Cytokeratin-18 is Elevated Prior to Conventional Measures of Liver Disease in Fontan-Associated Liver Disease.

The Fontan procedure is used to palliate complex forms of congenital heart disease. This results in adverse hepatic sequelae now known as Fontan-associated liver disease (FALD). Conventional laboratory measures of liver disease do not correlate well with FALD severity. Cytokeratin-18 (CK-18) is a measure of cell death and is sensitive in detecting other causes of liver disease. Our aim was to assess the use of a novel measure of liver disease, CK-18, in Fontan patients. This is a single-center, prospective, cross-sectional study of Fontan patients aged 8-21 years old. We performed ultrasound elastography, echocardiography, magnetic resonance imaging, and serum laboratory testing. Novel laboratory test CK-18 levels in Fontan subjects were compared to healthy age-matched controls. Thirteen Fontan patients were evaluated with a median age 15 years (10, 14), 4 Hypoplastic left heart syndrome, 11 were male, and 5 were symptomatic. Fontan patients had normal AST/ALT, but a significantly elevated liver stiffness by elastography (median 13.4 kPa). Hepatic stiffness by elastography was associated with diastolic-indexed (rho = 0.58, p = 0.04) ventricular volumes. Compared to 10 aged-matched controls, CK-18 was higher in the Fontan group-cleaved CK-18 protein (p < 0.01) and full CK-18 protein, (p = 0.02). CK-18 was positively associated with AST and ALT. Elevated CK-18 levels were found in Fontan patients compared to controls suggesting hepatic cell death even in these relatively healthy Fontan patients. CK-18 was elevated prior to changes in traditional testing. CK-18 may be a useful sensitive marker of liver disease in FALD.

Lifestyle interventions in pregnancy targeting GDM prevention: looking ahead to precision medicine.

Gestational diabetes mellitus (GDM) is the most prevalent pregnancy-related endocrinopathy, affecting up to 25% of pregnancies worldwide. Pregnant individuals who develop GDM have an increased risk of complications during pregnancy and birth, as well as future development of type 2 diabetes mellitus and CVD. This increased risk is subsequently passed along to the offspring, perpetuating a cycle of metabolic dysfunction across generations. GDM prevention strategies have had mixed results for many years, but more recent systematic reviews and meta-analyses have suggested potential new avenues of prevention. The objective of this review is to summarise the literature examining the efficacy of lifestyle interventions for the prevention of GDM and to uncover if specific individual-level characteristics influence this outcome. Based on the present literature, we determined that future trials should be designed to understand if initiation of lifestyle intervention in the preconception period is more effective to reduce GDM. Furthermore, trials initiated during pregnancy should be developed through the lens of precision prevention. That is, trials should tailor intervention approaches based on individual-level risk defined by the presence of modifiable and non-modifiable risk factors. Finally, future interventions might also benefit from just-in-time adaptive intervention designs, which allow for interventions to be modified in real-time based on objective assessments of an individual's response.

Assessment of Eating Behaviors and Perceptions of Time-Restricted Eating During Pregnancy.

BACKGROUND: The maternal metabolic milieu is challenged during pregnancy and may result in unwarranted metabolic complications. A time-restricted eating (TRE) pattern may optimize the metabolic response to pregnancy by improving glucose metabolism and reducing circulating glucose concentrations, as it does in nonpregnant individuals. OBJECTIVES: The objectives of this study were to 1) assess eating timing in pregnant women; 2) understand the perceptions of adopting a TRE pattern; 3) determine the barriers and support mechanisms for incorporating a TRE pattern; and 4) identify those most willing to adopt a TRE pattern during pregnancy. METHODS: This was a cross-sectional quantitative and quasi-qualitative online survey study for women who were pregnant at the time of study completion or had given birth in the prior 2 years. Group analyses were performed based off willingness to try a TRE pattern using chi-squared analyses, independent samples t-tests, or an analysis of variance. Three separate reviewers reviewed qualitative responses. RESULTS: A total of 431 women (BMI, 27.5 ± 0.3 kg/m2) completed the study. Of the participating women, 23.7% reported willingness to try a TRE pattern during pregnancy. Top barriers to adopting a TRE pattern during pregnancy were concerns for 1) safety; 2) nausea; and 3) hunger. The highest ranked support mechanisms were: 1) the ability to choose the eating window; 2) more frequent prenatal visits to ensure the health of the baby; and 3) receiving feedback from a dietician/nutritionist. Women who did not identify as White/Caucasian expressed a higher willingness to try a TRE pattern during pregnancy (P = 0.01). Women who were nulliparous expressed a higher willingness to try a TRE pattern (P = 0.05). DISCUSSION: TRE, an alternative dietary strategy shown to optimize metabolic control, may be effective to prevent and manage pregnancy-related metabolic impairments. To create an effective TRE intervention during pregnancy, the input of pregnant mothers is necessary to increase adherence and acceptability.

