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1.
Ann R Coll Surg Engl ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563065

ABSTRACT

We present a case of a 70-year-old gentleman who was referred to our tertiary 2-week-wait penile cancer clinic with a penile mass that was ulcerated, painful and discharging. This was suspicious for penile cancer and a radical circumcision was performed to remove the diseased foreskin en bloc with the lesion that was arising from the inner foreskin. Histopathology did not reveal cancer; however, we identified spirochaetes in keeping with syphilis. This was confirmed on serology. The patient was referred to the genitourinary medicine team and treated with antibiotics. This case demonstrates a rare presentation of genital syphilis in an elderly gentleman initially referred with concerns of penile cancer. Although, rare, especially in this age group, syphilis should be considered as a differential diagnosis in a patient presenting with an ulcerated, discharging, firm penile mass, especially given that the incidence of syphilis has been rising in recent years.

3.
Pancreas ; 53(4): e368-e377, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38518063

ABSTRACT

ABSTRACT: There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.


Subject(s)
Diabetes Mellitus , Pancreatitis, Chronic , Humans , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Pain , Pancreatitis, Chronic/therapy , Pancreatitis, Chronic/drug therapy , United States
5.
Ann R Coll Surg Engl ; 105(7): 678-680, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37652086

ABSTRACT

Dermoid cysts of the spermatic cord are rare, with only a few adult cases published in the literature. We report a patient with a 10cm inguinal mass referred to us for a suspected paratesticular sarcoma. Imaging suggested a cyst but, due to the recent increase in size, the cyst contents were evacuated and the cyst wall was biopsied. Histopathology revealed a dermoid cyst, which is a benign variant of cystic teratomas. Histopathological examination was required here due to the uncertainty. Careful interpretation was required, as cystic teratomas very occasionally undergo a malignant transformation.


Subject(s)
Dermoid Cyst , Spermatic Cord , Teratoma , Adult , Male , Humans , Spermatic Cord/diagnostic imaging , Spermatic Cord/surgery , Dermoid Cyst/diagnostic imaging , Dermoid Cyst/surgery , Biopsy
6.
Pediatr Radiol ; 53(11): 2210-2220, 2023 10.
Article in English | MEDLINE | ID: mdl-37500799

ABSTRACT

BACKGROUND: Pediatric radiologists can identify a liver ultrasound (US) pattern predictive of progression to advanced liver disease. However, reliably discriminating these US patterns remains difficult. Quantitative magnetic resonance imaging (MRI) may provide an objective measure of liver disease in cystic fibrosis (CF). OBJECTIVE: The purpose of this study was to determine if quantitative MRI, including MR elastography, is feasible in children with CF and to determine how quantitative MRI-derived metrics compared to a research US. MATERIALS AND METHODS: A prospective, multi-institutional trial was performed evaluating CF participants who underwent a standardized MRI. At central review, liver stiffness, fat fraction, liver volume, and spleen volume were obtained. Participants whose MRI was performed within 1 year of US were classified by US pattern as normal, homogeneous hyperechoic, heterogeneous, or nodular. Each MRI measure was compared among US grade groups using the Kruskal-Wallis test. RESULTS: Ninety-three participants (51 females [54.8%]; mean 15.6 years [range 8.1-21.7 years]) underwent MRI. MR elastography was feasible in 87 participants (93.5%). Fifty-eight participants had an US within 1 year of MRI. In these participants, a nodular liver had significantly higher stiffness (P<0.01) than normal or homogeneous hyperechoic livers. Participants with a homogeneous hyperechoic liver had a higher fat fraction (P<0.005) than others. CONCLUSION: MR elastography is feasible in children with CF. Participants with a nodular pattern had higher liver stiffness supporting the US determination of advanced liver disease. Participants with a homogeneous hyperechoic pattern had higher fat fractions supporting the diagnosis of steatosis.


