Cystic Disease Research Articles

Social-environmental phenotypes of rapid cystic fibrosis lung disease progression in adolescents and young adults living in the United States

BackgroundCystic fibrosis (CF) is a genetic disease but is greatly impacted by non-genetic (social/environmental and stochastic) influences. Some people with CF experience rapid decline, a precipitous drop in lung function relative to patient- and/or center-level norms. Those who experience rapid decline in early adulthood, compared to adolescence, typically exhibit less severe clinical disease but greater loss of lung function. The extent to which timing and degree of rapid decline are informed by social and environmental determinants of health (geomarkers) is unknown. MethodsA longitudinal cohort study was performed (24,228 patients, aged 6–21 years) using the U.S. CF Foundation Patient Registry. Geomarkers at the ZIP Code Tabulation Area level measured air pollution/respiratory hazards, greenspace, crime, and socioeconomic deprivation. A composite score quantifying social-environmental adversity was created and used in covariate-adjusted functional principal component analysis, which was applied to cluster longitudinal lung function trajectories. ResultsSocial-environmental phenotyping yielded three primary phenotypes that corresponded to early, middle, and late timing of peak decline in lung function over age. Geographic differences were related to distinct cultural and socioeconomic regions. Extent of peak decline, estimated as forced expiratory volume in 1 s of % predicted/year, ranged from 2.8 to 4.1 % predicted/year depending on social-environmental adversity. Middle decliners with increased social-environmental adversity experienced rapid decline 14.2 months earlier than their counterparts with lower social-environmental adversity, while timing was similar within other phenotypes. Early and middle decliners experienced mortality peaks during early adolescence and adulthood, respectively. ConclusionWhile early decliners had the most severe CF lung disease, middle and late decliners lost more lung function. Higher social-environmental adversity associated with increased risk of rapid decline and mortality during young adulthood among middle decliners. This sub-phenotype may benefit from enhanced lung-function monitoring and personalized secondary environmental health interventions to mitigate chemical and non-chemical stressors.

An incidental diagnosis of an unusually located echinococcus alveolaris.

Hydatid cyst disease is a zoonotic infection caused by the genus Echinococcus. Hydatid cysts are usually located in the liver or lungs whereas the brain is an unusual location. A 45-year-old male patient was diagnosed with an intracranial mass suggesting a metastasis in the frontal region shown in the cranial computed tomography (CT) scan following a cranial trauma. The histological evaluation revealed an acellular laminated lesion surrounded with reactive changes, compatible with a cuticle. These findings were evaluated in favour of a hydatid cyst caused by Echinococcus multilocularis. Alveolar echinococcosis is a zoonotic disease caused by the genus Echinococcus multilocularis. Hydatid cyst is a common public health issue in the countries where livestock farming is common. Primary or metastatic tumours and abscesses should be considered in the differential diagnosis of hydatid cysts regardless of their location.

Moringa oleifera leaf meal supplementation improves nutrient digestibility, milk yield, and reproductive performances in dairy cows during early lactation.

The study aimed to evaluate the effects of Moringa oleifera leaf meal (MOLM) supplementation on nutrient utilization, milk yield, and reproductive performance of early lactating Sahiwal cows. Control cows (GC) received a basal diet, while the treatment cows (GM) were supplemented with concentrate comprising 12% MOLM. Ovarian activity and uterine involution were monitored by trans-rectal ultrasonography on the 21st, 28th, 35th, and 42nd days postpartum. The result indicated that MOLM-supplemented cows required fewer days (P ≤ 0.05) to complete uterine involution. As lactation progresses, there was a significant reduction (P ≤ 0.05) in the diameter of the cervix and uterine horns in GM than GC. There was a significant increase in the number of follicles on the 21st day and average milk yield in GM than GC. The incidence of endometritis and cystic ovarian disease was less in MOLM supplemented group. The use of MOLM in the diet reduced the total cost per cow per successful service. It is concluded that MOLM can be safely included at 12% in the diet of early lactating cows to modulate the reproductive performances of dairy cows. Dairy farmers can use moringa leaf meal to feed their dairy cows, which is cheaper and improves production and reproduction performance.