Marijuana in pediatric and adult congenital heart disease heart transplant listing: A survey of provider practices and attitudes.

Despite increasing legalization and use of marijuana, there is no consensus among pediatric heart transplant institutions or providers regarding users' eligibility for cardiac transplant. We sent a survey to pediatric and ACHD transplant providers (physicians, surgeons, transplant coordinators, and pharmacists) assessing their current institution's policies and their personal opinions about marijuana use in patients being considered for heart transplantation. Of the respondents, 84% practice in the United States and Canada. Most providers (80%) care for both pediatric and ACHD patients. Respondents included cardiologists (77%) and surgeons (11%), with the remaining being coordinators and pharmacists. Most providers (73%) reported their institution had no policy regarding marijuana use in heart transplant candidates. Only 20% of respondents' institutions consider mode of consumption, with 87% and 53% approving of oral and transdermal routes, respectively, and only 7% approving of vaporized or smoked routes. While 73% of providers would consider illegal marijuana use an absolute/relative contraindication to heart transplant listing, the number decreases to 57% for legal recreational users and 21% for legal medical users. Most providers personally believe marijuana to be physically and mentally/emotionally harmful to pediatric patients (67% and 72%, respectively). Many institutions lack a policy regarding marijuana use in pediatric and ACHD heart transplant candidates, and there is considerable disagreement among providers on the best practice. With increasing legalization and use of marijuana, each institution will have to address this issue thoughtfully to continue to provide high-quality, consistent, and equitable care for pediatric and ACHD heart transplant candidates.

New-onset diabetes after pediatric heart transplantation: A review of the Pediatric Heart Transplant Study.

NDT is a well-defined complication after solid organ transplantation. Little has been published describing the incidence, risk factors, and effect on outcome after pediatric heart transplantation. We performed a retrospective evaluation of pediatric patients from the PHTS registry from 2004 to 2014. Group comparison, associated factors, incidence using Kaplan-Meier method, and risk factor and outcome analysis for NDT at 1 year post-transplant. Of the 2185 recipients, 1756 were alive and followed at 1 year. Overall freedom from NDT was 98.9%, 94.7%, and 92.6% at 1, 5, and 10 years, respectively. Patients with NDT were more likely to be black (non-Hispanic; P = 0.002), older at time of transplant (P < 0.0001), and have a higher BMI percentile at time of transplant (P < 0.0001). Adjusted risk factors for NDT at 1 year were older age at transplant (years; >12 years, OR: 8.8 and 5-12 years, HR: 8.0), obese BMI percentile at time of transplant (OR: 3.8), and steroid use at 30 days after transplant (OR: 4.7). Though uncommon, NDT occurs with a constant hazard after pediatric heart transplant; it occurs more often in older patients at transplant, those who are of black race, those who are obese, and those who use steroids. Therefore, targeted weight reduction and selective steroid use in at-risk populations could reduce the incidence of early NDT. Further data are needed to determine the risk imparted by transplantation, factors that predict late-onset NDT, and whether NDT alters the outcome after transplant.

An unusual case of anemia in a cardiac transplant recipient.

Anemia is a well-described comorbidity in patients with heart failure and has been associated with decreased survival rates after heart transplant. The causes of anemia are broad, and identification of the underlying etiology is critical for management. Herein, we report an unusual case of severe anemia complicating cardiac transplantation.

Dynamics of gut microbiota in autoimmune lupus.