Subject(s)
Cystic Fibrosis , Elasticity Imaging Techniques , Liver Diseases , Child , Female , Humans , Cystic Fibrosis/diagnostic imaging , Cystic Fibrosis/pathology , Feasibility Studies , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/pathology , Liver Diseases/pathology , Magnetic Resonance Imaging/methods , Prospective Studies
7.
Int J Obstet Anesth ; 55: 103899, 2023 08.
Article in English | MEDLINE | ID: mdl-37329691

ABSTRACT

BACKGROUND: Spinal anaesthesia, the most common form of anaesthesia for caesarean section, leads to sympathetic blockade and profound maternal hypotension resulting in adverse maternal and neonatal outcomes. Hypotension, nausea and vomiting remain common but until the publication of the National Institute of Health and Care Excellence (NICE) 2021 guidance, no national guideline existed on how best to manage maternal hypotension following spinal anaesthesia for caesarean section. A 2017 international consensus statement recommended prophylactic vasopressor administration to maintain a systolic blood pressure of >90% of an accurate pre-spinal value, and to avoid a drop to <80% of this value. This survey aimed to assess regional adherence to these recommendations, the presence of local guidelines for management of hypotension during caesarean section under spinal anaesthesia, and the individual clinician's treatment thresholds for maternal hypotension and tachycardia. METHODS: The West Midlands Trainee-led Research in Anaesthesia and Intensive Care Network co-ordinated surveys of obstetric anaesthetic departments and consultant obstetric anaesthetists across 11 National Health Service Trusts in the Midlands, England. RESULTS: One-hundred-and-two consultant obstetric anaesthetists returned the survey and 73% of sites had a policy for vasopressor use; 91% used phenylephrine as the first-line drug but a wide range of recommended delivery methods was noted and target blood pressure was only listed in 50% of policies. Significant variation existed in both vasopressor delivery methods and target blood pressures. CONCLUSIONS: Although NICE has since recommended prophylactic phenylephrine infusion and a target blood pressure, the previous international consensus statement was not adhered to routinely.


Subject(s)
Anesthesia, Obstetrical , Anesthesia, Spinal , Cesarean Section , Hypotension , Vasoconstrictor Agents , Humans , Female , Pregnancy , Adult , Hypotension/etiology , Anesthesia, Spinal/adverse effects , Anesthesia, Obstetrical/adverse effects , United Kingdom , Surveys and Questionnaires , Vasoconstrictor Agents/administration & dosage , Vasoconstrictor Agents/adverse effects
8.
J Cyst Fibros ; 22(4): 745-755, 2023 07.
Article in English | MEDLINE | ID: mdl-37032248

ABSTRACT

BACKGROUND: This study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). METHODS: Prospective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3-12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. RESULTS: 722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years. CONCLUSIONS: Research US finding of HTG identifies children with CF with a 30-50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD. CLINICAL TRIAL REGISTRATION: Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF: NCT 01,144,507 (observational study, no consort checklist).


Subject(s)
Cystic Fibrosis , Liver Diseases , Humans , Child , Prospective Studies , Cohort Studies , Cystic Fibrosis/complications , Cystic Fibrosis/epidemiology , Cystic Fibrosis/pathology , Platelet Count , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiology
9.
Pediatr Pulmonol ; 58(3): 811-818, 2023 03.
Article in English | MEDLINE | ID: mdl-36448312

ABSTRACT

INTRODUCTION: The success of highly effective modulator therapy (HEMT) has led to consideration of simpler regimens for people with CF (PwCF) with opportunities to modify burdensome regimens. Despite the intuitive appeal of discontinuing chronic therapies no longer necessary, this process should be pursued systematically to ensure safety, adherence, and validate patient-centered preferences. We designed a questionnaire to determine the state of use of acid-suppressive medications (ASM) and pancreatic enzyme therapy (PERT), current self-withdrawal and provider-directed withdrawal practices, and interest in a standardized withdrawal study. METHODS: In collaboration with CF Foundation (CFF), a questionnaire was developed and distributed to members of Community Voice (CV, comprised of PwCF and their loved ones), and CF providers regarding the need to study simplifying the gastrointestinal (GI) regimen for PwCF on HEMT. RESULTS: Approximately 20-40% of CV or CF providers have decreased or stopped ASM for those on HEMT. For PERT, CV and CF providers have decreased dose (34%-48% and approximately 25%, respectively) more often than having stopped it altogether (13%-24% and 3%-12%, respectively). Cumulatively, there is interest in pursuing research in this area (86% CV and 89% CF providers) and willingness to enroll in such a study (80% CV and 89% CF providers). CONCLUSION: Systematically studying the withdrawal of common GI medications, ASM and PERT, is important to CV and CF providers. Decreases in dosing and withdrawal are already taking place without evidence to support this practice. This questionnaire is the first step in designing a GI medication simplification study in PwCF on HEMT.


