning modern aspects of diagnosis and neurosurgical correction of the foramen magnum stenosis in patients with different types of mucopolysaccharidoses. The existing surgical approaches to determining the indications and choosing the method of surgical treatment and some aspects of the use of enzyme replacement therapy and hematopoietic stem cell transplantation are presented. A variety of options for surgical correction of pathology at the craniovertebral level have been demonstrated in patients with different types of mucopolysaccharidosis, however the described recommendations can be considered from the point of view of traditions of the hospitals or personal experience of surgeons, but not as recognized standards of treatment this pathology. Further accumulation of individual observations or clinical series is required to conduct a comparative analysis of the effectiveness of various approaches on a sufficiently large and homogeneous material to determine standards for the diagnosis and treatment of craniovertebral junction pathology in patients with mucopolysaccharidoses.

Exploring intensivist involvement: Patient characteristics, interventions and outcomes.

Intensivists play a critical role in the management of intensive care units (ICUs) and in providing high quality care. While international guidelines recommend intensivist staffing for improved patient outcomes, there is a shortage of qualified intensivists in many regions, including Türkiye. This study aimed to assess the impact of introducing a full-time intensivist to a medical ICU on patient characteristics, outcomes, and ICU interventions. This retrospective study analyzed data from the Internal Medicine ICU at Van Yüzüncü Yıl University Dursun Odabaş Medical Center over two periods: Pre- and post-intensivist recruitment. The study included adult patients admitted to the ICU from February 2018 to January 2020. Patient demographics, reasons for ICU admission, APACHE-II and SOFA scores, ICU interventions, and outcomes were recorded and compared between the two periods. Of the 868 patients admitted during the study period, 820 were included in the analysis. There were no significant differences in demographic characteristics between the pre- and post-intensivist periods. However, patients in the post-intensivist period had higher APACHE-II and SOFA scores. Intensive care units mortality rates were comparable between the two periods. The post-intensivist period saw increased use of invasive mechanical ventilation and non-invasive ventilation compared to the pre-intensivist period. Renal replacement therapy usage and enteral nutrition provision also increased in the post-intensivist period. ICU and hospital lengths of stay remained similar between the two periods. The introduction of a full-time intensivist to the medical ICU led to changes in ICU interventions, including increased use of mechanical ventilation and renal replacement therapy. Despite these changes, ICU mortality rates remained unchanged. Further research is needed to explore the longterm impact of intensivist staffing on patient outcomes in Türkiye.

Joint effects about antibiotics combined using with antibiotics or phytochemicals on Aeromonas hydrophila

Aeromonas hydrophila is highly prevalent in aquaculture animals and aquaculture environment. Due to the abuse of antibiotics, A. hydrophila can change the antibiotic resistance spectrum directly and affect human health indirectly. The use of combined drugs replacement therapy and the long-term coexistence with drug-resistant bacteria are the reality that human beings have to face in dealing with the problem of antibiotic resistance in the future. This study showed the characteristics and trends through abundant results of combined effects related with the combinations of antibiotic and the combinations of antibiotic and phytochemical on A. hydrophila, and revealed the antagonism probability of combinations of antibiotic and phytochemical is significantly higher than that of the combinations of antibiotic. Meanwhile, the combinations of antibiotic and phytochemical could protect the host cells which also achieved the same effectiveness as combination of antibiotics, and the enrichment pathway was proved to be relatively discrete. In addition, the possible mechanism about the reverse “U" shape of the combined effect curve on wild/antibiotic-resistant bacteria was clarified, and it was confirmed that the antagonism for the combinations of antibiotic and phytochemical might has the significance in inhibiting the evolution of bacterial resistance mutations. This study was aims to provide theoretical basis and some clues for the antibiotic resistance control associated with A. hydrophila.

High estrogen induces trans-differentiation of vascular smooth muscle cells to a macrophage-like phenotype resulting in aortic inflammation via inhibiting VHL/HIF1a/KLF4 axis.

