Efficacy of home healthcare on the management of tracheostomy patients.

OBJECTIVES: To evaluated the home healthcare efficacy in managing tracheostomy patients at King Abdulaziz Medical City under the Ministry of National Guard Health Affairs. Home healthcare is care provided to patients in the convenience of their homes to ensure high-quality care based on healthcare providers' supervision. METHODS: This retrospective cohort study utilizing a non-probability consecutive sampling technique, including all available tracheal patients with no exclusion criteria, was carried out in Riyadh, Saudi Arabia, between January 2019 and June 2022. The collected data included patient demographic variables and respiratory settings (ventilation type, daily ventilation need, tracheostomy duration, and ventilator settings). The outcomes included mortality rate and therapeutic outcomes of tracheal management. RESULTS: Of the 183 patients in the study, the most common type of respiratory-related infection was pneumonia (53%). Unlike respiratory-related causes, The mortality rate of patients admitted to the intensive care unit that was unrelated to respiratory causes was statistically significant (57%) (p=0.003). The mortality rate of patients who used aerosol tracheal collars (34%) was markedly higher than mechanically ventilated patients (57%) (p=0.004). The mortality rate following discharge from HHC was 40%, and was higher among patients aged >70 years (47%) (p=0.04). CONCLUSION: Pneumonia was associated with the majority of ventilator-related infections and resulted in hospital readmissions. Ensuring proper practices and caregiver education is crucial to decrease the incidence of ventilator-related infections.

Musculoskeletal disorder prevalence and its correlation with stress in medical students: A cross sectional survey.

Background: The study aimed to evaluate musculoskeletal disorder (MSD) prevalence and its correlation with stress in medical students at Umm Al-Qura University (UQU) in Saudi Arabia. Methods: A total of 416 participants participated in this study by answering an online questionnaire. We included medical students from UQU of both genders, ranging from the first year to the sixth year. A questionnaire was used to capture sociodemographic data. The data were collected using the Kessler Psychological Distress Scale (K-10) and Standardized Nordic questionnaire. Results: Among 416 medical students surveyed, 219 (52.60%) were males. A significant proportion of participants, 294 (70.70%), reported experiencing pain during the last 12 months. Female students exhibited significantly higher scores of MSDs compared to their male counterparts. Students who reported working between 51-90 hours per week had a significantly higher MSD score than those who worked 0-50 hours or 91 or more hours. The findings of this study indicated that the most prevalent MSDs were low back pain (50.20%), followed by neck pain (31.70%), and female medical students exhibited significantly higher stress levels than male medical students. Conclusions: Musculoskeletal disorders represent a prevalent health issue among medical students, there is a significant association between factors such as being a female and body mass index. Additionally, psychological stress is a widespread concern among medical students, given the demanding nature of their lifestyle. Interestingly, our findings revealed that there exists a moderately positive relationship between musculoskeletal disorders and stress in this particular population.

Hand Hygiene Knowledge and Practices Among Visitors to the Holy Masjid (Masjid Al-Haram) During the Month of Ramadan in 2023.

Introduction Visits to the Holy Masjid are considered mass gatherings (MGs), defined as concentrations of people at a specific location for a certain objective over a predetermined amount of time. Such gatherings might strain the host nation's preparation and reaction capabilities, increasing the chances of spreading infectious diseases. Aim To evaluate the comprehension of hand hygiene (HH) and proper HH habits among visitors to the Holy Masjid during the month of Ramadan in 2023. Methods A total of 690 visitors to the Holy Masjid were interviewed for this cross-sectional study. The questionnaire was developed using model questions from another published survey. Results Of the participants, 541 (78.4%), predominantly female, had generally good knowledge about HH. A total of 282 (40.9%) participants used nothing to clean their hands after shaking hands with someone. Four hundred and eighty (69.6%) participants were aware that poor HH does not spread HIV/AIDS, and 504 (73%) stated that consistent HH does not reduce the body's natural immunity. A total of 530 (76.8%) participants with good knowledge about HH cleaned their hands before meals, compared to 131 (19%) participants with poor knowledge of HH. Conclusion Based on the results of our study, the participants' awareness of HH was generally high, with most recognizing the role of good HH in preventing common infectious diseases, such as gastrointestinal and respiratory infections. However, certain aspects of HH, such as the necessity and proper use of alcohol-based hand sanitizers, were not well understood. Regular, focused awareness-raising initiatives are recommended to enhance HH knowledge and practices among visitors to the Holy Masjid.