Subject(s)
Cystic Fibrosis , Humans , Cystic Fibrosis/drug therapy , Cystic Fibrosis Transmembrane Conductance Regulator/therapeutic use , Pancreas , Clinical Protocols , Surveys and Questionnaires
10.
J Cyst Fibros ; 22(2): 266-274, 2023 03.
Article in English | MEDLINE | ID: mdl-36319569

ABSTRACT

BACKGROUND AND AIMS: People with cystic fibrosis (PwCF) suffer from gastrointestinal (GI) symptoms affecting their quality of life (QOL). Despite the relevance of GI symptoms to the overall health of PwCF, a paucity of studies only have comprehensively assessed the prevalence, severity and QOL of GI symptoms in both children and adults with Cystic Fibrosis (CF). METHODS: Eligible participants ≥2 years of age across 26 US CF centers were followed for 4 weeks. Three validated GI electronic patient-reported outcome measures (ePROMs) with a recall period of 2 weeks and a stool-specific questionnaire were administered weekly over four weeks. Total and domain scores of ePROMs were evaluated overall and in subgroups using linear mixed-effect models. RESULTS: Of 402 enrolled, 58% were ≥ 18 years of age (52% male). The mean (SD) of the total score for PAC-SYM was 0.52 (0.55), for PAGI-SYM was 0.63 (0.67), and for PAC-QOL was 0.67 (0.55). For specific ePROM questions, prevalence of moderate to very severe symptoms were as follows: straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating (16.4%), distension (16.4%), abdominal pain (upper-5.1%, lower-7.5%). Comparing participants ≥18 versus <18, a higher prevalence of bloating (63.7% versus 27.3%), lower abdominal pain (39.8% vs 26.2%), stomach fullness (75.6% versus 56.2%), and abdominal distension (60.2% versus 34.9%) was found. Both age groups reported high treatment dissatisfaction as measured with PAC-QOL, mean 1.39 (95% CI: 1.30, 1.47). CONCLUSION: GI symptoms were reported in all age ranges irrespective of gender, with higher prevalence observed amongst older and female subgroups. Dissatisfaction with GI targeted treatments were reported in a large proportion of participants despite therapy, highlighting an unmet need for clinical interventions. CLINICALTRIALS: GOV: NCT03801993.


Subject(s)
Cystic Fibrosis , Gastrointestinal Diseases , Adult , Child , Humans , Male , Female , Infant , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Cystic Fibrosis/epidemiology , Quality of Life , Prospective Studies , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Abdominal Pain/diagnosis , Abdominal Pain/epidemiology , Abdominal Pain/etiology
11.
J Cyst Fibros ; 22(2): 248-255, 2023 03.
Article in English | MEDLINE | ID: mdl-35985930

