The Myth of "Reliable Research" in Pediatric Gender Medicine: A critical evaluation of the Dutch Studies-and research that has followed.

Two Dutch studies formed the foundation and the best available evidence for the practice of youth medical gender transition. We demonstrate that this work is methodologically flawed and should have never been used in medical settings as justification to scale this "innovative clinical practice." Three methodological biases undermine the research: (1) subject selection assured that only the most successful cases were included in the results; (2) the finding that "resolution of gender dysphoria" was due to the reversal of the questionnaire employed; (3) concomitant psychotherapy made it impossible to separate the effects of this intervention from those of hormones and surgery. We discuss the significant risk of harm that the Dutch research exposed, as well as the lack of applicability of the Dutch protocol to the currently escalating incidence of adolescent-onset, non-binary, psychiatrically challenged youth, who are preponderantly natal females. "Spin" problems-the tendency to present weak or negative results as certain and positive-continue to plague reports that originate from clinics that are actively administering hormonal and surgical interventions to youth. It is time for gender medicine to pay attention to the published objective systematic reviews and to the outcome uncertainties and definable potential harms to these vulnerable youth.

Reconsidering Informed Consent for Trans-Identified Children, Adolescents, and Young Adults.

In less than a decade, the western world has witnessed an unprecedented rise in the numbers of children and adolescents seeking gender transition. Despite the precedent of years of gender-affirmative care, the social, medical and surgical interventions are still based on very low-quality evidence. The many risks of these interventions, including medicalizing a temporary adolescent identity, have come into a clearer focus through an awareness of detransitioners. The risks of gender-affirmative care are ethically managed through a properly conducted informed consent process. Its elements-deliberate sharing of the hoped-for benefits, known risks and long-term outcomes, and alternative treatments-must be delivered in a manner that promotes comprehension. The process is limited by: erroneous professional assumptions; poor quality of the initial evaluations; and inaccurate and incomplete information shared with patients and their parents. We discuss data on suicide and present the limitations of the Dutch studies that have been the basis for interventions. Beliefs about gender-affirmative care need to be separated from the established facts. A proper informed consent process can both prepare parents and patients for the difficult choices that they must make and can ease professionals' ethical tensions. Even when properly accomplished, however, some clinical circumstances exist that remain quite uncertain.

Carotid endarterectomy without angiography: can clinical evaluation and duplex ultrasonographic scanning alone replace traditional arteriography for carotid surgery workup? A prospective study.

BACKGROUND: The aim of this study was to determine whether clinical evaluation and duplex ultrasonography (DUS) alone can replace contrast cerebral arteriography (CA) for the detection of patients suitable for surgery at our institution. METHODS: During an 18-month period, 100 patients underwent DUS and CA during evaluation for carotid endarterectomy (CEA). All patients were studied prospectively; in each case an initial decision for or against CEA on the basis of DUS evaluation of the internal carotid arteries (ICAs) was subsequently compared with the surgeon's final management plan after CA. Of the 200 ICAs evaluated, 113 were considered for CEA but 14 were excluded from the study because the patient could not be evaluated before and after CA. This left 99 ICAs (86 patients) available for comparative analysis. RESULTS: The outcome of the 2 diagnostic modalities was perfectly consistent in 95.3% of the ICAs (kappa = 0.969). The clinical management decision was altered by the CA findings in only 2 cases (2%). Of the 99 ICAs considered suitable, 97 underwent CEA. No arteriographic complications occurred among the 100 patients undergoing CA. The perioperative stroke risk and mortality rates were 0%. CONCLUSIONS: Ninety-eight percent of the ICAs considered for surgery would have received appropriate clinical treatment on the strength of the patients' neurologic history and the outcome of DUS alone. Our results indicate that DUS is sufficient to establish the need for surgery in symptomatic and asymptomatic patients being considered for CEA and can replace CA in most clinical circumstances.

Cranial and cervical nerve injuries after carotid endarterectomy: a prospective study.

