Insights from an Italian Delphi panel: exploring resistance to first-generation somatostatin receptor ligands and guiding second-line medical therapies in acromegaly management.

PURPOSE: First-line medical therapy for acromegaly management includes first-generation somatostatin receptor ligands (fgSRLs), but resistance limits their use. Despite international guidelines, the choice of second-line therapy is debated. METHODS: We aim to discuss resistance to fgSRLs, identify second-line therapy determinants and assess glycemia's impact to provide valuable insights for acromegaly management in clinical practice. A group of Italian endocrinologists expert in the pituitary field participated in a two-round Delphi panel between July and September 2023. The Delphi questionnaire encompassed a total of 75 statements categorized into three sections: resistance to fgSRLs therapy and predictors of response; determinants for the selection of second-line therapy; the role of glycemia in the therapeutic management. The statements were rated on a 6-point Likert scale. RESULTS: Fifty-nine (79%) statements reached a consensus. IGF-1 levels resulted central for evaluating resistance to fgSRLs, that should be defined considering also symptomatic clinical response, degree of tumor shrinkage and complications, using clinician- and patient-reported outcome tools available. Factors to be evaluated for the choice of second-line medical therapy are hyperglycemia-that should be managed as in non-acromegalic patients-tumor remnant, resistant headache and compliance. Costs do not represent a main determinant in the choice of second-line medical treatment. CONCLUSION: The experts agreed on a holistic management approach to acromegaly. It is therefore necessary to choose currently available highly effective second-line medical treatment (pegvisomant and pasireotide) based on the characteristics of the patients.

Bilateral testicular masses and adrenal insufficiency: is congenital adrenal hyperplasia the only possible diagnosis? First two cases of TARTS described in Addison-only X-linked adrenoleukodystrophy and a brief review of literature.

BACKGROUND: Testicular adrenal rest tumors (TARTs) are benign masses deemed to originate from pluripotent testicular steroidogenic cells that grow under chronic ACTH stimulation. These lesions, occasionally misdiagnosed as Leydig cell tumors (LCTs), are typically described in patients with congenital adrenal hyperplasia (CAH). X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of beta-oxidation with accumulation of very long chain fatty acids (VLCFAs) in various tissues, and a rare cause of primary adrenal insufficiency (PAI). TARTs have never been associated with X-ALD. CASE 1 DESCRIPTION: A 19-year old male, who had previously undergone bilateral enucleation of presumed LCTs, was referred to our unit. Follow-up scans showed persistent bilateral lesions compatible with TARTs. Biochemical exams revealed PAI but excluded CAH. A serum VLCFAs panel was consistent with X-ALD, with gene testing confirming the diagnosis. Histological revision of the previously resected testicular lesions was compatible with TARTs. Start of glucocorticoid replacement therapy was associated with a reduction of testicular masses. CASE 2 DESCRIPTION: A 26-year old X-ALD male was diagnosed with bilateral testicular lesions compatible with TARTs. These lesions increased after ACTH elevation following switch to modified-release hydrocortisone. Clinical and sonographic findings allowed for a "watchful-waiting" approach, avoiding unnecessary surgery. CONCLUSION: These are the first cases reported of TARTs in patients with X-ALD-associated PAI. Testicular lesions in patients with an early onset of ACTH elevation, regardless of the cause, should always be thoughtfully investigated, as they may reveal themselves as TARTs. We suggest that all patients affected from chronic ACTH elevation of a young age of onset should undergo testicular ultrasound in order to evaluate the presence of these lesions. GRT in these patients might also help preserving fertility.

cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion.

cAMP effects have been initially attributed to protein kinase A (PKA) activation. Subsequently, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets. Aim of this study was to investigate cAMP effects in pancreatic-NET (P-NET) and bronchial carcinoids and in corresponding cell lines (QGP-1 and H727) on cell proliferation and adhesion and to determine PKA and Epac role in mediating these effects. We found that cAMP increased cyclin D1 expression in P-NET and QGP-1 cells, whereas it had opposite effects on bronchial carcinoids and H727 cells and it promoted cell adhesion in QGP-1 and H727 cells. These effects are mimicked by Epac and PKA specific analogs, activating the small GTPase Rap1. In conclusion, we demonstrated that cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1.

Reduction in colonization and nosocomial infection by multiresistant bacteria in a neonatal unit after institution of educational measures and restriction in the use of cephalosporins.