Cystic adventitial disease.

Cystic adventitial disease.

A case report of tubular apocrine adenoma of lower eyelid

Moll glands are sweat apocrine glands close to the eyelid margin. Tumors derived from Moll glands are rare, although Moll glands cysts are frequent. They originate from their glandular tissue or tubules. In this report we present a rare case of a lower eyelid skin tubular apocrine adenoma occurred in the right eye lower eyelid of a caucasian 45 year old woman. The lesion was nodular and dome shaped and its size was 1.5 × 3.5 × 2 mm. After a complete excision the lesion was analyzed by our pathology unit. Histologic sections were stained with haematoxylin and eosin, alcian blue, periodic acid-Schiff (PAS). Additionally, the following immunohistochemical markers were used: cytokeratin 7 (CK7), cytokeratin 8/18 (CK8/18), cytokeratin 20 (CK20), S-100 protein and gross cystic disease protein 15 (GCDFP-15) (4,5). The immunohistochemical and phenotypic features resulted suggest the diagnosis of lower eyelid tubular apocrine adenoma probably originated from Moll glands. These findings allowed us to diagnose a very rare and benign cutaneous lesion of eyelid skin.

Recessive Variants in NEK1 and NEK8 Are Associated with Cystic Kidney and Kidney Stone Disease

Recessive Variants in NEK1 and NEK8 Are Associated with Cystic Kidney and Kidney Stone Disease

Improving detection of cystic fibrosis related liver disease using liver fibrosis assessment tools

Background & aimsCystic Fibrosis related liver disease (CFLD) is the 3rd largest cause of death in Cystic Fibrosis (CF). As advances in pulmonary therapies have increased life-expectancy, CFLD has become more prevalent. Current guidelines may underdiagnose liver fibrosis, particularly in its early stages. Newer modalities for the assessment of fibrosis may provide a more accurate assessment. FibroScan is validated in assessing fibrosis for several aetiologies including alcohol and fatty liver, the CFLD cohort have an entirely different phenotype so the cut off values are not transferrable. We appraised fibrosis assessment tools to improve diagnosis of CFLD. MethodsA prospective cohort (n = 114) of patients from the Manchester Adult Cystic Fibrosis Centre, UK were identified at annual assessment. Demographic data including co-morbidity, CFTR genotyping, biochemistry and imaging were used alongside current guidelines to group into CFLD and CF without evidence of liver disease. All patients underwent liver stiffness measurement (LSM) and assessment of serum-based fibrosis biomarker panels. A new diagnostic criterion was created and validated in a second, independent cohort. Results12 of 114 patient classified as CFLD according to the European Cystic Fibrosis Society best practice guidelines. No specific risk factors for development of CFLD were identified. Liver enzymes were elevated in patients with CFLD. Serum biomarker panels did not improve diagnostic criteria. LSM accurately predicted CFLD. A new diagnostic criterion was proposed and validated in a separate cohort, accurately predicating CFLD in 10 of 32 patients (31 %). ConclusionWe present a cohort of patients with CF assessed for the presence of liver fibrosis using blood biomarkers and LSM based platforms. We propose a new, simplified diagnostic criteria, capable of accurately predicting liver disease in patients with CF.Clinical trials number: NCT04277819

Multiple Unilateral Subcapsular Cortical Hemorrhagic (MUCH) Cystic Disease of the Kidney: First Case in Brazil of a Possible New Clinical Entity of Unknown Etiology

Multiple Unilateral Subcapsular Cortical Hemorrhagic (MUCH) Cystic Disease of the Kidney: First Case in Brazil of a Possible New Clinical Entity of Unknown Etiology

Poplitea Artery Entrapment Syndrome

Popliteal artery entrapment syndrome (PAES) is a rare pathological compression of the popliteal artery, mostly unilateral. Its diagnosis is a challenge due to low recurrence and confusion with other injuries that affect the lower limb. Delay in its repair can cause arterial stenosis, emboli, aneurysm, inability to perform physical activities, thromboembolism and acute limb ischemia. Young men without comorbidities who may exercise regularly with intermittent claudication that affects their daily activities should draw attention to research and treatment of the syndrome. Investigation is extremely important to rule out differential diagnoses, such as chronic compartment syndrome, neurogenic claudication, peripheral atherosclerosis and cystic disease of the popliteal artery.

