Subtypes of Histopathologically Classical Aldosterone-Producing Adenomas Yield Various Transcriptomic Signaling and Outcomes

Author(s):  
Vin-Cent Wu ◽  
Kang-Yung Peng ◽  
Yu-Ping Kuo ◽  
Hsuan Liu ◽  
Bertrand Chin-Ming Tan ◽  
...  

There have been no reports of outcome differences between distinctive subgroups in patients with unilateral primary aldosteronism with histopathologically classical adenomas. The characteristics and incidence of complete clinical success in the patients with unilateral primary aldosteronism could be associated with the concomitant existence of multiple aldosterone-producing micronodules/nodules. Altogether, 74 classical adenomas (mean, 52.9 years and 40 men [54.1%]) were identified among 98 operated patients with unilateral primary aldosteronism. Among them accompanying multiple aldosterone-producing micronodules/nodules (group A) were identified in 38 (51.3%) of the adrenal glands; these patients showed lower likelihood (42.1%) to achieve complete clinical success than that (80.6%) of those with aldosterone-producing adenoma/nodules alone (group B, P =0.001). Additionally, group A adenomas were associated with less complete clinical success (odds ratio, 5.53, P =0.005) in the multivariable regression analysis. Group A patients also had higher baseline aldosterone production (absolute aldosterone ratio) from the contralateral adrenal gland ( P =0.039). Based on the patterns of genes with highly differential expressions as uncovered by RNA-seq analysis, Group A adenomas showed distinct transcriptomic profiles in comparison to the gene expressions from Group B adenomas. Pathway enrichment analysis revealed that HTR2B-mediated calcium pathway, in terms of HTR2B , and PLCE1 was prominently downregulated in Group A adenomas. There was 51.3% of the patients with unilateral primary aldosteronism with classical group A adenomas. These patients were more likely to have hypertension-persistence after adrenalectomy. The functional signatures of Group A adenomas showed attenuated HTR2B-mediated PLC/IP3/Ca2 + pathway; this may provide some mechanistic explanation to various clinical outcomes.

2021 ◽  
Vol 09 (07) ◽  
pp. E1108-E1115
Author(s):  
Sudhir Maharshi ◽  
Shyam Sunder Sharma ◽  
Sandeep Ratra ◽  
Bharat Sapra ◽  
Dhruv Sharma

Abstract Background and study aims Walled-off necrosis (WON) is a known complication of acute necrotizing pancreatitis (ANP). There is no study comparing nasocystic irrigation with hydrogen peroxide (H2O2) versus biflanged metal stent (BMS) in the management of WON. The aim of this study was to compare the clinical efficacy of both the treatment strategies. Patients and methods This study was conducted on patients with symptomatic WON who were randomized to nasocystic irrigation with H2O2 (Group A) and BMS placement (Group B). Primary outcomes were clinical and technical success while secondary outcomes were procedure time, adverse events, need for additional procedures, duration of hospitalization, and mortality. Results Fifty patients were randomized into two groups. Group A (n = 25, age 37.8 ± 17.6 years, 16 men) and Group B (n = 25, age 41.8 ± 15.2 years, 17 men). There were no significant differences in baseline characteristics between the two groups. The most common etiology of pancreatitis was alcohol, observed in 27 (54 %) patients. Technical success (100 % vs 96 %, P = 0.98), clinical success (84 % vs 76 %, P = 0.76), requirement of additional procedures (16 % vs 24 %, P = 0.70) and adverse events (4 vs 7, P = 0.06) were comparable in both the groups. The duration to clinical success (34.4 ± 12 vs 14.8 ± 10.8 days, P = 0.001) and procedure time (36 ± 15 vs 18 ± 12 minutes, P = 0.01) were longer in Group A compared to Group B. Conclusions Nasocystic irrigation with H2O2 and BMS are equally effective in the management of WON but time to clinical success and procedure time is longer with nasocystic irrigation.


2021 ◽  
Vol 11 (7) ◽  
pp. 249-256
Author(s):  
Pradeep Krishna Reddy ◽  
Jayashree Dey ◽  
Yashodhara S Joshi

