Hypersensitivity Reactions to Taxanes: A Comprehensive and Systematic Review of the Efficacy and Safety of Desensitization.

Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first line therapy. Drug desensitization induces transient immunological tolerance and has allowed the reintroduction of taxanes in highly allergic patients. Increase the knowledge of hypersensitivity reactions (HSR) during the administration of taxanes. A systematic review regarding the safety and efficacy of rapid drug desensitization (RDD) for taxanes HSR. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered in PROSPERO(CRD42021242324) and a comprehensive search was conducted in Medline, Embase, Web of Science and Scopus databases. 25 studies encompassing 10 countries were identified and 976 patients with initial HSR to paclitaxel (n = 707) and docetaxel (n = 284), that underwent a total of 2,396 desensitizations. The most common symptoms were cutaneous (74.6%) with paclitaxel and respiratory (72.6%) with docetaxel. Severe initial hypersensitivity reactions including anaphylaxis occurred in 39.6% and 13% of paclitaxel and docetaxel cases respectively and during the first (87.4%) or second exposure (81.5%). Patients tolerated well RDD and breakthrough reactions (BTR) occurred in 32.2% of paclitaxel-treated patients and in 20.6% of docetaxel treated patients. Premedications included corticosteroids, antihistamines and leukotriene receptor antagonists. The most commonly used protocol was the BWH 3 bags 12 steps, all protocols showed a success rate between 95-100%, with no reported deaths. RDD is a safe and effective procedure in patients with HSR to taxanes and protocols should be standardized for wide range implementation.

Case 311: Generalized Lymphatic Anomaly.

HISTORY: A 14-year-old boy presented with asthenia, low back pain, and abdominal distention. The onset of symptoms was slow and progressive over a few months. The patient had no contributing past medical history. At physical examination, all vital signs were normal. Only pallor and positive fluid wave test results were noted; there was no lower limb edema, mucocutaneous lesions, or palpable lymph node enlargement. Laboratory work-up revealed a decreased hemoglobin concentration of 9.3 g/dL (normal range, 12-16 g/dL) and a decreased hematocrit level of 29.8% (normal range, 37%-45%), but all other laboratory values were normal. Contrast-enhanced CT of the chest, abdomen, and pelvis was performed.

Case 311.

HISTORY: A 14-year-old boy presented with asthenia, low back pain, and abdominal distention. The onset of symptoms was slow and progressive over a few months. The patient had no contributing past medical history. At physical examination, all vital signs were normal. Only pallor and positive fluid wave test results were noted; there was no lower limb edema, mucocutaneous lesions, or palpable lymph node enlargement. Laboratory work-up revealed a decreased hemoglobin concentration of 9.3 g/dL (normal range, 12-16 g/dL) and a decreased hematocrit level of 29.8% (normal range, 37%-45%), but all other laboratory values were normal. Contrast-enhanced CT of the chest, abdomen, and pelvis was performed (Figs 1-3).

Complete metabolic response after carboplatin desensitization in Peritoneal Carcinomatosis.

INTRODUCTION: High-grade serous primary peritoneal cancer is highly sensitive to platinum-based chemotherapy with response rates above 80%. Incidence of immediate hypersensitivity reactions to carboplatin is estimated to be between 15% and 20%, usually seen after a mean of 6-8 infusions, with patients developing moderate to severe reactions. CASE REPORT: A 62-year-old female patient with stage IIIC primary high-grade serous carcinoma of the peritoneum was diagnosed and chemotherapy with carboplatin and Paclitaxel was indicated by the oncology service and patient shows response. At 6 months the patient returns, a new PET/CT reports progression of the disease. Carboplatin/paclitaxel cycles are restarted and in the eight cycle of carboplatin within 40 min of administration, she presented severe anaphylaxis with skin, pulmonary, cardiac and atypical symptoms. Infusion is suspended and intramuscular epinephrine with hydrocortisone and chlorphenamine are administered resolving symptoms. MANAGEMENT AND OUTCOME: Intradermal skin test with carboplatin at the concentration of 10 mg / ml (dilution 1: 100) was positive. Due to the symptoms presented and to continue the safe reintroduction to carboplatin, a 4 bag 16-step drug desensitization protocol was carried out at a total dose of 620 mg with no hypersensitivity reactions. DISCUSSION: Prolonged carboplatin use is associated with an increased incidence of carboplatin-related hypersensitivity reactions. And in patients that present hypersensitivity reactions, a safe and effective carboplatin desensitization protocol can be carried out to reach the administration of a full dose. Desensitization protocol induces tolerance to a drug temporarily and is dependent on continuous exposure.

