Effects of early life psychosocial adversity have received a great deal of attention, such as maternal separation in experimental animal models and abuse/neglect in young humans. More recently, long-term effects of the physical stress of repetitive procedural pain have begun to be addressed in infants hospitalized in neonatal intensive care. Preterm infants are more sensitive to pain and stress, which cannot be distinguished in neonates. The focus of this review is clinical studies of long-term effects of repeated procedural pain-related stress in the neonatal intensive care unit (NICU) in relation to brain development, neurodevelopment, programming of stress systems, and later pain sensitivity in infants born very preterm (24–32 weeks’ gestational age). Neonatal pain exposure has been quantified as the number of invasive and/or skin-breaking procedures during hospitalization in the NICU. Emerging studies provide convincing clinical evidence for an adverse impact of neonatal pain/stress in infants at a time of physiological immaturity, rapidly developing brain microstructure and networks, as well as programming of the hypothalamic-pituitary-adrenal axis. Currently it appears that early pain/stress may influence the developing brain and thereby neurodevelopment and stress-sensitive behaviors, particularly in the most immature neonates. However, there is no evidence for greater prevalence of pain syndromes compared to children and adults born healthy at full term. In addressing associations between pain/stress and outcomes, careful consideration of confounding clinical factors related to prematurity is essential. The need for pain management for humanitarian care is widely advocated. Non-pharmacological interventions to help parents reduce their infant’s stress may be brain-protective.
End-of-life decisions are made daily in intensive care units worldwide. There are numerous factors affecting these decisions, including geographical location as well as religion and attitudes of caregivers, patients, and families. There is a spectrum of end-of-life care options from full continued care, withholding treatment, withdrawing treatment, and active life-ending procedures.
The fetal “programming of adult diseases” has been previously reviewed. The descriptions were comprehensive, dealing with the effects of nutritional deprivation on the development of adult metabolic and cardiovascular diseases. During the past decade, research into this “programming” also expanded to the development of osteoporosis. The present review deals with the imbalance of bone mineral metabolism, “programmed” by maternal/fetal/infantile nutritional deprivation, and is illustrated with a family history from the Budapest Ghetto.
The growing practice of endoscopic surgery has changed the therapeutic management of selected head and neck cancers. Although a negative surgical margin in resection of neoplasm is the most important surgical principle in oncologic surgery, controversies exist regarding assessment and interpretation of the status of margin resection. The aim of this review was to summarize the literature considering the assessment and feasibility of negative margins in transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). Free margin status is being approached differently in vocal cord cancer (1–2 mm) compared with other sites in the upper aerodigestive tract (2–5 mm). Exposure, orientation of the pathological specimen, and co-operation with the pathologist are crucial principles needed to be followed in transoral surgery. Piecemeal resection to better expose deep tumor involvement and biopsies taken from surgical margins surrounding site of resection can improve margin assessment. High rates of negative surgical margins can be achieved with TLM and TORS. Adjuvant treatment decision should take into consideration also the surgeon’s judgment with regard to the completeness of tumor resection.
Thyroid cancer has been increasing in incidence, with the number of reported cases in the US rising by 25% over the last 3 years. With growing technological advances in the field and improved contributions of diagnostics, surgical decision-making and operative planning have taken on new challenges. Herein, we review the current clinical practice recommendations and active areas of surgical controversy, reflective of the most recently published professional consensus guidelines and a systematic review of the literature.
Objective: To compare pathologic results obtained via in-office transnasal fiberoptic laryngoscopy (TFL) to those of subsequent direct laryngoscopy in order to assess the accuracy of TFL as a diagnostic tool.
Patients: One hundred and seventeen patients with suspicious laryngeal lesions.
Methods: All patients underwent in-office biopsies. All patients with malignant diagnosis were referred to treatment. All patients with benign diagnosis or carcinoma in situ were referred to direct laryngoscopy for definitive diagnosis. The pathological results of the specimens from both procedures were compared.
Results: Adequate tissue for diagnostic purposes was obtained in 110 of 117 in-office transnasal fiberoptic laryngoscopy biopsies (94.0%). The biopsy results revealed invasive carcinoma in 42 patients (38.2%), carcinoma in situ (CIS) in 17 patients (15.4%), and benign lesions in 51 patients (46.4%). All patients with benign pathologies and carcinoma in situ were referred to biopsy under direct laryngoscopy (five patients refused and were removed from the statistics). The final pathologies identified from the biopsies on direct laryngoscopy revealed that there was an underestimation of the transnasal fiberoptic laryngoscopy results in 33 patients (a false negative rate of 31.4%, 33/105) and an overestimation in one patient. The sensitivity of transnasal fiberoptic laryngoscopy biopsy compared with direct laryngoscopy biopsy was 70.6% and the specificity was 96.7%.
