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Journal of Reproductive Immunology Jun 2024Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin,...
Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin, has been implicated in the progression of preeclampsia (PE). This heterogeneous syndrome (defined by hypertension with or without proteinuria after 20 weeks of pregnancy) remains a major global health burden with long-term consequences for both mothers and child. Previously, we showed that in vivo systemic human (hsFLT1) overexpression led to reduced placental efficiency and PE-like syndrome in mice. Galectins (gal-1, -3 and -9) are critical determinants of vascular adaptation to pregnancy and dysregulation of the galectin-glycan circuits is associated with the development of this life-threatening disease. In this study, we assessed the galectin-glycan networks at the maternal-fetal interface associated with the hsFLT1-induced PE in mice. We observed an increase on the maternal gal-1 expression in the decidua and junctional zone layers of the placenta derived from hs FLT1 pregnancies. In contrast, placental gal-3 and gal-9 expression were not sensitive to the hsFLT1 overexpression. In addition, O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation were down-regulated in hsFLT1 placentas. Thus, the gal-1-glycan axis appear to play an important role counteracting the anti-angiogenic status caused by sFLT1, becoming critical for vascular adaptation at the maternal-fetal interface.
PubMed: 38908337
DOI: 10.1016/j.jri.2024.104284 -
BMC Cancer Jun 2024Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best...
PURPOSE
Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG.
METHODS
A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis.
RESULTS
The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction.
CONCLUSIONS
Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.
Topics: Humans; Temozolomide; Female; Male; Adult; Pyridines; Glioma; Adolescent; Retrospective Studies; Child; Brain Neoplasms; Young Adult; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Middle Aged; Treatment Outcome
PubMed: 38907215
DOI: 10.1186/s12885-024-12373-9 -
Endocrine Jun 2024Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in...
BACKGROUND
Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications.
METHODS
Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003-2004 and 2006-2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI]).
RESULT
In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150-4.114] and 1.335 [0.909-1.961]), incident (2.088 [1.185-3.680] and 1.753 [1.275-2.409]), and persistent proteinuria (1.314 [0.418-4.134] and 2.098 [1.274-3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082-2.051] and 1.164 [0.988-1.371]), incident (1.570 [1.161-2.123] and 1.291 [1.112-1.500]), and persistent proteinuria (2.309 [1.407-3.788] and 1.272 [0.945-1.712]).
CONCLUSION
Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria.
PubMed: 38907116
DOI: 10.1007/s12020-024-03928-8 -
Nefrologia Jun 2024There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the...
BACKGROUND
There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables.
MATERIAL AND METHODS
A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16-65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed.
RESULTS
Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ± 18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05).
CONCLUSIONS
C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS.
PubMed: 38906767
DOI: 10.1016/j.nefroe.2023.04.007 -
International Urology and Nephrology Jun 2024Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in...
BACKGROUND AND AIM
Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in clinical and outcome features of CD-associated IgA nephropathy (CD-IgAN) and primary IgA nephropathy (PIgAN).
METHODS
Clinical data of patients diagnosed with IgAN by kidney biopsy were collected in the Sixth Affiliated Hospital of Sun Yat-sen University from January 1st, 2016 to June 1st, 2023. 17 patients with CD-IgAN and 87 patients with PIgAN were enrolled in this retrospective study.
RESULTS
Compared with PIgAN patients, CD-IgAN patients had lower levels of urinary protein excretion (1.57 g per 24 h vs. 0.33 g per 24 h, p < 0.01), but higher levels of estimated glomerular filtration rate (77.63 ± 40.11 ml per min per 1.73m vs. 104.53 ± 32.97 ml per min per 1.73m, p = 0.008). From the point of renal pathology of PIgAN, patients with CD-IgAN had a less incidence of tubular atrophy or interstitial fibrosis (p = 0.001). CD-IgAN patients had a higher incidence of complete remission of proteinuria (45.8% vs. 81.8%, p = 0.031) or hematuria (10.4% vs. 45.4%, p = 0.019) than PIgAN patients after twelve-month treatments.
