Huge Bilateral Ovarian Cysts With Concurrent Hypothyroidism: A Case Report.

A 19-year-old girl with a short stature and presenting low intelligence quotient, illegible speech, and a greatly distended abdomen was seen at the gynecological outpatient department. She underwent investigation and was found to have large abdominopelvic multicystic ovaries with no malignant features and CA125 levels within the normal range for premenopausal women. Her thyroid-stimulating hormone (TSH) was markedly elevated. She received a diagnosis of untreated severe hypothyroidism with benign giant ovarian cysts, posing a grave risk of cyst rupture and imminent complications. The parents were counseled, and they accepted the risk, agreeing to conservative therapy. Levothyroxine replacement therapy was initiated, and after one month, her TSH levels normalized. Follow-up ultrasonography after one month of her therapy revealed a marked decrease in ovarian cyst size. Thyroid replacement therapy was continued, and at the end of three months, the cysts disappeared, and the ovaries, much smaller, showed polycystic ovarian morphology. Careful analysis of clinical signs, investigations, and appropriate therapy helped avoid unnecessary surgery.

Correlation between steroid receptor expression and response to progestational therapy in patients with atypical endometrial hyperplasia or cancer.

Background: Conservative management of atypical endometrial hyperplasia (AEH) or endometrial cancer (EMCA) often relies on the treatment of synthetic progestins, which show varied success and response rates. We evaluate the correlation between steroid receptor expression and response to progestin therapy in patients with AEH and EMCA. Methods: Retrospective cohort study collected data for patients with AEH or EMCA who had an endometrial sample after receiving conservative therapy utilizing either Megestrol acetate or Levonorgestrel Intrauterine device (IUD). Immunohistochemistry (IHC) was performed on pre- and post- treatment biopsy samples to assess androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) expression. IHC scores (1-12) were calculated based on staining intensity and percentage of positive cells. Results and analysis: We identified 15 patients with AEH and EMCA between 2015 and 2023 with the majority of African American ethnicity (53 %). Fourteen patients (93 %) received Megestrol acetate, and 1 patient received Levonorgestrel IUD alone. Three patients ultimately underwent hysterectomy. Seven (46.6 %) endometrial samples had strong positivity for AR, PR and ER expression on pre-treatment biopsies, and only 3 (20 %) of them maintained strong positivity for the 3 receptors in the post-treatment. Patients who successfully responded to the treatment demonstrated a significantly greater decrease in IHC scores after the treatment compared to those who did not respond (p = 0.009). Conclusion: Steroid receptor expression could be used as a possible biomarker for response to progestin therapy in patients undergoing conservative management for AEH and EMCA.

A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.

ABSTRACT: Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.

Signet cell rectal carcinoma with prostatic involvement detected by FAPI-04 PET-MRI fusion.

A 60-year-old male patient diagnosed with mucinous adenocarcinoma of lower third of rectum underwent abdominoperineal resection and permanent colostomy followed by adjuvant chemotherapy. Response evaluation with F-18 FDG PET-CT showed a complete metabolic response. After 6 months, CEA levels started increasing and clinically a recurrence was suspected. A restaging FDG PET-CT showed no obvious malignant disease. Patient presented again within a month with complaints of urinary retention and haematuria. CEA levels were further elevated, and Ga-68 FAPI-04 (FAPI) PET-CT was performed. FAPI PET-CT revealed prostatic and seminal vesicle disease involvement. Additionally, an MRI of pelvis was done and fused with FAPI PET for confirmation of prostatic involvement.

Systemic Markers of Lung Function and Forced Expiratory Volume in 1 Second Decline across Diverse Cohorts.

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airway obstruction and accelerated lung function decline. Our understanding of systemic protein biomarkers associated with COPD remains incomplete. Objectives: To determine what proteins and pathways are associated with impaired pulmonary function in a diverse population. Methods: We studied 6,722 participants across six cohort studies with both aptamer-based proteomic and spirometry data (4,566 predominantly White participants in a discovery analysis and 2,156 African American cohort participants in a validation). In linear regression models, we examined protein associations with baseline forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC). In linear mixed effects models, we investigated the associations of baseline protein levels with rate of FEV1 decline (ml/yr) in 2,777 participants with up to 7 years of follow-up spirometry. Results: We identified 254 proteins associated with FEV1 in our discovery analyses, with 80 proteins validated in the Jackson Heart Study. Novel validated protein associations include kallistatin serine protease inhibitor, growth differentiation factor 2, and tumor necrosis factor-like weak inducer of apoptosis (discovery ß = 0.0561, Q = 4.05 × 10-10; ß = 0.0421, Q = 1.12 × 10-3; and ß = 0.0358, Q = 1.67 × 10-3, respectively). In longitudinal analyses within cohorts with follow-up spirometry, we identified 15 proteins associated with FEV1 decline (Q < 0.05), including elafin leukocyte elastase inhibitor and mucin-associated TFF2 (trefoil factor 2; ß = -4.3 ml/yr, Q = 0.049; ß = -6.1 ml/yr, Q = 0.032, respectively). Pathways and processes highlighted by our study include aberrant extracellular matrix remodeling, enhanced innate immune response, dysregulation of angiogenesis, and coagulation. Conclusions: In this study, we identify and validate novel biomarkers and pathways associated with lung function traits in a racially diverse population. In addition, we identify novel protein markers associated with FEV1 decline. Several protein findings are supported by previously reported genetic signals, highlighting the plausibility of certain biologic pathways. These novel proteins might represent markers for risk stratification, as well as novel molecular targets for treatment of COPD.