A Meta-Analysis of Association between Remdesivir and Mortality among Critically-Ill COVID-19 Patients.

BACKGROUND: The World Health Organization guidelines did not make a recommendation on use of remdesivir based on disease severity. Little is known regarding effectiveness of remdesivir in critically ill coronavirus disease 2019 (COVID-19) patients. This has led to a state of dilemma for doctors leaving them skeptical of whether they should continue to recommend the drug or not. MATERIALS AND METHODS: A systematic search adhering to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines was conducted from inception until February 20, 2020. Electronic bibliographic databases (PubMed, Cochrane database, Scopus, Embase) were included. Using dichotomous data for select values, the unadjusted odds ratios (ORs) were calculated applying Mantel Haenszel (M-H) using random-effects model. The primary outcome of interest was all-cause mortality in ventilated and non-ventilated patients. RESULTS: The Remdesivir arm was associated with similar rates of 28-day all-cause mortality (OR: 0.93, 95% confidence interval [CI]: 0.80 - 1.08; P = 0.33). Remdesivir was not found to be favorable for ventilated patients. Non ventilated COVID-19 patients showed a significant lower in-hospital mortality rate as compared with patients requiring mechanical ventilatory support (OR: 6.86, 95% CI: 5.39 - 268.74; P <0.0001). CONCLUSION: Non-ventilated patients were associated with significant lower all-cause mortality rates. Prudent use of remdesivir is recommended in critically ill COVID-19 patients.

Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization.

The objective of this study was to explore the role of the aryl hydrocarbon receptor (AhR) in ambient particulate matter (PM)-mediated activation of dendritic cells (DCs) and Th17-immune responses in vitro. To assess the potential role of the AhR in PM-mediated activation of DCs, co-stimulation, and cytokine expression, bone marrow (BM)-derived macrophages and DCs from C57BL/6 wildtype or AhR knockout (AhR-/-) mice were treated with PM. Th17 differentiation was assessed via co-cultures of wildtype or AhR-/- BMDCs with autologous naive T cells. PM2.5 significantly induced AhR DNA binding activity to dioxin responsive elements (DRE) and expression of the AhR repressor (AhRR), cytochrome P450 (CYP) 1A1, and CYP1B1, indicating activation of the AhR. In activated (OVA sensitized) BMDCs, PM2.5 induced interleukin (IL)-1ß, CD80, CD86, and MHC class II, suggesting enhanced DC activation, co-stimulation, and antigen presentation; responses that were abolished in AhR deficient DCs. DC-T cell co-cultures treated with PM and lipopolysaccharide (LPS) led to elevated IL-17A and IL-22 expression at the mRNA level, which is mediated by the AhR. PM-treated DCs were essential in endowing T cells with a Th17-phenotype, which was associated with enhanced expression of MHC class II and cyclooxygenase (COX)-2. In conclusion, PM enhances DC activation that primes naive T cell differentiation towards a Th17-like phenotype in an AhR-dependent manner.

Correction: Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas.

[This corrects the article DOI: 10.1371/journal.pgen.1006546.].

Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas.

For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations.

How Often Does Femoroacetabular Impingement Occur After an Innominate Osteotomy for Acetabular Dysplasia?

