Low dose of aPCC after the initial treatment in acquired haemophilia A is useful to reduce bleeding relapses: Data from the FAIR registry.

BACKGROUND: Bypassing agents are the first line therapy in patients with acquired haemophilia A (AHA). Activated prothrombin complex concentrate (aPCC) proved to be effective as initial treatment, but 20% of patients (pts) had relapses. aPCC as short-term prophylaxis to reduce subsequent bleeds is still not clear. AIM: To evaluate whether a short-term prophylaxis with low dose of aPCC can reduce bleeding relapses after initial AHA treatment, maintaining safety. METHODS: The FAIR Registry is a retrospective-prospective study started on December 2012, that collected data on all pts with AHA treated with aPCC in 12 Italian Haemophilia Centers. All statistical analyses were carried out in the 56 pts included in the registry. RESULTS: 31 retrospective and 25 prospective pts were evaluated.101 bleeds requiring treatment were reported, 84.1% spontaneous, 71.3% involving muscles or skin. Major bleeds were 38,6%. Low-dose aPCC as short-term prophylaxis was started after the first resolved episode in 15/56 pts, 58% of whom prospective, in a mean dose of 54.2 ±â€¯23.0 IU/kg, higher (61.4 ±â€¯23.4 IU/kg) in the prospective group than in the retrospective one (44.3 ±â€¯19.7 IU/kg) and it was continued up to a mean of 20.5 ±â€¯17.6 days, similar in both groups. A total of 32 bleeding relapses were reported, 87.5% in the retrospective group. Only 9.4% occurred during short-term prophylaxis (p < 0.05). In our Registry no thromboembolic events were found. CONCLUSION: Initial AHA treatment with aPCC proved to be highly effective, but a consecutive low dose as short-term prophylaxis seems to demonstrate a significant reduction in bleeding relapses maintaining safety.

Inguinal hernia in neonates and ex-preterm: complications, timing and need for routine contralateral exploration.

BACKGROUND/PURPOSE: Aim of this study was to present a series of neonates and ex-preterm babies who underwent inguinal hernia repair focusing on complications and possible indication to perform routine contralateral groin exploration. METHODS: This is a retrospective study of a series of consecutive patients weighing less than 5 kg who underwent inguinal hernia repair between January 2007 and December 2012. Only the affected side was treated. Patients have been routinely followed up postoperatively. We resorted to available outpatients' charts and admission notes to record demographic data, surgical details, complications and the occurrence of metachronous hernias. A questionnaire was administered to all patients' relatives to confirm the long-term outcome. RESULTS: One hundred fifty-four patients were operated for a total of 184 herniotomies (88 right sided, 36 left sided and 30 bilateral). Median length of follow-up was 42 months (range 6 months-7.5 years). Thirteen patients (13/124 = 10.5 %) developed metachronous hernia that proved to be significantly more frequent in patients weighing less than 1,500 g at birth (p < 0.05). We observed 10 % of complications, including 2.7 % testicular atrophy and 4.5 % recurrence. Atrophy proved to occur more frequently in patients who experienced preoperative incarceration (p < 0.05). No other risk factors were identified. CONCLUSIONS: The results of our series demonstrated that, though technically demanding, herniotomy in the neonate and ex-preterm is associated with a relatively low incidence of complications. Based on our results and in accordance with literature data, we do not advocate routine contralateral exploration in case of unilateral hernia but surgery to be performed only on the symptomatic side, as soon as possible after initial diagnosis. Very low birth weight patients should be followed with care in the early postoperative period due to the higher likelihood of developing a metachronous hernia.

Shifting from open surgical cut down to ultrasound-guided percutaneous central venous catheterization in children: learning curve and related complications.

PURPOSE: Tunneled indwelling central venous catheters (CVC) are essential in the management of children with cancer, hematological, nephrological disorders and for parenteral nutrition. The aim of this study is to present the experience of a single center of the transition from traditional open surgical cut down procedure (OSC) to ultrasound (US)-guided percutaneous CVC insertion, focusing on learning curve and related complications. METHODS: All CVCs inserted between April 2008 and November 2009 in children at the Gaslini Children Hospital were revised, and data on methods of cannulation, intraoperative and device-related complications and re-intervention were recorded. RESULTS: 194 CVCs were positioned in 188 patients. 128 out of 194 CVCs were positioned through an OSC technique, whereas the remaining 66 CVCs were inserted percutaneously with US guidance. Of the 27 recorded complications, 15 were mechanical events, 7 cases developed infection, whereas the remaining 5 (2.6%) were classified as intraoperative complications. A second surgical procedure was described in 23 (11.8%) cases. CONCLUSION: Shifting from OSC to US-guided percutaneous CVC insertion inevitably involves a challenging learning curve which is generally associated with high complication rates. Complications progressively decrease once a good experience in US guidance and percutaneous technique has been obtained.

