The remission rate with plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) exceeds 80%, but the disease relapses in up to 20–30% of the cases. Clinical characteristics and response to ...treatment of relapsed TTP are not well defined. The objective of the present study was to compare the clinical and biological characteristics at presentation and the response to treatment between de novo and relapsed TTP. For such purpose, a total of 102 episodes of idiopathic TTP (70 de novo and 32 relapses) included in a recent multicentric prospective cohort study were analysed. All patients were homogeneously treated with daily PE and costicosteroids. In comparison with de novo TTP, episodes of relapsed TTP showed a higher Hb level (median, 122 g/l versus 91 g/l,
p
< 0.001) and lower serum lactate dehydrogenase (2.2- versus 4.5-fold above the upper limit of normality,
p
< 0.001). Neurological symptoms and fever were less frequently observed in patients with relapsed TTP than in patients with de novo TTP. Patients with relapsed TTP needed fewer PE sessions (five versus ten,
p
= 0.02) and a smaller volume of plasma (221 ml/kg versus 468 ml/kg,
p
= 0.004) to achieve remission than those with de novo TTP. There was no significant difference in the rate of recrudescence under treatment, the need of complementary treatments or the frequency of refractoriness to PE therapy. In conclusion, relapsed TTP has a milder clinical profile and responds more easily to PE than de novo TTP.
To assess whether subjects with Philadelphia negative myeloproliferative neoplasms (Ph-MPNs) show differences in the presence of vascular, cardiac or renal target organ damage (TOD) and other ...vascular function parameters as compared to individuals without this condition.
An observational study was conducted. Fifty-seven subjects diagnosed with Ph-MPNs used as cases and 114 subjects without Ph-MPNs as controls. We matched the subjects with and without Ph-MPNs using the propensity scores in a 1:2 ratio using the variables gender, type 2 diabetes mellitus, high blood pressure, hyperlipidaemia and smoking. Vascular, cardiac and renal TOD were established according to the criteria of the European Society of Hypertension and Cardiology guidelines. Arterial stiffness was also assessed using the cardio-ankle vascular index (CAVI).
Mean age was 63.50±11.70 and 62.90±8.32 years in subjects with and without Ph-MPNs, 32 females (56%) in the first group and 62 (54%) in the second. Subjects with Ph-MPNs have a higher percentage of carotid injury than subjects without Ph-MPNs (35.1% vs. 21.1%) and higher albumin/creatinine ratio. In the logistic regression analysis, subjects with Ph-MPNs had an OR=2.382 (IC95% 1.066–5.323) for carotid injury versus those without haematological disease.
Subjects with Ph-MPNs have twice the risk of by carotid injury than those without haematological disease.
Evaluar si los sujetos con neoplasias mieloproliferativas Filadelfia negativos (NMPs-FN) muestran diferencias en cuanto a presencia de lesión de órgano diana (LOD) vascular, cardiaca o renal y en otros parámetros de función vascular con respecto a los individuos sin esta patología.
Se realizó un estudio observacional. Se incluyeron 57 sujetos con diagnóstico de NMPs-FN utilizados como casos y 114 sujetos sin NMPs-FN como controles. Emparejamos a los sujetos con y sin NMPs-FN con la técnica de Propensity Score en la proporción 1:2, utilizando las variables sexo, diabetes mellitus tipo2, hipertensión arterial, hiperlipemia y consumo de tabaco. La LOD vascular, cardiaca y renal se estableció siguiendo los criterios de las guías de las sociedades europeas de hipertensión y cardiología. La rigidez arterial también se evaluó con el índice vascular corazón-tobillo (CAVI).
La edad media fue de 63,50±11,70 y 62,90±8,32 años en los sujetos con y sin NMPs, 32 mujeres (56%) en el primer grupo y 62 (54%) en el segundo. Los sujetos con NMPs-FN tienen un mayor porcentaje de lesión carotídea que los sujetos sin NMPs-FN (35,1% frente al 21,1%) y un mayor ratio albúmina/creatinina. En el análisis de regresión logística, los sujetos con NMPs-FN tenían un OR=2,382 (IC95%: 1,066 a 5,323) para la lesión carotídea frente a los que no presentaban enfermedad hematológica.
Los sujetos con NMPs-FN presentan el doble de riesgo de lesión de órgano diana vascular que los sujetos que no presentaban enfermedad hematológica.