INTRODUCTION: Previous administration of third-generation cephalosporins predisposes to colonization and infections by multiresistant Enterobacter sp. The emergence of multiresistant bacteria infections in a neonatal unit during 1995, especially Enterobacter cloacae, stimulated this study. OBJECTIVE: To evaluate the efficacy of measures to control colonization and nosocomial infection by multiresistant bacteria in a neonatal unit. SETTING: A tertiary care university hospital. PATIENTS AND METHODS: This study was conducted from October 1995 through December 1999 in 4 phases: a cross-sectional study, a longitudinal study with intervention measures, monthly cross-sectional studies, and determination of nosocomial infections caused by multiresistant bacteria (oxacillin-resistant Staphylococcus aureus and gram-negative bacteria resistant to either aminoglycosides or third-generation cephalosporins). Specimens for surveillance culture were obtained through umbilical and rectal swabs, and tracheal aspirates from intubated babies. The intervention measures were as follows: (1) appropriated training of the whole health care team, emphasizing measures to reduce cross-colonization, and the importance of rational usage of antibiotics and (2) suppression of usage of third-generation cephalosporins. Risk factors were analyzed through univariate and multivariate logistic regression. RESULTS: In the first phase, 32% (10/31) of the patients were colonized by multiresistant bacteria (29% by multiresistant E cloacae ). In the second phase, 342 patients were evaluated; 33% of them were colonized by E cloacae, and a multiresistant strain was isolated in 10.8% (37/342) of the babies. A logistic regression model indicated parenteral nutrition and antibiotic usage as risk factors for colonization by multiresistant E cloacae. In the third phase, for 6 months, only 2 patients were colonized by multiresistant E cloacae. In the fourth phase, the analysis of bacterial resistance profile indicated a reduction of nosocomial infections due to multiresistant bacteria from 18 cases in 1995 to 2 cases per year until 1999. CONCLUSION: These results have shown that the measures adopted were effective.

Nasal MRSA colonization of AIDS Patients cared for in a Brazilian university hospital.

Weekly culture surveillance was conducted over a 2-year period to determine the incidence of methicillin-resistant Staphylococcus aureus nasal colonization among acquired immunodeficiency syndrome patients cared for in a day-care unit and in an infectious diseases unit. Analysis of genomic DNA profiles showed a predominant pattern in both units.

[Isoniazid-induced hepatic failure. Report of a case]. / Insuficiência hepática pelo uso de isoniazida. Relato de caso.

Isoniazid and pyrazinamide are both well-known hepatotoxic drugs. When isoniazid is used, the hepatic lesion appears before than when pyrazinamide is used. This paper intends to relate a case of a 5-month-old patient who had lungs' and meningeal tuberculosis and who developed toxic hepatitis accomplished by hepatic failure while he was being treated with isoniazid, pyrazinamide and rifampicin. The clinic manifestations and the laboratory alterations were detected in the fifth day of treatment and the recovery was fast; and almost complete by the end of the first week, in which the use of isoniazid had been suspended. Although it was necessary to take the patient to the intensive care unit, he had a good recovery, without sequels.

Enterobacter cloacae sepsis outbreak in a newborn unit caused by contaminated total parenteral nutrition solution.

OBJECTIVE: The study aimed to investigate an outbreak caused by Enterobacter cloacae in a neonate intensive care unit. DESIGN: A descriptive study of an outbreak of sepsis in high-risk neonates was used. SETTING: The study was set in a tertiary care university teaching hospital. PATIENTS: The patients were 11 neonates infected with Enterobacter cloacae whose symptoms and signs of sepsis developed during a 16-hour period. All but one neonate received parenteral nutrition. Isolates from blood cultures, in-use parenteral nutrition solutions, and control aliquots of parenteral nutrition solution were typed by pulsed-field gel electrophoresis. RESULTS: Enterobacter cloacae was found in the refrigerated aliquots of parenteral nutrition solution, in blood cultures from infected newborns, and from in-use parenteral nutrition solutions. All these strains of Enterobacter cloacae had the same antibiotic susceptibility pattern and the same genomic DNA profile. The strain isolated from the one patient who did not receive parenteral nutrition presented a different susceptibility profile and genotype. CONCLUSION: The source of the nosocomial sepsis was the parenteral nutrition solution in 10 neonates. This contamination apparently occurred during preparation of the parenteral solution.

[Risk factors associated with the acquisition of multiresistant bacteria in a pediatric nursery] / Fatores de risco relacionados à aquisição de bactérias.

