Biomedical subjects

Elizabeth Garrett-Mayer

Publications and source records attributed to Elizabeth Garrett-Mayer.

At least 19 recordsLinked to original sources

PubMed2007

Response to joint attention in toddlers at risk for autism spectrum disorder: a prospective study.

Response to joint attention (RJA) is impaired in preschoolers with autism spectrum disorder (ASD) and is pivotal to social and communication development. Response to joint attention was examined at 14 and 24 months in 51 children at high risk for autism (siblings of children with autism). Outcome groups at age 3 years included ASD (n = 16), broader autism phenotype (n = 8), and non-broader autism phenotype (n = 27). The ASD group made minimal improvement in RJA between 14 and 24 months, but stability of RJA across tasks increased for all three groups. Significantly, lower RJA was observed for the ASD group at 24 months. Response to joint attention performance at 14 months predicted ASD outcome. Response to joint attention is an important screening and early intervention target.

Attention↗

PubMed2006

A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia.

Outcomes for older adults with acute myelogenous leukemia (AML) are poor due to both disease and host-related factors. In this phase 2 study, we tested the oral farnesyltransferase inhibitor tipifarnib in 158 older adults with previously untreated, poor-risk AML. The median age was 74 years, and a majority of patients had antecedent myelodysplastic syndrome. Complete remission (CR) was achieved in 22 patients (14%); partial remission or hematologic improvement occurred in 15 patients, for an overall response rate of 23%. The median duration of CR was 7.3 months and the median survival of complete responders was 18 months. Adverse karyotype, age 75 years or older, and poor performance status correlated negatively with survival. Early death in the absence of progressive disease was rare, and drug-related nonhematologic serious adverse events were observed in 74 patients (47%). Inhibition of farnesylation of the surrogate protein HDJ-2 occurred in the large majority of marrow samples tested. Baseline levels of phosphorylated mitogen-activated protein kinase and AKT did not correlate with clinical response. Tipifarnib is active and well tolerated in older adults with poor-risk AML and may impart a survival advantage in those patients who experience a clinical response.

Adult↗

PubMed2006

Evaluation of a nutrition education intervention for women residents of Washington, DC, public housing communities.

We designed, implemented and evaluated an educational intervention to increase fruit and vegetable consumption among urban African-American women. Women aged 20-50 years (n=212) from 11 public housing communities participated in seven 90-min classes with a professional nutritionist. Our prospective pre- and post-test design, with 4-month follow-up, assessed the relationship between attendance and dietary change, using three 24-hour recalls per time point. Mean change in average daily dietary values for fruits and vegetables, calories and percent calories from fat (post-test versus pre-test, follow-up versus pre-test) was compared by class attendance, to evaluate the impact of class attendance on dietary change. Attendance varied from zero (35%) to five to seven classes (42%). Baseline dietary recalls showed average daily consumption of 3.05 servings of fruits and vegetables, 2416 calories and 35.8% calories from fat. No improvements in fruit and vegetable consumption, but statistically significant decreases in total calories and percent calories from fat, were seen at both endpoints. Women attending five to seven classes had the greatest dietary improvements, averaging, at post-test and follow-up, respectively, 246.2 and 324.5 fewer calories and 3.08 and 2.97% fewer calories from fat. Results suggest that, for some residents of low-resource communities, small group interventions are popular, effective vehicles for nutrition education.

Adult↗

PubMed2006

Prevalence and determinants of physician bedside rationing: data from Europe.

BACKGROUND: Bedside rationing by physicians is controversial. The debate, however, is clouded by lack of information regarding the extent and character of bedside rationing. DESIGN, SETTING, AND PARTICIPANTS: We developed a survey instrument to examine the frequency, criteria, and strategies used for bedside rationing. Content validity was assessed through expert assessment and scales were tested for internal consistency. The questionnaire was translated and administered to General Internists in Norway, Switzerland, Italy, and the United Kingdom. Logistic regression was used to identify the variables associated with reported rationing. RESULTS: Survey respondents (N=656, response rate 43%) ranged in age from 28 to 82, and averaged 25 years in practice. Most respondents (82.3%) showed some degree of agreement with rationing, and 56.3% reported that they did ration interventions. The most frequently mentioned criteria for rationing were a small expected benefit (82.3%), low chances of success (79.8%), an intervention intended to prolong life when quality of life is low (70.6%), and a patient over 85 years of age (70%). The frequency of rationing by clinicians was positively correlated with perceived scarcity of resources (odds ratio [OR]=1.11, 95% confidence interval [CI] 1.06 to 1.16), perceived pressure to ration (OR=2.14, 95% CI 1.52 to 3.01), and agreement with rationing (OR=1.13, 95% CI 1.05 to 1.23). CONCLUSION: Bedside rationing is prevalent in all surveyed European countries and varies with physician attitudes and resource availability. The prevalence of physician bedside rationing, which presents physicians with difficult moral dilemmas, highlights the importance of discussions regarding how to ration care in the most ethically justifiable manner.