Gut microbiota has been recognized as an important environmental factor in health, as well as in metabolic and immunological diseases, in which perturbation of the host gut microbiota is often observed in the diseased state. However, little is known on the role of gut microbiota in systemic lupus erythematosus. We investigated the effects of host genetics, sex, age, and dietary intervention on the gut microbiome in a murine lupus model. In young, female lupus-prone mice resembling women at childbearing age, a population with the highest risk for lupus, we found marked depletion of lactobacilli, and increases in Lachnospiraceae and overall diversity compared to age-matched healthy controls. The predicted metagenomic profile in lupus-prone mice showed a significant enrichment of bacterial motility- and sporulation-related pathways. Retinoic acid as a dietary intervention restored lactobacilli that were downregulated in lupus-prone mice, and this correlated with improved symptoms. The predicted metagenomes also showed that retinoic acid reversed many lupus-associated changes in microbial functions that deviated from the control. In addition, gut microbiota of lupus-prone mice were different between sexes, and an overrepresentation of Lachnospiraceae in females was associated with an earlier onset of and/or more severe lupus symptoms. Clostridiaceae and Lachnospiraceae, both harboring butyrate-producing genera, were more abundant in the gut of lupus-prone mice at specific time points during lupus progression. Together, our results demonstrate the dynamics of gut microbiota in murine lupus and provide evidence to suggest the use of probiotic lactobacilli and retinoic acid as dietary supplements to relieve inflammatory flares in lupus patients.

B-type natriuretic peptide trends after pediatric heart transplantation.

BNP is increasingly utilized in the management of pediatric HT recipients. Performing a retrospective single-center chart review, we sought to describe BNP changes during the first year after HT and identify factors that affect its trend. After exclusion for rejection, 316 BNP levels from 50 patients were evaluated. BNP underwent an exponential decline 120 days after HT followed by a plateau. Log10 BNP decline strongly correlated with time (r = -0.70, p < 0.0001). Initial BNP was less in pretransplant VAD (p = 0.0016) and lower post-HT inotrope use (p = 0.0043). Infant recipients, IT >4 h, and those bridged medically were associated with higher plateau BNP. Multivariable logistic regression demonstrated IT >4 h independently predicted plateau BNP in the upper quartile (OR 7.1, p = 0.02). No significant change in BNP coincided with rejection (N = 6 patients) without severe hemodynamic compromise. BNP correlated modestly with right atrial pressure (r = 0.4652, p < 0.0001) and pulmonary capillary wedge pressure (r = 0.2660, p < 0.001), but poorly with echocardiogram (r = -0.18, p = 0.003). Trending BNP could help provide insight into how the graft recovers after HT and IT >4 h independently predicted higher plateau BNP and may reflect subtle changes in graft performance.

Cardiorespiratory Fitness as a Predictor of Non-Cardiovascular Disease and Non-Cancer Mortality in Men.

OBJECTIVE: To evaluate the association of 5 major cause-specific non-cardiovascular disease (CVD) and non-cancer deaths with cardiorespiratory fitness (CRF). METHODS: Patients were 36,645 men (43.3±9.3 years) free of known CVD and cancer at baseline who completed a maximal treadmill graded exercise test during a preventive examination at the Cooper Clinic (Dallas, Texas) between 1971 and 2003. CRF was quantified as maximal treadmill exercise test duration and grouped as low (referent), moderate, and high. Cause-specific non-CVD non-cancer deaths were (1) diabetes or kidney disease, (2) chronic respiratory disease, (3) acute respiratory and infectious disease, (4) injuries, and (5) other non-CVD non-cancer deaths. RESULTS: A total of 694 non-CVD non-cancer deaths occurred during an average of 17 years of follow-up. After adjustment for covariates, hazard ratios (95% confidence intervals) for moderate and high CRF, respectively, were 0.57 (0.47 to 0.69) and 0.43 (0.34 to 0.54) for overall non-CVD non-cancer deaths (P<.0001); 0.39 (0.28 to 0.54) and 0.17 (0.10 to 0.28) for diabetes or kidney disease (P<.001); 0.36 (0.22 to 0.59) and 0.09 (0.04 to 0.20) for chronic respiratory diseases (P<.001 for all); 0.74 (0.47 to 1.16) and 0.34 (0.19 to 0.61) for acute respiratory and infectious diseases (P<.01 for both); and 0.48 (0.35 to 0.66) and 0.38 (0.26 to 0.55) for any other non-CVD non-cancer deaths (P<.0001 for both). CONCLUSION: Higher levels of CRF were significantly associated with lower risk of mortality from the 5 major non-CVD non-cancer causes. These results suggest that improvement in CRF may reduce non-CVD non-cancer deaths, which account for a significant proportion of adult mortality.

Physical Activity, Cardiorespiratory Fitness, and the Obesity Paradox with Consideration for Racial and/or Ethnic Differences: A Broad Review and Call to Action.