Estrogen is thought to have a role in slowing down aging and protecting cardiovascular and cognitive function. However, high doses of estrogen are still positively associated with autoimmune diseases and tumors with systemic inflammation. First, we administered exogenous estrogen to female mice for three consecutive months and found that the aorta of mice on estrogen develops inflammatory manifestations similar to Takayasu arteritis (TAK). Then, in vitro estrogen intervention was performed on mouse aortic vascular smooth muscle cells (MOVAS cells). Stimulated by high concentrations of estradiol, MOVAS cells showed decreased expression of contractile phenotypic markers and increased expression of macrophage-like phenotypic markers. This shift was blocked by tamoxifen and Krüppel-like factor 4 (KLF4) inhibitors and enhanced by Von Hippel-Lindau (VHL)/hypoxia-inducible factor-1α (HIF-1α) interaction inhibitors. It suggests that estrogen-targeted regulation of the VHL/HIF-1α/KLF4 axis induces phenotypic transformation of vascular smooth muscle cells (VSMC). In addition, estrogen-regulated phenotypic conversion of VSMC to macrophages is a key mechanism of estrogen-induced vascular inflammation, which justifies the risk of clinical use of estrogen replacement therapy.

Bridging Gaps: Analyzing Breast Imaging-Reporting and Data System (BI-RADS) 0 Rates and Associated Risk Factors in Disproportionally Affected Communities.

Introduction Disparities in access to breast cancer screening led to the creation of the Linda Fenner 3D Mobile Mammography Center (LFMMC), successfully increasing screening for uninsured women in Miami-Dade. However, a higher-than-expected rate of inconclusive mammograms (Breast Imaging-Reporting and Data System(BI-RADS) 0) was found, which could lead to unnecessary procedures, stress, costs, and radiation. Methods In this retrospective cross-sectional study, we analyzed data from 3,044 uninsured women aged over 40 (younger if positive family history of breast cancer) from Miami-Dade without breast symptoms or breast cancer history. Women's demographic characteristics, primary language spoken, body mass index (BMI), use of hormone replacement therapy and birth control, history of benign biopsy, breast surgery,family breast cancer, and menopausal status were assessed as potential risk factors for an inconclusive (BI-RADS 0) screening mammogram result. Multivariable logistic regression analyses were used to evaluate associations. Results The average age of women was 51 years (SD = 9); 59% were White, and 30% were African American. The overall frequency of BI-RADS 0 was 35%. Higher odds of BI-RADS 0 were found for women who were younger, single, premenopausal, and with benign biopsy history. Conversely, obesity and breast implant history decreased the odds of BI-RADS 0. Conclusion We found a high frequency of BI-RADS 0 in the LFMMC sample. Potential reasons include a higher risk for breast cancer or a younger sample of women screened. Future research should explore radiologists' reasoning for assigning BI-RADS 0 results and testing alternative screening strategies for younger women.

Patient-reported use of pancreatic enzyme replacement treatment (PERT) in pancreatic cancer in New Zealand and Australia: a cross-sectional survey study

PurposeThis study investigated pancreatic enzyme replacement therapy (PERT) use in people diagnosed with pancreatic cancer in New Zealand (NZ) and Australia (AU).MethodsA cross-sectional survey study was conducted using a mixed-media campaign to recruit people with pancreatic cancer and collect information about current PERT use. The questionnaire gathered data on participant demographics, awareness of PERT, prescribing practices and efficacy of enzyme replacement.ResultsOver 300 people with pancreatic cancer were recruited, 135 from New Zealand and 199 from Australia. Every region, state and territory was represented except for the West Coast (NZ) and the Northern Territory (AU), the lowest populated areas in both countries. In New Zealand, 60% of participants had heard about PERT, compared to 69.3% in Australia. Dosing regimens were inconsistent in both countries, with 18% and 27% of participants being prescribed PERT considered best practice in New Zealand and Australia, respectively. Before PERT commencement, 70% of participants experienced symptoms of malabsorption, with all symptoms improving after therapy was established. The majority of participants were compliant with their medication.ConclusionPERT use in pancreatic cancer in New Zealand and Australia was highly variable and not compliant with international guidelines in which PERT is recommended as standard therapy. Enzyme replacement is effective for improving the symptoms of malabsorption in patients with pancreatic cancer. Clinician education may be needed to help improve the use of PERT in people with pancreatic cancer.