The aim of this study was to design an aggressive nonlethal animal model that would simulate surgical treatment of the abdominal aorta with a view to studying the systemic inflammatory response. ...Fourteen pigs were subjected to two sequential experiments. Experiment A was performed to determine the response to two degrees of hemorrhage: (A1) 40% bleeding; and (A2) 60% bleeding over 15 minutes followed by midline laparotomy and aortic dissection. Experiment B included two methods of aortic repair: (B1) aortic resection and replacement with a prosthesis; and (B2) aortic bypass without aortic resection. In the latter two groups, suprarenal aortic cross-clamping was placed for 30 minutes after a 40% hemorrhage. We analyzed various inflammatory markers and mortality. The 40% bleeding (vs. 60%) elicited a smaller decrease in mean arterial pressure (110 ± 6 vs. 89 ± 9 mmHg) but did not cause irreversible shock or mortality. After the 40% hemorrhage, the B1 aortic repair caused two cases of paraplegia. We have developed a model to study the combined effect of bleeding and aortic cross-clamping.
Abstract
Background
Pain control in critical limb ischemia (
CLI
) varies considerably between individuals.
Objective
To evaluate pharmacogenetically the response to transdermal buprenorphine (
BUP
‐
...TTS
) in patients with
CLI
who are awaiting revascularization.
Methods
One hundred and seven patients with
CLI
were treated with
BUP
‐
TTS
. The following were analyzed: (1) pain perception (visual analog scale (
VAS
) before and 4 days after treatment) and (2) genetics: glucuronosyltransferase (
UGT
2B7), cytochrome (
CYP
3A4), and μ‐opioid receptor (
OPRM
1) gene polymorphisms.
Results
Ninety‐three patients completed the study. The
VAS
score by the fourth day of analgesia dropped from 6.82 to 3.38 (
P
< 0.05). The analgesic response to
BUP
‐
TTS
was greater in men than in women (
P
= 0.019). Patients who were
AA
homozygotes for the
CYP
3A4 gene showed the best response to analgesic treatment (
P
= 0.003). The combination of the
CYP
3A4 gene with
UGT
2B7 or
OPRM
1 was favorable to the effect of the
CYP
3A4 gene (
P
= 0.045 and
P
= 0.026, respectively). The combination of
UGT
2B7 with
OPRM
1 was ineffective (
P
= 0.648). The 3 polymorphisms together had no effect on response to treatment (
P
= 0.461).
Conclusions
BUP
‐
TTS
is efficacious in the control of pain in patients with
CLI
. The homozygous
AA
carriers of the
CYP
3A4 gene respond better to treatment with
BUP
‐
TTS
.
Human papillomavirus (HPV) infection, particularly with type 16, causes a growing fraction of oropharyngeal cancers, whose incidence is increasing, mainly in developed countries. In a double-blind ...controlled trial conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine against cervical infections and lesions, we estimated VE against prevalent oral HPV infections 4 years after vaccination.
A total of 7,466 women 18-25 years old were randomized (1∶1) to receive the HPV16/18 vaccine or hepatitis A vaccine as control. At the final blinded 4-year study visit, 5,840 participants provided oral specimens (91·9% of eligible women) to evaluate VE against oral infections. Our primary analysis evaluated prevalent oral HPV infection among all vaccinated women with oral and cervical HPV results. Corresponding VE against prevalent cervical HPV16/18 infection was calculated for comparison. Oral prevalence of identifiable mucosal HPV was relatively low (1·7%). Approximately four years after vaccination, there were 15 prevalent HPV16/18 infections in the control group and one in the vaccine group, for an estimated VE of 93·3% (95% CI = 63% to 100%). Corresponding efficacy against prevalent cervical HPV16/18 infection for the same cohort at the same visit was 72·0% (95% CI = 63% to 79%) (p versus oral VE = 0·04). There was no statistically significant protection against other oral HPV infections, though power was limited for these analyses.
HPV prevalence four years after vaccination with the ASO4-adjuvanted HPV16/18 vaccine was much lower among women in the vaccine arm compared to the control arm, suggesting that the vaccine affords strong protection against oral HPV16/18 infection, with potentially important implications for prevention of increasingly common HPV-associated oropharyngeal cancer. ClinicalTrials.gov, Registry number NCT00128661.
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