Carotid body tumor contemporary management in a high-volume center.

BACKGROUND: The aim of this study is to report our results with carotid body tumor (CBT) surgical management. METHODS: Between 2010 and 2018, 100 CBTs (mean age: 48.0 years, range 21-80 years old) were treated in our center. The patients were classified in 3 groups according to the size: group I (<3 cm), group II (3 to 5 cm) and group III (>5 cm). RESULTS: Surgical resection was performed in 88 patients and conservative treatment in 2 cases. Nine patients were treated for bilateral involvement and one of them was also treated again for a relapse. Postoperatively, cranial nerve injury (CNI) was significantly higher in group II [3 (8.3%) vs. 16 (31.4%) vs. 2 (15.4%); P=0.030] with no statistical differences between the CN involved. At univariate analysis for CNI, CBT group (P=0.030), maximum diameter (P=0.046), patients presenting with dysphonia (P=0.035) and dysphagia (P=0.007) and patients suffering from any intraoperative complication (P=0.047) were statistically significant. At multivariate analysis the only significant variable was CBT group II (P=0.016). For blood loss, CBT group III (P<0.001), Shamblin class III (P<0.001), Pulmonary disease (P=0.034) and surgery time (P<0.001) were statistically significant. The follow-up of 79 patients (87.8%) showed a 100% overall survival at median follow-up of 37.7 months (range 2-84.7 months) with freedom from local recurrence of 97.8% (77/79). CONCLUSIONS: Surgical resection remains the gold standard to obtain complete recovery, although tumor size is to be considered a risk factor for CNI because large CBTs remain at high risk for CNIs.

Chlamydia pneumoniae and acute aortic syndrome: a call for a multi-institutional study.

Chlamydia Pneumoniae (CP) infection is strongly associated with coronary artery disease, as well as with atherosclerosis of the carotid and peripheral arteries. However, the role of CP in the pathogenesis of aortic disease remains controversial. Our present experience suggests no correlation between a current infection with C. pneumoniae and acute aortic dissection. Well-designed large prospective studies are needed in order to clarify the pathophysiologic role of CP infection in acute and chronic aortic disease.

Pol zeta ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability.

Pol zeta is an error-prone DNA polymerase that is critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) and possible contribution to DNA double-strand break (DSB) repair in class switch recombination (CSR), we ablated Rev3, the catalytic subunit of Pol zeta, selectively in mature B cells in vivo. The frequency of somatic mutation was reduced in the mutant cells but the pattern of SHM was unaffected. Rev3-deficient B cells also exhibited pronounced chromosomal instability and impaired proliferation capacity. Although the data thus argue against a direct role of Pol zeta in SHM, Pol zeta deficiency directly interfered with CSR in that activated Rev3-deficient B cells exhibited a reduced efficiency of CSR and an increased frequency of DNA breaks in the immunoglobulin H locus. Based on our results, we suggest a nonredundant role of Pol zeta in DNA DSB repair through nonhomologous end joining.

Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus.

Monoallelic demethylation and rearrangement control allelic exclusion of the immunoglobulin kappa-chain locus (Igk locus) in B cells. Here, through the introduction of pre-rearranged Igk genes into their physiological position, the critical rearrangement step was bypassed, thereby generating mice producing B cells simultaneously expressing two different immunoglobulin-kappa light chains. Such 'double-expressing' B cells still underwent monoallelic demethylation at the Igk locus, and the demethylated allele was the 'preferred' substrate for somatic hypermutation in each cell. However, methylation itself did not directly inhibit the activation-induced cytidine-deaminase reaction in vitro. Thus, it seems that the epigenetic mechanisms that initially bring about monoallelic variable-(diversity)-joining rearrangement continue to be involved in the control of antibody diversity at later stages of B cell development.

Hand and wrist arterial aneurysms.

Hand and wrist aneurysms are a rare pathology, but recently the number of cases is increasing because of iatrogenic injuries such as catheter placement for endovascular procedures, invasive blood pressure monitoring, and arterial blood collection. In the period between January 1992 and January 2005, seven patients were treated at our institution for hand and wrist aneurysms. Five were true aneurysms and two were false aneurysms. All patients underwent surgery: four had aneurysmectomy and ligation of the arterial stumps and three had lesion removal, with arterial break suture in two cases and reconstruction with interposition of reversed autologous vein in the other case. In all cases, we did not have any postoperative ischemic or neurological complications. Symptoms like pain, paresthesia, and disesthesia combined with the minimal morbidity associated with repair suggest that operative repair of these aneurysms should be routinely performed.

Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization.