Conclusions: TFL with biopsy is easy, safe, and cost-effective but raises serious doubts about its clinical value due its low sensitivity rate for diagnosing suspicious lesions of the larynx. As such, it is recommended that all patients with a suspicious lesion diagnosed by TFL biopsy as being benign or CIS should be referred to direct laryngoscopy for verification of the findings.
Purpose. This is a population study of patients who were treated for vulvar cancer in a tertiary center in northern Israel, aimed to report clinical findings, treatment, and outcome.
Methods. A retrospective chart review of all medical records of consecutive patients who were treated for vulvar cancer in the years 1993–2012 was conducted. Data extracted from the medical records included demographics, histology, size of lesion, stage of disease at diagnosis, type of treatment, radiation dose, follow-up, recurrence, and survival.
Results. The study included 44 patients with a median age of 69.8 years (range, 42–93 years). Thirty-five (79.5%) of the patients were of Jewish descent, five were Arabic, and four were of other descent. The most common histology type was squamous cell carcinoma in 35 (79.5%) patients. Most patients were staged FIGO II–III at time of diagnosis. Surgery was the most common primary treatment modality (54.2%). Twenty-three (52.2%) patients had recurrent disease. Older age and more advanced stage at diagnosis were associated with increased mortality.
Conclusion. Vulvar cancer is common among elderly women with co-morbidities who present in advanced disease stage; all these factors are significant for survival.
Heparanase, a β-D-endoglucuronidase abundant in platelets that was discovered 30 years ago, is an enzyme that cleaves heparan sulfate side chains on the cell surface and in the extracellular matrix. It was later recognized as being a pro-inflammatory and pro-metastatic protein. We had earlier demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. We had shown that heparanase up-regulated the expression of the blood coagulation initiator tissue factor (TF) and interacted with the tissue factor pathway inhibitor (TFPI) on the cell surface membrane of endothelial and tumor cells, leading to dissociation of TFPI and resulting in increased cell surface coagulation activity. Moreover, we have demonstrated that heparanase directly enhanced TF activity which led to increased factor Xa production and subsequent activation of the coagulation system. Recently, heparanase inhibitory peptides derived of TFPI-2 were demonstrated by us to inhibit heparanase procoagulant activity and attenuate sepsis in mouse models.
Venous thromboembolism (VTE), the third most frequent acute cardiovascular syndrome, may cause life-threatening complications and imposes a substantial socio-economic burden. During the past years, several landmark trials paved the way towards novel strategies in acute and long-term management of patients with acute pulmonary embolism (PE). Risk stratification is increasingly recognized as a central cornerstone for an adequate diagnostic and therapeutic management of the highly heterogeneous population of patients with acute PE. Recently published European Guidelines emphasize the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for identification of normotensive PE patients at intermediate risk for an adverse short-term outcome. In this patient group, systemic full-dose thrombolysis was associated with a significantly increased risk of intracranial bleeding, a complication which discourages its clinical application unless hemodynamic decompensation occurs. A large-scale clinical trial program evaluating new oral anticoagulants in the initial and long-term treatment of venous thromboembolism showed at least comparable efficacy and presumably increased safety of these drugs compared to the current standard treatment. Research is continuing on catheter-directed, ultrasound-assisted, local, low-dose thrombolysis in the management of intermediate-risk PE.
Rasagiline (Azilect) is a highly selective and potent propargylamine inhibitor of monoamine oxidase (MAO) type B. Like other similar propargylamine inhibitors, rasagiline binds covalently to the N5 nitro-gen of the flavin residue of MAO, resulting in irreversible inactivation of the enzyme. Therapeutic doses of the drug which inhibit brain MAO-B by 95% or more cause minimal inhibition of MAO-A, and do not potentiate the pressor or other pharmacological effects of tyramine. Metabolic conversion of the com-pound in vivo is by hepatic cytochrome P450-1A2, with generation of 1-aminoindan as the major me-tabolite. Rasagiline possesses no amphetamine-like properties, by contrast with the related compound selegiline (Deprenyl, Jumex, Eldepryl). Although the exact distribution of MAO isoforms in different neurons and tissues is not known, dopamine behaves largely as a MAO-A substrate in vivo, but follow-ing loss of dopaminergic axonal varicosities from the striatum, metabolism by glial MAO-B becomes increasingly important. Following subchronic administration to normal rats, rasagiline increases levels of dopamine in striatal microdialysate, possibly by the build-up of β-phenylethylamine, which is an ex-cellent substrate for MAO-B, and is an effective inhibitor of the plasma membrane dopamine trans-porter (DAT). Both of these mechanisms may participate in the anti-Parkinsonian effect of rasagiline in humans. Rasagiline possesses neuroprotective properties in a variety of primary neuronal preparations and neuron-like cell lines, which is not due to MAO inhibition. Recent clinical studies have also demon-strated possible neuroprotective properties of the drug in human Parkinsonian patients, as shown by a reduced rate of decline of symptoms over time.