Despite decades of extensive research and clinical insights on the increased risk of all-cause and disease-specific morbidity and mortality due to obesity, the obesity paradox still presents a unique perspective, i.e., having a higher body mass index (BMI) offers a protective effect on adverse health outcomes, particularly in people with known cardiovascular disease (CVD). This protective effect may be due to modifiable factors that influence body weight status and health, including physical activity (PA) and cardiorespiratory fitness (CRF), as well as non-modifiable factors, such as race and/or ethnicity. This article briefly reviews the current knowledge surrounding the obesity paradox, its relationship with PA and CRF, and compelling considerations for race and/or ethnicity concerning the obesity paradox. As such, this review provides recommendations and a call to action for future precision medicine to consider modifiable and non-modifiable factors when preventing and/or treating obesity.

Non-exercise estimated cardiorespiratory fitness and incident type 2 diabetes in adults.

AIM(S): To examine the association between non-exercise estimated cardiorespiratory fitness (eCRF) and incident type 2 diabetes. METHODS: In a sample of 13,616 men and women without diabetes at baseline, incident type 2 diabetes were determined as fasting plasma glucose level ≥ 7 mmol/l (126 mg/dL), self-report, or insulin usage at follow-up. eCRF was calculated in metabolic equivalents (METs) at baseline using sex-specific algorithms, including physical activity, smoking status, age, body mass index, waist circumference, and resting heart rate. Cox regression models were performed, and hazard ratios (HRs), 95 % confidence intervals (CIs), and p values were reported. RESULTS: Each 1-MET unit increase in eCRF was associated with an 11 % lower risk of incident type 2 diabetes (p < 0.0001). Men in the upper and middle eCRF tertiles were at 46 % (95 % CI, 0.42-0.68) and 29 % (95 % CI, 0.57-0.88) lower risk of incident type 2 diabetes compared to the lower eCRF tertile (p < 0.0001). For women, there were no significant findings between eCRF tertiles and incident type 2 diabetes (p ≥ 0.11 for all). CONCLUSIONS: Higher eCRF was associated with a lower incidence of type 2 diabetes in men. Further research needs to examine the association between eCRF and type 2 diabetes in women.

Influence of Food Security Status and Diet Quality on Maternal Gestational Weight Gain.

BACKGROUND: Recommended gestational weight gain (GWG) is crucial for health of women and their offspring. Food security status is hypothesized to influence diet quality and GWG. Therefore, we examined the relationship between diet quality and GWG by food security status. METHODS: Participants (n = 679) were enrolled in the Initial Vanguard Study of the National Children's Study. GWG was calculated as third trimester weight minus prepregnancy weight. Food security status and diet quality (Healthy Eating Index [HEI]-2015) were assessed using the Household Food Security Survey and a Diet History Questionnaire, respectively. General linear models evaluated the relationship between GWG and HEI-2015 by food security status. RESULTS: A greater proportion of women experienced food security (81.3%) compared with food insecurity (18.7%). In women with food security, GWG was negatively associated with HEI-2015 in women having overweight (r = -0.421, P = .003) and positively associated with HEI-2015 in women with inadequate GWG (r = 0.224, P = .019). Conversely, no significant relationships were found between GWG and HEI-2015 in women with food insecurity. DISCUSSION: Improved diet quality potentially lowers GWG in women with food security. However, in vulnerable populations, including women with food insecurity, improvements in diet quality may not effectively enhance GWG.

Outcomes of heart transplants in children with heterotaxy syndrome.

OBJECTIVES: End-stage congenital heart disease (CHD) in children with heterotaxy syndrome might necessitate a heart transplant (HTx). An HTx in heterotaxy patients can be associated with several technical (e.g. redo, systemic/pulmonary-venous/situs anomalies, pulmonary artery reconstruction) and extra-cardiac (e.g. ciliary dyskinesia, infections, gastrointestinal) challenges. Our goal was to determine if heterotaxy syndrome is associated with increased early or late transplant risks. METHODS: The United Network for Organ Sharing transplant database was merged with the Paediatric Health Information System administrative database to identify children with heterotaxy who received an HTx. Characteristics and outcomes were compared between children with heterotaxy and contemporaneous non-heterotaxy congenital and non-congenital cardiomyopathy control groups. RESULTS: After we merged the databases, we divided our cohort of 1122 patients into 3 groups: the heterotaxy (n = 143), group the non-heterotaxy congenital (n = 428) group and the cardiomyopathy (n = 551) group. There were differences in the characteristics between the 3 groups, with the heterotaxy group being comparable to the non-heterotaxy congenital group. The waiting list duration was longer for the heterotaxy than for the non-heterotaxy congenital and cardiomyopathy groups (91 vs 63 vs 56 days, P < 0.001). Early post-transplant complications were similar for all groups except for operative mortality, which was 1% for the cardiomyopathy and 4% for the heterotaxy and non-heterotaxy congenital groups (P < 0.001). The post-transplant hospital stay was shorter for the cardiomyopathy (57 days) compared to the non-heterotaxy congenital (99 days) and heterotaxy (89 days) groups (P < 0.001). Whereas rejection prior to discharge was comparable between the heterotaxy and the CHD groups, it was higher at 1 year for the heterotaxy (22%) than for the non-heterotaxy congenital (19%) and cardiomyopathy (13%) groups (P < 0.001). Survival at 5 years was superior for the cardiomyopathy (87%) compared to the heterotaxy (69%) and non-heterotaxy congenital groups (78%) (P < 0.001). For the heterotaxy group, no risk factors affecting survival were identified on multivariable analysis. CONCLUSIONS: Regardless of the complexity, an HTx in selected children with heterotaxy is associated with good mid-term outcomes. Despite early results that are comparable to those of other patients with CHD, the increasing rejection rate at 1 year and the relatively accelerated attrition at mid-term warrant further follow-up. Due to database limitations in defining morphologic and surgical details, further work is warranted to delineate anatomical and surgical variables that could affect survival.