We previously demonstrated that male mice deficient in the soluble adenylyl cyclase (sAC) are sterile and produce spermatozoa with deficits in progressive motility and are unable to fertilize zona-intact eggs. Here, analyses of sAC(-/-) spermatozoa provide additional insights into the functions linked to cAMP signaling. Adenylyl cyclase activity and cAMP content are greatly diminished in crude preparations of sAC(-/-) spermatozoa and are undetectable after sperm purification. HCO(3)(-) is unable to rapidly accelerate the flagellar beat or facilitate evoked Ca(2+) entry into sAC(-/-) spermatozoa. Moreover, the delayed HCO(3)(-)-dependent increases in protein tyrosine phosphorylation and hyperactivated motility, which occur late in capacitation of wild-type spermatozoa, do not develop in sAC(-/-) spermatozoa. However, sAC(-/-) sperm fertilize zona-free oocytes, indicating that gamete fusion does not require sAC. Although ATP levels are significantly reduced in sAC(-/-) sperm, cAMP-AM ester increases flagellar beat frequency, progressive motility, and alters the pattern of tyrosine phosphorylated proteins. These results indicate that sAC and cAMP coordinate cellular energy balance in wild-type sperm and that the ATP generating machinery is not operating normally in sAC(-/-) spermatozoa. These findings demonstrate that sAC plays a critical role in cAMP signaling in spermatozoa and that defective cAMP production prevents engagement of multiple components of capacitation resulting in male infertility.

Midterm clinical success and behavior of the aneurysm sac after endovascular AAA repair with the Excluder graft.

OBJECTIVE: Recent studies have reported different sac behavior after endovascular repair of abdominal aortic aneurysms, depending on the endografts. This study was designed to evaluate mid-term outcome and sac behavior after treatment with the Gore Excluder stent-graft. METHODS: Between June 1999 and January 2005, 109 selected patients with suitable anatomy were treated electively for abdominal aortic aneurysm with the Excluder stent graft. Data were prospectively collected in a computerised database and included demographics, details of the aortoiliac anatomy, procedural and clinical success, and postoperative complications. Postoperative sac size and the presence of endoleaks were assessed with computed tomography scans obtained at 1, 6, and 12 months, and yearly thereafter. All diameter measures in patients followed for > 1 year (84.4%) were analyzed. RESULTS: Assisted primary technical success was achieved in 108 cases (99.1%). No type I endoleaks and 12 (11.1%) type II endoleaks were recorded < or = 1 month from the procedure. Mean follow-up was 29.6 +/- 16.1 months. We recorded one new-onset type IA endoleak, complete resolution of five type II endoleaks, and eight new-onset type II endoleaks. The overall prevalence of type II endoleaks was 14%. Shrinkage at 1, 2, 3, and 4 years was observed in 20.7%, 30.5%, 38.9%, and 36.8% of cases. The presence of type II endoleak influenced the trend of aneurysm size throughout the 4 years. Aneurysms without endoleak shrank more than aneurysms with type II endoleak (P < .0001). We observed two cases of sac enlargement due to the presence of endoleaks. No cases of endotension with sac enlargement, late open conversion, or aneurysm-related deaths were observed. Unchanged aneurysmal sacs remained stable during follow-up, with no adverse events. CONCLUSIONS: Endovascular treatment with the Excluder device in selected patients produces low rates of shrinkage, but this peculiar sac behavior does not affect mid-term clinical success.

Mice deficient for the type II topoisomerase-like DNA transesterase Spo11 show normal immunoglobulin somatic hypermutation and class switching.

Somatic hypermutation in B cells undergoing T cell dependent immune responses generates high affinity antibodies that provide protective immunity. B cells also switch from the expression of immunoglobulin (Ig) M and IgD to that of other Ig classes through somatic DNA recombination. Recent work has implicated DNA strand breaks, possibly DNA double strand breaks (DSB), as the initiating lesions in both class switch recombination and hypermutation, although the etiology of these lesions is not understood. Spo11, a protein structurally related to archaeal type II topoisomerases, generates DSB that initiate meiotic recombination. This characteristic, together with its expression pattern, marks this enzyme as a potential candidate for the initiation of hypermutation, and perhaps also for Ig class switching. To investigate whether Spo11 is involved in these processes, we studied the T cell dependent immune response of Spo11-deficient (Spo11(-/-)) mice against the hapten nitrophenyl (NP). We found that V186.2-bearing IgG1 transcripts had normal levels and patterns of somatic hypermutation. Furthermore, Spo11(-/-) mice showed normal serum levels of all Ig isotypes. These results indicate that Spo11 is not required for Ig hypermutation or class switch recombination.

DNA polymerase kappa deficiency does not affect somatic hypermutation in mice.

