The contribution of the Israeli trauma system to the survival of road traffic casualties.

BACKGROUND: According to the World Health Organization, over one million people die annually from traffic crashes, in which over half are pedestrians, bicycle riders and two-wheel motor vehicles. In Israel, during the last decade, mortality from traffic crashes has decreased from 636 in 1998 to 288 in 2011. Professionals attribute the decrease in mortality to enforcement, improved infrastructure and roads and behavioral changes among road users, while no credit is given to the trauma system. Trauma systems which care for severe and critical casualties improve the injury outcomes and reduce mortality among road casualties. GOALS: 1) To evaluate the contribution of the Israeli Health System, especially the trauma system, on the reduction in mortality among traffic casualties. 2) To evaluate the chance of survival among hospitalized traffic casualties, according to age, gender, injury severity and type of road user. METHODS: A retrospective study based on the National Trauma Registry, 1998-2011, including hospitalization data from eight hospitals. OUTCOMES: During the study period, the Trauma Registry included 262,947 hospitalized trauma patients, of which 25.3% were due to a road accident. During the study period, a 25% reduction in traffic related mortality was reported, from 3.6% in 1998 to 2.7% in 2011. Among severe and critical (ISS 16+) casualties the reduction in mortality rates was even more significant, 41%; from 18.6% in 1998 to 11.0% in 2011. Among severe and critical pedestrian injuries, a 44% decrease was reported (from 29.1% in 1998 to 16.2% in 2011) and a 65% reduction among bicycle injuries. During the study period, the risk of mortality decreased by over 50% from 1998 to 2011 (OR 0.44 95% 0.33-0.59. In addition, a simulation was conducted to determine the impact of the trauma system on mortality of hospitalized road casualties. Presuming that the mortality rate remained constant at 18.6% and without any improvement in the trauma system, in 2011 there would have been 182 in-hospital deaths compared to the actual 108 traffic related deaths. A 41% difference was noted between the actual number of deaths and the expected number. CONCLUSIONS: This study clearly shows that without any improvement in the health system, specifically the trauma system, the number of traffic deaths would be considerably greater. Although the health system has a significant contribution on reducing mortality, it does not receive the appropriate acknowledgment or resources for its proportion in the fight against traffic accidents.

Pulmonary artery blood flow patterns in fetuses with pulmonary outflow tract obstruction.

OBJECTIVES: Fetuses with pulmonary outflow tract obstruction (POTO) have altered blood flow to the pulmonary vasculature. We sought to determine whether pulmonary vascular impedance, as assessed by the pulsatility index (PI), is different in fetuses with POTO compared with normal controls. METHODS: Branch pulmonary artery PI was evaluated in age-matched normal control fetuses (n=22) and 20 POTO fetuses (pulmonary stenosis n=15, pulmonary atresia n=5). Pulsed-wave Doppler was performed in the proximal (PA1), mid (PA2) and distal (PA3) branch pulmonary artery. The direction of flow in the ductus arteriosus was noted. The study and control groups were compared with Student's t-test and ANOVA. A linear mixed model evaluated the relationship between PI and ductus arteriosus flow patterns. RESULTS: There was no difference in PI between control, pulmonary stenosis and pulmonary atresia subjects at PA1 and PA2; however, there was a significant difference at PA3. Subjects with pulmonary atresia had a lower PI at PA3 than did controls (P=0.003) and pulmonary stenosis subjects (P=0.003). Subjects with retrograde flow in the ductus arteriosus had lower PIs in PA2 and PA3 than did those with antegrade flow (P=0.01 and 0.005, respectively). The PI in PA3 was lower in fetuses that required prostaglandin postnatally than in those that did not (P=0.008). CONCLUSIONS: Fetuses with pulmonary atresia or severe pulmonary stenosis with retrograde flow in the ductus arteriosus have decreased PI in the distal pulmonary vasculature. Our findings indicate the capacity of the fetal pulmonary vasculature to vasodilate in response to anatomical obstruction of flow.