Adult↗

PubMed2006

Quantitative multiplex methylation-specific PCR analysis doubles detection of tumor cells in breast ductal fluid.

PURPOSE: The challenges of cytology for accurate diagnosis of breast cancer are well recognized. We previously showed that normal and tumor tissue can be distinguished using a technique called quantitative multiplex methylation-specific PCR (QM-MSP). We hypothesized that quantitative analysis of methylated genes will provide enhanced detection of cancer cells present in cytologic specimens. EXPERIMENTAL DESIGN: QM-MSP was done on ductal lavage cells from a set of 37 ductal lavage samples from women undergoing mastectomy (27 with cancer and 3 without). Duct histology information was available for each lavaged duct. QM-MSP data was assessed by measuring cumulative methylation index and by receiver operating characteristic threshold analysis. To determine the baseline level of methylation for each gene in this population, cells from 60 ducts of women at high risk of developing breast cancer were analyzed. RESULTS: QM-MSP findings on a panel of nine genes were correlated to duct histology and ductal lavage cytology. Cytology detected cancer in 33% (7 of 21 ducts) with a specificity of 99% (92 of 93). QM-MSP detected cancer as calculated by cumulative methylation index with a sensitivity of 62% (13 of 21) and specificity of 82% (62 of 76) and by receiver operating characteristic threshold analysis with a sensitivity of 71% (15 of 21) and specificity of 83% (63 of 76). CONCLUSIONS: Compared with cytology, QM-MSP doubled the sensitivity of detection of cancer. This study provides proof of principle by showing the advantages of using methylation analyses to query cytologic specimens and indicates its potential use in diagnosis and in stratifying risk.

Body Fluids↗

PubMed2006

The accuracy of surrogate decision makers: a systematic review.

BACKGROUND: Clinicians currently rely on patient-designated and next-of-kin surrogates to make end-of-life treatment decisions for incapacitated patients. Surrogates are instructed to use the substituted judgment standard, which directs them to make the treatment decision that the patient would have made if he or she were capacitated. However, commentators have questioned the accuracy with which surrogates predict patients' treatment preferences. METHODS: A systematic literature search was conducted using PubMed, the Cochrane Library, and manuscript references, to identify published studies that provide empirical data on how accurately surrogates predict patients' treatment preferences and on the efficacy of commonly proposed methods to improve surrogate accuracy. Two of us (D.I.S. and D.W.) reviewed all articles and extracted data on the hypothetical scenarios used to assess surrogate accuracy and the percentage of agreement between patients and surrogates. RESULTS: The search identified 16 eligible studies, involving 151 hypothetical scenarios and 2595 surrogate-patient pairs, which collectively analyzed 19 526 patient-surrogate paired responses. Overall, surrogates predicted patients' treatment preferences with 68% accuracy. Neither patient designation of surrogates nor prior discussion of patients' treatment preferences improved surrogates' predictive accuracy. CONCLUSIONS: Patient-designated and next-of-kin surrogates incorrectly predict patients' end-of-life treatment preferences in one third of cases. These data undermine the claim that reliance on surrogates is justified by their ability to predict incapacitated patients' treatment preferences. Future studies should assess whether other mechanisms might predict patients' end-of-life treatment preferences more accurately. Also, they should assess whether reliance on patient-designated and next-of-kin surrogates offers patients and/or their families benefits that are independent of the accuracy of surrogates' decisions.

Advance Directives↗

PubMed2006

Epigenetic suppression of secreted frizzled related protein 1 (SFRP1) expression in human breast cancer.