BACKGROUND: The purpose of this study was to review the outcome of patients who had cranial and cervical nerve injuries after carotid endarterectomy (CEA). METHODS: This prospective study reviewed 200 consecutive CEAs. Preoperative and postoperative cranial nerve assessment was completed on all patients. Neurologic evaluation included routine direct fiberoptic laryngoscopy. Patients found to have no neurologic injury had no further follow-up. Patients with postoperative peripheral neurologic dysfunction were enrolled for regular long-term follow-up to assess delayed recovery. RESULTS: Overall, 25 (12.5%) nerve injuries were identified in 24 patients. There were 11 (5.5%) hypoglossal, 8 (4%) recurrent laryngeal, 2 (1%) superior laryngeal, 2 (1%) marginal mandibular, and 2 (1%) greater auricular nerve injuries. None of the patients were lost to follow-up. All nerve dysfunctions were transient, with all but 4 nerves recovering completely within 6 months. The recovery took from 1 week to 37 months, with a mean recovery time of 5.8 months. Two patients with recurrent laryngeal nerve dysfunction were found to have prolonged full recovery time (i.e., 31 and 37 months, respectively). Two patients successfully underwent contralateral CEA, although movement of the opposite vocal cord was not fully restored. CONCLUSIONS: Cranial nerve injury after CEA is a common occurrence and can be classified as a "major" or "minor" complication, depending on the severity of the clinical consequences. Extended follow-up will identify the specific subset of patients with a late complete nerve recovery.

Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study.

BACKGROUND: Although carotid eversion endarterectomy (CEE) has obtained consensus providing excellent early and late results, conventional carotid endarterectomy (CEA) with or without patching continues to be considered the gold standard surgical procedure. The few studies published to date comparing CEE with CEA in a small series of patients have failed to show substantial advantages of one technique over the other, and further randomized comparative studies are still required. The purpose of this study was to compare the outcome of CEA with routine patch closure (CEAP) with that of CEE and reimplantation (CEER) of the internal carotid artery in the common carotid artery. METHODS: Three hundred thirty-six primary CEAs performed in 310 patients were randomized into 2 groups, 167 CEAPs and 169 CEERs. Surviving patients underwent duplex ultrasound scan control at 30 days, 6 months, 12 months, and every postoperative year thereafter. The mean follow-up was 34 months (range, 1 to 69 months). Demographic characteristics, risk factors, associated diseases, and indications for surgery were comparable in the 2 groups. RESULTS: Although the rate of intraoperative electroencephalogram changes was comparable in the 2 groups, the incidence of shunting was statistically higher in the CEAP group (28.1% vs 1.2%, P < .00001). The carotid cross-clamping time was significantly lower in the CEER group (P = .01). Although all deaths were in the CEAP group, the overall perioperative death and stroke-related death rates were comparable in the 2 groups. The perioperative stroke rate was statistically higher in the CEAP group (2.9% vs 0%, P = .03). Although the recurrent stenosis rate was comparable in the 2 groups (1.2% vs 0%), the CEAP group had a statistically higher rate of combined recurrent stenoses and occlusions (4.9% vs 0%, P = .003). The late mortality rate was similar in both groups. CONCLUSIONS: Although the outcome of CEAP in this series is consistent with that of the main reported trials, the CEER procedure is less likely than CEAP to cause perioperative stroke and death and seems superior in reducing the incidence of recurrent stenosis and late occlusive events.

Carotid endarterectomy in women: early and long-term results.

BACKGROUND: Although many randomized trials and other multicenter studies have demonstrated the benefits of carotid endarterectomy (CEA) in selected symptomatic and asymptomatic patients, including women, there is a remarkable lack of reports regarding the outcome of CEA with respect to sex. To analyze and compare the outcome of CEA in men and women in a single-group experience, we reviewed a consecutive series of 619 CEAs performed in 539 patients, 371 men (423 CEAs) and 168 women (196 CEAs). METHODS: Data collection was retrospective up to August 1, 1992 and prospective for all 405 patients treated thereafter. RESULTS: Women were significantly less likely than men to have overt evidence of coronary artery disease (P < .001) and had a significantly higher incidence of diabetes (P < .001). No perioperative death occurred in the female group (P = NS), and no statistical difference was found in perioperative stroke risk incidence. Women had a significantly higher incidence of late occlusive events (P = .01), which were all asymptomatic. No late stroke occurred in the female group (P = NS). Life-table cumulative survival rates at 1, 3, 5, and 7 years were 99.3%, 90.5%, 85.9%, and 82.3%, respectively, in women, and 98.9%, 91.9%, 85.2%, and 79.6% in men (log-rang P = .8). CONCLUSIONS: These findings show that perioperative stroke risk and mortality rates, as well as late stroke-free, mortality, and recurrence rates, in patients undergoing CEA, are comparable in men and women. Further, larger comparative studies are necessary to provide more information on the benefit and durability of CEA in asymptomatic patients, but the results of this study suggest that the early and late outcomes are excellent and comparable in symptomatic and asymptomatic men and women.

