Growth hormone therapy: Comparison of short- and long-term outcomes between children with Growth Hormone Deficiency and Small for Gestational Age.

Introduction Direct comparisons of both short-term and long-term auxological outcome of growth hormone therapy (GHT) between growth hormone deficiency (GHD) and small for gestational age (SGA) are scarce. Methods 103 patients with GHD and 53 patients with SGA treated at our tertiary center were investigated. Short-term and long-term outcomes were compared between these groups using multi-variable linear regression models with adjustment for age, sex and height at therapy start, also allowing for sex-specific group comparisons. Results Mean delta height standard deviation scores (SDS) after 1 year of treatment was significantly higher in GHD (0.90, CI 0.82 to 0.99) compared to SGA (0.67, C I 0.54 to 0.79)(p= 0.003) with no sex difference. As expected, the mean increase in height SDS at final height (FH) was significantly higher in GHD (2.21, CI 2.00 to 2.42) compared to SGA (1.05, CI 0.75 to 1.35)(p<0.001), leading to a target height corrected FH of -0.39 SDS (CI -0.62 to -0.15) in GHD and -1.22 SDS (CI-1.57 to -0.87) in SGA ( p<0.001). Girls with GHD had a better long-term outcome, as did boys with SGA when compared to the respective opposite sex. The cut-off of delta height of 0.5 SDS during the first year had a low sensitivity to detect long-term non-responders. We found a relation between short-term and long-term outcome in GHD, but not in SGA (adjusted R2 = 0.66 vs. 0.01). Conclusion In contrast to GHD, we observed practically no relationship between 1st-year and long-term outcome in SGA patients treated with GH.

Vosoritide Therapy in Children with Achondroplasia: Early Experience and Practical Considerations for Clinical Practice.

INTRODUCTION: Vosoritide is the first precision medical therapy approved to increase growth velocity in children with achondroplasia. Sharing early prescribing experiences across different regions could provide a framework for developing practical guidance for the real-world use of vosoritide. METHODS: Two meetings were held to gather insight and early experience from experts in Europe, the Middle East, and the USA. The group comprised geneticists, pediatric endocrinologists, pediatricians, and orthopedic surgeons. Current practices and considerations for vosoritide were discussed, including administration practicalities, assessments, and how to manage expectations. RESULTS: A crucial step in the management of achondroplasia is to determine if adequate multidisciplinary support is in place. Training for families is essential, including practical information on administration of vosoritide, and how to recognize and manage injection-site reactions. Advocated techniques include establishing a routine, empowering patients by allowing them to choose injection sites, and managing pain. Patients may discontinue vosoritide if they cannot tolerate daily injections or are invited to participate in a clinical trial. Clinicians in Europe and the Middle East emphasized the importance of assessing adherence to daily injections, as non-adherence may impact response and reimbursement. Protocols for monitoring patients receiving vosoritide may be influenced by regional differences in reimbursement and healthcare systems. Core assessments may include pubertal staging, anthropometry, radiography to confirm open physes, the review of adverse events, and discussion of concomitant or new medications-but timing of these assessments may also differ regionally and vary across institutions. Patients and families should be informed that response to vosoritide can vary in both magnitude and timing. Keeping families informed regarding vosoritide clinical trial data is encouraged. CONCLUSION: The early real-world experience with vosoritide is generally positive. Sharing these insights is important to increase understanding of the practicalities of treatment with vosoritide in the clinical setting.

Formulation and characterisation of metyrapone suppositories for the first effective long-term use in an infant with McCune-Albright syndrome-related Cushing syndrome.

OBJECTIVES: The aim of this project was to develop a rectal formulation of metyrapone suitable for application in an infant hospitalised with McCune-Albright syndrome (MAS)-related Cushing syndrome and to provide a detailed description of the formulation protocol including quality control parameters. METHODS: Suppositories with a drug load of up to 100 mg metyrapone were prepared. Mass variation, content uniformity and drug release were analysed according to the guidelines set out by the European Pharmacopoeia. Monitoring of the drug content for 6 weeks allowed for estimation of the storage stability at 2-8°C. RESULTS: A protocol for the reproducible preparation of suppositories with intended metyrapone content of 30-100 mg was established. The suppositories were well tolerated by the patient and the clinical outcome is promising. The suppository preparations complied with the regulations from the European Pharmacopoeia. Further, a stability of the rectal formulation of at least 1 month was confirmed, facilitating medication supply for home care. CONCLUSIONS: An adequate and easy to follow protocol for preparation of high-quality metyrapone suppositories, with sufficient stability for practical use and fulfilling major pharmaceutical quality parameters, was established. The protocol can be easily replicated by skilled personnel in a community pharmacy facilitating treatment of the infant in home care.

SUCCESSFUL USE OF METYRAPONE SUPPOSITORIES IN AN INFANT WITH NEONATAL CUSHING AND MCCUNE ALBRIGHT SYNDROME- A CASE REPORT.

A female toddler was diagnosed at age ten months with peripheral precocious puberty and hypercortisolism related to McCune Albright Syndrome with additional systemic complications. We present the first successful, long-term use of metyrapone as suppositories, with striking clinical and biochemical improvement and no side-effects.