A Novel Kidney-Selective AMPK Activator Slows Renal Cystic Disease and Fibrosis in PKD Mice

A Novel Kidney-Selective AMPK Activator Slows Renal Cystic Disease and Fibrosis in PKD Mice

“Genotype-First” Approach to Analyzing the Diversity and Prevalence of Genes in a Cohort of Cystic Disease Patients

“Genotype-First” Approach to Analyzing the Diversity and Prevalence of Genes in a Cohort of Cystic Disease Patients

Pattern and Clinical Characteristics of Cystic Kidney Disease Patients in a Tertiary Centre, South-West Nigeria: A Retrospective Study

Background: Cystic kidney disease is a group of disorders that are characterized by the formation of cysts in the kidneys.It is a major cause of end-stage renal disease (ESRD) worldwide. Objectives: This study aimed to determine the pattern and clinical characteristics of patients with cystic kidney disease who presented at a tertiary hospital in South-West Nigeria. Methods and Materials: We reviewed the records of patients admitted with cystic kidney disease over an 8-year period at Ekiti State University Teaching Hospital. Data extracted included patients’ demographics, clinical presentations, and treatment outcomes. We compared the data between patients with ADPKD and other types of kidney cysts and summarised the treatment outcomes among the patients. Result: The prevalence of cystic kidney disease was 9.2% and the mean age of the patients was 52.87 years with a male predominance. The most common type of kidney cyst was simple renal cysts (53.2%), followed by ADPKD (40.4%). Incidental findings with no symptoms were the most common mode of presentation (61.7%), followed by abdominal pain (38.3%) and palpable abdominal swelling (36.2%). Nephrolithiasis was documented in 4.3% while the frequency of hypertension, haematuria and urinary tract infection was 55.3%, 14.9% and 8.5 %respectively. More than one in five ADPKD patients (21.1%) developed end-stage renal disease. Overall, the majority 41(87.2%) were managed conservatively. Conclusion: This study contributes valuable insights into the pattern and clinical features of cystic kidney disease in SouthWest Nigeria, further enriching the existing data on this condition within the region.

A rare case of hydatid cyst disease in the adrenal gland

A rare case of hydatid cyst disease in the adrenal gland

CASE REPORT: A SUCCESSFUL TREATMENT STRATEGY FOR CYSTIC OVARIAN DISEASE IN A DAIRY COW

A 5-year-old multiparous lactating Holstein cow was reported to have cystic ovarian disease with a history of whitish vaginal discharge on the 80th day postpartum. On the 83rd day postpartum, transrectal ultrasonography revealed a thick-walled cystic structure with visible cobwebs in the cavity, measuring 4.2[Formula: see text]cm × 3.4[Formula: see text]cm in diameter on the right ovary. The serum progesterone (P4) concentration was 6.82[Formula: see text]ng/mL, leading to a diagnosis of luteinized follicular cyst. Transvaginal aspiration of the cyst was performed to decrease the compression of ovarian stroma by the cyst, followed by intramuscular administrations of cloprostenol and buserelin. A 1.9[Formula: see text]cm diameter corpus luteum was detected on the right ovary nine days after aspiration, with a serum P4 concentration of 1.29[Formula: see text]ng/mL. Continual hormone treatment was followed, consisting of an injection of buserelin and an intravaginal progesterone-releasing device inserted for seven days. After seven days, two corpora lutea were noted on the right ovary with an average diameter of 2.8[Formula: see text]cm and 1.8[Formula: see text]cm, respectively. The device was removed and the cow showed a P4 concentration of 11.22[Formula: see text]ng/mL on that day. Estrus induction was conducted with two low doses of cloprostenol followed by an injection of gonadorelin, to induce a complete luteolysis and the following ovulation to fit a fixed-timed artificial insemination (AI). Pregnancy was confirmed 33 days after AI. Although the number of days open was 102 in this case, it took a total of 19 days from treatment to pregnancy.

