Decision making for the central compartment in differentiated thyroid cancer

The central compartment is a common site for nodal spread from differentiated thyroid carcinoma, often occurring in patients without clinical or ultrasonographic (US) evidence of neck lymph node metastasis (cN0). However, the role of elective central compartment neck dissection (CND) among patients with DTC remains controversial. We performed a systematic literature review, also including review of international guidelines, with discussion of anatomic and technical aspects, as well as risks and benefits of performing elective CND. The recent literature does not uniformly support or refute elective CND in patients with DTC, and therefore an individualized approach is warranted which considers individual surgeon experience, including individual recurrence and complication rates. Patients (especially older males) with large tumors (>4 cm) and extrathyroidal extension are more likely to benefit from elective CND, but elective CND also increases risk for hypoparathyroidism and recurrent nerve injury, especially when operated by low-volume surgeons. Individual surgeons who perform elective CND must ensure the number of central compartment dissections needed to prevent one recurrence (number needed to treat) is not disproportionate to their individual number of central compartment dissections per related complication (number needed to harm).     

Total intravenous anesthesia with propofol and remifentanil for elective non-cardiac surgery

BACKGROUND: Remifentanil is a highly effective mu opioid agonist with predictable pharmacokinetics and a close concentration-effect relationship. Moreover, studies on anesthetic drugs interactions show that optimal propofol concentrations decrease more significantly with remifentanil as compared with other opioids and recovery appears to be much faster than when propofol is combined with other opioids combinations. This intervention study was designed to evaluate the efficacy of propofol combined with remifentanil in elective non cardiac inpatient surgery. METHODS: N. 405 patients undergoing intraperitoneal, head-neck, intrathoracic, major orthopaedics, breast and major vascular surgery received: remifentanil (1 microgram.kg-1 at induction; 0.50 microgram.kg-1.min-1 at laryngoscopy; 0.25 microgram.kg-1.min-1 at skin incision; 0.25-0.30 microgram.kg-1.min1 from skin incision to end of skin suture) and propofol (0.5-1 mg.kg-1 at induction; 5 mg.kg-1.h-1 at laryngoscopy; 5 mg.kg-1.h-1 at skin incision and 5 mg.kg1.h1 thereafter). Intraoperative end-points included somatic responses, tachycardia and hypertension to laryngoscopy and surgery. Incidence of intraoperative bradycardia, hypotension and muscle rigidity were also recorded. Postoperative end-points included Aldrete score > or = 9, pain immediately following emergence and PONV. RESULTS: Propofol-remifentanil combination effectively controlled responses to laryngoscopy and surgical stress. Drug related adverse events were transient bradycardia (< 50 bpm) and hypotension (SBP < or = 80 mmHg) respectively: at prelaryngoscopy 11.60-1.48% and at pre-skin incision 10.61-0.98%. N. 365 patients were discharged from PACU and the median time to first Aldrete score > or = 9 was 22.3 min. The most frequent postoperative event was shivering recorded in n. 46 patients (12%). Postoperative analgesic medication was requested by n. 16 patients (4.4%) and PONV was noted in n. 6 patients (1.6%). CONCLUSIONS: When combined with propofol, remifentanil effectively provided for profound analgesia during surgery, stable anesthetic conditions, simplicity of use and predictable recovery.     

Inherited long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and a fetal-maternal interaction cause maternal liver disease and other pregnancy complications.

Fetal-maternal interactions are critical determinants of maternal health during pregnancy and perinatal outcome. This review explores the causative relationship of a fetal disorder of mitochondrial fatty acid oxidation, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, and the serious maternal liver diseases of pregnancy-preeclampsia, the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet counts), and acute fatty liver of pregnancy. Features of the metabolic adaptation necessitated during the fetal-neonatal transition; common phenotypes of pediatric fatty acid oxidation disorders, including neonatal hypoketotic, hypoglycemia and hepatic crisis; and clinical abnormalities of HELLP and acute fatty liver of pregnancy are presented. Evidence that a common mutation in the alpha-subunit (LCHAD) of trifunctional protein, E474Q, is always one of the mutant alleles in fetal isolated LCHAD deficiency associated with these disorders of pregnancy that cause high maternal, fetal, and newborn morbidity and mortality is reviewed. Recommendations for molecular testing for LCHAD deficiency in families with life-threatening maternal liver disease are given.     