A case report of conus intramedullary mansoni neuroschistosomiasis.

Background: Conus schistosomiasis is an extremely rare entity in which patients present with a wide range of neurological symptoms such as low back pain, paresthesia, fever, myalgia, paraparesis, and paraplegia. This neglected tropical parasitic disease causes significant neurological morbidity. The migration of parasitic worms and their eggs into the central nervous system can lead to profound and life-altering disabilities. Early, accurate diagnosis, and treatment can lead to the complete resolution of symptoms. Case Description: A 5-year-old boy from South Sudan presented with complaints of sudden onset, progressive bilateral lower limb weakness for the past month, inability to walk or stand without assistance, and urinary incontinence. Magnetic resonance imaging spine showed an irregular enhancing lesion within the conus. The various possibilities, such as Astrocytoma, and granulomatous disorders were considered. However, a biopsy revealed the lesion to be Conus schistosomiasis, a rare condition with only a few cases reported in children. Typical clinicoradiological presentation and the treatment paradigm have been discussed in this manuscript. Appropriate management of this lesion can avert surgical intervention needed for either a diagnosis or treatment. Conclusion: This case report aims to emphasize the importance of considering schistosomiasis as an important differential diagnosis of a conus intramedullary lesion, especially in patients from tropical endemic countries. The neurological recovery in this infestation is directly related to early diagnosis and treatment. Therefore, it is essential to recognize this entity, as early detection and management would result in significant neurological improvement without undergoing surgery.

Inhibition and eradication of Pseudomonas aeruginosa biofilms by secondary metabolites of Nocardiopsis lucentensis EMB25.

Millions of people worldwide have been impacted by biofilm-associated disorders, which are impregnable owing to frequent changes in surface antigens and gene expression. Globally, about 11% of nosocomial infections, including cystic fibrosis, chronic wound infections, and post-surgical infections, are caused by Pseudomonas aeruginosa, the most prevalent Gram-negative bacterial species. Moreover, biofilms are highly resistant to the host's immune system, and exhibit increased tolerance to stress factors such as starvation, dehydration, and antimicrobials. Here, we have isolated a rare halophilic actinobacteria, Nocardiopsis lucentensis EMB25, and utilized the secondary metabolites for inhibition and eradication of P. aeruginosa biofilm. For the first time, N. lucentensis EMB25 bacteria was explored to study the anti-effect of secondary metabolites on pre-established biofilm. The secondary metabolites targeted the quorum sensing pathway and were found to bind to LasR and RhlR, as confirmed via molecular docking. Also, the reduction in virulence factors, rhamnolipids and pyocyanin further supported the study as these two are regulated by LasR and RhlR. In addition, the downregulation of various QS system genes lasA, lasB, rhlA, rhlB, and pqsA confirmed that the secondary metabolites act on two main regulators of the quorum sensing pathway, LasR, and RhlR. The findings of this study support the bioprospecting of previously unknown and extreme-condition actinobacteria as a rich source of novel bioactives against infections caused by bacterial biofilms.

Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals.

Integrating genetic information with metabolomics has provided new insights into genes affecting human metabolism. However, gene-metabolite integration has been primarily studied in individuals of European Ancestry, limiting the opportunity to leverage genomic diversity for discovery. In addition, these analyses have principally involved known metabolites, with the majority of the profiled peaks left unannotated. Here, we perform a whole genome association study of 2,291 metabolite peaks (known and unknown features) in 2,466 Black individuals from the Jackson Heart Study. We identify 519 locus-metabolite associations for 427 metabolite peaks and validate our findings in two multi-ethnic cohorts. A significant proportion of these associations are in ancestry specific alleles including findings in APOE, TTR and CD36. We leverage tandem mass spectrometry to annotate unknown metabolites, providing new insight into hereditary diseases including transthyretin amyloidosis and sickle cell disease. Our integrative omics approach leverages genomic diversity to provide novel insights into diverse cardiometabolic diseases.

Prediction of Sentinel Lymph Node Biopsy Status in Breast Cancers with PET/CT Negative Axilla.