Comments and illustrations of the WFUMB CEUS liver guidelines: Cystic fibrosis associated liver disease.

In this series of articles with comments and illustrations on the World Federation for Medicine and Biology (WFUMB) guidelines on contrast-enhanced ultrasound (CEUS) the topics of very rare focal liver lesions (FLL) are discussed. Improving the detection and characterization of the most common FLL are the main topics of these guidelines. The focus of this review is on the many manifestations of cystic fibrosis-related liver disease (CFLD). These include focal biliary fibrosis, liver cirrhosis, vascular manifestations with nodular regenerative hyperplasia and portal hypertension with or without cirrhosis. This article describes the diverse changes of liver involvement in cystic fibrosis and their appearance on ultrasound, duplex sonography, and contrast enhanced ultrasonography. This knowledge and the imaging should help to recognize liver manifestations in time and enable a correct interpretation of ultrasound images in CF in the corresponding clinical situation.

State of the Science and Ethical Considerations for Preimplantation Genetic Testing for Monogenic Cystic Kidney Diseases and Ciliopathies.

There is a broad phenotypic spectrum of monogenic polycystic kidney diseases (PKDs). These disorders often involve cilia-related genes and lead to the development of fluid-filled cysts and eventual kidney function decline and failure. Preimplantation genetic testing for monogenic (PGT-M) disorders has moved into the clinical realm. It allows prospective parents to avoid passing on heritable diseases to their children, including monogenic PKD. The PGT-M process involves embryo generation through in vitro fertilization, with subsequent testing of embryos and selective transfer of those that do not harbor the specific disease-causing variant(s). There is a growing body of literature supporting the success of PGT-M for autosomal-dominant and autosomal-recessive PKD, although with important technical limitations in some cases. This technology can be applied to many other types of monogenic PKD and ciliopathies despite the lack of existing reports in the literature. PGT-M for monogenic PKD, like other forms of assisted reproductive technology, raises important ethical questions. When considering PGT-M for kidney diseases, as well as the potential to avoid disease in future generations, there are regulatory and ethical considerations. These include limited government regulation and unstandardized consent processes, potential technical errors, high cost and equity concerns, risks associated with pregnancy for mothers with kidney disease, and the impact on all involved in the process, including the children who were made possible with this technology.

Identification of genes in a genomic DNA sequence

Today, newer pyrosequencing methods have drastically cut the cost of sequencing and may eventually allow every person the possibility of personalized genome information. Being able to read how our genes are expressed offers the promise of advanced medical treatments, but it will certainly require considerable work to generate, understand, organize, and apply this massive amount of data to human disease. This study describes the results of the CFTR, MEFV, GALT, PAH, BCKDHB and DBT genes analysis of Azerbaijanian patients. The molecular diagnostics methods using specific primers to identify CFTR, MEFV, GALT, PAH, BCKDHB and DBT genes many mutations. A total 15 different mutations (R261Q, V245V, P281L, R241C, L385L, V399V, E280K, R261X, A434D, R176X, Ex6-96A> G, R241C, R243Q, R252Q, Y356X) and 2 different polymorphisms (Q232Q,V245V) were detected of the PAH gene. 4 different mutations (P325L, H132Q, Q334K, N314D ) were detected of the GALT gene, 6 different mutations (Phe508del, Phe508del/5T, R117H/R334W, R553X and 965 (T-C)) were found in the CFTR gene, polymorphisms (D102D, G138G, A165A, R202Q, R314R, G474G, G476G, D510D) were detected of the MEFV gene, 2 different mutations were found of the BCKDHB gene and one mutation detected of the DBT gene in patients from Azerbaijani population. To prophylaxis the phenylketonuria, galactosemia, maple syrup urine disease, cystic fibrosis disease and Fammilian Mediterranian Fever it is recommended to screen genetically newborns, to consult medical-genetically risky families, and to carry out prenatal diagnostics during pregnancies for those families.