A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family.

Giant axonal neuropathy is a severe autosomal recessive neurodegenerative disorder of childhood that affects both the peripheral and central nervous systems. It is caused by mutations in the GAN gene linked to chromosome 16q24.1 At least 45 distinct disease-causing mutations have been identified throughout the gene in families of various ethnic origins, with different symptomatologies and different clinical courses. To date, no characteristic mutation or phenotype-genotype correlation has been established. We describe a novel missense mutation in four siblings born to consanguineous parents of Arab original with clinical and molecular features compatible with giant axonal neuropathy. The phenotype was characterized by a predominant motor and sensory peripheral neuropathies and severe skeletal deformities.

Malignant transformation in pediatric spinal intramedullary tumors: case-based update.

BACKGROUND: In children, intramedullary spinal cord neoplasms are rare. These are typically low-grade neuroepithelial tumors, most commonly astrocytomas, ependymomas, and gangliogliomas. Malignant transformation, while common in recurrent adult low-grade gliomas, is an unusual event in pediatric low-grade neoplasms, specifically in intramedullary spinal cord tumors. ILLUSTRATIVE CASES: We report two cases of malignant transformation in low-grade neuroepithelial tumors of the pediatric intramedullary spinal cord. Two children with intramedullary tumors, one with a WHO grade I ganglioglioma and one with a low-grade astrocytoma, were treated surgically, diagnosed histologically, and followed through the course of their disease. Both patients' tumors transformed to higher grades without prior irradiation or chemotherapy, and without a genetic predisposition to tumorigenesis. DISCUSSION: Malignant transformation can occur in low-grade intramedullary neoplasms in children. This is a novel documented event for pediatric intramedullary spinal cord tumors and a rare event for all pediatric low-grade neuroepithelial tumors without induction by irradiation. A survey of the relevant literature reveals an underwhelming number of studies focusing on malignant transformation in children's CNS tumors relative to adults. Further investigation into molecular mechanisms of pediatric low-grade neoplasms may reveal more aggressive tumor sub-variants predisposed to malignant degeneration.

Comparative analysis of cerebrovascular resistance in fetuses with single-ventricle congenital heart disease.

OBJECTIVE: We sought to determine whether the presence or absence of aortic obstruction impacts cerebrovascular resistance in fetuses with single-ventricle (SV) congenital heart disease (CHD). METHODS: Pulsatility indices (PIs) were recorded for the middle cerebral artery (MCA) and the umbilical artery (UA) from 18 to 40 weeks' gestation in 59 fetuses (163 examinations) with SV-CHD with unobstructed aortic flow, yet decreased pulmonary flow, in 72 fetuses (170 examinations) with obstructed aortic flow and hypoplastic left heart syndrome (HLHS) and in 92 normal fetuses (92 examinations). The cerebral-to-placental resistance (CPR) was calculated as the MCA-PI/UA-PI. Z-scores were generated for the MCA-PI and the UA-PI in order to make comparisons independent of gestational age. Statistical analyses were performed using one-way ANOVA with post-hoc testing. Trends in these variables over the course of gestation were assessed using linear regression and univariate ANOVA. RESULTS: The MCA-PI and the CPR were significantly lower in SV fetuses with aortic obstruction compared with SV fetuses with pulmonary obstruction and with normal fetuses. Moreover, the MCA-PI decreased significantly for SV fetuses with aortic obstruction over the course of gestation. In contrast, the MCA-PI was higher over the course of gestation in SV fetuses with pulmonary obstruction compared with normal fetuses. CONCLUSION: In fetuses with SV-CHD, cerebrovascular resistance varies substantially between fetuses with and without aortic obstruction. Compared with normal fetuses, cerebrovascular resistance is decreased in SV fetuses with aortic obstruction, yet increased in SV fetuses with pulmonary obstruction. In fetuses with SV physiology, inherent differences in cerebral blood flow may underlie postnatal neurodevelopmental outcomes.

