Therapies and outcomes of congenital hyperinsulinism-induced hypoglycaemia.

Congenital hyperinsulinism is a rare disease, but is the most frequent cause of persistent and severe hypoglycaemia in early childhood. Hypoglycaemia caused by excessive and dysregulated insulin secretion (hyperinsulinism) from disordered pancreatic ß cells can often lead to irreversible brain damage with lifelong neurodisability. Although congenital hyperinsulinism has a genetic cause in a significant proportion (40%) of children, often being the result of mutations in the genes encoding the KATP channel (ABCC8 and KCNJ11), not all children have severe and persistent forms of the disease. In approximately half of those without a genetic mutation, hyperinsulinism may resolve, although timescales are unpredictable. From a histopathology perspective, congenital hyperinsulinism is broadly grouped into diffuse and focal forms, with surgical lesionectomy being the preferred choice of treatment in the latter. In contrast, in diffuse congenital hyperinsulinism, medical treatment is the best option if conservative management is safe and effective. In such cases, children receiving treatment with drugs, such as diazoxide and octreotide, should be monitored for side effects and for signs of reduction in disease severity. If hypoglycaemia is not safely managed by medical therapy, subtotal pancreatectomy may be required; however, persistent hypoglycaemia may continue after surgery and diabetes is an inevitable consequence in later life. It is important to recognize the negative cognitive impact of early-life hypoglycaemia which affects half of all children with congenital hyperinsulinism. Treatment options should be individualized to the child/young person with congenital hyperinsulinism, with full discussion regarding efficacy, side effects, outcomes and later life impact.

Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study).

OBJECTIVES: We evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (ATV/r + 3TC) was non-inferior to ATV/r plus two nucleosides (ATV/r + 2NUCs) at 96 weeks of follow-up. METHODS: SALT is a multicentre, open-label, non-inferiority clinical trial in HIV-1-infected virologically suppressed patients. Hepatitis B virus surface antigen-negative subjects with no previous treatment failure/resistance mutations and HIV-1-RNA <50 copies/mL for ≥6 months were randomized (1 : 1) to ATV/r + 3TC or ATV/r + 2NUCs. The primary endpoint was HIV-1-RNA <50 copies/mL in the PP population. Non-inferiority was demonstrated if the lower bound of the 95% CI for the difference was not below -12%. RESULTS: Some 286 patients were analysed. At week 96, 74.4% had HIV-1-RNA <50 copies/mL in the ATV/r + 3TC arm versus 73.9% in the ATV/r + 2NUCs arm (95% CI for the difference, -9.9%-11.0%). In both groups, similar values were observed for patients with confirmed virological failure in ATV/r + 3TC versus ATV/r + 2NUCs (9 versus 5), death (1 versus 0), discontinuation due to ART-related toxicity (7 versus 11), withdrawal from the study (7 versus 9) and loss to follow-up (6 versus 6). One patient taking ATV/r + 2NUCs developed resistance mutations (M184V and L63P). Similar values were obtained for change in mean CD4 count [19 versus 18 cells/mm3 (95% CI for the difference, -49.3-50.7), grade 3-4 adverse events (70.7% versus 70.2%) and changes in the global deficit score, -0.3 (95% CI, -0.5 to -0.1) for ATV/r + 3TC, versus -0.2 (95% CI, -0.4 to -0.1) for ATV/r + 2NUCs]. CONCLUSIONS: The long-term results of switching to ATV/r + 3TC show that this strategy is effective, safe and non-inferior to ATV + 2NUCs in virologically suppressed HIV-infected patients.

Is routine endocrine evaluation necessary after paediatric traumatic brain injury?

BACKGROUND: Traumatic brain injury (TBI) is a common event in childhood. It is a recognised cause of hypopituitarism both in adult and paediatric patients. Routine endocrine evaluation has been proposed for adult TBI-survivors; nevertheless, incongruous data have been reported in children. AIM: The goal of this study was to describe the prevalence of pituitary dysfunction after TBI in a cohort of children. MATERIAL/SUBJECTS AND METHODS: This is a cross-sectional study comprising retrospective medical record review and prospective testing. Children with brain injury discharged from the Paediatric Intensive Care Unit from year 2004 to 2009 were recruited. Height and weight were recorded, systemic examination was performed and baseline pituitary function tests were undertaken. Provocative tests were performed only if abnormal basal levels were detected. RESULTS: Thirty-six patients were collected; the mean age at assessment was 7.2 years and the mean interval since injury 3.3 years. All patients had skull fracture or intracranial haemorrhage; 36.6 % of them had moderate to severe TBI. No abnormalities were found on examination. Low serum IGF 1 levels were detected in four patients and two patients had low serum cortisol levels with inappropriately normal plasma ACTH concentrations. No evidence of pituitary dysfunction was observed in these patients after clinical follow-up, repeated baseline hormone levels or dynamic function tests. CONCLUSIONS: No endocrine sequelae have been detected in this population. The routine endocrine evaluation in children with mild to moderate TBI might not be justified, according to our findings.