Correlation between nasal mucociliary clearance time and gastroesophageal reflux disease: our experience on 50 patients.

OBJECTIVES: It is increasingly suggested that gastroesophageal reflux disease (GERD) could play an important role in chronic rhinosinusitis. The aim of our study was to evaluate the nasal mucociliary clearance time in GERD patients and if any correlations could be assumed. METHODS: Fifty GERD patients endoscopically diagnosed underwent an ear, nose and throat evaluation. The saccharin test and the 20-Item Sino-nasal Outcome Test (SNOT-20) were administered to 50 participants who correspond to our inclusion criteria. The saccharin test is a validated proof to verify the nasal mucociliary clearance time and the SNOT-20 is a disease-specific, health-related quality of-life questionnaire widely used for the assessment of rhinosinusitis. RESULTS: Thirty-seven (74%) patients showed a significant increment in their saccharin test values in comparison with the others subjects (23.79+/-5.58 vs 8.15+/-2.06min; P=0.0001). This group of patients reported only typical gastroesophageal symptoms (GES) without any other complaint. Gastroesophageal endoscopic findings revealed some interesting and unexpected results in this subgroup. The remainder of patients considered (13/50; 26%) showed normal values for nasal mucociliary clearance time and they referred only typical extraesophageal symptoms (EES). In any case and in both groups rhinosinusitis complaints were present. The SNOT-20 test results were normal in all patients even if a significant difference for GES group could be highlighted (19.3 vs 7.4; P<0.005). CONCLUSION: This study supports the assumption of possible and important correlations between nasal mucociliary clearance time and GERD. GERD could be an altering factor for nasal function also in absence of laryngo-pharyngeal symptoms although to verify this interesting hypothesis more validated data are necessary.

[The treatment of pectus excavatum: results of a mininvasive surgical technique on the first 50 patients]. / Il trattamento moderno del pectus excavatum: risultati della tecnica mini-invasivasui primi 50 pazienti.

AIM: Pectus excavatum is the commonest thoracic congenital malformation, but its treatment remains not well known. The authors present the results of the mini-invasive repair at G. Gaslini Institute of Genoa, Italy. METHODS: Nuss mini-invasive repair avoids anterior scars. The correction is achieved by the introduction under thoracoscopy of a retrosternal curve bar that is rotated by 180 degrees . Postoperatory pain is managed by an epidural catheter. In all the operated patients we evaluated the clinical pre-operatory parameters (spirometric, radiological and cardiological data), the surgical details and the results. RESULTS: Fifty patients were operated, 43 of them males, ranging from 7 and 22 years of age, with an average of 17 years of age. Only 8 of them were asymptomatic and required surgery for psychological reasons. The 74% presented some stress dyspnea. Some impairment in spirometric parameters were observed in 28% and mitral valve prolapse in 30%. The only significant intra-operative complication was a bleeding from a thoracic wall vessel that required a left emergency minimal thoracotomy. Postoperative complications were: 2 pneumothorax (drained for 24 hours), 2 transitory pulmonary atelectasis, 1 hemothorax in a patient with coagulation deficit, 3 wound problems (1 infection and 2 hematomas). The esthetical score after surgery, according to the patients, was 9.15 on average, in a scale from 1 to 10. None rated less than 7. The pain score with the same scale was rated 6.8 on average. CONCLUSION: The Nuss technique is safe and guarantees very satisfactory esthetical results.

Prothrombin complex concentrates for urgent anticoagulation reversal in patients with intracranial haemorrhage.

BACKGROUND: Intracranial haemorrhage (ICH) is a serious and potentially fatal complication of oral anticoagulant therapy (OAT). Prothrombin complex concentrates (PCCs) produce a rapid and effective reversal of OAT effects, but little evidence exists on their efficacy and safety in the management of ICH in patients on OAT. AIM: To evaluate the efficacy and safety of PCCs for the rapid reversal of OAT in patients with ICH. METHODS: Patients suffering from acute ICH while receiving OAT were eligible for this prospective cohort study if their international normalized ratio (INR) was > or = 2.0. Stratified 35-50 IU kg(-1) PCC doses were infused based on initial INR. RESULTS: A total of 92 patients (50 males; mean age 74 years, range 34-92 years) were included. The median INR at presentation was 3.3 (range 2-9). At 30 min after PCC administration the median INR was 1.4 (range 0.9-3.1), declining to < or = 1.5 in 75% of patients. The benefit of PCC was maintained for a long time, since in 98% of all post-infusion time points through 96 h the median INR remained < or = 1.5 (median 1.19; range 0.9-2.3). During hospitalization neither thrombotic complications nor significant adverse events were observed and 11 patients died (11.9%). None of the deaths was judged to be related to PCC administration. CONCLUSIONS: PCC administration is an effective, rapid and safe treatment for the urgent reversal of OAT in patients with ICH. Broader use of PCC in this clinical setting appears to be appropriate.