Enhanced shedding of cytomegalovirus in semen of human immunodeficiency virus-seropositive homosexual men.

Site-specific shedding of cytomegalovirus (CMV) was assessed in a longitudinal study of homosexual and bisexual men. At initial testing, CMV was cultured from the semen of 33% (19 of 58) of asymptomatic and mildly symptomatic men who were seropositive for human immunodeficiency virus (HIV) at the time of entry into the study, whereas it was cultured from the semen of 17% (10 of 58) of the men who were HIV seronegative. CMV was isolated much more frequently from semen than from urine or throat washing specimens, and it was rarely recovered from stool or blood, regardless of the subject's HIV serostatus. CMV was cultured from the semen of 31% (16 of 52) of the men relatively early after seroconversion to HIV (mean, 12.8 months). CMV was persistently isolated from the semen of a greater proportion of the HIV-seropositive men than from the semen of the HIV-seronegative men during a 4.5-year follow-up period (52 of 110 - [47%] and 15 of 58 [26%] men, respectively). There was an increased relative risk for shedding of CMV in semen in association with decreased CD4+ cell numbers and increased levels of serum immunoglobulin A. However, there was no association of CMV shedding with an increased risk for the development of AIDS.     

Chromosomal in situ suppression hybridization of immunologically classified mitotic cells in hematologic malignancies.

Chromosomal in situ suppression (CISS) hybridization was performed with library DNA from sorted human chromosomes 8, 9, 15, 17, 21, and 22 on immunologically stained bone marrow cells of four patients with a hematologic neoplasm, including two patients with myelodysplastic syndrome and trisomy 8, one patient with promyelocytic leukemia bearing the translocation t(15;17)(q22;q11-12), and one patient with chronic myeloid leukemia and the translocation t(9;22)(q34;q11). In all patients, the results of conventional karyotype analysis could be confirmed by one- or two-color CISS hybridization using the appropriate chromosome-specific libraries. Our results show that CISS hybridization can detect both numerical and structural chromosome changes in immunologically classified cells with high specificity and reliability. The fact that chromosome spreads of very poor quality can now be included in such analyses is a decisive advantage of this approach. In addition, the suitability of this approach for interphase cytogenetics is discussed.     

Protection by deferoxamine from endothelial injury: a possible link with inhibition of intracellular xanthine oxidase

Hydroxyl radical scavengers and xanthine oxidase inhibitors protect cultured bovine pulmonary endothelial cells (BPAEC) from lytic injury by the endotoxin lipopolysaccharide (LPS). We hypothesized that exposure of BPAEC to cytotoxic concentrations of LPS activated intracellular xanthine oxidase, and that intracellular iron-dependent hydroxyl radical formation (a Fenton reaction) ensued, resulting in cell lysis. To test this, the protective effects of deferoxamine against H2O2 and LPS-induced cytotoxicity to BPAEC was assessed by 51Cr release. Preincubation with 0.4 mM deferoxamine conferred 67 +/- 15% (mean +/- SE) protection from LPS-induced cytotoxicity but 48 h of preincubation were required to induce significant protection. Significant protection form a classical Fenton reaction model, injury by 50 microM H2O2, could be induced by a 1-h preincubation with a 0.4 mM deferoxamine. The dissociated time course suggested that deferoxamine might work by different mechanisms in these models. The effects of LPS and deferoxamine on BPAEC-associated xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity were assessed using a spectrofluorophotometric measurement of the conversion of pterin to isoxanthopterin. BPAEC had 106 +/- 7 microU/mg XD+XO activity; XO activity constituted 48 +/- 1% of total XO+XD activity. LPS at a cytotoxic concentration did not alter XO, XD, or percent XO. Deferoxamine had striking proportional inhibitory effects on XO and XD in intact cells. XO+XD activity fell to 6 +/- 1% of control levels during a 48-h exposure of BPAEC to deferoxamine. Deferoxamine did not inhibit XO+XD ex vivo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carcinomas of the Thyroid with Ewing Family Tumor Elements (CEFTEs): A Diagnostic Challenge Before Surgery