Doppler ultrasound for the assessment of conservatively treated blunt splenic injuries: a prospective study.

INTRODUCTION: The type and need for follow-up of non-operatively managed blunt splenic injuries remain controversial. The use of Doppler ultrasound to identify post-traumatic splenic pseudoaneurysms, considered to be the main cause of "delayed" splenic rupture, has not been well described. PATIENTS AND METHODS: A 5-year prospective study was performed from 2004 to 2008. All patients with blunt splenic injury diagnosed with computerized tomography, who were treated non-operatively, were included in the study. Doppler ultrasound examination was performed 24-48 h post-injury. Consecutive Doppler ultrasound examinations were done on 7, 14 and 21 days post-injury for patients diagnosed with a splenic pseudoaneurysm. Demographic and clinical data were collected. Ambulatory follow-up continued for 4 weeks after hospital discharge. RESULTS: A total of 38 patients were enrolled in the study. Grading of splenic injury demonstrated 19 (50%) patients with Grade I, 16 (42%) with Grade II and 3 (8%) with Grade III injuries. Two patients (5%) had pseudoaneurysms. All pseudoaneurysms underwent complete resolution within 2 weeks after diagnosis. No patients received blood products, or had angio-embolization or surgery during the study period. All patients were found to be asymptomatic and stable at the 4-week follow-up. CONCLUSIONS: Doppler ultrasound can be an effective and a safe noninvasive modality for evaluation and follow-up of patients with blunt splenic injury. The utility and cost-effectiveness of routine surveillance requires further study.

Is there an optimal time for laparoscopic cholecystectomy in acute cholecystitis?

BACKGROUND: Laparoscopic cholecystectomy (LC) is safe in acute cholecystitis, but the exact timing remains ill-defined. This study evaluated the effect of timing of LC in patients with acute cholecystitis. METHODS: Prospective data from the hospital registry were reviewed. All patients admitted with acute cholecystitis from June 1994 to January 2004 were included in the cohort. RESULTS: Laparoscopic cholecystectomy was attempted in 1,967 patients during the study period; 80% were women, mean patient age was 44 years (range, 20-73 years). Of the 1,967 LC procedures, 1,675 were successful, and 292 were converted to an open procedure (14%). Mean operating time for LC was 1 h 44 min (SD +/- 50 min), versus 3 h 5 min (SD +/- 79 min) when converted to an open procedure. Average postoperative length of stay was 1.89 days (+/- 2.47 days) for the laparoscopic group and 4.3 days (+/- 2.2 days) for the conversion group. No clinically relevant differences regarding conversion rates, operative times, or postoperative length of stay were found between patients who were operated on within 48 h compared to those patients who were operated on post-admission days 3-7. CONCLUSIONS: The timing of laparoscopic cholecystectomy in patients with acute cholecystitis has no clinically relevant effect on conversion rates, operative times, or length of stay.

Frontotemporal dementia with ubiquitinated neuronal inclusions and visuospatial impairment.

Dementia with ubiquitinated neuronal inclusions has been described only with frontotemporal dementia (FTD). The authors report a patient with progressive FTD accompanied by prominent impairments in visuospatial cognitive functions. Pathology was characterized by ubiquitin-positive intranuclear and cytoplasmic neuronal inclusions. Cortical pathology was widespread and posteriorly accentuated but spared the hippocampal dentate gyrus.

Hereditary inclusion body myopathy: the Middle Eastern genetic cluster.

