The surgical treatment of cerebrospinal fistula: Qualitative and quantitative analysis of indications and results

Cerebrospinal fistula might occur in different ways. CSF closure techniques have undergone significant evolution that has led to the consolidation of the transnasal endoscopic approach. Despite the existence of multiple publications, meaningful information is still lacking in clinical practice and the literature about the ideal method, material, and timing for repair of CSF. The purpose of this review was to summarize the success rate of endoscopic CSF leak repair as well as whether specific techniques or materials influence the primary success rate through a review of the latest advancements in endoscopic CSF management published in the past 10 years. The principles of multilayer reconstructions and the routine use of vascularized flaps in expanded endonasal surgery have reduced postoperative CSF leaks' failure rates between 5% and 10% (4% in this meta‐analysis). Effective endoscopic anterior skull base (ASB) closure may be achieved by multiple reconstructive techniques, which should be tailored case by case according to the patient and defect conditions.     

Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta‐analysis

The purpose of this systematic review and meta‐analysis was to estimate the overall and type‐specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16^INK4a overexpression in relation to HPV‐status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16^INK4a overexpression in relation to HPV‐status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6‐38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16^INK4a. This meta‐analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.     

Pediatric transplantation in Europe during the COVID-19 pandemic: Early impact on activity and healthcare

The current pandemic SARS-CoV-2 has required an unusual allocation of resources that can negatively impact chronically ill patients and high-complexity procedures. Across the European Reference Network on Pediatric Transplantation (ERN TransplantChild), we conducted a survey to investigate the impact of the COVID-19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified and restricted to selected ones, and the use of telemedicine tools has increased. Additionally, a total of 14 COVID-19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate-severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID-19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long-term consequences for pediatric transplantation candidates, recipients, and their families.     

Autologous osteochondral transplantation for the treatment of knee lesions: results and limitations at two years’ follow-up

Purpose

Focal chondral and osteochondral knee lesions are a common condition, particularly hard to treat, and often involve young active patients with high expectations in terms of symptomatic relief and return to sports. Autologous osteochondral transplantation allows the defect area to be restored with hyaline cartilage. The aim of this study is to analyse whether it represents a safe and effective treatment option for small–medium-sized knee chondral and osteochondral lesions in a young and active population.

Methods

Thirty-one patients (18 men, 13 women; mean age 32?±??ten; mean BMI 24?±?3) affected by focal knee chondral and osteochondral lesions were enrolled and treated with autologous osteochondral transplantation. They were prospectively followed-up for 24 months with the IKDC-subjective, IKDC-objective, and Tegner scores. Adverse events and failures were also reported, as well as the Bandi score to detect symptoms from the donor area.

Results

A significant increase was reported in all the clinical scores adopted. In particular, the IKDC-subjective score increased from a basal value of 40.3?±?16.2 to 62.6?±?18.0 at the 12 months’ evaluation, with a further significant increase up to 71.6?±?20.5 at the final 24 months’ follow-up (p?p?=?0.003), although it was not possible to regain the same pre-injury sports activity level of 5.0?±?2.2. Two failures were reported. The Bandi score revealed patients complaining of mild and moderate symptoms, not correlated to the lesion size. The presence of symptoms ascribable to the donor area was significantly correlated with a lower clinical outcome.

Conclusions

Autologous osteochondral transplantation proved to be, at short-term evaluation, a suitable option to treat small–medium sized chondral and osteochondral lesions. However, clinical improvement is slow and a significant percentage of patients develop symptoms attributable to the donor area, thus reducing the overall benefit of this procedure.     

Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) for primary surgical prevention of breast cancer‐related lymphedema: Over 4 years follow‐up

Breast cancer‐related lymphedema (LE) represents an important morbidity that jeopardizes breast cancer patients' quality of life. Different attempts to prevent LE brought about improvements in the incidence of the pathology but LE still represents a frequent occurrence in breast cancer survivors. Over 4 years ago, Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) was proposed and long‐term results are reported in this study. From July 2008 to December 2012, 74 patients underwent axillary nodal dissection for breast cancer treatment together with LYMPHA procedure. Volumetry was performed preoperatively in all patients and after 1, 3, 6, 12 months, and once a year. Lymphoscintigraphy was performed in 45 patients preoperatively and in 30 also postoperatively after at least over 1 year. Seventy one patients had no sign of LE, and volumetry was coincident to preoperative condition. In three patients, LE occurred after 8–12 months postoperatively. Lymphoscintigraphy showed the patency of lymphatic‐venous anastomoses at 1–4 years after operation. LYMPHA technique represents a successful surgical procedure for primary prevention of arm LE in breast cancer patients. © 2014 Wiley Periodicals, Inc. Microsurgery 34:421–424, 2014.     

Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations

We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5‐associated malformations include bottom‐of‐the‐sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway. Ann Neurol 2014;75:782–787     

Brainstem arteriovenous malformation presenting with dyspraxic handwriting in a young girl

We report the case of a 11-year-old girl who developed an isolated hand-writing disorder with dysgraphia at the beginning of the school year in the sixth grade. A brain magnetic resonance angiography showed a round arteriovenous malformation sited in the left side of the midbrain extending to the ipsilateral medio-basal thalamus. Child neurologists should never neglect a thorough neurological evaluation in case of isolated worsening of handwriting, to rule out possible underlying organic causes.     

Nicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice

Rationale

We have recently reported nicotine-induced stimulation of reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression levels in the brain of heterozygous reeler mice (HRM), a putative animal model for the study of symptoms relevant to major behavioral disorders.

Objectives

We aimed to evaluate long-term behavioral effects and brain molecular changes as a result of adaptations to nicotine exposure in the developing HRM males.

Methods

Adolescent mice (pnd 37–42) were exposed to oral nicotine (10 mg/l) in a 6-day free-choice drinking schedule. As expected, no differences in total nicotine intake between WT (wild-type) mice and HRM were found.

Results

Long-term behavioral effects and brain molecular changes, as a consequence of nicotine exposure during adolescence, were only evidenced in HRM. Indeed, HRM perseverative exploratory behavior and poor cognitive performance were modulated to WT levels by subchronic exposure to nicotine during development. Furthermore, the expected reduction in the expression of mRNA of reelin and GAD67 in behaviorally relevant brain areas of HRM appeared persistently restored by nicotine. For brain-derived neurotrophic factor (BDNF) mRNA expression, no genotype-dependent changes appeared. However, expression levels were increased by previous nicotine in brains from both genotypes. The mRNA encoding for nicotine receptor subunits (α7, β2 and α4) did not differ between genotypes and as a result of previous nicotine exposure.

Conclusion

These findings support the hypothesis of pre-existing vulnerability (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative short- and long-term effects associated with nicotine modulation.     

Detection of Genotype-Specific Antibody Responses to Glycoproteins B and H in Primary and Non-Primary Human Cytomegalovirus Infections by Peptide-Based ELISA

Background: Strain-specific antibodies to human cytomegalovirus (HCMV) glycoproteins B and H (gB and gH) have been proposed as a potential diagnostic tool for identifying reinfection. We investigated genotype-specific IgG antibody responses in parallel with defining the gB and gH genotypes of the infecting viral strains. Methods: Subjects with primary (n = 20) or non-primary (n = 25) HCMV infection were studied. The seven gB (gB1-7) and two gH (gH1-2) genotypes were determined by real-time PCR and whole viral genome sequencing, and genotype-specific IgG antibodies were measured by a peptide-based enzyme-linked immunosorbent assay (ELISA). Results: Among subjects with primary infection, 73% (n = 8) infected by gB1-HCMV and 63% (n = 5) infected by gB2/3-HCMV had genotype-specific IgG antibodies to gB (gB2 and gB3 are similar in the region tested). Peptides from the rarer gB4-gB7 genotypes had nonspecific antibody responses. All subjects infected by gH1-HCMV and 86% (n = 6) infected by gH2-HCMV developed genotype-specific responses. Among women with non-primary infection, gB and gH genotype-specific IgG antibodies were detected in 40% (n = 10) and 80% (n = 20) of subjects, respectively. Conclusions: Peptide-based ELISA is capable of detecting primary genotype-specific IgG responses to HCMV gB and gH, and could be adopted for identifying reinfections. However, about half of the subjects did not have genotype-specific IgG antibodies to gB.