Retraction: Cerebral Venous Infarct After Recovery From COVID-19 Pneumonia.

[This retracts the article DOI: 10.7759/cureus.19763.].

Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias.

BACKGROUND: Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear. AIMS: We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias. METHODS: Excess foreskin tissue was obtained from 11 boys undergoing hypospadias repair (cases) and 12 undergoing routine circumcision (controls) (median age [range], 1.5 [1.2-2.7] years) and small resistance arteries were isolated. Vessels were mounted on wire myographs and vascular reactivity was assessed in the absence/presence of 17ß-estradiol, dihydrotestosterone (DHT), and testosterone. RESULTS: In controls, testosterone and 17ß-estradiol increased contraction (percent of maximum contraction [Emax]: 83.74 basal vs 125.4 after testosterone, P < .0002; and 83.74 vs 110.2 after estradiol, P = .02). 17ß-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine, P < .0001; and Emax: 14.6 vs 20.5 to sodium nitroprusside, P < .0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, P = .01) and 17ß-estradiol (Emax: 156.9 vs 23.6, P < .0001) reduced contraction. Androgens, but not 17ß-estradiol, increased endothelium-dependent and endothelium-independent vasorelaxation in cases (Emax: 77.3 vs 51.7 with testosterone, P = .02; and vs 48.2 with DHT to acetylcholine, P = .0001; Emax: 43.0 vs 39.5 with testosterone, P = .02; and 39.6 vs 37.5 with DHT to sodium nitroprusside, P = .04). CONCLUSION: In healthy boys, testosterone and 17ß-estradiol promote a vasoconstrictor phenotype, whereas in boys with hypospadias, these sex hormones reduce vasoconstriction, with androgens promoting vasorelaxation. Differences in baseline artery function may therefore be sex hormone-independent and the impact of early-life variations in androgen exposure on vascular function needs further study.

Pharmacological Management for Pediatric Irritable Bowel Syndrome: A Review.

Irritable bowel syndrome is a multifactorial disease with chronic symptoms that interfere with the quality of life of patients. It represents one of the most common causes of functional abdominal pain in the pediatric population. Various theses with little evidence tried to explain the pathophysiology of the disease. Neurological origin was one of the theories explaining the disease, either by the disturbance of neurotransmitters like dopamine, noradrenaline, and serotonin, which have some evidence of their relation to GI tract functions. Other factors like bio-psycho-social factors that affect the pediatric population are represented in bullying, unrealistic academic expectations from the parents, continuous educational stress, and difficult relationships with peers. Other factors may be genetic abnormalities of the receptors or visceral hypersensitivity. Treatment strategies for the disease varied from physical activity like yoga to a diet like a low-FODMAP diet. Pharmacological treatment of the disease targets the presenting symptoms, represented by antispasmodic drugs treating abdominal pain/discomfort, antipsychotics that regulate the disturbance in the brain-gut axis, and other drugs targeting diarrhea or constipation that present with the patient according to the type of IBS and the condition of the patient.

Emergence of an apparent yield phenomenon in the mechanics of stochastic networks with inter-fiber cohesion.

In this work we investigate the contribution of inter-fiber cohesion to defining the mechanical behavior of stochastic crosslinked fiber networks. Fibers are athermal and store energy primarily in their bending and axial deformation modes. Cohesion between fibers is defined by an interaction potential. These structures are in equilibrium with the inter-fiber cohesive forces before external load is applied and their mechanical behavior is probed in uniaxial tension. Two types of configurations are considered: a state with high initial free volume in which contacts between fibers are scarce, and a state with low free volume and large number of fiber contacts. While in the absence of cohesion the response is hyperelastic, we observe that a yield point-like phenomenon develops as the strength of cohesion increases in both network types considered; we refer to this as an 'unlocking phenomenon'. The small strain stiffness increases as cohesion becomes more pronounced. The stiffness and unlocking stress are expressed in terms of network parameters and cohesion strength through a product of two functions, one dependent on network parameters only, and the other is a function of the cohesion strength. While the small strain response is controlled by cohesion, the large strain behavior is shown to be largely controlled by the network. Therefore, varying the strength of cohesion has no effect on strain stiffening. These observations provide a physical basis for the unlocking observed in both athermal and thermal network materials and are expected to facilitate the design of soft materials with novel properties.

Awareness of Hernias and Their Risk Factors Among Adults in the Western Region of Saudi Arabia.

