Eleftherios C. Vamvakas

Trends in the incidence of delayed hemolytic and delayed serologic transfusion reactions

BACKGROUND: An increasing incidence of delayed hemolytic and delayed serologic transfusion reactions (DHTRs/DSTRs) has been seen at the Mayo Clinic since 1978. Recently, the average length of stay (LOS) for inpatients and the average number of red cell transfusions per inpatient (TPI) decreased, and the albumin and papain technique for RBC antibody detection was replaced by a polyethylene glycol technique. These changes may have affected the incidence of DHTRs/DSTRs.

Allogeneic blood transfusion and postoperative duration of mechanical ventilation: effects of red cell supernatant, platelet supernatant, plasma components and total transfused fluid

Background and Objectives In patients undergoing open‐heart surgery, allogeneic blood transfusion (ABT) may be related to an enhanced inflammatory response and impaired pulmonary function, resulting in a need for prolonged mechanical ventilation. Transfused red blood cell (RBC) supernatant, platelet supernatant or plasma components, may exercise varying effects on pulmonary function, because these fluids differ in their content of soluble biological‐response modifiers.

WBC-containing allogeneic blood transfusion and mortality: a meta-analysis of randomized controlled trials

BACKGROUND: An association between allogeneic blood transfusion (ABT) and mortality was reported by one team of investigators from randomized controlled trials (RCTs) comparing recipients of non‐WBC‐reduced versus WBC‐reduced RBCs in open‐heart surgery. A meta‐analysis was undertaken to examine whether this finding can be generalized across clinical settings and/or transfused RBC components.

The differentiation of delayed hemolytic and delayed serologic transfusion reactions: incidence and predictors of hemolysis

BACKGROUND: After differentiation of the entities of clinically detectable delayed hemolytic (DHTR) and delayed serologic transfusion reactions (DSTR), previous investigators calculated a DHTR:DSTR incidence ratio of 18:72 from a retrospective review of patients with serologic evidence of DHTR or DSTR. There are no published data on factors that may influence the occurrence of DHTR versus DSTR in a given patient. STUDY DESIGN AND METHODS: Retrospective review was conducted of 292 patients at the Mayo Clinic who, between 1980 and 1992, received a clinical diagnosis of DHTR or DSTR concurrently with a serologic diagnosis. Red cell alloantibody specificity, the activity of the patients reticuloendothelial system, and concurrent immunosuppression were evaluated as potential predictors of the occurrence of DHTR versus DSTR in different patients. RESULTS: The incidence of DHTR or DSTR was 1 in 1899 allogeneic red cell units transfused, with a DHTR:DSTR ratio of 36:64. Alloantibody specificity was the only variable that affected the occurrence of DHTR versus DSTR at the clinical level, with the anti‐Jka and anti‐Fya specificities, as well as multiple coexisting specificities, significantly associated with detectable hemolysis (p < 0.05). CONCLUSION: Clinically detectable DHTRs are found to occur more commonly than previously believed when the clinical and serologic diagnoses are made concurrently and appropriate work‐ups for hemolysis are ordered. The association of certain alloantibody specificities with detectable DHTRs may have implications for clinical transfusion practice.

RBC alloantibody specificity and antigen potency in Olmsted County, Minnesota

BACKGROUND: While RBC antigen frequencies for whites of Northern European ancestry are known, the relative frequencies of RBC antibodies within this population have not been determined. The distribution of RBC alloantibodies by sex and age was studied, as were the immunogenicity of RBC antigens and the occurrence of RBC alloantibody clusters in a geographically defined population.

Non–Acquired Immunodeficiency Syndrome-Defining Malignancies in Patients Infected With Human Immunodeficiency Virus

CONTEXT Non-acquired immunodeficiency syndrome (AIDS)-defining malignancies that occur in patients infected with human immunodeficiency virus (HIV) and the demographics and pathologic features associated with these malignancies have not been completely defined. OBJECTIVE This study describes the age of onset of malignant disease in patients seropositive for HIV and in control patients presumed to be negative for HIV, but with the same primary site. We compare the demographics and histopathology for both groups. DESIGN From 1993 to 1997, 57 cases involving HIV-positive patients with malignancies from 16 primary sites were recorded in the Cancer Registry files at Bellevue Hospital; 519 cases involving patients negative for HIV were recorded during this same period. We compared the age at diagnosis, sex, race, tumor histology, stage, and grade between these 2 groups. RESULTS The average age of HIV-positive patients was 47.6 years, compared with 60.3 years in the control group (P <.001). When the 16 cancer sites were compared individually, HIV-positive patients were significantly younger at onset of lung (HIV-positive patients/control group) (19/245), skin (11/77), penile (3/5), laryngeal (3/18), tongue (5/16), and colorectal (2/38) carcinomas. Patients infected with HIV had a more frequent history of smoking (41/328; P =.04) and illicit drug use (30/49; P <.001). The HIV-positive patients also were found to have a lower clinical stage of disease, compared with controls, largely due to the higher prevalence of stage 0 tumors (13/46; P =.01). CONCLUSIONS The finding of younger age at diagnosis in HIV-positive compared to presumed HIV-negative patients may be related in part to earlier detection, as well as preexisting immunosuppression. The specific sites for which a significant difference in age between the HIV-positive and control cases was observed may be related to the mechanisms of immunosurveillance in parts of the body that have ready access to the outside environment. Knowledge of younger age of onset for these malignancies should prompt closer physical examination of these sites by clinicians.

