Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization.

BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

The sellar barrier and intraoperative CSF leak in elderly patients.

Cerebral spinal fluid (CSF) leak is a significant complication in pituitary surgery, increasing both patient morbidity and mortality. In a recent publication, Campero et al. observed worse postoperative prognosis and increased risk of intraoperative CSF leak in patients with reduced sellar barrier thickness. The objective of this study was to analyze the association between sellar barrier thickness and intraoperative CSF leak in older individuals. A retrospective review was conducted of 44 transsphenoidal surgery resections for pituitary adenomas, 24 microscopic and 20 purely endoscopic procedures. Presence of intraoperative CSF fistula was significantly greater in patients with weak sellar barrier (thickness under 1 mm), compared to strong sellar barrier (52.94% vs 3.70% p < 0.0001, respectively). Application of this novel concept may help improve surgical technique selection as well as predict risk of intraoperative CSF leak and need for eventual use of flaps for reconstruction.

[Placement of ventricle peritoneal shunt in the adult patient. A new protocol]. / Implante de shunt ventrículo peritoneal en el paciente adulto. Un nuevo protocol.

INTRODUCTION: Ventriculoperitoneal shunting is considered a relatively straightforward procedure, though it might ensure multiple complications. Our surgical team developed and implemented a new protocol since June 2016. The objective of this paper is to describe and illustrate the surgical technique step by step and to demonstrate that the use of the "new protocol" significantly reduces the complications associated with the procedure. METHODS: A retrospective descriptive study of 184 patients related with cerebrospinal fluid derivation systems from June 2014 to November 2017. One hundred and fourteen patients complied with the inclusion criteria. They were divided into two groups according to the protocol involved, previous (n = 59) and new (n = 55). The technique was described by photographic archive and surgical protocols. RESULTS: The technique consisting in seven phases was described. With the used of the new protocol the complications decreased significantly. After the new protocol, no ventriculoperitoneal shunt associated infections were observed. CONCLUSION: The technique for ventriculoperitoneal shunt consisting in seven phases was described thoroughly. This technique as well as a series of rules constitutes the new protocol. The implementation of the latter lessened the number of complications associated with the procedure. The "zero infection" rate is not a utopia.

Multicenter study on parathyroidectomy (PTX) in Italy: preliminary results.

BACKGROUND: When medical therapy is unable to achieve biochemical control of secondary hyperparathyroidism, parathyroidectomy (PTX) is indicated, fortunately in a minority of patients. Thus, data on PTX prevalence and biochemical control are limited and, in particular in Italy, date back to 1999. METHODS: We designed a prospective, observational and multicenter study to collect data from dialysis units distributed throughout the Italian regions. Clinical data were collected with a dedicated data sheet. RESULTS: From January to December 2010, 149 Centers serving a total of 12,515 patients provided data on 528 living PTX cases (PTX prevalence = 4.2%). Prevalence was higher in hemo- than in peritoneal dialysis (4.5 vs. 1.9%, X2 = 21.52; p < 0.001), with non-significant regional differences (range 0.8-7.4%). PTX patients were younger (57.6 ± 12.5 vs. 67.1 ± 14.5 years; p < 0.001), more frequently female (56 vs. 38%, X2 = 68.05, p < 0.001) and had been on dialysis for a longer time (14.63 ± 8.37 vs. 4.8 ± 6.0 years, p < 0.001) compared to the 11,987 who did not undergo neck surgery. Median time since surgery was 6.0 years (3.0-9.0; 50%, IQR). The most frequent type of surgery was subtotal PTX (sPTX = 55.0%), significantly higher than total PTX (tPTX = 38.7%) or total PTX plus auto-transplantation (aPTX = 6.3%) (X2 = 5.18; Bonferroni post-hoc test, sPTX vs. tPTX + aPTX = p < 0.05). As for parathyroid hormone (PTH), calcium and phosphate control, cases targeting the KDOQI ranges were 18, 50.1 and 54.4%, respectively. The most prevalent biochemical condition was low PTH (62.7%). CONCLUSION: PTX prevalence in Italy is stable compared to previous observations, is higher in hemodialysis than in peritoneal dialysis and results in a suboptimal biochemical control.

Homeostatic control of polyamine levels under long-term salt stress in Arabidopsis: changes in putrescine content do not alleviate ionic toxicity.

Salt stress has been frequently studied in its first osmotic phase. Very often, data regarding the second ionic phase is missing. It has also been suggested that Putrescine or/and Spermine could be responsible for salt resistance. In order to test this hypothesis under long-term salt stress, we obtained Arabidopsis thaliana transgenic plants harboring pRD29A::oatADC or pRD29A::GUS construction. Although Putrescine was the only polyamine significantly increased after salt acclimation in pRD29A::oatADC transgenic lines, this rendered in no advantage to this kind of stress. The higher Spermine levels found in WT and transgenic lines when compared to control conditions along with no increment on Putrescine levels in WT plants under salt acclimation, leads us to analyze Spermine effect on pADC1 and pADC2 expression. Increasing levels of this polyamine inhibits these promoters expression while enhances pRD29A expression, making Spermine the polyamine responsible for salt acclimation, and the transgenic lines developed in this work suitable for studying Putrescine roles in conditions where its biosynthesis would be inhibited in the WT genotype.

Contribuiçäo ao plano de vacinaçäo anti-sarampo / Vaccination plan against measles

Este trabalho mostra os resultados positivos da intensificaçäo da campanha de vacinaçäo contra o sarampo, denominada "Plano Impacto", realizada nos dias 30 e 31 de julho de 1984 com o apoio da Secretaria da Saúde do Estado de Säo Paulo. Pelo "Plano Impacto", vacinou-se aproximadamente 3,6 vezes mais que nos dias normais da campanha de vacinaçäo. A cobertura vacinal após a campanha foi de 89,7%, oferecendo uma segurança à imunidade populacional local. Avaliou-se o lucro imediato de cada criança vacinada, representado pela näo hospitalizaçäo por sarampo ou suas complicaçöes (Cr$ 102,94 - Cr$ 3.356,71), confrontando-o com o custo de uma dose da vacina (Cr$608,00). Discutiu-se também a idade ideal para vacinaçäo contra o sarampo, que depende da epidemiologia local da doença. Questionou-se o risco dado pela mudança desta idade (de 7 a 9 meses) adotada desde o mês de abril de 1984, no Brasil