Exploratory analysis of clinical benefit of ipilimumab and nivolumab treatment in patients with metastatic melanoma from a single institution.

PURPOSE: We retrospectively analysed overall survival (OS) and potential predictive biomarkers of OS in patients with metastatic melanoma treated with ipilimumab plus nivolumab in a single institution. METHODS AND PATIENTS: Electronic medical records of patients with advanced melanoma receiving ≥ 1 dose of a combined ipilimumab plus nivolumab regimen between March 3, 2016 and March 7, 2020 in a single institution, were reviewed. OS was analysed using the Kaplan-Meier method. Sub-group analyses were conducted to examine several endpoints according to relevant clinical, molecular and pathological variables using logistic and Cox models. RESULTS: Forty-four cases were reviewed, 38 (86.4%), of whom had cutaneous melanoma, 21 (47.7%) were BRAF mutant, 21 (47.7%) presented high lactate dehydrogenase (LDH) values, 23 (52.3%) had ≥ 3 disease sites, and 10 (22.7%) patients had brain metastases. The median follow-up was 37.7 months, and the median OS was 21.1 months (95% CI 8.2-NR). In the multivariate analysis, the OS was significantly longer in patients with an Eastern Cooperative Oncology Group (ECOG) score of 0, LDH ≤ upper limit of normal, absence of liver metastases and neutrophil-to-lymphocyte ratio (NLR) < 5 (all p ≤ 0.05, log-rank test). These factors allowed the classification of patients into three prognostic risk groups (low/intermediate/high risk) for death. CONCLUSION: Overall survival of real-world patients from our cohort receiving ipilimumab plus nivolumab was lower than in previous studies. The ECOG score, LDH values, the presence of liver metastases and the NLR were independent prognostic factors for survival.

Exploratory analysis of clinical benefit of ipilimumab and nivolumab treatment in patients with metastatic melanoma from a single institution

PurposeWe retrospectively analysed overall survival (OS) and potential predictive biomarkers of OS in patients with metastatic melanoma treated with ipilimumab plus nivolumab in a single institution.Methods and patientsElectronic medical records of patients with advanced melanoma receiving ≥ 1 dose of a combined ipilimumab plus nivolumab regimen between March 3, 2016 and March 7, 2020 in a single institution, were reviewed. OS was analysed using the Kaplan–Meier method. Sub-group analyses were conducted to examine several endpoints according to relevant clinical, molecular and pathological variables using logistic and Cox models.ResultsForty-four cases were reviewed, 38 (86.4%), of whom had cutaneous melanoma, 21 (47.7%) were BRAF mutant, 21 (47.7%) presented high lactate dehydrogenase (LDH) values, 23 (52.3%) had ≥ 3 disease sites, and 10 (22.7%) patients had brain metastases. The median follow-up was 37.7 months, and the median OS was 21.1 months (95% CI 8.2–NR). In the multivariate analysis, the OS was significantly longer in patients with an Eastern Cooperative Oncology Group (ECOG) score of 0, LDH ≤ upper limit of normal, absence of liver metastases and neutrophil-to-lymphocyte ratio (NLR) < 5 (all p ≤ 0.05, log-rank test). These factors allowed the classification of patients into three prognostic risk groups (low/intermediate/high risk) for death.ConclusionOverall survival of real-world patients from our cohort receiving ipilimumab plus nivolumab was lower than in previous studies. The ECOG score, LDH values, the presence of liver metastases and the NLR were independent prognostic factors for survival.

[The usefulness of two-dimensional echocardiography in the diagnosis of an interventricular aneurysm]. / Utilidad de la ecocardiografía bidimensional para el diagnóstico del aneurisma del septo interventricular.