Expression of Secreted frizzled related protein 1 (SFRP1), a recently identified tumor suppressor gene encoding a WNT signaling antagonist, has been found to be frequently down-regulated in breast cancer and is associated with disease progression and poor prognosis. Here, we investigated the role of epigenetic silencing of SFRP1 in breast cancer cell lines and primary breast tumors. Through analyses by methylation-specific PCR and bisulfite sequencing, promoter methylation of SFRP1 was detected in 88% (7/8) of breast cancer cell lines, 17% (1/6) of grade 1 of ductal carcinoma in situ (DCIS), 69% (9/13) of grade 2 and 3 of DCIS, 68% (19/28) of invasive ductal carcinomas (IDC) and 33% (6/18) of lobular carcinomas but not in any (0/14) of normal mammoplasty specimens and mammary epithelial organoids examined. Real-time RT-PCR studies indicated that loss or downregulation of SFRP1 expression in tumors is frequently associated with promoter hypermethylation. In addition, breast cancer cell lines with SFRP1 promoter hypermethylation reexpressed SFRP1 mRNA after treatment with 5-azaC, implying that DNA methylation is the predominant epigenetic mechanism for SFRP1 gene silencing. These findings suggest that frequent downregulation of SFRP1 expression in breast cancer can be attributed, in large part, to aberrant promoter hypermethylation in conjunction with or without histone deacetylation. Based on the frequency of tumor-specific hypermethylation in this gene, SFRP1 could provide a valuable marker for breast cancer.

Acetylation↗

PubMed2006

Resistance of cancers to immunologic cytotoxicity and adoptive immunotherapy via X-linked inhibitor of apoptosis protein expression and coexisting defects in mitochondrial death signaling.

The ability of cancers to evade immune surveillance and resist immunotherapy raises a fundamental question of how tumor cells survive in the presence of a competent immune system. Studies to address this question have primarily focused on mechanisms by which tumor cells avoid recognition by or induce tolerance in the immune system. However, little is known about whether cancer cells also acquire an intrinsic ability to resist killing by immune effectors. We find that cancer cells enhance their ability to withstand an attack by cytotoxic immune effector cells via acquisition of specific genetic alterations that interfere with the shared mitochondrial death signaling pathway entrained by granzyme B, IFN-gamma, and Apo2 ligand/tumor necrosis factor-related apoptosis inducing ligand (Apo2L/TRAIL), three key mediators of immunologic cell-mediated cytotoxicity. We show that the coexistence of specific mitochondrial signaling defects (either deletion of Bax, overexpression of Bcl-x(L), or deletion of Smac) with expression of X-linked inhibitor of apoptosis protein decreases the sensitivity of cancer cells to IFN-gamma/Apo2L/TRAIL- or granzyme B-induced apoptosis, lymphocyte-mediated cytotoxicity in vitro, and adoptive cellular immunotherapy in vivo. Conversely, negating X-linked inhibitor of apoptosis protein expression or function in tumor cells with defective mitochondrial signaling enables direct activation of caspase-3/-7 by granzyme B or Apo2L/TRAIL, and restores their susceptibility to immunologic cytotoxicity. These findings identify an important mechanism by which cancers evade elimination by immune effector cells and suggest that cancer immunotherapy might be improved by concurrent strategies to alleviate or circumvent the intrinsic mitochondrial death signaling defects that help cancer cells resist immunologic cytotoxicity.

Adenocarcinoma↗

PubMed2006

Ductal access for prevention and therapy of mammary tumors.

In cancer patients and in those at high risk, systemic exposure to agents for therapy or prevention is accompanied by undesirable side effects. We hypothesized that it is possible to prevent and treat breast cancer by introducing anticancer agents into the mammary ductal network. Here, we show the efficacy of intraductally administered anticancer agents 4-hydroxytamoxifen and pegylated liposomal doxorubicin (PLD) in the prevention and treatment of breast cancer using the rat N-methyl-N'-nitrosourea-induced and spontaneous HER-2/neu transgenic mouse (neu-N) models of breast cancer. Intraductal administration of PLD to neu-N mice caused regression of established tumors and prevented tumor development more effectively than i.v. injection (P < 0.0001). Intraductal administration resulted in lower circulating levels of PLD compared with i.v. administration, with no evidence of systemic toxicity or long-term histopathologic changes in the mammary gland. Compared with systemic administration, intraductal injection provides direct access to breast lesions with higher local and lower systemic drug exposure. These studies suggest that this approach has potential for application to prevention and neoadjuvant therapy of early breast cancer.

Animals↗

PubMed2006

Graft-versus-host reactions and the effectiveness of donor lymphocyte infusions.