Sulodexide oral administration influences blood viscosity and fibrinolysis.

The aim of this study was to verify the effects of oral administration of a new enteric-coated formulation of sulodexide on blood viscosity and fibrinolysis. Six outpatients suffering from peripheral artery occlusive disease were administered orally two enteric-coated tablets containing 50 mg of sulodexide, twice daily for seven days. On the first and seventh administration days, the following parameters were evaluated: plasminogen activator inhibitor (PAI-1) activity, PAI-1 antigen, tissue plasminogen activator (t-PA) and whole blood, serum and plasma viscosity, before (0 time) and 2, 4 and 8 hours after ingestion of the drug. Following the first administration (50 mg), a slight reduction of PAI was registered; after 7 days' administration, a clear-cut lowering of functional and antigenic PAI was observed, together with an increase of t-PA. As to the drug's influence on blood viscosity, after 7 days the most evident reduction was that registered for plasma viscosity. No side effects were observed throughout the treatment period.

Subclavian carotid transposition for symptomatic subclavian artery stenosis or occlusion. A comparison with the endovascular procedure.

BACKGROUND: Although subclavian-carotid transposition (SCT), among all extrathoracic revascularization procedures, has emerged as the treatment of choice for symptomatic subclavian artery (SA) stenosis or occlusion, some authors advocate percutaneous transluminal angioplasty with stenting as the optimum primary therapy. AIM: to assess safety, efficacy and durability of SCT in the treatment of symptomatic SA stenosis or occlusion. DESIGN: review of a prospectively maintained vascular surgical registry. SETTING: University vascular surgical service. PATIENTS: 39 patients requiring surgery for symptomatic stenosis or occlusion of the proximal SA from September 1985 to August 1999. INTERVENTION: SCT. MEASURES: data were collected prospectively from hospital charts and office medical records to determine demographics, risk factors, presenting clinical manifestation, blood pressure differentials, location of the SA lesion and early postoperative outcome. Long-term follow-up was available in all patients. Patency of the revascularization was determined by physical examination and non-invasive laboratory studies. RESULTS: The perioperative mortality and morbidity rates were 2.5% (1 of 39) and 2.5% (1 of 39), respectively. Immediate relief of symptoms was achieved in 100% of cases. Mean follow-up was 6.8 years. Revascularization neither failed during the follow-up period, nor did patients have recurrent symptoms. The overall survival rates at 1, 3, 5 and 10 years were 100%, 100%, 86% and 68%. Overall late mortality rate was 18.4%: no death was stroke related. CONCLUSIONS: SCT is a very safe and effective surgical procedure for the treatment of symptomatic SA atherosclerotic disease, ensuring an excellent long-term patency.

Carotid endarterectomy in symptomatic and asymptomatic patients aged 75 years or more: perioperative mortality and stroke risk rates.

The aim of this retrospective study was to determine whether age per se constitutes a contraindication to surgery in the elderly patient undergoing carotid endarterectomy (CEA) with regard to operative mortality and stroke risk morbidity. During an 8-year period, 96 patients aged 75 years or more underwent 103 CEAs. The age range was 75 to 89 years, with a median age of 79 and a mean age of 79.4 years. Fifty-nine CEAs with patch closure and 44 carotid eversion endarterectomies and reimplantation were performed for symptomatic (70.9%) and asymptomatic (29.1%) carotid lesions under general anesthesia and with continuous perioperative electroencephalographic (EEG) monitoring. In light of the efficacy and success achieved in this experience, advanced age does not seem in itself to contraindicate the performance of CEA; the surgical risk for elderly patients appears sufficiently low to justify the operation. A more aggressive approach may be warranted in elderly patients because of the morbidity and cost of the disease that it effectively prevents.

Results of electroencephalographic monitoring during 369 consecutive carotid artery revascularizations.