CONCLUSIONS
CD-IgAN manifests a milder progression of renal function than those PIgAN. After the treatment, proteinuria or hematuria are more prone to remit in patients with CD-IgAN.
PubMed: 38904865
DOI: 10.1007/s11255-024-04106-5 -
Current Aging Science 2024Sarcopenia is one of the most common geriatric syndromes in the elderly. It is defined as a decrease in muscle mass and function, and it can lead to physical disability,... (Review)
Review
Sarcopenia is one of the most common geriatric syndromes in the elderly. It is defined as a decrease in muscle mass and function, and it can lead to physical disability, falls, poor quality of life, impaired immune system, and death. It is known that, the frequency of sarcopenia increases in the kidney patient population compared to healthy individuals. Although it is known that kidney disease can lead to sarcopenia; our knowledge of whether sarcopenia causes kidney disease is limited. Prior studies have suggested that protein energy wasting may be a risk of de novo CKD. Proteinuria is an important manifestation of kidney disease and there is a relationship between sarcopenia and proteinuria in diabetes, geriatric population, kidney transplant, and nephrotic syndrome. Does proteinuria cause sarcopenia or ? Are they both the results of common mechanisms? This issue is not clearly known. In this review, we examined the relationship between sarcopenia and proteinuria in the light of other studies.
Topics: Humans; Sarcopenia; Proteinuria; Aged; Aging; Risk Factors; Muscle, Skeletal; Age Factors
PubMed: 38904152
DOI: 10.2174/0118746098232969231106091204 -
Frontiers in Medicine 2024Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD...
Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report.
PubMed: 38903807
DOI: 10.3389/fmed.2024.1383309 -
BMC Public Health Jun 2024Anaemia among preeclamptic (PE) women is a major undefined health issue in Bangladesh. This study explored the risk factors associated with anaemia and mapped the...
BACKGROUND
Anaemia among preeclamptic (PE) women is a major undefined health issue in Bangladesh. This study explored the risk factors associated with anaemia and mapped the regional influences to understand the geographical inequalities.
METHODS
Data from 180 respondents were prospectively collected from the Preeclampsia ward of Dhaka Medical College Hospital (DMCH), Bangladesh. Anaemia was defined as a blood haemoglobin level less than 11.0 g/dl. Preeclampsia was defined as systolic blood pressure (SBP) ≥ 140 mmHg and diastolic blood pressure (DBP) ≥ 90 mmHg with proteinuria. Factors associated with anaemia were explored using the chi-square test. Logistic regression (LR) was done to determine the level of association with the risk factors.
RESULTS
Among the participants, 28.9% were identified as having early onset and 71.1% reported late onset of PE. 38.9% of the subjects were non-anaemic, whereas mild, moderate, and severe anaemia was found among 38.3%, 17.8%, and 5% of patients respectively. The following factors were identified; including age range 25-34 (OR: 0.169, p < 0.05), a lower education level (OR: 3.106, p < 0.05), service-holder mothers (OR: 0.604, p < 0.05), pregnancy interval of less than 24 months (OR: 4.646, p < 0.05), and gestational diabetes mellitus (OR: 2.702, p < 0.05). Dhaka district (IR: 1.46), Narayanganj district (IR: 1.11), and Munshiganj district (IR: 0.96) had the highest incidence rates.
CONCLUSION
Determinants of anaemia must be considered with importance. In the future, periodic follow-ups of anaemia should be scheduled with a health care program and prevent maternal fatality and fetus morbidity in patients with PE.
Topics: Humans; Female; Bangladesh; Anemia; Pregnancy; Pre-Eclampsia; Adult; Cross-Sectional Studies; Risk Factors; Young Adult; Health Status Disparities; Socioeconomic Factors; Prospective Studies
PubMed: 38902634
DOI: 10.1186/s12889-024-18176-8 -
Nutrition & Diabetes Jun 2024Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and...
BACKGROUND
Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and immunomodulatory effects have not yet been fully elucidated.