Healthful Eating Behaviors among Couples Contribute to Lower Gestational Weight Gain.

Through longitudinal analysis from the GLOWING cohort study, we examined the independent and joint relationships between couples' eating behaviors and gestational weight gain (GWG). Pregnant persons (n = 218) and their non-pregnant partners (n = 157) completed an Eating Inventory. GWG was calculated as gestation weight at 36 weeks minus that at 10 weeks. General linear models were used to examine the relationships between GWG and the pregnant persons, non-pregnant partners, and couples (n = 137; mean of pregnant persons and non-pregnant partners) cognitive restraint (range 0-21), dietary disinhibition (range 0-18), and perceived hunger (range 0-14), with higher scores reflecting poorer eating behaviors. The adjusted models included race/ethnicity, education, income, marital status, and age. The pregnant persons and their non-pregnant partners' cognitive restraint, dietary disinhibition, and perceived hunger scores were 9.8 ± 4.7, 4.8 ± 3.2, and 4.4 ± 2.5 and 6.6 ± 4.6, 5.4 ± 3.4, and 4.7 ± 3.2, respectively. Higher cognitive restraint scores among the pregnant persons and couples were positively associated with GWG (p ≤ 0.04 for both). Stratified analyses revealed this was significant for the pregnant persons with overweight (p ≤ 0.04). The non-pregnant partners' eating behaviors alone were not significantly associated with GWG (p ≥ 0.31 for all). The other explored relationships between GWG and the couples' eating behaviors were insignificant (p ≥ 0.12 for all). Among the pregnant persons and couples, reduced GWG may be achieved with higher levels of restrained eating. Involving non-pregnant partners in programs to optimize GWG may be beneficial.

Associations between Sleep and Body Composition in Older Women and the Potential Role of Physical Function.

Purpose: The relationship between sleep and adiposity in older women remains unclear partly due to the reliance of body mass index as a measure of adiposity. The purpose of this study was to investigate associations between objectively measured sleep characteristics and body composition measured by dual energy x-ray absorptiometry (DXA) in older women. A secondary purpose was to examine if physical function mediates this relationship. Methods: Non-obese older women (ages 60-75 years, n=102) were included in the study. Total sleep time (TST), time in bed (TIB), sleep efficiency (SE), and wake after sleep onset (WASO) were determined by actigraphy. A battery of tests was used to assess physical function. Results: With adjustment for age, there was a negative association between TST and TIB with lean mass. Both grip strength and dominant leg extension were associated with TST, TIB, and lean mass; the associations between TST and TIB with lean mass were lost after adjusting for grip strength or leg extension strength. Additionally, SE was negatively associated with total, gynoid, and trunk lean mass, and there was a positive association between TST and percent trunk fat, and WASO and gynoid lean mass, with age adjusted. Conclusions: Sleep characteristics, TST, TIB, SE, and WASO, were associated body composition measures in this sample of older women. The relationship between TST and TIB with body composition was mediated, in part, by grip strength and leg extension strength.

Understanding Barriers and Facilitators to Physical Activity Engagement to Inform a Precision Prescription Approach during Pregnancy.