A continuous intraoperative EEG monitoring was performed in 369 consecutive carotid artery revascularizations (CARs) (321 patients) to minimize the intraoperative neurological morbidity. There were 227 carotid endarterectomies and patch graft angioplasty (198 patients), 79 carotid eversion endarterectomies (70 patients) and 58 internal carotid artery reimplantations into the common carotid artery (48 patients). Indications for CARs were TIAs (141, 43.9%), amaurosis fugax (60, 18.6%) and fixed or partial nonprogressing stroke (14, 4.3%). One hundred and six patients (33.1%) were asymptomatic. EEG abnormalities consistent with cerebral ischemia occurred in 97 (26.3%) operations. The indwelling shunt (IS) was used in 73 cases; in the remaining 24 (24.7%), IS was not used on purpose because the surgical procedure was carried out successfully within 5-6 min after the appearance of EEG changes. All patients awoke from the anesthesia without any neurological deficit. Five patients presented with a major stroke within postoperative day 1 and 2, and 1 patient died on postoperative day 10. In 2 of these cases, the intraoperative EEG monitoring was absolutely normal and the IS was not used: the carotid occlusion was due to technical errors. The most striking finding of this series is the absence of false-negative results in continuous EEG monitoring. EEG monitoring appears an available and useful method for the detection of cerebral ischemia secondary to carotid cross-clamping and contributes to put at zero the intraoperative complications of the surgical procedure.

The elongation of the internal carotid artery: early and long-term results of patients having surgery compared with unoperated controls.

The purposes of this study are to (1) demonstrate the association of elongations of the internal carotid artery (ICA), that is, kinking, coiling, tortuousity, and angulation, and the neurologic symptoms with high stroke risk; (2) compare the results of the surgical treatment versus the medical treatment alone; (3) contribute to the knowledge of the natural history of these anatomical particularities. From January 1992 to December 1994, 113 patients with ICA kinking, coiling, tortuousity, and angulation were randomized either to surgery (group I, n = 55) or not (group II, n = 58). Patients, who presented a carotid hemodynamically significant lesion (>60%) at the origin and associated distal elongation were excluded. The groups were comparable with regard to sex, age, risk factors for atherosclerosis, associated diseases, symptoms and anatomic feature of the contralateral ICA. Follow-up was obtained in all patients: it consisted of clinical evaluation and Duplex scan control at 3-month intervals during the follow-up period (6-36 months; average, 23). Histologic specimens were obtained in all surgically treated arteries. Early results were excellent: in group I, no patient died, no patient presented major or minor stroke. Only one patient had an immediate transient ischemic attack (TIA) which spontaneously recovered within 24 hours. All symptomatic patients examined the complete disappearance of clinical signs. There were no late deaths due to stroke and no late major or minor neurologic deficit occurred. All reconstructed ICAs were patent. In group II, three patients experienced a major stroke with hemiplegia due to ICA occlusion. Most of the symptomatic patients (37) of group II remained stable, while seven of them had worsening of symptoms and were referred for surgery. To conclude, all surgically treated patients had the complete relief of preoperative neurologic symptoms; none of the medically treated patients had an improvement. Although there was no statistically significant difference between the two groups with regard to stroke risk, three medically treated patients progressed to total occlusion. This suggests that kinking, coiling, tortuousity, and angulations of the ICA are not merely an anatomic curiosity but a potentially disabling, even fatal condition.

A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.

OBJECTIVE: To compare the clinical outcome and restenosis incidence of patients who underwent carotid endarterectomy with patch closure (CEAP) on one side and carotid eversion endarterectomy (CEE) on the other. SUMMARY BACKGROUND DATA: Although a few investigators have compared the results of CEAP versus CEE, no reports have compared the outcome of CEAP versus CEE in the same patient. METHODS: Eighty-six patients were randomly selected for sequential surgical treatment involving either CEAP/CEE or CEE/CEAP. All patients underwent postoperative duplex ultrasound study and clinical follow-up at 1, 6, and 12 months and every year thereafter. Various factors were analyzed to ascertain any association with restenosis, and Kaplan-Meier analysis was used to estimate the risk of restenosis. RESULTS: Demographic and clinical data were similar in the CEAP and CEE groups. The selective shunting rate was statistically higher in the CEAP group. There were no perioperative deaths. Although the incidence of perioperative ipsilateral stroke was not significant, CEAP patients had a rate of combined transient ischemic attacks and strokes that approached statistical significance. The mean follow-up was 40 months. CEAP patients had a significantly higher incidence of restenosis and combined occlusive events and restenoses. Kaplan-Meier analysis showed that CEE had a significantly better cumulative patency rate than CEAP and that freedom from restenoses at 24 and 36 months was 87% and 83% for CEAP and 98% and 98% for CEE, respectively. CONCLUSIONS: CEE is less likely to cause perioperative neurologic complications and restenoses than CEAP. The significantly higher rate of unilateral recurrence suggests that local factors play a more important role than systemic factors in the occurrence of restenosis.