Objective To assess the awareness of hernia and its risk factors among adults in the western region of Saudi Arabia. Our hypothesis was that the studied population was in need of education regarding this matter.  Methods This cross-sectional study was conducted in the western region of Saudi Arabia from November to December 2022, using a Google form. The generated questionnaire consisting of two parts was distributed electronically through social media platforms. The targeted population included adults from the western region of Saudi Arabia. The data were obtained using Microsoft Excel and analyzed using Statistical Package for Social Sciences (SPSS) v. 26 software (IBM Corp., Armonk, NY). Results A total of 1570 adults from the western region of Saudi Arabia were included in our study. We found that 13% of the participants had good overall knowledge about hernia, 31% had poor knowledge, and 56% had moderate knowledge. Alarmingly, 55% of the participants had a poor attitude, and 27% were evaluated as having poor practice. In addition, we found a significant association between people's level of knowledge and multiple factors, including age (p-value < 0.001), marital status (p-value< 0.001), and occupation (p-value< 0.001).  Conclusion Based on our research, more than half of our population had a moderate level of knowledge regarding hernias including their risk factors and complications, with alarming levels of poor attitudes toward the disease. Healthcare workers were our participants' leading source of medical information, which directs us towards fully equipping them with the knowledge to educate the public effectively.

The implication of LPS/TLR4 and FXR receptors in hepatoprotective efficacy of indole-3-acetic acid and chenodeoxycholic acid.

AIM: Valproic acid (VPA) belongs to the first-generation antiepileptic drugs, yet its prolonged use can cause life-threatening liver damage. The importance of our study is to investigate the protective effect of indole-3-acetic acid (IAA), chenodeoxycholic acid (CDCA) and their combination on VPA-induced liver injury focusing on lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4) pathway and farnesoid X receptor (FXR). METHODS: Thirty rats were randomly assigned into five groups, normal control group, VPA group received 500 mg/kg of VPA intraperitoneally. The remaining groups were orally treated with either 40 mg/kg of IAA, 90 mg/kg of CDCA, or a combination of both, along with VPA. All treatments were administered one hour after the administration of VPA for three weeks. KEY FINDINGS: VPA group showed significant elevations in the liver weight/body weight ratio, serum aminotransferases, triglyceride, and total cholesterol levels. Hepatic glutathione (GSH) level and superoxide dismutase (SOD) activity were significantly decreased, while malondialdehyde (MDA) level, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1ß), lipopolysaccharide (LPS) and caspase 3 were significantly increased. Likewise, immunohistochemical analysis revealed that TLR4 expression was elevated, whereas FXR expression was downregulated in hepatocytes. IAA substantially ameliorated all previously altered parameters, whereas CDCA treatment showed a partial improvement compared to IAA. Surprisingly, combination therapy of IAA with CDCA showed an additive effect only in the hepatic expression of TLR4 and FXR proteins. SIGNIFICANCE: IAA could be a promising protective agent against VPA-induced liver injury.

Internal jugular vein phlebectasia: A systematic review of therapeutic approaches in Pediatrics.

OBJECTIVES: Internal jugular vein phlebectasia (IJVP) is a rare type of vascular abnormality that causes dilatation of internal jugular vein in the neck. There is presently no consensus on the most effective method of treatment for this condition, that is commonly seen in children. We conducted a systematic review of the literature reported till date to comprehend the key features of IJVP and its most effective therapeutic modalities. METHODS: Five databases were searched until October 10, 2022 for articles of any design (including case reports) reporting IJVP in pediatric subjects. Individual patient data on demographics, clinical features of this entity and the differential diagnosis, methods of imaging, management, and outcome of illness were recorded. The quality assessment was performed using the Joanna Briggs Institute's Critical Appraisal Checklist for studies. RESULTS: A total of 51 articles including 169 cases were retrieved and included in the analysis. Of the 169 patients, most of them were male children, and in 77% of cases right internal Juglar vein was involved. All patients had some symptoms suggestive of IJVP with most common ones being neck swelling or tenderness, and difficulty in breathing. In 90% of cases, it was observed that the neck swelling typically increases in size with Valsalva maneuver. Once jugular vein phlebectasia was clinically suspected, ultrasonography, CECT, or color Doppler flow imaging were used to confirm the diagnosis. The management of most of the cases was either conservative or surgical, and in surgery mostly ligation was performed. There have not been any cases of serious complications, therefore, according to included studies, a conservative approach is recommended with continuous monitoring. Out of the 51 studies included, most of them had low risk of bias. CONCLUSION: Internal jugular vein phlebectasia, a rare benign condition, is most commonly found in children, and affects predominantly the right internal jugular vein. Although most patients did well with merely conservative treatment, still management of this vascular anomaly has to be on a case-by-case basis.