OBJECTIVE: To identify the risk factors in patients who had a multiresistant bacteria during their staying in a Pediatric Intensive Care Unit and in a pediatric nursery of a tertiary teaching hospital.METHODS: Chart review of the patients who stayed in the units from January, 1995 to July, 1997 and had a multiresistant microorganism isolated (both infection and colonization). A case-control study was done using McNemar test for group comparison and using stepwise logistic regression to select independent risk factors. The following risk factors were tested: prior hospital staying, underlying disease, intensive care unit admission, surgical procedure, urinary catheter, central venous line, ventilator, prior antibiotic therapy and skin lesion.RESULTS: Among 52 patients, 66 multiresistant bacteria were identified (among them, 33 were gram-negative bacilli and 33 were methicillin-resistant S. aureus). The logistic regression analysis of the case-control study identified 2 risk factors: prior antibiotic therapy and skin lesion. A single risk factor was indicated for patients with gram-negative bacilli. Nevertheless, for patients with methicillin-resistant S. aureus, central venous lines and skin lesion were significant.CONCLUSION: Prior antibiotic therapy and skin lesion were the factors associated with the acquisition of multiresistant bacteria. Besides skin lesion, for oxacilin-resistant S. aureus colonized patients, central venous catheter use was a risk factor. The strategies employed to limit the spread of those bacteria in the hospital should consider these three factors.

[Cerebrovascular disease in children: I. Epileptic manifestations]. / Doença cerebrovascular na infância. I. Manifestações epilépticas.

Seizures may occur as a complication of cerebrovascular disease (CVD) and its prevalence, clinical presentation, risk factors and evolution have been reported by few authors. We evaluated 39 children with CVD and analyzed the association with seizures. Seizures occurred in 24 (61.5%) patients and were classified as partial (29.2%), generalized (54.2%) and secondarily generalized (16.6%). Infants had a significantly higher prevalence of seizures (p = 0.0362) than children at other ages. Cortical localization was associated with a significantly higher prevalence of seizures (p = 0.0101). There were no differences between ischemic and hemorrhagic strokes. Fourteen patients had no seizures after the acute phase of the CVD, the 2 previously epileptic patients had their seizures controlled with antiepileptic drugs, 3 developed epilepsy, 2 died during the acute phase and in 3 patients there was not enough time yet to make a clear diagnosis of epilepsy.

[Factors that can interfere in the result of blood culture in pediatric intensive care unit] / Fatores que podem interferir no resultado de hemocultura em unidade de terapia intensiva pediátrica.

OBJECTIVE: To analyze factors that can interfere with the results of blood culture in a pediatric population, as there are few reports of standardization of blood culture in Pediatrics. METHODS: During three months 100 blood samples, collected at the Pediatric Intensive Care Unit of the "Hospital das Clínicas" of the Medical School of the Campinas State University (UNICAMP) were analyzed with respect to site and manner of collecting, age of the patients, clinical diagnosis, type of antiseptic substance used and blood volume withdrawn for sample. RESULTS: Two samples were sufficient to diagnose bacteremia. The positivity of the samples were related to the age of the patients. The rate of contamination related to the total number of samples was of 5%. All the false-positive samples were collected from children less than one year of age. The blood culture diagnosed bacteremia by multiresistant agents even in patients using antibiotics. CONCLUSIONS: The contamination of the samples (false-positives) was related with the age of the children, probably with the difficulty to obtain the blood. The interference of the antibiotics were demonstrated, specially in Pediatric Intensive Care Unit. Blood culture was useful to identify multiresistant agents in children receiving broad spectrum antibiotics. Because of the importance of blood culture and the knowledge of factors that can interfere with the results, one should be critical regarding indication and way of collecting the exam in order to avoid iatrogenic problems to the patients.

[Pseudo-tumoral schistosomiasis: case report]. / Esquistossomose pseudo-tumoral: relato de um caso.

The schistosomiasis is an endemic disease in Brazil. The most frequent forms are: intestinal, hepatosplenic and hepatointestinal. Rare forms also manifest such as pseudo-tumoral form. The objective of this paper is to report a 8 years-old boy, from Minas Gerais State, with pseudo-tumoral schistosomiasis. He was submitted an exploratory laparotomy and a biopsy from abdominal mass was made. The histologic studies showed a chronic inflammatory process, with a large number of S. mansoni eggs. The treatment was a single-dose of oxaminiquine (20 mg/kg), with a positive evolution, with non-sequel observed after two years of follow-up.

[Brain abscess in childhren: A ten cases report] / Abscesso cerebral na infância: relato de 10 casos.