ABSTRACT

BACKGROUND: Nodular liver (NOD) in cystic fibrosis (CF) suggests advanced CF liver disease (aCFLD); little is known about progression of liver disease (LD) after detection of sonographic NOD. METHODS: Clinical, laboratory, and ultrasound (US) data from Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in CFLD Study participants with NOD at screening or follow-up were compared with normal (NL). Linear mixed effects models were used for risk factors for LD progression and Kaplan-Meier estimator for time-to-event. RESULTS: 54 children with NOD (22 screening, 32 follow-up) and 112 NL were evaluated. Baseline (BL) and trajectory of forced expiratory volume, forced vital capacity, height/BMI z-scores were similar in NOD vs NL. Platelets were lower in NOD at BL (250 vs 331×103/microL; p < 0.001) and decreased by 8600/year vs 2500 in NL. Mean AST to Platelet Ratio Index (1.1 vs 0.4; p < 0.001), Fibrosis-4 Index (0.4 vs 0.2, p < 0.001), and spleen size z-score (SSZ) [1.5 vs 0.02; p < 0.001] were higher in NOD at BL; SSZ increased by 0.5 unit/year in NOD vs 0.1 unit/year in NL. Median liver stiffness (LSM) by transient elastography was higher in NOD (8.2 kPa, IQR 6-11.8) vs NL (5.3, 4.2-7, p < 0.0001). Over 6.3 years follow-up (1.3-10.3), 6 NOD had esophageal varices (cumulative incidence in 10 years: 20%; 95% CI: 0.0%, 40.0%), 2 had variceal bleeding, and 2 underwent liver transplantation; none had ascites or hepatic encephalopathy. No NL experienced liver-related events. CONCLUSIONS: NOD developed clinically evident portal hypertension faster than NL without worse growth or lung disease.


Subject(s)
Cystic Fibrosis , Elasticity Imaging Techniques , Esophageal and Gastric Varices , Hypertension, Portal , Humans , Child , Follow-Up Studies , Cystic Fibrosis/complications , Cystic Fibrosis/epidemiology , Cystic Fibrosis/pathology , Esophageal and Gastric Varices/pathology , Gastrointestinal Hemorrhage/pathology , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/etiology
12.
J Pediatr Gastroenterol Nutr ; 75(5): 635-642, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36070552

ABSTRACT

OBJECTIVES: Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health-Related Quality of Life (HRQOL) in children enrolled in a multi-center study of CFLD to determine the impact of early CFLD on general and disease-specific QOL. METHODS: Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child-reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire-revised (CFQ-R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling-Lawley trace tested for differences among US groups. RESULTS: Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ-R at baseline. Parents of NOD reported no change in PedsQL/CFQ-R over the next year. Child-report PedsQL/CFQ-R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ-R scores related to weight. CONCLUSIONS: Early undiagnosed or pre-symptomatic liver disease had no impact on generic or disease-specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.


Subject(s)
Cystic Fibrosis , Liver Diseases , Humans , Child, Preschool , Quality of Life , Prospective Studies , Health Status , Cystic Fibrosis/complications , Cystic Fibrosis/diagnostic imaging , Surveys and Questionnaires , Liver Diseases/etiology , Liver Diseases/complications
14.
Radiography (Lond) ; 28(4): 964-972, 2022 11.
Article in English | MEDLINE | ID: mdl-35849887

ABSTRACT

INTRODUCTION: The British Institute of Radiology (BIR) and American Association of Physicists in Medicine (AAPM) have recommended that gonad shielding is no longer used during pelvic X-ray examinations. The BIR guidance states that shielding may still be considered for use on males, but should not be used on females. This paper aimed to evaluate if this decision was supported by evidence from practice, by comparing the accuracy of gonad shield placement in paediatric males and females. METHODS: A systematic review of databases including EMBASE, MEDLINE and PubMed was performed in February 2021. Studies were considered eligible if they provided data on the use of gonad shielding during pelvic X-ray examinations on male and female patients under the age of 18. Nine studies met the inclusion criteria and data extraction was performed. Quality appraisal was undertaken, and a meta-analysis of shielding accuracy was performed on seven studies. RESULTS: The results from the meta-analysis (2187 total radiographs) demonstrated that female patients were significantly more likely (OR 1.38, 95% CI 0.88-1.87) than males to have gonad shields placed inaccurately (p value < 0.001). CONCLUSION: Gonad shield placement on paediatric female patients is significantly less accurate than on males, and so the results support the AAPM and BIR guidance to stop the practice for females. Shield application may also be frequently inaccurate for males, but the review does not provide clear evidence for or against continuing the practice for males. IMPLICATIONS FOR PRACTICE: Discontinuing the use of gonad shields in paediatric pelvic radiography on female patients is supported. Any continued use on male patients, or for reasons such as psychological reassurance, should be subject to enhanced training and audit to ensure benefits outweigh any risks.