The General Population's Perspectives on Implementation of Artificial Intelligence in Radiology in the Western Region of Saudi Arabia.

Background  Artificial intelligence (AI) is a broad spectrum of computer-executed operations that mimics the human intellect. It is expected to improve healthcare practice in general and radiology in particular by enhancing image acquisition, image analysis, and processing speed. Despite the rapid development of AI systems, successful application in radiology requires analysis of social factors such as the public's perspectives toward the technology. Objectives The current study aims to investigate the general population's perspectives on AI implementation in radiology in the Western region of Saudi Arabia. Methods A cross-sectional study was conducted from November 2022 and July 2023 utilizing a self-administrative online survey distributed via social media platforms. A convenience sampling technique was used to recruit the study participants. After obtaining Institutional Review Board approval, data were collected from citizens and residents of the western region of Saudi Arabia aged 18 years or older. Results A total of 1,024 participants were included in the present study, with the mean age of respondents being 29.6 ± 11.3. Of them, 49.9% (511) were men, and 50.1% (513) were women. The comprehensive mean score of the first four domains among our participants was 3.93 out of 5.00. Higher mean scores suggest being more negative regarding AI in radiology, except for the fifth domain. Respondents had less trust in AI utilization in radiology, as evidenced by their overall distrust and accountability domain mean score of 3.52 out of 5. The majority of respondents agreed that it is essential to understand every step of the diagnostic process, and the mean score for the procedural knowledge domain was 4.34 out of 5. The mean score for the personal interaction domain was 4.31 out of 5, indicating that the participants agreed on the value of direct communication between the patient and the radiologist for discussing test results and asking questions. Our data show that people think AI is more effective than human doctors in making accurate diagnoses and decreasing patient wait times, with an overall mean score of the efficiency domain of 3.56 out of 5. Finally, the fifth domain, "being informed," had a mean score of 3.91 out of 5. Conclusion The application of AI in radiologic assessment and interpretation is generally viewed negatively. Even though people think AI is more efficient and accurate at diagnosing than humans, they still think that computers will never be able to match a specialist doctor's years of training.

Assessment of Anxiety Associated With MRI Examination Among the General Population in the Western Region of Saudi Arabia.

Background While magnetic resonance imaging (MRI) is one of the most efficient diagnostic methods used today, some patients may find an MRI examination to be a frightening experience. The proximity to the machine during screening and being in a confined space can cause a feeling of claustrophobia. Severe anxiety during MRI screening can cause the patient to move, which lowers the quality of the imaging and diagnostic test, and can result in the early termination of the MRI examination and the patient declining further testing. Objectives The objective of this study is to evaluate MRI examination-associated anxiety among Saudi Arabia's general population in the western region of the country. Methods Altogether, 465 participants who had undergone an MRI examination in the western region of Saudi Arabia were recruited for this cross-sectional study. We used the Magnetic Resonance Imaging-Anxiety Questionnaire (MRI-AQ) to collect data. Results Regarding anxiety symptoms, 82.8% of the participants believed that they had control over the event, 80.2% were concerned beforehand, 74% required more specific information, just 48% had difficulty breathing, and 51% were panicked. On the other hand, 57.4% felt safe, 56.8% were calm, and 49.2% were relaxed. The majority of the participants (55.9%, 260) reported moderate MRI-related anxiety. Conclusion More than half of our respondents had mild to moderate MRI-related anxiety. The majority needed more detailed information, panicked, and had breathing problems. Statistically, females showed a significantly higher level of anxiety compared with male participants.

Primary Penile Squamous Cell Cancer-Related Malignant Priapism in a Cystectomized Patient: A Case Report.

Priapism is one of the most common urologic emergencies and is characterized by a prolonged and painful erectile state unrelated to sexual stimulation or sexual desire. Neoplasm-associated priapism is a rare condition and is usually caused by corporeal metastases of other pelvic area malignancies. Primary penile malignancy-related malignant priapism is extremely rare. In this reported case, an 82-year-old male presented with priapism. The penile doppler ultrasound and pelvic magnetic resonance imaging were compatible with ischemic priapism and corporal mass. Subsequently, the patient underwent total penectomy and bilateral superficial inguinal lymphadenectomy. The pathology report was consistent with primary penile squamous cell cancer (SCC), so the patient underwent adjuvant radiotherapy. However, he developed multiple metastases and could survive for about six months. The patient had undergone radical cystectomy (RC) and urethrectomy 19 and 2 years ago due to urothelial carcinoma, respectively. To the best of our knowledge, this is the second case of malignant priapism due to primary penile SCC and represents one of the longest urethral recurrence periods after RC. When a patient presents with malignant priapism, primary penile malignancies should be considered in differential diagnosis, even if the patient has a history of pelvic area malignancies.