Somatic hypermutation (SH) in B cells undergoing T cell-dependent immune responses generates high-affinity antibodies that provide protective immunity. Most current models of SH postulate the introduction of a nick into the DNA and subsequent replication-independent, error-prone short-patch synthesis by one or more DNA polymerases. The Pol kappa (DinB1) gene encodes a specialized mammalian DNA polymerase called DNA polymerase kappa (pol kappa), a member of the recently discovered Y family of DNA polymerases. The mouse PolK gene is expressed at high levels in the seminiferous tubules of the testis and in the adrenal cortex, and at lower levels in most other cells of the body including B lymphocytes. In vitro studies showed that pol kappa can act as an error-prone polymerase, although they failed to ascribe a clear function to this enzyme. The ability of pol kappa to generate mutations when extending primers on undamaged DNA templates identifies this enzyme as a potential candidate for the introduction of nucleotide changes in the immunoglobulin (Ig) genes during the process of SH. Here we show that pol kappa-deficient mice are viable, fertile and able to mount a normal immune response to the antigen (4-hydroxy-3-nitrophenyl)acetyl-chicken gamma-globulin (NP-GC). They also mutate their Ig genes normally. However, pol kappa-deficient embryonic fibroblasts are abnormally sensitive to killing following exposure to ultraviolet (UV) radiation, suggesting a role of pol kappa in translesion DNA synthesis.

Endovascular stenting for stenoses in surgically reconstructed brachiocephalic bypass grafts: immediate and midterm outcomes.

PURPOSE: To report the use of endovascular stenting for treatment of patients with symptomatic obstruction of brachiocephalic surgical reconstructions. METHODS: Twenty-two patients (17 men; mean age 65+/-6 years) with 24 symptomatic obstructions of brachiocephalic Dacron bypass grafts (2 aorto-innominate, 9 subclavian-carotid, and 11 carotid-subclavian) were treated with balloon-expandable stents delivered via a percutaneous brachial access or surgical exposure of the common carotid artery. A distal protection device was utilized in the 9 patients with subclavian-carotid bypass grafts. All patients were followed by clinical and Doppler examinations. RESULTS: Procedural success was 100%; 1 (4.5%) patient developed transient intraprocedural aphasia owing to intolerance to the distal protection balloon occlusion. All 22 patients reported complete relief of their presenting symptoms. Over a 29-month follow-up, 3 (13.6%) restenoses were found, but none was due to stent compression. CONCLUSIONS: Stenting for obstructed brachiocephalic reconstructions appears to be a safe, effective, and durable therapeutic strategy.

Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect.

To acquire the ability to fertilize, spermatozoa undergo complex, but at present poorly understood, activation processes. The intracellular rise of cAMP produced by the bicarbonate-dependent soluble adenylyl cyclase (sAC) has been suggested to play a central role in initiating the cascade of the events that culminates in spermatozoa maturation. Here, we show that targeted disruption of the sAC gene does not affect spermatogenesis but dramatically impairs sperm motility, leading to male sterility. sAC mutant spermatozoa are characterized by a total loss of forward motility and are unable to fertilize oocytes in vitro. Interestingly, motility in sAC mutant spermatozoa can be restored on cAMP loading, indicating that the motility defect observed is not caused by a structural defect. We, therefore, conclude that sAC plays an essential and nonredundant role in the activation of the signaling cascade controlling motility and, therefore, in fertility. The crucial role of sAC in fertility and the absence of any other obvious pathological abnormalities in sAC-deficient mice may provide a rationale for developing inhibitors that can be applied as a human male contraceptive.

Combined carotid endarterectomy and coronary artery bypass grafting

Objective: To evaluate the perioperative and long-term outcomese of combined coronary artery bypass grafting and carotid endartectomy performed in our Institute.Methods: From January 1992 to Apri1 2004, 158 patients with a mean age of 66.3 years (range 42-81) underwent combined carotid endartectomy and coronary artery bypass grafting. Selection criteria were symptomatic ot asymptomatic 70-99 por cento carotid stenosis and unstable coronary symptoms or coronary anatomy judged to preclude safe endarterectomy. Carotid duplex scanning was introduced as a routine screening test from 1996 for patients candidate to coronary artery bypass grafting. Patients presenting fop carotid endartectomy were subjected to further cardiological study only if deemed to be at high cardiac risk. Results: Perioperative mortality was 5.7 por cento. Causes of death were: myocardial infarction with multiorgan failure (four patients),irreversible left ventricular fibrillation (three patients) and low ejection syndrome complicated by stroke and ventricular fibrillation (two patients). The perioperative stroke cate was 1.3 por cento. Mean follow-up was 49 months (range 1-138): 22 patients were lost at follow-up and of remaining 136 patients 21 (15.4 por cento) died. Causes of late mortality were: eight myocardial infarctions, tive cancers, six congestive heartfailure and two abdominal aortic aneurysm rupture. Late stroke rate was 2.2 por cento (two patients with contralateral stroke and one with ipsilateral stroke). One asymptomatic carotid occlusion and three [ carotid restenosis were also observed. Discussion: The low stroke cate observed in our series suggest the use of combined carotid endartectomy and coronary artery bypassgrafting in patients with significant symptomatic and asymptomatic carotid artery stenosis that need myocardial revascularization. Poor len-ventricular function, unstable angina and bilateral carotid artery stenosis, account for the high perioperative mortality associated with this approach.