Subject(s)
Gonads , Radiation Protection , Child , Female , Humans , Male , Pelvis/diagnostic imaging , Physical Examination , Radiography
15.
J Eur Acad Dermatol Venereol ; 36(10): 1851-1856, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35695159

ABSTRACT

BACKGROUND: Pseudoepitheliomatous keratotic and micaceous balanitis (PEKMB) is a clinicopathological entity characterized clinically by micaceous scale on the glans, and histologically by acanthosis, hyperkeratosis and pseudoepitheliomatous hyperplasia. We present a series of eight cases of this rare condition, the first series of more than two cases to be reported. OBJECTIVES: To determine the clinical and histological characteristics of cases of PEKMB, and evaluate treatments used and clinical course. METHODS: This monocentric case series was conducted at the University College London Hospitals tertiary male genital dermatology clinic between April 2018 and August 2020. Eight patients with PEKMB were evaluated. Data were collected on demographics, clinical presentation, histological features, presence of human papilloma virus (HPV), history of lichen sclerosus, treatment of PEKMB and subsequent response, and presence or development of squamous cell carcinoma (SCC) or penile intraepithelial neoplasia (PeIN) during follow-up. RESULTS: Eight Caucasian males presented with clinical and histological evidence of PEKMB. Seven had a background of lichen sclerosus; two had failed treatment with superpotent topical steroids and four had symptoms for three or more years prior to circumcision. There was no clinical or histological relationship with HPV infection, and p16 staining was negative. HPV PCR, performed in two cases, was negative. Basal atypia, insufficient to amount to PeIN, was present in six patients. One patient progressed to PeIN during follow-up, and no patient progressed to invasive malignancy. Five patients were treated successfully with glans resurfacing and split skin graft reconstruction. CONCLUSIONS: Our observations demonstrate that PEKMB represents a form of chronic, undiagnosed or misdiagnosed, inadequately treated or treatment refractory, unstable lichen sclerosus. The significant potential for squamous carcinogenesis (differentiated PeIN and verrucous carcinoma) can be mitigated by timely diagnosis and treatment. Glans resurfacing and split skin graft reconstruction appears to be a successful treatment modality in patients with refractory disease.


Subject(s)
Balanitis , Carcinoma in Situ , Keratosis , Lichen Sclerosus et Atrophicus , Papillomavirus Infections , Penile Neoplasms , Skin Neoplasms , Balanitis/diagnosis , Carcinoma in Situ/pathology , Humans , Keratosis/pathology , Lichen Sclerosus et Atrophicus/complications , Lichen Sclerosus et Atrophicus/pathology , Male , Papillomaviridae , Penile Neoplasms/diagnosis , Penile Neoplasms/pathology , Penile Neoplasms/surgery
16.
Science ; 376(6593): 555, 2022 05 06.
Article in English | MEDLINE | ID: mdl-35536898

ABSTRACT

Later this year, I will step down as president of the University of Maryland, Baltimore County (UMBC), after 30 years. I know this to be true-faculty members have the power. Presidents, provosts, and senior leaders at an institution set a tone and create the setting for successful programs. But ultimately, it is the commitment of professors and teaching staff that determines whether students-all students-can pursue their interests and achieve their goals. It takes high expectations for both students and educators.


Subject(s)
Faculty , Students , Humans , Teaching
17.
J Cyst Fibros ; 21(5): 830-836, 2022 09.
Article in English | MEDLINE | ID: mdl-35585010