Endocervical gland involvement by cervical intraepithelial neoplasia grade III. predictive value for residual and/or recurrent disease

The prognostic significance for residual or recurrent disease of cervical intraepithelial neoplasia Grade III in endocervical glands by cone biopsy was examined in 341 consecutive patients diagnosed from 1979 through 1983 and followed through 1988. Treatment by hysterectomy, within 8 weeks of cone biopsy, was done in 96 patients. The only variable that could predict residual disease at hysterectomy was positive margins (P = 0.059). However, both positive margins and positive glands were (independently of one another and after the effects of length of follow‐up, hospital of admission, and age at time of first diagnosis were held constant) highly significant predictors of residual or recurrent disease in the 245 women who did not undergo a hysterectomy (P = 0.000 for each). The authors therefore conclude that information concerning gland involvement on cone biopsy specimens should influence patient management.

Meta‐analysis of randomized controlled trials comparing the risk of postoperative infection between recipients of allogeneic and autologous blood transfusion

Background and Objectives A previous meta‐analysis of randomized controlled trials (RCTs), comparing the risk of postoperative infection between recipients of allogeneic blood or autologous blood obtained by preoperative autologous blood donation (PABD), did not detect an immunomodulatory (TRIM) effect of allogeneic blood transfusion (ABT). If such a TRIM effect was mediated by white blood cell (WBC)‐derived soluble mediators accumulating during storage, however, stored autologous blood obtained by PABD would not prevent the TRIM effect, whereas unstored autologous blood obtained by acute normovolemic haemodilution (ANH), intraoperative blood recovery (IBR), or postoperative blood recovery (PBR), would abrogate the TRIM effect.

Immunohistochemical comparison of uterine papillary serous and papillary endometrioid carcinoma: clues to pathogenesis.

Twenty-four predominantly papillary carcinomas of the endometrium, 10 serous and 14 endometrioid, were compared using a variety of immunohistochemical antibodies, including p53, estrogen and progesterone receptors, carcinoembryonic antigen, and E-cadherin. These were selected to attempt to find clues to explain the disparate behavior of these two tumor subtypes. We found that 6 of 8 (75%) serous carcinomas had a p53 reactivity score of 300, whereas 90% of endometrioid tumors had a p53 reactivity score of less than 20 (p = 0.0008). Combined estrogen and progesterone hormone reactivity was positive in 13 (100%) of endometrioid lesions compared with 4 of 8 (50%) of serous lesions (p = 0.0117). The significantly greater p53 expression and its significantly diminished hormone receptor expression indicate that papillary serous carcinomas belong to the type II group of endometrial carcinomas that occur in a background of atrophic endometrium, are high grade, present with high stage disease, and have a poor prognosis. In contrast, papillary endometrioid carcinomas, which belong to type I carcinomas, often arise in a background of estrogen-stimulated endometrial hyperplasia, are usually well-differentiated, and have a good prognosis. Early p53 mutations in papillary serous carcinoma as well as in endometrial intraepithelial serous carcinoma may partially explain their proclivity for early intra-abdominal dissemination. Carcinoembryonic antigen expression was similar in both groups and therefore is not useful to characterize possible differences in the cell of origin. The reactivity scores for E-cadherin were also similar in the two tumor subtypes, thus not supporting the hypothesis that decreased cell to cell adhesion molecules might contribute to early dissemination of serous lesions.

Histology of leiomyomata in patients treated with leuprolide acetate.

SummaryThis study examined the histologic changes associated with administration of leuprolide acelate, a gonadotropin-releasing hormone agonist, in leiomyomata. Thirty-seven women treated with leuprolide acetate who subsequently underwent myomectomy or hysterectomy were matched by age (±3 years), race, and uterine size (±2 weeks) with untreated controls. Tissue samples of leiomyomata (four to 10 slides per patient) were examined “blinded” by two pathologists and evaluated for cellularity, edema, myxoid change, hyalinization, fibrosis, inflammation, infarction, and vascular changes (thrombosis, intimal fibrosis, thickening of the vessel wall with narrowing of the lumen, perivascular fibrosis). A matched case-control analysis was conducted for each morphologic characteristic. Cellularity, hyalinization, and fibrosis were graded as 1 + versus 2 +; all other characteristics were graded as present or absent. The analysis showed that leuprolide acctate-treated leiomyomata had significantly increased hyalinization (p < 0.005) and decreased cellularity (p < 0.10) as compared with controls; there was also thickening of blood vessel walls with narrowing of the lumen (p < 0.01). A subgroup of leuprolide acetate-treated patients categorized as clinical responders (having >30% reduction in tumor size) more frequently had thickening of vessel walls (p < 0.05) and vascular thrombosis (p < 0.10) than did nonresponders. Our data suggest that a leuprolide acetate-induced hypoestrogenic state may cause vasoconstriction, thickening of blood vessel walls, and thrombosis, leading to ischemia, hyalinization, and atrophy of the leiomyoma.