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IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world among patients undergoing renal biopsy. Approximately 30% of patients with IgAN develop end-stage kidney disease 20 years after renal biopsy. It is a glomerulopathy with a very broad clinical presentation, making it difficult to stratify and treat. IgAN is characterized by dysregulation of the immune system, which causes an abnormal synthesis of IgA1 that is deglycosylated causing its mesangial deposition. IgAN pathogenesis is incompletely understood; the current multi-hit hypothesis of IgAN pathogenesis does not explain the range of glomerular inflammation and renal injury associated with mesangial IgA deposition. Although associations between IgAN and glomerular and circulating markers of complement activation are established, the mechanism of complement activation and contribution to glomerular inflammation and injury are not defined. On the other hand, the renal-gut connection can also play an important role in the pathogenesis of IgAN with possible therapeutic implications. In order to standardize the histological findings, the Oxford Classification has allowed clarifying renal lesions that confer potential risk of progression. Currently, except for the blockade of the renin-angiotensin-aldosterone system, no other therapies are available in clinical setting for the treatment of IgAN, although the range of new drugs under investigation is extensive. The incorporation in the next trials of clinical parameters such as the amount of hematuria and histological lesions may allow more personalized therapeutic approaches. To summarize, in recent years, several important efforts have taken place in the understanding of IgAN, but still, further studies are warranted to elucidate the best therapeutic strategies according to the risk to improve the prognosis of this entity.
The development of a clinical guideline is a challenging process. National and international organizations have established a variety of approaches, grading systems, evaluation scales and voting modes, however a practical description which illustrates all steps from starting the initiative to publication and dissemination of the guideline is usually not provided. We describe a structured guideline procedure that can be adjusted to the requirements of other multinational guidelines.
Clinical scientists with experience of organizing and contributing to guidelines initiated this guideline project. A balance between scientific evidence and clinical experience was achieved by involving European specialist societies and physicians from 18 European countries. For persons contributing to the guideline process, different levels of involvement were defined. The tasks were assigned to different groups of persons, which formed scientific institutions.
We describe organizational structures and institutions, a stepwic guidelines by adjusting the acceptance criteria for statements and recommendations.
Area deprivation index (ADI) associates with prognosis in non-dialysis CKD. However, no study has evaluated this association in CKD patients under unrestricted nephrology care.
We performed a long-term prospective study to assess the role of deprivation in CKD progression and mortality in stage 1-4 CKD patients under regular nephrology care, living in Naples (Italy). We used ADI calculated at census block levels, standardized to mean values of whole population in Naples, and linked to patients by georeference method. After 12 months of "goal-oriented" nephrology treatment, we compared the risk of death or composite renal outcomes (end-stage kidney disease or doubling of serum creatinine) in the tertiles of standardized ADI. Estimated glomerular filtration rate (eGFR) decline was evaluated by mixed effects model for repeated eGFR measurements.
We enrolled 715 consecutive patients (age 64 ± 15 years; 59.1% males; eGFR 49 ± 22 mL/min/1.73 m2). Most (75.2%) were at the lowest national ADI quintile. At refer all-cause death due to an excess of non-CV mortality.
Circulating tumor cells (CTCs) have been identified and shown to have prognostic and predictive roles in several types of carcinoma. More recently, aneuploid CTCs have become subject of a growing interest, as aneuploidy is considered a hallmark of cancer often associated with poor prognosis. Here, we aimed to identify for the first time aneuploid CTCs in soft-tissue sarcoma (STS) patients and show supportive in silico evidence on the prognostic role of aneuploidy in mesenchymal cancers.
In our pilot study, we collected blood from 4 metastatic STS patients and 4 age- and sex-matched healthy controls. After sample processing, cells were cyto-centrifuged onto glass slides and FISH was performed using 5 probes. The in silico analysis was performed using data from The Cancer Genome Atlas cohort of STS patients, using the validated Aneuploidy Score. We divided the patients in two populations (aneuploidy-high, Ane-Hi, and aneuploidy-low, Ane-Lo) using the median value of the Aneuploidy Score as a cutoff. Kaplan-way. learn more We also showed that the Aneuploidy Score has a prognostic value both in terms of progression-free survival and overall survival in STS patients using The Cancer Genome Atlas data, regardless of the histology.Bats are nocturnal mammals known for their ability to echolocate, yet all bats can see, and most bats of the family Pteropodidae (fruit bats) do not echolocate - instead they rely mainly on vision and olfaction to forage. We investigated whether echolocating bats, given their limited reliance on vision, have poorer spatial resolving power (SRP) than pteropodids and whether tongue click echolocating fruit bats differ from non-echolocating fruit bats in terms of visual performance. We compared the number and distribution of retinal ganglion cells (RGCs) as well as the maximum anatomical SRP derived from these distributions in 4 species of bats Myotis daubentonii, a laryngeal echolocating bat from the family Vespertilionidae, Rousettus aegyptiacus, a tongue clicking echolocating bat from the family Pteropodidae, and Pteropus alecto and P. poliocephalus, 2 non-echolocating bats (also from the Pteropodidae). We find that all 3 pteropodids have a similar number (≈200,000 cells) and distribution of RGCs and a similar maximum SRP (≈4 cycles/degree). M. daubentonii has fewer (∼6,000 cells) and sparser RGCs than the pteropodids and thus a significantly lower SRP (0.6 cycles/degree). M. daubentonii also differs in terms of the distribution of RGCs by having a unique dorsal area of specialization in the retina. Our findings are consistent with the existing literature and suggest that M. daubentonii likely only uses vision for orientation, while for pteropodids vision is also important for foraging.