BACKGROUND: Recessively inherited hereditary inclusion body myopathy (HIBM) with quadriceps sparing was initially described only in Jews originating from the region of Persia. The recent identification of the gene responsible for this myopathy and the common "Persian Jewish mutation" (M712T) enabled the re-evaluation of atypical phenotypes and the epidemiology of HIBM in various communities in the Middle East. OBJECTIVE: To test for the M712T mutation in the DNA from HIBM patients in the Middle East. METHODS: DNA from all suspected HIBM patients was tested for the M712T mutation. Unaffected members of families with genetically proven HIBM were studied too. In the majority of families, haplotype construction with markers spanning the 700-kb region of the HIBM gene was performed. RESULTS: One hundred twenty-nine HIBM patients of 55 families (Middle Eastern Jews, Karaites, and Arab Muslims of Palestinian and Bedouin origin) were homozygous for the M712T mutation, and all carried the same haplotype. Five clinically unaffected subjects were also homozygous for the common mutation and haplotype, including two older adults (ages 50 and 68 years). Atypical features with this same mutation were marked quadriceps weakness in five patients, proximal weakness only in two patients, facial weakness in three patients, and a muscle biopsy showing perivascular inflammation in one patient. CONCLUSIONS: The phenotypic spectrum of recessive HIBM is wider than previously described, and the diagnostic criteria for this myopathy must be changed. The Middle Eastern cluster is the result of a founder mutation, with incomplete penetrance, that is approximately 1,300 years old and is not limited to Jews.

Germline SDHD mutation in paraganglioma of the spinal cord.

Hereditary paraganglioma of the head and neck is associated with germline mutations in the SDHD gene, which encodes a mitochondrial respiratory chain protein. Paragangliomas of the central nervous system are very rare, occur almost exclusively in the cauda equina of the spinal cord and are considered non-familial. In the present study, we screened 22 apparently sporadic paragangliomas of the cauda equina for SDHD mutations. One spinal paraganglioma and similar cerebellar tumours that developed 22 years later in the same patient contained a missense mutation at codon 12 (GGT-->AGT, Gly-->Ser) and a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). There was no family history of paragangliomas but DNA from white blood cells of this patient showed the same sequence alterations, indicating the presence of a germline mutation. All other cases of spinal paraganglioma had the wild-type SDHD sequence, except one case with a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). This is the first observation indicating that inherited SDHD mutations may occasionally cause the development of paragangliomas in the central nervous system.

Tumour necrosis factor mediates bacterial translocation after haemorrhagic shock and endotoxaemia.

OBJECTIVE: To assess the extent of bacterial translocation after haemorrhagic shock and reperfusion, and the involvement of tumour necrosis factor (TNF) in its mediation. DESIGN: Controlled, randomised prospective experiment. SUBJECTS: 87 rats in 7 groups. INTERVENTIONS: Haemorrhagic shock was induced in rats for 1 hour. Endotoxaemia was induced in a second group by the injection of lipopolysaccharide. A third group was injected with exogenous TNF. Some of the animals were further treated with anti-TNF. MEASUREMENTS: After 24 hours, bacterial translocation in blood and in several remote organs, and serum TNF concentrations were measured. RESULTS: High bacterial counts were found in all remote organs of rats with haemorrhagic shock or endotoxaemia. Their serum TNF concentrations were significantly higher than in the corresponding sham-operated controls. Anti-TNF significantly reduced the extent of bacterial translocation. Rats, the only treatment of which was exogenous TNF, developed substantial bacterial translocation. CONCLUSION: Bacterial translocation is associated with increased serum TNF, and can be minimised by anti-TNF. This, and the triggering of translocation in unprovoked animals by TNF alone, suggest that TNF may be the stimulator, and not the consequence, of bacterial translocation.

Peritoneal cultures and antibiotic treatment in patients with perforated appendicitis.