Ochrobactrum anthropi infection in dialysis patients: A case report and literature summary.

INTRODUCTION: Ochrobactrum anthropi, a ubiquitous Gram-negative bacterium of low virulence, is an increasingly recognized cause of infection in immunocompromised hosts such as patients with kidney failure treated by dialysis. CASE REPORT: We report the case of a male hemodialysis patient with a central venous catheter, who developed an asymptomatic blood stream infection caused by Ochrobactrum anthropi. The infection was cured, and the dialysis catheter salvaged with intravenous meropenem and an antibiotic lock solution with ciprofloxacin. CONCLUSION: We identified 13 further cases of Ochrobactrum infection in hemodialysis patients and 10 cases in peritoneal dialysis patients in the literature. Antibiotic treatment depends on the results of susceptibility testing. In many patients, however, removal of the central venous or peritoneal dialysis catheter is required to cure the infection.

Hafnia alvei Urosepsis in a Kidney Transplant Patient.

Hafnia alvei, a gram-negative facultative anaerobic, rod-shaped bacterium, is a rare cause of infection in humans. We report on a renal transplant patient who developed H. alvei pyelonephritis and urosepsis. The source of infection remains enigmatic but is most likely the intestinal tract. Appropriate antibiotic therapy with cefepime followed by oral ciprofloxacin brought about rapid resolution of symptoms and complete recovery. H. alvei may cause severe infection in transplant patients without predisposing factors such as hospitalization, invasive procedures, or antibiotic treatment.

Clostridium perfringens liver abscess after pancreatic resection.

BACKGROUND: Liver abscess is a rare complication after pancreatectomy. Clostridium perfingens is a rare cause of intrahepatic infections. CASE REPORT: A 65-year-old woman with pancreatic cancer underwent explorative laparotomy, during which encasement of the hepatic artery by the tumor was found. Neoadjuvant radiochemotherapy with capecitabine was started, which caused tumor regression, and duodenopancreatectomy was performed. The portal vein was occluded and infiltrated by cancer and therefore was resected and not reconstructed. After a slow recovery, the patient developed hemorrhage at the gastrojejunal anastomosis, which was controlled by fibrin injection. Within a few days, she presented with signs of sepsis, and blood cultures yielded Clostridium perfringens, Streptococcus oralis, Staphylococcus aureus, and Candida albicans. The source of the sepsis proved to be a 9-cm liver abscess, which was drained; cultures grew C. perfringens, Hafnia alvei, and Enterobacter cloacae. Despite antibiotic treatment, the patient died from sepsis and multiorgan failure 27 days after pancreatic surgery. CONCLUSION: Such rare infections can follow pancreatic resection with neoadjuvant radiochemotherapy. Clostridium perfringens-associated liver abscess maintains a high mortality rate.

A case of fulminant post-transplant lymphoproliferative disorder and septicemia.

The fulminant form of post-transplant lymphoproliferative disorder (PTLD) is very uncommon and occurs in approximately 1% of PTLD patients. Approximately 85% of these lesions are of B-cell origin, and most of them are associated with Epstein-Barr virus infection. Fulminant PTLD is frequently associated with a systemic inflammatory response syndrome, and may be difficult to differentiate from septicemia. We describe the case of a 59-yr-old man who suffered from prolonged septicemia in the immediate post-transplant period, and presented again four months after cardiac transplantation with fever, painful liver edge and gastrointestinal bleeding. The diagnosis of fulminant PTLD with advanced multiorgan infiltration by a diffuse large-cell lymphoma of B-cell phenotype was made. During treatment with rituximab, the patient died from Enterococcus faecium septicemia. The sequence of septicemia, PTLD and, finally again, septicemia is an unusual challenge and urges for an aggressive diagnostic approach, where markers like procalcitonin may aid in the discrimination of fulminant PTLD from septicemia.

Vaccine strategies of meningococcal disease: results of a 10-year population-based study.

UNLABELLED: Invasive meningococcal disease (IMD) is an important cause of morbidity and mortality in children and adults. This study was conducted to determine a possible increase in IMD in recent years with special interest focused on serogroup C disease. From January 1st 1993 to December 31st 2002, IMD was studied in one million residents of Austria. We used active, population-based surveillance data from the Office of Public Health. A total of 126 patients with positive blood and/or cerebrospinal fluid culture or positive swabs for Neisseria meningitidis were studied. The median age of all patients was 9.5 years (range 1 month to 63 years). The average incidence of all IMD subgroups was 1.05 cases per 100,000 person years and was highest in children 0-4 years old (7.08 cases per 100,000 person years) followed by young adults aged 15 to 19 years (4.35 cases per 100,000 person years). Serogroup C IMD occurred in 1.30 cases/100,000 person years in patients aged 0 to 4 years and in 1.92 cases/100,000 person years in patients aged 15 to 19 years. Overall mortality was 11.1%. There was a significant increase (P =0.001) in IMD due to serogroup B disease within the last 10 years. In contrast, serogroup C disease did not increase during the last decade. CONCLUSION: Currently, we do not recommend mass vaccination against serogroup C disease in Austria, but young adults aged 15 to 19 years display a high incidence of meningococcal C disease. In this age group, vaccination against serogroup C disease should be considered.