Studies on the sialidoses: properties of human leucocyte neuraminidases.

At least two components of neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18) can be distinguished in human leucocytes on the basis of pH optimum, thermolability at 30 degrees C and the effect of the detergent octyl-beta-D-glucoside. With 4-methylumbelliferyl-alpha-D-N-acetylneuraminate as substrate, the A component has a pH optimum of 5.0, is labile at 30 degrees C and is unaffected by 0.2 M octyl-beta-glucoside. The B component has a pH optimum of 4.0-4.2, is stable at 30 degrees C but loses most of its activity in the presence of 0.2 M octyl-beta-glucoside. Both A and B components are membrane-bound but only the A component is solubilized by octyl-beta-glucoside in an active form. Molecular weights of neuraminidases by gamma-ray radiation inactivation (a method that does not require solubilization of the enzyme) were found to be 240 000 +/- 19 000 for the B component, 203 000 +/- 17 000 for the A component and 238 000 +/- 8000 for the octyl-beta-glucoside-solubilized A component. Gel filtration of soluble A component on Sephacryl S-300, in the presence of octyl-beta-glucoside, showed a single peak of activity eluted at or near the void volume suggesting that the enzyme is still in an aggregated form. Profound deficiency of neuraminidase activity was found for both A and B components in leucocytes of patients affected with sialidoses type 1 and 2 (less than 15% normal) and intermediate activity in obligate heterozygotes. These results suggest that the A and B components of leucocyte neuraminidase are closely related from the genetic point of view and that rapid diagnosis of sialidoses can be done by fluorimetric assay of neuraminidase in leucocytes.

Neuraminidase activity in the mucolipidoses (types I, II and III) and the cherry-red spot myoclonus syndrome.

Two neuraminidase (EC 3.2.1.18) comonents, A and B, were distinguished in cultured skin fibroblasts on the basis of thermolability at 37 degrees C. The more labile component (A) t1/2 = 4.7--5.3 min at 37 degrees C, comprises 66--90% of total neuraminidase activity when determined using sodium (4-methylumbelliferyl-alpha-D-N-acetylneuraminate) (MU-alpha-N) as substrate. Activity was assayed at 0 degrees C for 18 h instead of 37 degrees C to fully determine both thermolabile and thermostable components. Diminished activity was noted in cultured fibroblasts from mucolipidoses I, II and III (MLI, MLII, MLIII) and the cherry-red spot myoclonus syndrome (CRSM) patients when assayed at both 0 and 37 degrees C with either MU-alpha-N or each of a series alpha (2 leads to 3)- and alpha (2 leads to 6)-linked N-acetylneuraminyloligosaccharides. Increased sensitivity and rapidity of analyses were achieved using MJ-alpha-N as substrate in determining neuraminidase activity. Results from two obligate heterozygote MLI cell lines (14.5 and 8.0% of control activity) indicate that the MU-alpha-N substrate could be useful for heterozygote detection.

Neuraminidase in cultured fibroblasts and leucocytes of homozygotes and heterozygotes for the mucolipidosis II gene (I-cell disease).

The significance of neuraminidase deficiency reported to be the primary defect in mucolipidosis II has been evaluated by determination of this enzyme activity in cultured fibroblasts, culture medium, and leucocytes from homozygote and heterozygous carriers of the disease. A new and sensitive fluorometric assay of neuraminidase was used with sodium (4-methylumbeliferyl-alpha-D-N-acetylneuraminate) as substrate. We report: 1) nearly total deficiency of neuraminidase in mucolipidosis fibroblasts, 2) partial deficiency of this enzyme in leucocytes of one patient, 3) this decreased activity ceases to exist following Triton X-100 treatment, and 4) intermediary mean neuraminidase activity in fibroblasts and leucocytes from obligate heterozygotes. Although these results would be consistent with the suggestion that neuraminidase deficiency is the primary defect in this disease, evidence from the work of other authors suggests that the enzyme deficiency results from a secondary effect of the mucolipidosis II mutation.