Pneumomediastinum and Pneumopericardium as Uncommon Complications of COVID-19 Infection: A Review Article.

There is an emerging body of literature describing an increasing incidence of pneumomediastinum and, to a lesser extent, pneumopericardium as a complication of COVID-19. However, the literature lacks information regarding patients' characteristics and a general view of this unusual condition. The purpose of this paper is to summarize the current literature on this phenomenon. In this study, we summarize the risk factors/etiology, imaging modalities, management, and prognosis of known cases in the literature. In total, 48 articles were included in the study, ranging from case reports to case series. Most patients were male (83.3%). The overall mortality rate was 27.1% and the recovery rate was 62.5%.

The influence of obstructive sleep apnea on self-perceived dental aesthetics and need for orthodontic treatment among the general population in Makkah, Saudi Arabia.

OBJECTIVE: To assess the influence of obstructive sleep apnea on self-perceived dental appearance and need for orthodontic treatment. MATERIALS AND METHODS: A self-administered questionnaire was used in a random sample of a general adult population in Makkah region, Saudi Arabia. A total of 1014 participants completed the questionnaires, which included the STOP-BANG questionnaire, Oral Aesthetics Subjective Impact Score questionnaire, and Aesthetic Component of Index of Orthodontic Treatment Need questionnaire. Descriptive statistics and Chi-square tests were used to compare differences between the groups. RESULTS: Overall, 6.5% (66/1014) of the participants were classified as being at high risk of OSA of which 71.2% were males and 28.8% were females (P < 0.001), 57.6% were >50 years of age, 90.9% had obesity, and 81.8% had an enlarged neck circumference. But only 10.1% of the participants reported that they snore loudly. A positive self-perception of dental esthetics was found in 42 (6.2%) and 518 (76.6%) participants at high and low risk of OSA, respectively. Furthermore, of the participants in the high- and low-risk groups, 4.2% and 66.7% considered themselves in need of orthodontic treatment, respectively. CONCLUSIONS: The prevalence rate of people at intermediate to high risk of OSA was 26% of the general population and being at high risk of OSA had no influence on self-perceived dental esthetics and need for orthodontic treatment.

Patient Satisfaction with Resin Infiltration Treatment for Masking Noncavitated White Spot Lesions on Anterior Maxillary Teeth: Two Case Reports.

Aim: We assessed patient satisfaction with resin infiltration treatment outcomes for masking postorthodontic treatment noncavitated white spot lesions on anterior maxillary teeth. Background: White spot lesions (WSLs) are opaque white areas of demineralization. The lesion may remineralize over time, but the opaque color usually remains, retaining the undesirable tooth color. Case Description: Resin infiltration (RI) was administered to two patients with a total of 10 anterior maxillary teeth diagnosed with noncavitated WSLs. Immediately after treatment, patients were asked about their comfort during the RI treatment and their level of satisfaction with treatment outcomes. Two weeks post-treatment, the two patients were asked again about their level of treatment outcome satisfaction and if they thought they needed a second treatment. Both reported that they were comfortable during the treatment and were extremely satisfied with the achieved treatment outcomes immediately and two weeks after the treatment and did not feel that they would need to seek further treatment to reach the desired outcome. Conclusion: Resin infiltration is a comfortable, conservative treatment option providing satisfactory outcomes in masking noncavitated WSLs on anterior maxillary teeth after orthodontic treatment. Clinical Significance. Resin infiltration is a conservative treatment option to mask noncavitated WSLs after orthodontic treatment.

Nano-Curcumin Prevents Copper Reproductive Toxicity by Attenuating Oxidative Stress and Inflammation and Improving Nrf2/HO-1 Signaling and Pituitary-Gonadal Axis in Male Rats.