BACKGROUND: Femoroacetabular impingement is increasingly recognized as a cause of hip pain but its incidence after an innominate osteotomy for the correction of acetabular dysplasia has not been determined. This information would be essential for the orthopaedic surgeon because it has the potential to produce a poor outcome in the long term when trying to balance acetabular instability and overcorrection. QUESTIONS/PURPOSES: The purposes of our study were (1) to determine the frequency with which clinically relevant femoroacetabular impingement (FAI) occurs after an innominate osteotomy for the treatment of acetabular dysplasia; (2) to determine risk factors for the development of FAI; and (3) to compare postoperative radiographic and clinical outcomes in patients having undergone an innominate osteotomy for the correction of acetabular dysplasia both with and without FAI. METHODS: This was a retrospective review of 154 hips (132 patients) that had undergone an innominate osteotomy for acetabular dysplasia and were evaluated at a minimum followup of 10 years (mean = 12 years). Mean age at the time of surgery was 3 years, 114 hips had a concomitant open reduction, and 54 hips also had femoral shortening. One hundred eight hips had a Salter osteotomy and 46 had a Pemberton osteotomy. Radiographs were analyzed to determine the lateral center-edge angle (CE angle) and the presence of a crossover sign. The diagnosis of FAI was established when the CE angle was greater than 40°, there was a positive crossover sign, and the patient had groin pain when flexing the hip less than 90°. Comparisons between nonparametric variables were performed with a Mann-Whitney's U test. Categorical variables were compared with a chi-square test. Change in acetabular index (correction) was dichotomized considering 20° of correction as the cutoff point. Association is presented as odds ratio (95% confidence interval), and logistic regression was performed. RESULTS: According to our criteria, 18 of 154 hips had FAI (12%). Of the 18 patients with FAI, 10 had undergone a Pemberton osteotomy (10 of 46 [22%]) and eight a Salter osteotomy (eight of 108 [7%]). A change in the postoperative acetabular index greater than 20° was associated with a greater likelihood of developing FAI. The mean postoperative acetabular index was lower for the group with FAI, for whom it was 20°, compared with the group without FAI, for whom it was 27° (p = 0.04). The mean Iowa Hip Score for the group with FAI was 85, whereas for those without FAI, it was 93 (p = 0.03). CONCLUSIONS: FAI is not common after an innominate osteotomy for the treatment of acetabular dysplasia; however, overcorrection is related to a higher incidence. When FAI is present, it can affect the outcome. Overcorrection should be avoided when performing an innominate osteotomy for the treatment of acetabular dysplasia because it can create iatrogenic FAI and have an adverse effect on outcome. LEVEL OF EVIDENCE: Level III, therapeutic study.

A 176 amino acid polypeptide derived from the mumps virus HN ectodomain shows immunological and biological properties similar to the HN protein.

BACKGROUND: The hemagglutinin-neuraminidase (HN) protein is the major antigenic determinant of the Mumps virus (MuV) and plays an important role in the viral infectious cycle through its hemagglutination/hemadsorption (HA/HD) and neuraminidase (NA) activities. OBJECTIVE: analyze the biological and immunological properties of a polypeptide derived from a highly conserved region of the HN ectodomain. METHODS: a highly conserved region of the HN gene among several MuV genotypes was chosen to be cloned in a eukaryotic expression vector. The pcDNAHN176-construct was transfected into Vero cells and RNA expression was detected by RT-PCR, while the corresponding polypeptide was detected by immunofluorescence and immunochemistry techniques. The HD and NA activities were also measured. The immunogenic properties of the construct were evaluated using two systems: rabbit immunization to obtain sera for detection of the HN protein and neutralization of MuV infection, and hamster immunization to evaluate protection against MuV infection. RESULTS: A 567 nucleotide region from the HN gene was amplified and cloned into the plasmid pcDNA3.1. Vero cells transfected with the construct expressed a polypeptide that was recognized by a MuV-hyperimmune serum. The construct-transfected cells showed HD and NA activities. Sera from immunized rabbits in vitro neutralized two different MuV genotypes and also detected both the HN protein and the HN176 polypeptide by western blot. Hamsters immunized with the pcDNAHN176-construct and challenged with MuV showed a mild viral infection in comparison to non-immunized animals, and Th1 and Th2 cytokines were detected in them. CONCLUSIONS: The pcDNAHN176-construct was capable of expressing a polypeptide in Vero cells that was identified by a hyperimmune serum anti Mumps virus, and these cells showed the HD and NA activities of the complete MuV HN protein. The construct also elicited a specific immune response against MuV infection in hamsters.