ABSTRACT

BACKGROUND: Concerns related to stool consistency are common in the first year of life among children with cystic fibrosis (CF). However, normal stool patterns for infants with CF have not been described. METHODS: Secondary analysis was completed from the previously described BONUS cohort which followed 231 infants with CF through the first 12 months of life. Pain, stool category, stool frequency, feeding type, PERT dose, acid suppression medication, antibiotics usage, stool softener usage and fecal calprotectin were described at 3, 6, and 12 months. Repeated measure ANOVA was used to test the difference in mean stool number. Generalized linear mixed models were used to investigate the relationship between stool characteristics and various factors. RESULTS: The frequency of constipation was stable throughout the first year of life (10-13%) while watery stool significantly decreased from 21.3% at 3 months to 5.8% at 12 months (p=<0.001). The number of stools at months 6 (mean=2.40) and 12 (mean=2.50) are significantly lower than in month 3 (mean=2.83), p<0.025. Exclusive breast feeding was associated with an increased risk for constipation (OR=2.64  [1.60-4.37], p = 0.002) while exclusive formula feeding and acid suppression was associated with decreased risk for constipation (OR=0.40  [0.26-0.61], p=<0.0001 and OR=0.59  [0.39-0.89], p = 0.01 respectively). Pain was not significantly associated with stool consistency. CONCLUSION: Stool frequency and consistency evolves in infant with CF in a fashion similar to that reported in non-CF infants over the first year. Constipation was not associated with pain and was less common among infants receiving acid suppression or exclusively formula feeding.


Subject(s)
Cystic Fibrosis , Anti-Bacterial Agents , Breast Feeding , Child , Constipation/diagnosis , Constipation/epidemiology , Constipation/etiology , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Cystic Fibrosis/epidemiology , Feces , Female , Humans , Infant , Leukocyte L1 Antigen Complex
18.
Eur J Endocrinol ; 186(4): 441-455, 2022 Feb 28.
Article in English | MEDLINE | ID: mdl-35113805

ABSTRACT

BACKGROUND: Chronic wounds (e.g. diabetic foot ulcers) reduce the quality of life, yet treatments remain limited. Glucocorticoids (activated by the enzyme 11ß-hydroxysteroid dehydrogenase type 1, 11ß-HSD1) impair wound healing. OBJECTIVES: Efficacy, safety, and feasibility of 11ß-HSD1 inhibition for skin function and wound healing. DESIGN: Investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group phase 2b pilot trial. METHODS: Single-center secondary care setting. Adults with type 2 diabetes mellitus without foot ulcers were administered 400 mg oral 11ß-HSD1 inhibitor AZD4017 (n = 14) or placebo (n = 14) bi-daily for 35 days. Participants underwent 3-mm full-thickness punch skin biopsies at baseline and on day 28; wound healing was monitored after 2 and 7 days. Computer-generated 1:1 randomization was pharmacy-administered. Analysis was descriptive and focused on CI estimation. Of the 36 participants screened, 28 were randomized. RESULTS: Exploratory proof-of-concept efficacy analysis suggested AZD4017 did not inhibit 24-h ex vivoskin 11ß-HSD1 activity (primary outcome; difference in percentage conversion per 24 h 1.1% (90% CI: -3.4 to 5.5) but reduced systemic 11ß-HSD1 activity by 87% (69-104%). Wound diameter was 34% (7-63%) smaller with AZD4017 at day 2, and 48% (12-85%) smaller after repeat wounding at day 30. AZD4017 improved epidermal integrity but modestly impaired barrier function. Minimal adverse events were comparable to placebo. Recruitment rate, retention, and data completeness were 2.9/month, 27/28, and 95.3%, respectively. CONCLUSION: A phase 2 trial is feasible, and preliminary proof-of-concept data suggests AZD4017 warrants further investigation in conditions of delayed healing, for example in diabetic foot ulcers. SIGNIFICANCE STATEMENT: Stress hormone activation by the enzyme 11ß-HSD type 1 impairs skin function (e.g. integrity) and delays wound healing in animal models of diabetes, but effects in human skin were previously unknown. Skin function was evaluated in response to treatment with a 11ß-HSD type 1 inhibitor (AZD4017), or placebo, in people with type 2 diabetes. Importantly, AZD4017 was safe and well tolerated. This first-in-human randomized, controlled, clinical trial found novel evidence that 11ß-HSD type 1 regulates skin function in humans, including improved wound healing, epidermal integrity, and increased water loss. Results warrant further studies in conditions of impaired wound healing, for example, diabetic foot ulcers to evaluate 11ß-HSD type 1 as a novel therapeutic target forchronic wounds.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , Diabetes Mellitus, Type 2/complications , Diabetic Foot/drug therapy , Niacinamide/analogs & derivatives , Piperidines/therapeutic use , Skin/drug effects , Wound Healing/drug effects , Adult , Aged , Aged, 80 and over , Diabetic Foot/pathology , Double-Blind Method , Epidermis/drug effects , Epidermis/pathology , Female , Humans , Male , Middle Aged , Niacinamide/therapeutic use , Pilot Projects , Quality of Life , Skin/pathology , Skin/physiopathology , Treatment Outcome
19.
J Dermatolog Treat ; 33(2): 1047-1062, 2022 Mar.
Article in English | MEDLINE | ID: mdl-32705920