METHODS
Six-week-old db/db mice were fed a diet containing 12.5% resistant starch or a control diet matched for equivalent regular starch for 10 weeks. db/m mice receiving the control diet were utilised as non-diabetic controls. Freshly collected kidneys were digested for flow cytometry analysis of immune cell populations. Kidney injury was determined by measuring albuminuria, histology, and immunohistochemistry. Portal vein plasma was collected for targeted analysis of microbially-derived metabolites. Intestinal histology and tight junction protein expression were assessed.
RESULTS
Resistant starch limited the development of albuminuria in db/db mice. Diabetic db/db mice displayed a decline in portal vein plasma levels of acetate, propionate, and butyrate, which was increased with resistant starch supplementation. Diabetic db/db mice receiving resistant starch had a microbially-derived metabolite profile similar to that of non-diabetic db/m mice. The intestinal permeability markers lipopolysaccharide and lipopolysaccharide binding protein were increased in db/db mice consuming the control diet, which was not seen in db/db mice receiving resistant starch supplementation. Diabetes was associated with an increase in the kidney neutrophil population, neutrophil activation, number of C5aR1+ neutrophils, and urinary complement C5a excretion, all of which were reduced with resistant starch. These pro-inflammatory changes appear independent of fibrotic changes in the kidney.
CONCLUSIONS
Resistant starch supplementation in diabetes promotes beneficial circulating microbially-derived metabolites and improves intestinal permeability, accompanied by a modulation in the inflammatory profile of the kidney including neutrophil infiltration, complement activation, and albuminuria. These findings indicate that resistant starch can regulate immune and inflammatory responses in the kidney and support the therapeutic potential of resistant starch supplementation in diabetes on kidney health.
Topics: Animals; Mice; Kidney; Albuminuria; Male; Neutrophil Infiltration; Diabetic Nephropathies; Resistant Starch; Gastrointestinal Microbiome; Starch; Diabetes Mellitus, Experimental; Mice, Inbred C57BL
PubMed: 38902253
DOI: 10.1038/s41387-024-00305-2 -
The British Journal of General Practice... Jun 2024In the UK, chronic kidney disease (CKD) is a prevalent, silent and strong predictor of cardiovascular disease. Identification of CKD is poor in primary care,...
BACKGROUND
In the UK, chronic kidney disease (CKD) is a prevalent, silent and strong predictor of cardiovascular disease. Identification of CKD is poor in primary care, particularly in minority ethnic and socio-economically deprived groups.
AIM
To investigate feasibility of remote ACR testing to improve the detection and management of CKD in underserved groups.
METHOD
13 591 tests were sent out across South East London. Individuals with diabetes and no ACR in the past year were offered a remote ACR test to complete at home with a smartphone using a validated app (Healthy.io). We extracted data on demographics, medical comorbidities and medication. Analyses (Stata) describe who completed the test.
RESULTS
Twenty-seven practices agreed to participate. Analyses of 6082 tests sent show the test completion rate was 46.8%. Adjusted odds ratios demonstrated that people were less likely to complete testing if over 70 years (OR 0.71, 95% CI 0.57 to 0.89) and over 80 (OR 0.43, CI 95% 0.33 to 0.56) compared to <40 years old; people from CORE20 groups (most deprived quintile) were also less likely to complete testing (OR 0.68, 95% CI 0.61 to 0.76) and those with missing data and those with no recorded healthcare interactions within the last 5 years were also less likely to complete testing.
DISCUSSION
Remote ACR testing presents an opportunity to diagnose early CKD but there is still inequity in who completes testing. Engagement with stakeholders is needed to explore innovative ways to implement remote ACR testing to achieve equitable CKD screening.
Topics: Humans; Renal Insufficiency, Chronic; Quality Improvement; Primary Health Care; Male; Female; Middle Aged; Aged; Adult; London; Feasibility Studies; Healthcare Disparities; Albuminuria; Aged, 80 and over
PubMed: 38902069
DOI: 10.3399/bjgp24X737997