Physical activity during pregnancy is an important health behavior. However, many pregnant individuals are provided with little-to-no guidance to adequately engage in physical activity. The purpose of this quantitative and quasi-qualitative study of currently or previously pregnant women was to examine physical activity behaviors in pregnancy and understand barriers and facilitators to achieving physical activity recommendations. Overall, 431 women (18+ years), White/Caucasian (84.5%), married (84.9%), and currently pregnant (66.6%), completed an online survey study. Most women (69.4%) reported engaging in cardio-based physical activity and willing to engage in physical activity to meet guidelines between 2 and 5 days per week (77.4 -88.8%). The most frequently reported barriers were feeling too tired (72.8%) or uncomfortable (71.8%) and childcare needs (57.8%). Being able to choose time of day (96.0%), accessing home workouts (92.9%), and having a personalized prescription (95.6%) were the most reported facilitators. Open comment feedback resulted in additional barriers, such as ensuring proper energy intake, while motivation and support from other pregnant individuals were fundamental facilitators. Individualized physical activity prescription is lacking in routine prenatal care. To support pregnant individuals to achieve physical activity recommendations, developing a prescription with suitable modalities, at-home options, and consideration for physical activity timing are required.

Body weight and fat trajectories of Black and White women in the first postpartum year.

OBJECTIVE: The aim of this study was to examine changes in body weight and fat in Black and White women during the first postpartum year and to determine whether there is preferential retention of fat mass and abdominal fat. METHODS: Body composition was quantified by dual-energy x-ray absorptiometry in Black (n = 49) and White (n = 85) women at 6 to 8 weeks, 6 months, and 12 months after delivery of a singleton infant. RESULTS: Weight, fat mass, percent body fat, and fat in the trunk, android, gynoid, and limb regions decreased from 6 to 8 weeks to 12 months in White women, but not in Black women (fat mass, adjusted mean [SE]: 29.6 [1.3] to 26.9 [1.3] kg in White women and 34.5 [1.5] to 36.8 [1.8] kg in Black women). In the entire sample, fat mass was higher at 6 months than at 6 to 8 weeks, independent of weight change; visceral fat was higher at 12 months (686 [45] g) than at 6 to 8 weeks (611 [42] g) and 6 months (626 [43] g); and android fat was higher at 12 months than at 6 months, independent of fat change. CONCLUSIONS: Black women were less likely than White women to lose weight and fat in the postpartum period. There was preferential retention of fat in the abdominal area.

Access, Interest, and Barriers to Incorporation of Birth Doula Care in the United States.

Doula care improves maternal care, yet barriers exist to incorporating doula care. The purpose of this study was to evaluate interest and barriers to doula care. Overall, 508 women, 26-35 years of age (54.5%), White/Caucasian (89.8%), and married (88.6%), completed this study. Most reported ≥1 previous birth (97.6%). Respondents would "feel comfortable" (73.2%) and "more confident" (54.9%) with doula care at birth, and 57.9% reported their provider would be supportive of doula care. Only 39.0% expressed benefits to doula care during pregnancy compared to 72.6% at birth and 68.1% during postpartum. Most would hire a doula if health insurance covered some of the costs. Despite the recognized benefits and support of doula care, cost-associated barriers exist to the incorporation of doula care.

Relapsing polychondritis: Best Practice & Clinical Rheumatology.

Relapsing polychondritis (RP) is an uncommon inflammatory disorder that predominantly targets cartilaginous structures. The disease frequently affects the nose, ears, airways, and joints, but it can also impact organs that aren't primarily cartilage-based, such as blood vessels, skin, inner ear, and eyes. Given its infrequent occurrence and recurrent symptoms, patients often experience delays in proper diagnosis. Lately, based on the organs involved, the disease's diverse manifestations have been categorized into specific clinical groups, based on the most likely organ involvement including auricular, nasal, pulmonary, and musculoskeletal. More recently the discovery of a new disease, called (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) VEXAS syndrome, due to mutations in UBA1 gene, identified the cause of 8 % of the patients with a clinical diagnosis of RP. VEXAS is likely the cause of a previously described "hematologic subgroup" in RP. This discovery is proof of concept that RP is likely more than one disease (Beck et al., Dec 31 2020; Ferrada et al., 2021). People diagnosed with RP face numerous hurdles, with the quality of their lives and overall prognosis being affected. Diagnosing the condition is particularly challenging due to its fluctuating symptoms, the absence of specific markers, and the lack of universally recognized classification criteria. For a correct diagnosis, it's imperative for healthcare professionals to identify its unique clinical patterns. Moreover, there are no approved metrics to gauge the disease's severity, complicating patient management. This review seeks to equip clinicians with pertinent insights to better diagnose and attend to these complex patients.