Background and Aim Prior knowledge of axillary node status can spare a lot of patients with early breast cancer morbidity due to an unnecessary axillary dissection. Our study compared various metabolic and pathological features that can predict the sentinel lymph node biopsy (SLNB) status in patients with positron emission tomography/computed tomography (PET/CT) negative axilla. Patients and Methods All consecutive patients with early breast cancers (< 5 cm) with PET/CT negative axilla who underwent breast surgery and SLNB from November 2016 to February 2020 were included. Various primary tumor (PT) pathological variables and metabolic variables on PET/CT such as maximum standardized uptake value (PT-SUV max ), metabolic tumor volume (PT-MTV), and total lesion glycolysis (PT-TLG) were compared using univariate and multivariate analyses for prediction of SLNB status. Results Overall 70 patients, all female, with mean age 55.6 years (range: 33-77) and mean tumor size 2.2 cm (range: 0.7-4.5), were included. SLNB was positive in 20% of patients ( n = 14) with nonsentinel nodes positive in 4% ( n = 3) patients. Comparing SLNB positive and negative groups, univariate analysis showed significant association of SLNB with low tumor grade, positive lymphovascular invasion (LVI), positive estrogen receptor (ER) status with lower mean K i -67 index (34.41 vs. 52.02%; p = 0.02), PT-SUV max (5.40 vs. 8.68; p = 0.036), PT-MTV (4.71 cc vs. 7.46 cc; p = 0.05), and PT-TLG (15.12 g/mL.cc vs. 37.10 g/mL.cc; p = 0.006). On multivariate analysis, only LVI status was a significant independent predictor of SLNB status (odds ratio = 6.23; 95% confidence interval: 1.15-33.6; p = 0.033). Conclusion SLNB is positive in approximately 20% of early breast cancers with PET/CT negative axilla and SLNB status appears to be independent of PT size. SLNB+ PTs were more likely to be LVI+ and ER + ve, with lower grade/K i -67/metabolic activity (SUV max /MTV/TLG) compared with SLNB-ve tumors. Logistic regression analysis revealed LVI status as the only significant independent predictor of sentinel lymph node status.

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10-9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes.

Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program.

While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p < 2.2 × 10-16 with portability gains ranging from 5% to 28%) for both dichotomous COPD traits and across all smoking strata. Our study demonstrates the value of PTRS for improved cross-ethnic portability compared to PRS in predicting COPD risk.

Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease.

BACKGROUND: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. METHODS: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). RESULTS: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10-11. These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, ß=0.61±0.05, P=3.27×10-30) and MMP-3 (ß=-0.60±0.05, P=1.67×10-32), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, ß=0.34±0.04, P=1.34×10-17) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. CONCLUSIONS: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Association of clonal hematopoiesis with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, -5.7%; adjusted 95% CI, -8.8% to -2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.

A Model of Minor Histocompatibility Antigens in Allogeneic Hematopoietic Cell Transplantation.

Minor histocompatibility antigens (mHAg) composed of peptides presented by HLA molecules can cause immune responses involved in graft-versus-host disease (GVHD) and graft-versus-leukemia effects after allogeneic hematopoietic cell transplantation (HCT). The current study was designed to identify individual graft-versus-host genomic mismatches associated with altered risks of acute or chronic GVHD or relapse after HCT between HLA-genotypically identical siblings. Our results demonstrate that in allogeneic HCT between a pair of HLA-identical siblings, a mHAg manifests as a set of peptides originating from annotated proteins and non-annotated open reading frames, which i) are encoded by a group of highly associated recipient genomic mismatches, ii) bind to HLA allotypes in the recipient, and iii) evoke a donor immune response. Attribution of the immune response and consequent clinical outcomes to individual peptide components within this set will likely differ from patient to patient according to their HLA types.

Complete Pathological Response Noted in Explanted Liver After Y90-SIR-Spheres Therapy for Hepatocellular Carcinoma.

In the treatment of hepatocellular carcinoma, achieving complete pathological response (CPR) in explanted liver specimens following any locoregional treatments is associated with reduced recurrence rates and better posttransplant survival compared to the incomplete response. Here, we present the imaging findings of a patient who achieved CPR in the explanted liver following Y-90 SIR-Spheres® therapy.

Müllerianosis of the urinary bladder with unilateral complete renal agenesis: a rare coincidental finding causing delayed presentation.