OBJECTIVE: To question the common practice of sending material for microbiological examination during appendicectomy for perforated appendixes. DESIGN: Uncontrolled retrospective study. SETTING: Teaching hospital, Israel. SUBJECTS: 89 patients who had their perforated appendixes removed. INTERVENTIONS: Appendicectomy and antibiotic treatment. MAIN OUTCOME MEASURE: Whether a change in antibiotic regimen was required after bacteriological identification of bacteria isolated during the operation. RESULTS: In only 43 of the cultures (48%) taken during the operation were bacteria grown, and these were mainly Escherichia coli. In 65 patients (73%) there was no need to change the previously initiated antibiotic regimen, and in 23 (26%) it was changed purely on clinical grounds. In only one patient (1%) was the change the consequence of microbiological testing, as the organisms identified in 42 of the 43 cultures (98%) were sensitive to at least one of the antibiotics that had already been given. CONCLUSION: The practice of culturing samples taken from a ruptured appendix is redundant, because the antibiotic that has already been initiated is effective in most of the patients and the decision to modify the therapeutic regimen is dominated by clinical considerations.

Stab wounds to the gluteal region: a management strategy.

OBJECTIVE: To examine the utility of a protocol for treating stab wounds to the gluteal region. These are uncommon and potentially lethal, and the location of injury influences the rate and severity of associated injuries. This was a retrospective, uncontrolled study. METHODS: Patients who sustained gluteal stab wounds and were treated according to our predetermined protocol that classifies injuries as upper or lower zone were reviewed, and associated injuries and outcome were measured. RESULTS: Of 27 gluteal stab wounds in 17 patients, 53% were classified as upper zone and 47% as lower zone injuries. Sixty-six percent of the upper zone injuries had associated neurologic, vascular, or visceral injuries that required invasive procedures or surgery, compared with 12.5% for lower zone injuries (p < 0.05). CONCLUSION: Upper zone gluteal stab wounds require prompt multisystem evaluation with mandatory angiography and aggressive management. Lower zone wounds need observation and repeated evaluations.

[Combined approach in management of penetrating injury of vertebral artery].

Penetrating injuries of the vertebral artery are not common. Although surgical control of this type of injury is well-documented, the combined approach (surgery and packing for temporary control of bleeding, followed by angiography and embolization for permanent control) is now recognized and practiced. We describe a 40-year-old man who was stabbed in the neck. He was rushed to the operating theater in hemorrhagic shock. A vertebral artery injury was identified and packed. Angiography and embolization permanently controlled the bleeding. The combined approach is safe and we recommend it in those in whom bleeding from the vertebral artery is initially well controlled with packing.

Improving screening for melanoma by measuring similarity to pre-classified images.

A new method that can dramatically improve the sensitivity and especially the specificity of skin naevi screening for melanoma by physicians is introduced. The method is based on measuring the similarity to previously classified naevi images. As more naevi are being classified, the power of the method is enhanced. Thus physicians can benefit from experience accumulated by others and the screening can be performed effectively by physicians with less experience.

Muscular dystrophy due to dysferlin deficiency in Libyan Jews. Clinical and genetic features.

The cluster in Jews of Libyan origin of limb-girdle muscular dystrophy type 2B due to a dysferlin 1624delG mutation is described. The carrier frequency of this mutation is calculated to be approximately 10% in this population, in which the disease prevalence is at least 1 per 1300 adults. Twenty-nine patients from 12 families were all homozygous for the same mutation. However, clinical features were heterogeneous even within the same family: in half of the patients onset was in the distal muscles of the legs, which is similar to Miyoshi myopathy, while in others onset was in the proximal musculature, which is similar to other forms of limb-girdle dystrophies. Age at onset varied from 12 to 28 years (mean 20.3 +/- 5.5 years). One patient was presymptomatic at age 28 years. Progression was slow regardless of age of onset, patients remaining ambulatory until at least 33 years. Five patients described subacute, painful enlarged calves as an early, unusual feature. The variable features in this ethnic cluster contribute to the definition of the clinical spectrum of dysferlinopathies in general. The cause of the observed heterogeneity remains unclear.

Appendicitis in the elderly: what has changed?