Background and Objective: In supraspinatus tendinitis there is inflammatory and or degenerative changes of tendon. This study was done to assess the effectiveness of ultrasound and cryokinetics versus ultrasound and soft tissue massage (deep friction massage) in patients with acute supraspinatus tendinitis. Method: All subjects were clinically diagnosed by orthopaedician and were screened as per the inclusion and exclusion criteria. 60 patients were randomly divided into 2 groups with n= 30 each group, Group A- received ultrasound therapy and cryokinetics, whereas Group B- received ultrasound therapy and soft tissue massage. The treatment was given 1 session/day, 6 days/week. The total treatment duration was for 2 weeks. Outcome Measures: Patients were evaluated on day 1, day 7 and day 14. All the patients were assessed for pain and shoulder functional scale by taking VAS and SPADI. Results: Both the groups showed statistically significant changes in pre and post values. However, Group B showed greater improvement from baseline to week 1 on VAS and SPADI. After analysis group B showed significance with P<0.001*. Conclusion: Ultrasound therapy with cryokinetics, and ultrasound therapy with soft tissue massage both were effective in reducing pain intensity and increasing the shoulder functional scale but ultrasound therapy with soft tissue massage showed superior hand over ultrasound therapy with cryokinetics. Key words: Acute Supraspinatus Tendinitis, Ultrasound Therapy, Cryokinetics, Soft Tissue Massage, Visual Analogue Scale, Shoulder Pain And Disability Index.


1997 ◽  
Vol 75 (12) ◽  
pp. 2073-2081 ◽  
Author(s):  
D. J. S. Barr ◽  
S. I. Warwick ◽  
N. L. Desaulniers

Isozyme-based genetic diversity, morphological characters, and growth rate at different temperatures were compared in a worldwide collection of 125 isolates presumed to be Pythium irregulare Buisman. The isozyme data was analysed with previously published data for Pythium ultimum Trow and Pythium sylvaticum Campbell & Hendrix. UPGMA cluster analysis yielded a dendrogram with four distinct groups: P. ultimum, P. sylvaticum, and two for P. irregulare. Putative P. irregulare isolates were separated into 33 multilocus genotypes defined by 11 isozyme loci: group A contained 116 isolates in 25 genotypes, and group B, 8 isolates in 7 genotypes. One genotype with a single isolate was determined as P. sylvaticum. Based on the isozyme analysis, group B was considered a distinct taxonomic entity from group A, but lacked any unique morphological character. There was a wide range in oogonium and oospore sizes among different isolates of P. irregulare, with those in group B generally being larger. Some isolates in group A had well developed oogonial spines, but others were essentially spineless, whereas all those in group B were spineless. Both groups A and B contained isolates with distinctly aplerotic oospores and others with essentially plerotic oospores. Antheridial number and shape were highly variable both within and among isolates in the two groups. Growth rate over a range of temperatures varied among isolates in both groups and was not a reliable taxonomic criterion. The irregular shape of oogonia and, when present, oogonial spines were the only reliable characters for distinguishing P. irregulare isolates from other taxa. Key words: taxonomy, Oomycetes, Pythiaceae, Pythium ultimum, Pythium sylvaticum.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Mohammed Elkassaby ◽  
Mahmoud Alawy ◽  
Mohamed Zaki Ali ◽  
Wael A. Tawfick ◽  
Sherif Sultan

We investigated the safety and efficacy of primary aorto-uni-iliac (AUI) endovascular aortic repair (EVAR) without fem-fem crossover in patients with abdominal aortic aneurysm (AAA) and concomitant aortoiliac occlusive disease. 537 EVARs were implemented between 2002 and 2015 in University Hospital Galway, a tertiary referral center for aortic surgery and EVAR. We executed a parallel observational comparative study between 34 patients with AUI with femorofemoral crossover (group A) and six patients treated with AUI but without the crossover (group B). Group B patients presented with infrarenal AAAs with associated total occlusion of one iliac axis and high comorbidities. Technical success was 97% (n=33) in group A and 85% (n=5) in group B (P=0.31). Primary and assisted clinical success at 24 months were 88% (n=30) and 12% (n=4), respectively, in group A, and 85% (n=5) and 15% (n=1), respectively, in group B (P=0.125). Reintervention rate was 10% (n=3) in group A and 0% in group B (P=0.084). No incidence of postoperative critical lower limb ischemia or amputations occurred in the follow-up period. AUI without crossover bypass is a viable option in selected cases.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3609-3609 ◽  
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Efstathios Kastritis ◽  
Christina Bamia ◽  
Ioannis Melakopoulos ◽  
Dimitra Gika ◽  
...  