The ventricular septal defect (VSD) may close spontaneously in the first few years of life. The closure occurs by muscle's growth of the borders of the defect or by the appearance of an aneurysm of ventricular septum composed mostly by tricuspid tissue. We believe that the two-dimensional echocardiography is the best method to determine the mechanisms that take part in the aneurysm formation. The study was carried out on 58 patients with aneurysms of ventricular septum observed in 230 patients with ventricular septal defects. 29 were male and 29 were female patients. The mean age at the time of diagnosis of aneurysm was 30 months (range 1 month-13 years). Forty seven patients had a perimembranous ventricular septal defect (perimembranous inlet 29, perimembranous trabecular nine, perimembranous outlet nine and of mixed's type seven), muscular defect nine (muscular inlet seven, and muscular trabecular two) and VSD closed in two. The size of the defect was 0.47 +/- 0.2 cm (range 0.2-1.1). In 16 the defect was larger than 0.6 cm. Thirty two patients had associated anomalies. On study the aneurysm in relation with tricuspid valve leaflets: in 27 cases (46.3%), the aneurysm was entirely formed by tricuspid septal leaflets tissue (17 had perimembranous ventricular septal defect and seven muscular), in eight (13.6) the aneurysm had tricuspid valve leaflets and interventricular component of the membranous septum tissue (five perimembranous defect and two muscular) and in another 16 cases membranous septum tissue only. In 7 patients the origin of the aneurysm wasn't confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalencia de úlceras por presión y lesiones cutáneas asociadas a la humedad en el Hospital Universitario de Burgos / Pressure ulcers and moisture associated skin damage prevalence in the Burgos University Hospital

Objetivo: Determinar la prevalencia de úlceras por presión (UPP) y lesiones cutáneas asociadas a la humedad (LESCAH) en el Hospital Universitario de Burgos. Identificar las lesiones y sus características. Identificar las valoraciones del riesgo de padecer UPP registradas en la historia clínica y el uso de dispositivos de prevención. Identificar los registros de Enfermería relacionados con las UPP y LESCAH. Metodología: Estudio observacional descriptivo transversal, mediante inspección directa de cada paciente y revisión de la historia clínica. Realizado entre el 23 de febrero y el 10 de marzo del 2015. Resultados: La población estudiada fue de 404 pacientes. Se identificaron 195 lesiones: 24 LESCAH y 171 UPP. Las prevalencias resultantes fueron 5,69% para las LESCAH y 21,53% para las UPP. El 93,56% de las UPP pertenecen a los estadios I y II. Las localizaciones anatómicas más frecuentes fueron: codo (28,07%), talón (22,8%), oreja (18,12%) y sacro (11,11%). Se encontró registro de la valoración del riesgo mediante escala de Norton en 164 (48,59%) pacientes, presentando riesgo entre medio y muy alto, 46 (28,05%) pacientes. Contaban con algún dispositivo de prevención adicional 31 (7,67%) pacientes, mientras que 29 (7,17%) pacientes, con riesgo detectado, carecían de él. Conclusiones: La prevalencia resultante de UPP es elevada debido a la mayor detección de estadios leves. Se aconseja la realización de valoración del riesgo de padecer UPP a todos los pacientes ingresados. Así mismo, se considera necesario aumentar la formación en detección y prevención de los estadios más leves

Aim: Determine the prevalence of pressure ulcers (PU) and moisture associated skin damage (MASD) at Burgos University Hospital. Identify lesions and their characteristics. Identify the risk assessment surveys of PU recorded in the health record and the use of prevention devices. Identify nursing records related to PU and MASD. Methods: Transversal descriptive observational study, by direct observation of each patient and review of their health record. Conducted between February 23rd and March 10th, 2015. Results: The study population was 404 patients. 195 lesions were identified: 24 MASD and 171 PU. The resulting prevalences were 5.69% for MASD and 21.53% for PU. 93,56% of PU were stages I and II. The most common anatomic sites were: elbow (28,07%), heel (22,8%), ear (18,12%) and sacrum (11,11%). Using the Norton scale, PU risk was assessed in 164 patients (48.59%), with 46 patients (28.05%) exhibiting medium to high risk levels. 31 patients had additional prevention devices (7.67%), while 29 patients (7.17%) with identified risk had no device. Conclusions: The resulting prevalence of PU is high due to increased detection of mild stages. Conducting risk assessment of PU to all hospitalized patients is advised. Likewise it is pertinent to increase training in detection and prevention of the milder stages

[Renal tuberculosis treated with rifampicin, isoniazid and ofloxacin]. / Tratamiento de la tuberculosis renal con rifampicina, isoniazida y ofloxacino.

We describe the results of eight patients with renal tuberculosis treated with rifampin, isoniazid and ofloxacin. Ofloxacin was given orally, 200 mg b.i.d. for 6 months. During the first three months, rifampin (600 mg/daily) and isoniazid (330 mg/daily) were added. All M. tuberculosis strains isolated were sensitive to ofloxacin (MIC 1 mg/l). Follow-up cultures turned to be negative rapidly (during the first month of therapy), and no untoward effects were recorded. All patients had a 12-months follow-up period, and all were clinically cured. The treatment used was well accepted by all patients.