Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation.

BACKGROUND: Persistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia. PATIENT PRESENTATION: We report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported. CONCLUSIONS: Kabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.

Congenital emphysematous lung disease associated with a novel Filamin A mutation. Case report and literature review.

BACKGROUND: Progressive lung involvement in Filamin A (FLNA)-related cerebral periventricular nodular heterotopia (PVNH) has been reported in a limited number of cases. CASE PRESENTATION: We report a new pathogenic FLNA gene variant (c.7391_7403del; p.Val2464Alafs*5) in a male infant who developed progressive lung disease with emphysematous lesions and interstitial involvement. Following lobar resection, chronic respiratory failure ensued necessitating continuous mechanical ventilation and tracheostomy. Cerebral periventricular nodular heterotopia was also present. CONCLUSIONS: We report a novel variant of the FLNA gene, associated with a severe lung disorder and PNVH. The lung disorder led to respiratory failure during infancy and these pulmonary complications may be the first sign of this disorder. Early recognition with thoracic imaging is important to guide genetic testing, neuroimaging and to define optimal timing of potential therapies, such as lung transplant in progressive lung disease.

Preliminary Experience with a Novel System of Facet Fixation to Treat Patients with Lumbar Degenerative Disease. A New Perspective in Minimally Invasive Spine Surgery?

PURPOSE: We report our experience with a novel surgical device for the treatment of lumbar degenerative microinstability. Facet Wedge (DePuy Synthes, Raynham, Massachusetts, United States) is a novel technique of intra-articular lumbar facet fixation that provides a minimally invasive alternative to standard posterior fixation. MATERIALS AND METHODS: From November 2014 to July 2015, 38 patients underwent single-level Facet Wedge implantation. The main surgical indications included herniated disk (18 patients), spinal canal and foraminal stenosis (14 patients), and Meyerding grade I degenerative spondylolisthesis (6 patients). All the patients showed radiologic signs of microinstability: hyperintensity in both facet joints (facet fluid signal) in T2-weighted magnetic resonance imaging and a black disk as a sign of degenerative disease. No slippage was evident at dynamic radiograph. After a period of conservative treatment (minimum of 6 months), surgery was performed. All patients' follow-up lasted over at least 12 months. RESULTS: The low back visual analog scale score decreased significantly after surgery (from an average of 8.2 to 3.1 at final follow-up). Postoperatively, the Oswestry Disability Index showed a significant reduction (14.7 on average). No slippage or signs of adjacent segment degeneration was detected in neuroimaging follow-up. CONCLUSION: Facet Wedge allows facet fixation in lumbar degenerative microinstability. To the best of our knowledge, this is the first clinical series reported in the literature on this novel device.

Sequential boost in neoadjuvant irradiation for T3N0-1 rectal cancer: long-term results from a single-center experience.

PURPOSE: To evaluate the influence of radiation dose on tumor regression grade (TRG) and sphincter preservation rate in a series of cT3N0-1 rectal cancer patients treated with neoadjuvant chemoradiotherapy (CT-RT) with or without a sequential radiation boost. MATERIALS AND METHODS: Between May 2002 and September 2013, 116 cases were eligible for retrospective evaluation. Radiotherapy was delivered for a total dose of 45 Gy (no boost arm) or 50.4 Gy (boost arm). TRG was evaluated with the Dworak scale. RESULTS: Median follow-up was 62 months (range, 12-138 months). The 5-year overall survival and local control rates were 72% and 93%, respectively. Fifty-five patients (47%) were treated with a sequential radiation boost and 61 (53%) without a boost. Eighty patients (72%) presented T3N0 disease and 32 (28%) T3N1 disease. Concomitant capecitabine was administered in 92 cases (79%) and intravenous 5-fluorouracil in 24 cases (21%). Sphincter preservation was performed in 82% of patients in the boost arm and 66% in the no-boost arm. A higher TRG was related to a longer interval between neoadjuvant treatment and surgery (p<0.001). The probability of a TRG ≥2 was 2.5 times higher in the boost arm. A gain in local control, estimated at 4% during the first 3 years after CT-RT, favored the boost arm. CONCLUSIONS: The long-term results from our single-center experience confirm literature data on the role of a sequential boost in tumor response after neoadjuvant CT-RT in a series of cT3N0-1 rectal cancer patients.

Moderate hypofractionation and simultaneous integrated boost by helical tomotherapy in prostate cancer: monoinstitutional report of acute tolerability assessment with different toxicity scales.

INTRODUCTION: Based on radiobiology evidence, hypofractionated radiotherapy has the potential of improving treatment outcome in prostate cancer patients. In this study, we evaluated the safety, in terms of acutetoxicity, of using moderate hypofractionated radiotherapy delivered with Helical Tomotherapy (HT) to treat prostate cancer patients. MATERIALS AND METHODS: Between December 2012 and April 2014, 42 consecutive patients were treated with hypofractionated radiotherapy using HT. All patients received 70 Gy in 28 fractions to PTV1, which included the prostate. In the intermediate risk group, 61.6 Gy were delivered to PTV2, which included the seminal vesicles. In high risk patients, the pelvic nodes were added (PTV3) and received 50.4 Gy. Acute toxicity was recorded prospectively with RTOG and Common Terminology Criteria for Adverse Events 3.0, retrospectively with CTCAE 4.0. Expanded Prostate Cancer Index Composite (EPIC) was measured at baseline and 3 months after end of treatment, to investigate health related quality of life with regards to bladder and gastrointestinal function. RESULTS: Acute toxicity was acceptable, independently from the system used to score side effects. Moderate genitourinary toxicity was more frequent than gastrointestinal toxicity. No correlation between acute side effects and patients' characteristics or physical dose parameters was registered. EPIC evaluation showed a negligible difference in urinary and bowel function post-treatment, that did not reach statistical significance. CONCLUSIONS: Our experience confirms the safety of moderate hypofractionation delivered with HT in prostate cancer patients with low, intermediate and high risk.