Abstract Background. Bisphosphonates are widely used in the treatment of MM. ONJ can occur during treatment with bisphosphonates. We have shown that use of ZA and longer exposure are associated with higher frequency of ONJ in a series of patients with both MM and solid tumors. Dental problems or interventions are precipitating factors of ONJ. For this reason, since 2003, we have implemented assessment (and management if necessary) of all patients who are candidates for ZA or who are on treatment with ZA and have dental problems by specialists with particular experience on ONJ. In addition, we recommend improved oral hygiene and we avoid dental procedures during treatment with ZA. We have investigated whether the occurrence of ONJ decreased after the implementation of these measures. Patients and Methods. According to the policy of our center, all patients with MM who demonstrate lytic lesions or osteopenia receive ZA 4 mg i.v. every 4 weeks indefinitely. In our current analysis we included patients who received only ZA wheras patients who initially received pamidronate and were later switched to ZA were excluded. Patients were stratified into two groups depending on the date of initiation of treatment in relation to the start of implementation of the preventive measures (Group A: 26/8/1998–31/12/2002, Group B: 1/1/2003–1/12/2006). Occurrence of ONJ was studied as row percentages as well as incidence rate rates (IR: number of cases of osteonecrosis /person-months). The proportions of patients with ONJ between the two groups were compared with the Fisher’s exact test whereas the respective incidence rates were compared with the score test. The 95% confidence interval of the incidence rate ratio was also estimated. Results. One hundred twenty-eight patients with MM were included in the analysis (Group A: 35, Group B: 93; M/F: 66/62). Overall there were 10 cases of ONJ (8%): 8 cases in Group A (23%) and 2 cases in Group B (2%) (p&lt;0.001). The IR was 0.560/100 person-month for Group A and 0.118/100 person-month for Group B. The IRR was Group A/Group B: 4.76 (p=0.029, 95% CI: 1.01–22.40). Median time of exposure among patients with ONJ was 31 months for Group A and 8 months for Group B (p=0.044). Conclusions. The implementation of detailed assessment by experienced specialists of patients with MM and dental problems and the avoidance of dental procedures during treatment with ZA results in a significant 5-fold reduction of ONJ. Our data provide a basis for a safer use of ZA in MM.


2020 ◽  
Vol 25 (2) ◽  
pp. 116-124
Author(s):  
Uzzal Chandra Ghosh ◽  
Md Abu Yusuf Fakir ◽  
Husne Qumer Osmany ◽  
Dipankar Lodh ◽  
Md Zahirul Islam ◽  
...  

Background: Diabetes mellitus (DM) is a chronic systemic disease characterized by hyperglycemia due to absolute or relative deficiency of insulin and affects several systems including hearing. It was evidenced that hearing loss is twice as common in people with diabetes in comparison to other non-diabetic individuals. Although there is no epidemiological information are available in Bangladesh, but it can assume that the number would not be less. Methods: This study was a hospital based case-control study conducted at department of ENT & department of Endocrinology for 1.5 year following approval of the protocol. Total 110 people (55 cases and 55 controls) were selected and analysed in this study. All the patients were divided into two groups: Group A (all patients with Diabetes) and Group B (persons without diabetes). For analysis group A were considered as case and group B were as control. Written informed consent was taken from all case and control subjects. A detailed history taking including hearing loss, duration, onset, associated symptoms & diabetes duration, treatment were obtained from the subject. A detailed ENT examination including otoscopic examination and tuning fork test were also conducted for each patient. Moreover, audiometric assessment-PTA, blood investigation-RBS, HbA1C, & renal parameters like blood urea & serum creatinine were tested in each cases. Data analysis was done in the statistical program Statistical Package for Social Science (SPSS) version 16.0. Results: Out of total 55 patients in each group, mean age of Diabetic and non-diabetic were 46.78±8.02 SD and 46.72±8.09 SD (years) with slight female predominance (45.5% vs 54.5% in diabetic group and 49.1% vs 50.9% in non-diabetic group). Bangladesh J Otorhinolaryngol; October 2019; 25(2): 116-124


2021 ◽  
Vol 12 ◽  
pp. 383
Author(s):  
Igor Vilela Faquini ◽  
Ricardo Brandão Fonseca ◽  
Alyne Oliveira Correia ◽  
Auricelio Batista Cezar Junior ◽  
Eduardo Vieira De Carvalho Junior ◽  
...  