Symptomatic and asymptomatic carotid artery lesions in peripheral vascular disease: a prospective study.

PURPOSE: To assess the incidence and severity of internal carotid artery lesions in patients who were referred to a single institution with peripheral obliterative atherosclerotic disease (POAD) as their chief complaint, in order to identify symptomatic and asymptomatic subjects at risk of stroke who would benefit from surgery. MATERIALS AND METHODS: Consecutive patients with clinically and Doppler scan-proven POAD underwent prospective screening for the presence of carotid symptomatic and asymptomatic atherosclerotic lesions with duplex ultrasound scan (DUS). Associated risk factors for atherosclerosis, i.e. age, sex, diabetes, hypertension, hyperlipidemia, history of smoking and history of coronary artery disease were assessed and recorded. Univariate analysis was performed to correlate the risk factors with the presence of POAD and carotid lesions. RESULTS: Three-hundred and twelve consecutive patients were evaluated over an 18-month period. A 30% or greater carotid stenosis was detected by DUS in 189 patients (19 bilateral); 57 (30%) of these had neurologic symptoms, 19 of whom had a 70-99% carotid lesion, whereas 65 of the 132 asymptomatic patients had 60-99% carotid stenosis. Univariate analysis revealed no differences in the symptomatic and asymptomatic groups between patients who were potential candidates for carotid endarterectomy according to the North American Symptomatic Carotid Endarterectomy Trial and the Asymptomatic Carotid Atherosclerotic Study Group guidelines, respectively, and those who were not as regards associated atherosclerotic risk factors and severity of POAD. All but 2 (n = 17) symptomatic and 18 asymptomatic patients underwent carotid endarterectomy based on DUS criteria alone. The perioperative stroke risk and mortality rates were 0%. CONCLUSIONS: Routine carotid DUS screening of 312 consecutive patients with POAD revealed that 19 patients with symptoms and 65 (5 bilateral) without symptoms would benefit from surgery, representing 27% of the series considered.

Carotid artery lesions in patients with nondiabetic chronic renal failure.

Atherosclerotic complications are the leading cause of death in chronic renal failure (CRF) patients. Therefore, we wished to investigate the prevalence of carotid artery lesions (CALs) in these subjects. Two groups were evaluated by high-resolution echo Doppler: group 1 included 103 patients (68 males and 35 females) affected by nonnephrotic CRF and group 2 included 100 control subjects (60 males and 40 females). The prevalence of hypertension was 84% in both groups. The exclusion criteria included diabetes mellitus and symptoms of cerebrovascular disease. In the two groups we evaluated clinical history, physical examination, total cholesterol, triglycerides, fibrinogen, blood cell counts, blood urea nitrogen, creatinine, 24-hour proteinuria, and urine analysis. In group 1 patients the following lipid profile parameters were also evaluated: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), ApoAI, ApoAII, and ApoB. Group 1 had higher triglycerides and fibrinogen than group 2. A lower body mass index was found in group 1 than in group 2. The prevalence of CALs was significantly higher in the CRF patients than in the control subjects (62% v 47%; P = 0.04). The difference between the two groups was more striking among normotensive patients (62% v 19%; P = 0.03). All CRF patients affected by peripheral arterial disease and 86% of those having coronary artery disease had associated CALs. In CRF patients the severity of CALs was positively correlated to age, white blood cell count, triglycerides, and fibrinogen. Nondiabetic CRF patients have a higher prevalence of carotid artery lesions than control subjects. Several factors besides hypertension, including lipids, blood coagulation, and leukocytes, could contribute to the accelerated atherosclerosis of CRF patients.