OBJECTIVES: Considering that the brain abscess is rare in infants, with a high mortality rate, the objective of this paper is to report the clinical evolution of ten children with the diagnosis of brain abscess in the Pediatric Nursery of the Hospital das Clínicas of the Medical School of the Campinas State University (UNICAMP).METHODS: The data of the patients with diagnosis of brain abscess recorded between January 1986 and July 1995 were reviewed. The following data were analyzed: age, sex, clinical manifestations, physical examination, radiological data, etiological agent, treatment, complications and clinical evolution of the patients.RESULTS: The age of the patients varied from 2 to 13 years (median 3 years); 6 of them were female. The neurological manifestations predominated, and 2 patients had history of prior otorhinolaryngological infection (chronic otitis media and sinusitis). Two patients had congenital cyanogenic cardiopathy (Fallot tetralogy and Pulmonary Stenosis with Interventricular Communication). The diagnosis and follow-up were made with computed tomography of the brain. In six cases there were one sole abscess located more frequently in the frontal lobe. The treatment in majority of the cases was broad-spectrum antibiotic association and surgical drainage. Five patients had neurological sequelae (seizure, hydrocephalus and paresis); one death occurred.CONCLUSIONS: Although rare, the brain abscess has to be remembered in patients that have neurological alterations associated to risk factors, as otorhinolaryngological infections and congenital cyanotic cardiopathy, being mandatory the realization of computed tomography of the brain to confirm the diagnosis.

Relative frequency of nosocomial microorganisms at UNICAMP University Hospital from 1987 to 1994.

The frequency of microorganisms identified in nosocomial infections at Unicamp University Hospital from 1987 to 1994 was analysed. The most common microorganism was S. aureus (20.9%), which was found in surgical wound, bloodstream and arterial-venous infections. In urinary tract infections (UTI), gram-negative rods (56.5%) and yeasts (9%) predominated. A. baumannii isolates were observed to have increased in the last three years. There was a gradual increase in the frequency of coagulase-negative staphylococci and A. baumannii in bloodstream infections but there wasn't any change in Candida sp.

[Liver abscess in childhood: report of 8 cases]. / Abscesso hepático na infância: relato de oito casos.

The authors present eight cases of children with liver abscess diagnosed in the Pediatric Nursery of the "Hospital das Clínicas", State University of Campinas, SP, Brazil, during eight years. Five children were younger than five years. They were four boys and four girls. The symptomatology was inespecific. Staphylococcus aureus was the more frequent etiologic agent and in two cases it was seen Ascaris lumbricoides worm inside the abscess. The findings of ultrasound and computadorized tomography were similar. In most cases, were employed the association of broad spectrum antibiotics and percutaneous draining, and a good clinical outcome was observed in all patients.

Application of genomic DNA subtyping by pulsed field gel electrophoresis and restriction enzyme analysis of plasmid DNA to characterize methicillin-resistant Staphylococcus aureus from two nosocomial outbreaks.

Pulsed-field gel electrophoresis (PFGE) and restriction enzyme analysis of plasmid DNA (REAP) were applied to study the epidemiologic relationship among methicillin-resistant Staphylococcus aureus (MRSA) isolates from outbreaks in two hospitals in São Paulo, Brazil: 82 MRSA isolates, 73 from a university hospital and nine from a general adult intensive care unit of a private hospital, were collected from 62 patients: 95% of the MRSAs were also resistant to gentamicin and ciprofloxacin. REAP subtyping of both collections identified six different subtypes: 55 (72.6%) MRSAs from the university hospital and nine isolates from the private hospital shared the same epidemic REAP subtype. Discrimination by restriction of genomic DNA with Sma I followed by PFGE enabled the identification of 14 DNA subtypes. Based on the combined REAP-genomic DNA subtype, the predominant subtype in the university hospital was A/A (44 isolates) whereas the epidemic subtype in the private hospital was A/M (seven isolates). The application of two typing methods showed better discrimination among MRSAs than did either method alone.

Alcalose metabolica causada por antibioticos. / Metabolic alkalosis caused by antibiotics

Os autores apresentam quatro pacientes que desenvolveram alcalose metabolica e hipopotassemia durante o uso de antibioticos.O antibiotico mais associado com essas alteracoes foi a carbenicilina. Discutem-se os provaveis mecanismos implicados nessas alteracoes metabolicas

Doenca de Chagas congenita: reagudizacao pela corticoterapia. / Congenital Chagas disease: re-agudization by corticosteroid therapy

Os autores apresentam um caso de doenca de Chagas congenita, diagnosticado aos cinco meses de vida, de maneira casual, quando foi internado por fratura de cranio. Apresentam os achados clinicos-patologicos e justificam a disseminacao intensa e aguda da doenca pela corticoterapia a qual o paciente foi submetido

Insulina endovenosa continua no tratamento da cetoacidose diabetica. / Continuous endovenous insulin in the treatment of diabetic ketoacidosis

Estudou-se o tratamento da cetoacidose diabetica com insulina endovenosa continua Discutem-se os resultados sobre a dose de insulina usada, a evolucao da glicemia e o uso de bicarbonato.O disturbio foi controlado com bem menores quantidades de insulina que os esquemas classicos. Nao se encontraram alteracoes metabolicas. O metodo mostrou-se pratico, eficaz e seguro