Background: Endoscopic third ventriculostomy (ETV) has been shown to be a sufficient alternative to shunts in surgical treatment of obstructive hydrocephalus. Long-term failure, age limitations, and outcome by cause are some of the issues debated in literature. The objective of this article is to analyze the clinical success and failure of ETV and its main complications. Methods: A total of 209 patients with hydrocephalus were submitted to ETV, including a mixed population of children and adults (from 0 to 59 years). Patients were divided into five groups: A – tumors, B – aqueductal stenosis, C – myelomeningocele, D – infection and hemorrhage, and E – arachnoid cyst. Variables were analyzed: age, ETV success rate, cerebrospinal fluid (CSF) fistula, mortality, and complications. Results: The two main causes of hydrocephalus were tumors (44.9%) and aqueductal stenosis (25.3%). The overall success rate was of 82.8%, and patients in Group E had the highest rate 90.9%. Group A had a success rate of 89.3%, and Group B had a rate of 88.6%. The ETV success rate was significantly higher in patients older than 1 year (P < 0.001); the former also had a lower risk of CSF fistula (P < 0.0001). The overall mortality rate was 2.8%. Conclusion: Better results were observed in the groups of patients with tumors, aqueductal stenosis, and arachnoid cysts, while those whose primary causes of hydrocephalus were myelomeningocele, infections, or bleeding had higher rates of failure after the procedure. This study demonstrated that age under 1 year and hydrocephalus caused by myelomeningocele, bleeding, and infection were considered independent risk factors of poor prognosis in ETV.


2021 ◽  
pp. 152660282110503
Author(s):  
Denise Michelle Daniëlle Özdemir-van Brunschot ◽  
Giovanni Battista Torsello ◽  
Giulia Bernardini ◽  
Sarah Litterscheid ◽  
Giovanni Federico Torsello ◽  
...  

Purpose: We hypothesized that extending the proximal landing zone with the chimney technique could be beneficial in patients with a hyperangulated proximal aortic neck, defined as more > 60 degrees. Material and Methods: We retrospectively analyzed the outcome of prospectively collected data of patients treated by endovascular aneurysm repair (EVAR) for infrarenal aortic aneurysm with a hyperangulated proximal aortic neck. In all, 104 out of 130 patients were treated without (Group A) and 24 with the chimney endovascular aortic repair (ChEVAR, Group B). Primary outcome was technical and clinical success according to the reporting standards of the Society of Vascular Surgery. Results: The use of the chimney technique was associated with a significantly longer operation duration (167 vs. 93 min, p < .001), longer fluoroscopy time (44 vs.30 min, p = < .001), and larger amount of contrast medium used (149 vs. 127 ml, p = .03) but did not significantly improve technical (79.2% vs. 87.7%) and clinical success (54.2% vs. 68.9%). Aneurysm-related mortality was higher in group B (8.3% vs. = 0%, p < .001). Type IA endoleak was high in both groups at completion angiography (11.3% in Group A vs. 12.5% in Group B) and at follow-up (10.4% in Group A vs. 4.5% in Group B) without significant difference between the groups. Conclusions: Our data did not show a benefit of the primary use of the chimney technique in patients with a hyperangulated and short neck, although more studies are required to support this conclusion. Other strategies or new technologies are required for improving EVAR results in aneurysm patients with severe angulated proximal and short neck.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1136
Author(s):  
Kaya E. Witte ◽  
Oliver Hertel ◽  
Beatrice A. Windmöller ◽  
Laureen P. Helweg ◽  
Anna L. Höving ◽  
...  

Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term “NF-kB binding” was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.


2012 ◽  
Vol 166 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Miroslav Solar ◽  
Eva Malirova ◽  
Marek Ballon ◽  
Radek Pelouch ◽  
Jiri Ceral

ObjectiveConfirmatory testing of suspected primary aldosteronism (PA) requires an extensive medication switch that can be difficult for patients with severe complicated hypertension and/or refractory hypokalemia. For this reason, we investigated the effect of chronic antihypertensive medication on confirmatory testing results. To allow the results to be interpreted, the reproducibility of confirmatory testing was also evaluated.Design and methodsThe study enrolled 114 individuals with suspected PA who underwent two confirmatory tests. The patients were divided into two groups. In Group A, both tests were performed on the guidelines-recommended therapy, i.e. not interfering with the renin–angiotensin–aldosterone system. In Group B, the first test was performed on chronic therapy with the exclusion of thiazides, loop diuretics, and aldosterone antagonists; and the second test was performed on guidelines-recommended therapy. Saline infusion, preceded by oral sodium loading, was used to suppress aldosterone secretion.ResultsAgreement in the interpretation of the two confirmatory tests was observed in 84 and 66% of patients in Groups A and B respectively. For all 20 individuals in Group A who ever had end-test serum aldosterone levels ≥240 pmol/l, aldosterone was concordantly nonsuppressible during the other test. Similarly, for all 16 individuals in Group B who had end-test serum aldosterone levels ≥240 pmol/l on modified chronic therapy, aldosterone remained nonsuppressible with guidelines-recommended therapy.ConclusionConfirmatory testing performed while the patient is on chronic therapy without diuretics and aldosterone antagonists can confirm the diagnosis of PA, provided serum aldosterone remains markedly elevated at the end of saline infusion.


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