BACKGROUND: The course and outcome of appendicitis in the elderly differs from that of the general population. The rates of perforated appendices, error in diagnosis, postoperative complications and mortality may be related to the time lapse between onset of symptoms and admission, and hence delay in surgery. OBJECTIVES: To evaluate if these factors have improved in recent years. METHODS: A retrospective study was carried out of all 61 patients over age 60 who underwent appendectomies in a major metropolitan hospital during 1988-98. RESULTS: We found that most patients had appendectomies within the first 24 hours of admission and within 3 days of symptoms. Rate of perforation was 43%, error 5.6%, morbidity 41%, and mortality 3.2%. CONCLUSIONS: The high rate of appendix perforation in the elderly is not due to delay. The literature reveals little improvement in the statistics of the disease over the last five decades, despite advances in imaging and surgical technique. This may be explained by the increasing inclusion of octogenarian patients.

Splicing mutation in dysferlin produces limb-girdle muscular dystrophy with inflammation.

Mutations in dysferlin were recently described in patients with Miyoshi myopathy, a disorder that preferentially affects the distal musculature, and in patients with Limb-Girdle Muscular Dystrophy 2B, a disorder that affects the proximal musculature. Despite the phenotypic differences, the types of mutations associated with Miyoshi myopathy and Limb-Girdle Muscular Dystrophy 2B do not differ significantly. Thus, the etiology of the phenotypic variability associated with dysferlin mutations remains unknown. Using genetic linkage and mutation analysis, we identified a large inbred pedigree of Yemenite Jewish descent with limb-girdle muscular dystrophy. The phenotype in these patients included slowly progressive, proximal, and distal muscular weakness in the lower limbs with markedly elevated serum creatine kinase (CK) levels. These patients had normal development and muscle strength and function in early life. Muscle biopsies from 4 affected patients showed a typical dystrophic pattern but interestingly, in 2, an inflammatory process was seen. The inflammatory infiltrates included primarily CD3 positive lymphocytes. Associated with this phenotype, we identified a previously undescribed frameshift mutation at nucleotide 5711 of dysferlin. This mutation produced an absence of normal dysferlin mRNA synthesis by affecting an acceptor site and cryptic splicing. Thus, splice site mutations that disrupt dysferlin may produce a phenotype associated with inflammation.

Metastases to the retroperitoneum in patients with extremity soft tissue sarcoma: an unusual metastatic pattern.

BACKGROUND: Extremity soft tissue sarcoma (STS) metastasizes preferentially to the lungs via the hematogenous route. Metastases in extrapulmonary sites such as bone, brain, and subcutaneous tissues are observed less frequently. To the authors' knowledge, limb STS primarily metastasizing to the retroperitoneum has not been described to date. The current study reviews the clinical course, management, and patient prognosis in such a pattern of metastasis. METHODS: Records of patients with retroperitoneal metastases originating from an extremity STS between 1994-1998 were reviewed. Patient demographics, primary tumor site, other tumor sites, local recurrence, distant metastasis, treatment, and survival were analyzed. RESULTS: Ten patients were included in the study. All had primary STS of different histologic types and high histologic grade confined to a lower limb. The retroperitoneal metastases were diagnosed between 6-120 months (mean, 45 months) after diagnosis of the primary sarcoma. At that time, one patient had evidence of local recurrence of the primary tumor site, two patients had lung metastases, and one patient had diffuse bone metastases. Eight patients were eligible for surgery. In six of these patients the metastases were excised completely. The median follow up was 12 months. Of the six patients who underwent complete resection, 3 were alive at last follow-up with no evidence of disease after 12 months, 14 months, and 24 months, respectively. Two patients with recurrent retroperitoneal disease and one patient with retroperitoneal and lung metastases died despite systemic chemotherapy. CONCLUSIONS: Extremity STS can metastasize hematogenously to the retroperitoneum, a fact that mandates a high index of suspicion and abdominal imaging studies during the follow-up of such patients. Retroperitoneal metastases necessitate aggressive surgical resection to enable prolongation of survival.