Carcinomas of the thyroid with Ewing family tumor elements (CEFTEs) are small cell thyroid tumors characterized by epithelial differentiation and EWSR1-FLI1 rearrangements. In contrast to primary thyroid Ewing sarcomas, these rare tumors have a favorable prognosis. CEFTEs may co-exist with papillary thyroid carcinoma (PTC) foci and are thought to arise from either PTCs or main cells of solid cell nests (SCN). Due to their rare occurrence, characteristic clinical presentations, preoperatory sonographic (US) findings, and fine-needle aspiration (FNA) cytologic features were ill-defined until now. We report a case of a 40-year-old male who was referred to the thyroid clinic for a progressively enlarging, hard, painless, cervical mass. US examination revealed a hypoechoic nodule with lobulated margins and scant intranodular vascular signals of the right thyroid lobe. Evidence of extracapsular spread was not identified. FNA provided a Bethesda V cytology classification on conventional smears. Repeat FNA sampling with the use of a CytoFoam Core allowed a preoperative diagnosis consistent with undifferentiated thyroid carcinoma. Total thyroidectomy without lymph node dissection was performed. Histologic examination with subsequent molecular studies provided the diagnosis of papillary carcinoma of the thyroid with Ewing family tumour elements (CEFTEs). No additional treatment was rendered and the patient showed no evidence of local or distant disease by clinical examination, US, and ¹⁸FDG-TAC/PET after 6 months of follow-up. This is the first reported case of CEFTE with complete clinical, US, cytologic, and immunohistochemical preoperatory assessment.     

Effects of dexmedetomidine on kidney and brain tissue microcirculation and histology in ovine cardiopulmonary bypass: a randomised controlled trial

Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative inflammation and/or impaired tissue perfusion/oxygenation are thought to be contributors to these outcomes. It has been hypothesised that these problems may be ameliorated by the highly selective α₂-agonist, dexmedetomidine. We tested the effects of dexmedetomidine on renal and cerebral microcirculatory tissue perfusion, oxygenation and histology in a clinically relevant ovine model. Sixteen sheep were studied while conscious, after induction of anaesthesia and during 2 h of cardiopulmonary bypass. Eight sheep were allocated randomly to receive an intravenous infusion of dexmedetomidine (0.4–0.8 μg.kg^-1.h^-1) from induction of anaesthesia to the end of cardiopulmonary bypass, and eight to receive an equivalent volume of matched placebo (0.9% sodium chloride). Commencement of cardiopulmonary bypass decreased renal medullary tissue oxygenation in the placebo group (mean (95%CI) 5.96 (4.24–7.23) to 1.56 (0.84–2.09) kPa, p = 0.001), with similar hypoxic levels observed in the dexmedetomidine group (6.33 (5.33–7.07) to 1.51 (0.33–2.39) kPa, p = 0.002). While no differences in kidney function (i.e. reduced creatinine clearance) were evident, a greater incidence of histological renal tubular injury was observed in sheep receiving dexmedetomidine (7/8 sheep) compared with placebo (2/8 sheep), p = 0.041. Graded on a semi-quantitative scale (0–3), median (IQR [range]) severity of histological renal tubular injury was higher in the dexmedetomidine group compared with placebo (1.5 (1–2 [0–3]) vs. 0 (0–0.3 [0–1]) respectively, p = 0.013). There was no difference in cerebral tissue microglial activation (neuroinflammation) between the groups. Dexmedetomidine did not reduce renal medullary hypoxia or cerebral neuroinflammation in sheep undergoing cardiopulmonary bypass.