Müllerianosis is a rare benign lesion of the urinary bladder, which is constituted by two or more of the Müllerian-duct-derived tissues. We report a 45-year-old perimenopausal multiparous woman presenting with occasional episodes of dysuria and lower abdominal discomfort of recent duration. Ultrasound examination revealed a well-defined lesion in urinary bladder and the absence of left kidney. Contrast-enhanced CT of the abdomen confirmed the findings. During diagnostic cystoscopy, haemorrhagic polypoidal lesions were noted in the left side of the posterolateral wall and dome of urinary bladder along with the absence of left ureteric orifice. Transurethral resection of the bladder lesions was done and histology examination confirmed the diagnosis of Müllerianosis. She was administered Luteinizing hormone-releasing hormone (LHRH) agonist monthly. At 1 year of follow-up, cystoscopy showed only scar tissue. The case was reported for the rarity of Müllerianosis noted in a patient with unilateral agenesis of kidney, a possible cause of delayed presentation.

Evaluation of Diagnostic Accuracy and Impact of Preoperative Positron Emission Tomography/Computed Tomography in the Management of Early Operable Breast Cancers.

AIM: Our aim of this study was to evaluate the diagnostic accuracy of staging positron emission tomography/computed tomography (PET/CT) in early breast cancers (EBCs) and to assess its impact on disease management. PATIENTS AND METHODS: We retrospectively reviewed preoperative PET/CT scans of patients from January 2015 to December 2018 with Stage I/II, clinically T1-T2 N0-N1 breast cancers. The diagnostic performance of PET/CT for nodal (N) and distant metastases (M), its correlation with patient/tumor-specific factors, and its impact on disease management were analyzed using histopathology/clinical follow-up as standards of reference. RESULTS: Of 158 patients evaluated, 14% of patients were Stage I (T1N0), 60% were Stage IIA (T1N1, T2N0), and 26% were Stage IIB (T2N1). Sensitivity, specificity, and the diagnostic accuracy of PET/CT for axillary staging were 76%, 97%, and 84% and for distant metastasis evaluation were 100%, 98%, and 99%, respectively. The diagnostic accuracy of PET/CT for axillary staging was lower for low-grade, T1 tumors, postmenopausal group, and luminal A pathological subtype (77%, 84%, 81%, and 73%, respectively) compared to high-grade, T2 tumors, premenopausal group, and nonluminal A subtype (88%, 88%, 94%, and 87%, respectively). Distant metastases were detected on PET/CT in overall 16% (n = 25) of the patients (9% in Stage IIA and 27% in Stage IIB). PET/CT also incidentally identified clinically occult internal mammary nodes in 5% (n = 8) and organ-confined synchronous second malignancies in 5% (n = 8) of the patients. CONCLUSION: Preoperative PET/CT should be considered in all EBCs> 2 cm as it upstages the disease and alters management in about 24% of these patients. Given its high specificity for axillary staging PET/CT, patients with PET-positive axilla can be subjected to axillary dissection and those with PET-negative axilla to sentinel lymph node biopsy. The yield and diagnostic accuracy of PET/CT is less for low-grade tumors <2 cm and with luminal A subtype.

Primary Retroperitoneal Transitional Cell Carcinoma Identified on 18F-Fludeoxyglucose Positron Emission Tomography/Computed Tomography: An Exceedingly Rare Radio-Pathological Entity.

We report here initial staging and follow-up imaging findings of a case of primary retroperitoneal transitional cell carcinoma, one of the rarest nonurological tumors of the retroperitoneal space, to highlight the importance of 18F-fludeoxyglucose positron emission tomography/computed tomography in this infrequently encountered pathology.

Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico.

BACKGROUND: In cystic fibrosis (CF), the spectrum and frequency of CFTR variants differ by geography and race/ethnicity. CFTR variants in White patients are well-described compared with Latino patients. No studies of CFTR variants have been done in patients with CF in the Dominican Republic or Puerto Rico. METHODS: CFTR was sequenced in 61 Dominican Republican patients and 21 Puerto Rican patients with CF and greater than ​​​​60 mmol/L sweat chloride. The spectrum of CFTR variants was identified and the proportion of patients with 0, 1, or 2 CFTR variants identified was determined. The functional effects of identified CFTR variants were investigated using clinical annotation databases and computational prediction tools. RESULTS: Our study found 10% of Dominican patients had two CFTR variants identified compared with 81% of Puerto Rican patients. No CFTR variants were identified in 69% of Dominican patients and 10% of Puerto Rican patients. In Dominican patients, there were 19 identified CFTR variants, accounting for 25 out of 122 disease alleles (20%). In Puerto Rican patients, there were 16 identified CFTR variants, accounting for 36 out of 42 disease alleles (86%) in Puerto Rican patients. Thirty CFTR variants were identified overall. The most frequent variants for Dominican patients were p.Phe508del and p.Ala559Thr and for Puerto Rican patients were p.Phe508del, p.Arg1066Cys, p.Arg334Trp, and p.I507del. CONCLUSIONS: In this first description of the CFTR variants in patients with CF from the Dominican Republic and Puerto Rico, there was a low detection rate of two CFTR variants after full sequencing with the majority of patients from the Dominican Republic without identified variants.