Early onset Caroli’s disease with associated renal cystic disease presented with recurrent fever and epigastric pain: a case report

BackgroundCaroli’s disease is characterized by non-obstructive dilatation of intrahepatic biliary radicals with formation of calculi followed by recurrent episodes of cholangitis. It is a rare congenital malformation and often remains silent, diagnosed accidentally. But if kept unattended, and without any early intervention, it may lead to fatal residual complications. Hence, its early recognition is of utmost importance to prevent recurrent cholangitis, hepatic abscess, liver cirrhosis and cholangiocarcinoma. Hence, we feel that this case must be reported so as to increase awareness among physicians regarding this entity.Case presentationWe hereby report a case of 10-year-old boy who reported with complaints of recurrent episodes of fever, breathing difficulty and multiple episodes of epigastric abdominal pain with apparently healthy siblings. His routine investigation, laboratory parameters were within normal limits. Ultrasonography abdomen showed liver with normal echo-texture with varying sized multiple thin walled cysts involving both the lobes, right more than left with saccular dilatation of 2nd and 3rd order intra-hepatic biliary radicals without calcification without any colour flow on Doppler evaluation. The common hepatic and common bile ducts were normal in calibre and lumen. Magnetic resonance imaging abdomen had similar findings and upper GI endoscopy was also normal. He was finally diagnosed to be a case of Caroli’s disease and was managed with broad spectrum antibiotics, ursodeoxycholic acid, multivitamins, and calcium supplements. He made an uneventful recovery thereafter. Parents were counselled about the risk of cholangitis and cholangiocarcinoma and was referred to tertiary care centre for genetic counselling and for future need of liver transplantation.ConclusionAge presentation of Caroli’s disease varies. Majority present during adolescence and early adulthood. This often poses a diagnostic challenge owing its rare entity and silent presentation. A strong index of suspicion and prompt diagnosis is warranted to prevent its fatal residual complications.

Short salsalate administration affects cell proliferation, metabolism, and inflammation in polycystic kidney disease

Metabolic reprogramming is a driver of autosomal dominant polycystic kidney disease (ADPKD) progression and a potential therapeutic intervention route. We showed before that the AMP-associated protein kinase (AMPK) activator salsalate attenuates cystic disease progression. Here, we aim to study the early, direct effects of short salsalate treatment in adult-onset conditional Pkd1 deletion mice. Cystic mice were treated with salsalate for two weeks, after which NMR metabolomics and RNA sequencing analyses were performed. Pkd1 deletion resulted in clear metabolomic dysregulation. Short salsalate treatment has small, but significant, effects, reverting acetylcarnitine and phosphocholine concentrations back to wildtype levels, and showing associations with altered purine metabolism. RNA sequencing revealed that short salsalate treatment, next to restoring energy metabolism toward wildtype levels, also affects cell proliferation and inflammation, in PKD. We show that salsalate positively affects major dysregulated processes in ADPKD: energy metabolism, cell proliferation, and inflammation, providing more insights into its working mechanisms.

Cystic lung disease in adult Indigenous Australians in the Northern Territory of Australia.

Indigenous Australians have a high prevalence of chronic lung diseases. However, no previous studies have reported on cystic lung disease in an Indigenous patient cohort. This report describes 20 adult Indigenous patients noted to have incidental lung cysts on chest computed tomography (CT) while being referred to undergo lung function tests in the Northern Territory of Australia. Of the total 20 Indigenous patients demonstrating presence of pulmonary cysts on chest CT scan, 13/20 (65%) were males with a mean age of 49.9 years (range 24-74 years), with no significant difference in age between males and females. The majority reported a smoking history and spirometry demonstrated moderate reduction in lung function parameters. While there was no pattern in the size or location of cysts, most demonstrated multiple cysts (55% had ≥5 cysts) with bilateral involvement (65%), alongside a range of concurrent pulmonary radiological abnormalities. The aetiology for lung cysts was largely unknown. This is the first report to illustrate cystic lung disease within an Indigenous population. Further radiology studies are required to investigate the causes and prognostications of cystic lung disease in Indigenous patients.