ABSTRACT

INTRODUCTION: Penile intraepithelial neoplasia (PeIN) is a histological term for precancerous penile lesions. PeIN is important due to the high morbidity and mortality associated with progression to penile squamous cell carcinoma (PSSC). But PeIN is rare, contributing to a limited evidence-base for the relative efficacy of available treatment options. OBJECTIVES & METHODS: To consolidate and expand knowledge about PeIN and its treatment, we describe the clinical and histological characteristics, treatments and outcomes of 345 patients with PeIN, managed by our multidisciplinary team. Our results are compared and contrasted with those in the literature, following comprehensive review. RESULTS: 8.7% of patients had concomitant, invasive PSCC, whilst 91.3% demonstrated PeIN alone. 84% had undifferentiated PeIN, and 10.7% differentiated PeIN (5.2%, not specified). Clinical or histological evidence of HPV alone was present in 58%; features of lichen sclerosus alone in 12%; features of both in 29.4%. Only 14.4% of patients could be treated solely with topical agents or cryotherapy, whereas the remaining 85.6% underwent some form of surgical intervention, circumcision being the mainstay. Just 2.6% progressed to PSCC. CONCLUSIONS: Clinical management of PeIN can be rationally optimized with excellent outcomes. Circumcision is important. Topical treatments alone are disappointing.


Subject(s)
Carcinoma in Situ , Lichen Sclerosus et Atrophicus , Penile Neoplasms , Skin Neoplasms , Carcinoma in Situ/pathology , Carcinoma in Situ/therapy , Humans , Lichen Sclerosus et Atrophicus/pathology , Lichen Sclerosus et Atrophicus/therapy , Male , Penile Neoplasms/pathology , Penile Neoplasms/therapy , Penis/pathology , Skin Neoplasms/pathology
20.
Pediatr Clin North Am ; 68(6): 1273-1291, 2021 12.
Article in English | MEDLINE | ID: mdl-34736589

ABSTRACT

Pediatric pancreatitis describes a spectrum covering acute pancreatitis, acute recurrent pancreatitis, and chronic pancreatitis, each with varying clinical manifestations and risk factors requiring a tailored diagnostic approach. We emphasize management strategies based on age, risk factors, recurrence, and complications. A discussion of the role of therapeutic endoscopy is reviewed and highlights the growing role of endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in children with pancreatitis. Particular diagnostic challenges in autoimmune pancreatitis are reviewed with an emphasis on differentiating this entity from alternate pancreaticobiliary pathologies. Finally, we explore a multidisciplinary approach to acute recurrent and chronic pancreatitis.


Subject(s)
Pancreatitis/diagnosis , Pancreatitis/therapy , Acute Disease/therapy , Adolescent , Age Factors , Autoimmune Pancreatitis/diagnosis , Autoimmune Pancreatitis/therapy , Child , Child, Preschool , Cholangiopancreatography, Endoscopic Retrograde/methods , Endoscopy/methods , Fluid Therapy/methods , Humans , Infant , Malnutrition/epidemiology , Nutrition Therapy/methods , Pain Management/methods , Pancreatitis/epidemiology , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/therapy , Recurrence , Risk Factors
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