Inmunidad celular en pacientes con diagnóstico de retinosis pigmentaria / Cell Immunity and Retinosis Pigmentosa

En el Centro de Retinosis Pigmentaria se realizó un estudio descriptivo de 38 enfermos ingresados durante el periodo de enero a diciembre de 2006, a los cuales se les realizaron pruebas inmunológicas que fueron analizadas en el Centro de Inmunología y Biopreparados de la Facultad Ciencias Médicas de Holguín. Predominaron los pacientes masculinos entre 36 y 55 años, el 81,5 por ciento padecieron tabaquismo y alcoholismo. La prueba de roseta espontánea resultó el 5 por ciento de valores y la prueba de hipersensibilidad retardada reflejó respuesta baja a los anfígenos utilizados...(AU)

A descriptive study of 38 patients with Retinosis pigmentosa who entered to our Center from January to December 2006 was carried out. Immune lab test were performed, the samples were analyzed in the Center of Immunology at The faculty of Medicine of Holguín... A predominance of male patients between 36 and 55 years was found, the 81, 5 percent of them were heavy smokers and alcohol drinkers. The test of Spontaneous Rosette I resulted the 5 percent of values and the test of delayed hypersensitivity had a low response to the antigens utilized...(AU)

[Primary hyperparathyroidism: a report of 67 cases. The experience of 5 years at the IMSS Centro Médico Nacional Siglo XXI Specialties Hospital]. / Hiperparatiroidismo primario, reporte de 67 casos. Experiencia de los últimos cinco años en el Hospital de Especialidades Centro Médico Nacional Siglo XXI.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a frequent disease. It is characterized by hypercalcemia and elevation of parathyroid hormone (PTH) levels. The incidence is variable, being more frequent in women (3:1) in the perimenopauseal period. In the last decades, diagnosis of asymptomatic PHPT has increased due to automatized calcium determinations. Duration of the disease and serum concentrations of calcium and PTH determine symptomatology. Surgery is the definitive treatment. It is important to assess surgical criteria in asymptomatic patients. Successful treatment of this disease depends on a highly specialized team of parathyroid surgeons. MATERIAL AND METHODS: We reviewed the clinical and biochemical background of patients subjected to parathyroidectomy from January 1998 to August 2003 in our medical center. We then analyzed clinical and laboratory data, final histopathologic diagnosis, and surgery outcome. RESULTS: Sixty seven patients were included, with an average age of 50 years (+/- 11.9), 15 men and 52 women. Greatest frequency of PHPT was observed in patients between 40 and 60 years of age. Average calcium value was 11.7 mg/dl (+/- 1.23) and that of PTH was 194.5 pg/ml (+/- 93). Histopathologic diagnosis was adenoma in 56 (83.58%), hyperplasia in 9 (13.43%), and carcinoma in 2 (2.9%) patients. Cure of the disease was achieved in 65 patients (97%). PHPT is a surgically curable disease; it is necessary to confirm diagnosis and decide on surgical treatment in accordance with established criteria even if the disease is asymptomatic.

Síndrome hemolítico-urêmica induzida por mitomicina C / Hemolytic uremic syndrome by mitomycin C induced by mitomycin C

A mitomicina C é um antibiótico alquilante freqüentemente usado nos esquemas poliquimioterápicos para o tratamento dos tumores do trato gastrintestinal e de mama. Além dos efeitos tóxicos habituais dos agentes antineoplásicos, a mitomicina C pode induzir à síndrome hemolítico-urêmica com graus variáveis de insuficiência renal. Descreve-se um paciente portador de câncer gástrico que evolui a partir do quarto ciclo do esquema FAM com anemia hemolítica, insuficiência renal, plaquetopenia e hipertensäo arterial. Instituída a terapêutica com plasmaferese e transfusäo de plasma fresco, o paciente evolui satisfatoriamente. Discute-se o diagnóstico e a terapêutica dessa síndrome