Copper is essential for several cellular processes and is an important catalytic factor for many proteins. However, excess copper can provoke oxidative stress and reproductive toxicity. This study evaluated the effect of liposomal nano-curcumin (N-CUR) and CUR on testicular oxidative injury, inflammation, and apoptosis, and altered steroidogenesis and Nrf2/HO-1 signaling induced by copper sulfate (CuSO4). Rats received CuSO4 and N-CUR or CUR via oral gavage for 7 days. CuSO4 induced histopathological changes and altered pituitary-gonadal axis manifested by decreased serum gonadotropins and testosterone. Testicular steroidogenesis genes (StAR, 3ß-HSD, CYP17A1, and 17ß-HSD) and androgen receptor (AR) were downregulated in rats that received CuSO4. N-CUR and CUR prevented testicular tissue injury, increased circulating FSH, LH, and testosterone, and upregulated testicular steroidogenesis genes and AR. Additionally, N-CUR and CUR decreased testicular MDA, NO, NF-κB, iNOS, TNF-α, Bax, and caspase-3 while enhanced Bcl-2, Nrf2, and the antioxidants GSH, HO-1, SOD, and catalase. In conclusion, N-CUR and CUR prevented CuSO4-induced reproductive toxicity in male rats by suppressing oxidative injury and inflammatory response and boosting steroidogenesis, sex hormones, and Nrf2/HO-1 signaling. N-CUR was more effective in ameliorating tissue injury, oxidative stress, inflammation, and apoptosis and enhancing steroidogenesis and Nrf2/HO-1 than the native form.

Awareness among Pregnant Women about Epidural Analgesia: A Cross-Sectional Study.

Background: Epidural analgesia (EPA) is an effective anesthetic technique to overcome pain during labor. This study aimed to evaluate the current awareness of EPA among pregnant women. Methods: We carried out a cross-sectional study using a questionnaire to measure awareness about EPA among pregnant women visiting the obstetrics and gynaecology clinic in King Abdulaziz Medical City in Jeddah. Following the results, a group of women was selected and educated by trained medical students. Results: This study comprised 105 women. We found that 25 (23.8%) respondents revealed a complete lack of knowledge regarding EPA, 63 (60%) showed minimal awareness, and 17 (16.2%) were aware of EPA from various sources. The gravidity and history of EPA administration were significantly associated with knowledge. Multigravida women and those who had received EPA showed higher level of knowledge (p=0.048 and p < 0.001, respectively). In addition, there was a significant association between the level of education and request for EPA (p=0.027). Forty-one participants were enrolled in an educational program that explained the importance of EPA. Twenty (48.8%) women decided to undergo EPA during delivery; however, 7 (17.7%) refused and 14 (34.1%) were not sure about their decision. Conclusion: This study revealed a lack of awareness about EPA among pregnant women. Educational programs were effective as many participants chose EPA following the educational session as a form of pain relief during labor. We recommend the implementation of routine education on EPA in vaginal delivery during antenatal visits for all pregnant women.

Vascular dysfunction and increased cardiovascular risk in hypospadias.

AIMS: Hypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease. METHODS AND RESULTS: Our human study spanned molecular mechanistic to epidemiological investigations. Clinical vascular phenotyping was performed in adolescents with hypospadias and controls. Small subcutaneous arteries from penile skin from boys undergoing hypospadias repair and controls were isolated and functional studies were assessed by myography. Vascular smooth muscle cells were used to assess: Rho kinase, reactive oxygen species (ROS), nitric oxide synthase/nitric oxide, and DNA damage. Systemic oxidative stress was assessed in plasma and urine. Hospital episode data compared men with a history of hypospadias vs. controls. In adolescents with hypospadias, systolic blood pressure (P = 0.005), pulse pressure (P = 0.03), and carotid intima-media thickness standard deviation scores (P = 0.01) were increased. Arteries from boys with hypospadias demonstrated increased U46619-induced vasoconstriction (P = 0.009) and reduced acetylcholine-induced endothelium-dependent (P < 0.0001) and sodium nitroprusside-induced endothelium-independent vasorelaxation (P < 0.0001). Men born with hypospadias were at increased risk of arrhythmia [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.4-5.6, P = 0.003]; hypertension (OR 4.2, 95% CI 1.5-11.9, P = 0.04); and heart failure (OR 1.9, 95% CI 1.7-114.3, P = 0.02). CONCLUSION: Hypospadias is associated with vascular dysfunction and predisposes to hypertension and cardiovascular disease in adulthood. Underlying mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling. Our novel findings delineate molecular mechanisms of vascular injury in hypogonadism, and identify hypospadias as a cardiovascular risk factor in males.