With the increasing number of cases of breast cancer every year, the exploration of novel biomarkers has drawn attention. miR-331 has been demonstrated to play a role in various cancers, but its role in breast cancer is still unknown.
In this study, we included 121 patients with breast cancer treated at Affiliated Hospital of Weifang Medical University. Breast cancer tissues and adjacent normal tissues were collected during the surgery. The expression of miR-331 in breast cancer tissues and cell lines was detected by qRT-PCR assay. Then, with the help of Kaplan-Meier survival and Cox regression analyses, the role of miR-331 in the prognosis of breast cancer was analyzed. Finally, the effect of miR-331 on cell proliferation, migration, and invasion was investigated with CCK-8 assay and transwell assay.
miR-331 was significantly upregulated in breast cancer tissues compared with normal tissues. The overexpression of miR-331 was associated with lymph node metastasis, TNM stage, and poor prognosis. From the results of Cox regression analyses, it was found that miR-331 served as an independent indicator in the prognosis of breast cancer. In addition, miR-331 was also found to be upregulated in breast cancer cells, which promoted cell proliferation, migration, and invasion of breast cancer.
As shown from our data, miR-331 may be a potential prognostic biomarker in breast cancer. Moreover, the development and progression of breast cancer may involve miR-331. These findings suggest a novel therapeutic target for the treatment of breast cancer.
As shown from our data, miR-331 may be a potential prognostic biomarker in breast cancer. Moreover, the development and progression of breast cancer may involve miR-331. These findings suggest a novel therapeutic target for the treatment of breast cancer.
Febrile neutropenia (FN) is a potentially life-threatening complication of systemic chemotherapy (CT) that often requires hospital admission. Delay in diagnosis and treatment are associated with higher morbidity and mortality.
We aimed to determine the factors that influence FN episodes outcomes in the emergency room (ER).
This was a retrospective study of all FN episodes (with a collected blood culture [BC]) that occurred between 2012 and 2016 at our institution. FN was defined as a temperature ≥38°C and an absolute neutrophil count (ANC) <1,000/μL, expected to decrease to <500/μL in the following week.
Between 2012 and 2016, there were 173 FN episodes in 153/1,947 patients treated with intravenous CT. Most of these episodes (n = 121, 70%) were diagnosed in the ER, 29 in the outpatient clinic, and 23 as inpatients. In the ER, the median time was 36 min from hospital nurse triage to medical observation, and 52 min from medical observation to complete blood count specimen collection. There was a positive BC in 33 FN episodes, 72% with Gram-negative bacteria. A total of 160 FN episodes led to hospital admission and 13 were treated as outpatients. Mortality associated with the FN episode was 15% and an ANC <100/μL was predictive of increased mortality.
This study confirms that FN is a serious and common complication of IV CT which must be diagnosed and treated promptly. Profound neutropenia was the only predictive factor of mortality.
This study confirms that FN is a serious and common complication of IV CT which must be diagnosed and treated promptly. Profound neutropenia was the only predictive factor of mortality.Brugada syndrome (BrS) is a known cause of sudden cardiac death (SCD) characterized by abnormal electrocardiograms and fatal arrhythmias. The variants in KCND3 encoding the KV4.3 potassium-channel (the α-subunit of the Ito) have seldom been reported in BrS. This study aimed to identify novel KCND3 variants associated with BrS and elucidate BrS pathogenesis. High-depth targeted sequencing was performed and the electrophysiological properties of the variants were detected by whole-cell patch-clamp methods in a cultured-cell expressing system. The transcriptional levels of KV4.3 in different genotypes were studied by real-time PCR. Western blot was used to assess channel protein expression. A novel KCND3heterozygous variant, c.1292G>A (Arg431His, R431H), was found in the proband. Whole-cell patch-clamp results revealed a gain-of-function phenotype in the variant, with peak Ito current density increased and faster recovery from inactivation. The expression of mutant Kv4.3 membrane protein increased and the cytoplasmic protein decreased, demonstrating that the membrane/cytoplasm ratio was significantly different.
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