We retrospectively analyzed 83 consecutive recipients of donor lymphocyte infusions (DLI) after allogeneic transplantation for factors associated with disease response and graft-versus-host disease (GVHD). DLI was highly effective in relapsed chronic phase chronic myeloid leukemia (CML), with 71% of patients achieving durable complete remissions (CR). In relapsed acute myeloid leukemia, DLI led to durable CRs in 31% of patients; the rate was <20% in all other diseases. Achieving full donor chimerism and GVHD were predictive of CR. Grade II or higher acute or chronic GVHD occurred in 36 (43%) patients and contributed to death in 13 (16%). Even more patients, 33 (40%), died of their underlying malignancy, including 10 who developed active GVHD. In relapsed CML, most durable CRs occurred without clinically apparent GVHD, yet all responders achieved full donor chimerism, including 6 with coincident normal host hematopoiesis at the time of DLI. Thus, in CML, potent lymphohematopoietic graft-versus-host reactions occurred even in the absence of clinically apparent GVHD; this confirms the ability to dissociate these processes and argues against a leukemia-specific immunologic effect. DLI clearly has efficacy in the treatment of relapsed disease after allogeneic transplantation. However, with the exception of CML, most patients die of their underlying disease because of insufficient antitumor activity even with active GVHD.

Acute Disease↗

PubMed2006

Clinical outcome following autologous and allogeneic blood and marrow transplantation for relapsed diffuse large-cell non-Hodgkin's lymphoma.

High-dose chemotherapy followed by blood or marrow transplantation (BMT) is generally considered the best salvage option for patients with relapsed diffuse large-B-cell non-Hodgkin's lymphoma (DLCL). The relative roles for allogeneic and autologous BMT remain controversial. We reviewed the clinical outcome of 183 patients with relapsed DLCL who underwent BMT at Johns Hopkins University in 1985-2001. A total of 45 patients received T-cell-depleted HLA-matched allogeneic bone marrow (allo-BMT), and 138 patients received autologous marrow or peripheral blood stem cells (auto-BMT). The allo-BMT recipients had a higher proportion of patients with chemoresistant disease (P = .004) and had received more chemotherapy before BMT (P = .02). The auto-BMT recipients were older (P < .001) and were of more advanced-stage disease (P = .01). The 3-year overall survival (OS) was 23.7% (median survival, 129 days) after allo-BMT and 33.1% (median survival, 263 days), after auto-BMT (log-rank, P = .17). The 3-year OS for patients with sensitive disease was 51.9% after allo-BMT and 46.2% after auto-BMT (log-rank, P = .38). For patients with resistant disease, the 3-year OS was 12.1% after allo-BMT and 19.1% after auto-BMT (log rank, P = .08). In multivariate analysis, significant predictors of death were disease sensitivity (hazard rate [HR], 0.3; 95% confidence interval [CI] 0.2-04; P < .001), age >40 years (HR, 2.42; 95% CI, 1.7-3.4; P < .001), and stage at diagnosis (HR, 1.2; 95% CI, 1.0-1.4; P = .04). The 3-year event-free survival (EFS) for patients with sensitive disease was 52.7% after allo-BMT and 42.0% after auto-BMT (log-rank, P = .29). For patients with resistant disease, the 3-year EFS was 6.2% after allo-BMT and 19.4% after auto-BMT (log-rank, P = .1). The 3-year probability of relapse for chemosensitive patients was 30% after allo-BMT and 46.1% after auto-BMT (log-rank, P = .25). The 3-year relapse rate in patients with resistant disease was 75.0% after allo-BMT and 69.9% after auto-BMT (log-rank, P = .58). In multivariate analysis, only disease sensitivity status (HR, 0.4; 95% CI, 0.2-2.1; P < .001) and age >40 years (HR, 1.7; 95% CI, 1.1-2.9; P = .03) appear to have a significant impact on relapse. Transplant-related mortality (TRM) was the cause of death for 51.1% of allo-BMT recipients and 23.9% of auto-BMT recipients (P < .001). Mortality from lymphoma was 26.6% in allo-BMT recipients and 43.5% in auto-BMT recipients (P = .02). Auto-BMT and allo-BMT produced similar survival for patients with relapsed DLCL. For patients with sensitive disease, allo-BMT seemed to provide longer survival with less relapse; however, this was achieved at the cost of greater TRM.

Adolescent↗

PubMed2006

Development in infants with autism spectrum disorders: a prospective study.

BACKGROUND: Autism is rarely diagnosed before three years of age despite evidence suggesting prenatal abnormalities in neurobiological processes. Little is known about when or how development becomes disrupted in the first two years of life in autism. Such information is needed to facilitate early detection and early intervention. METHODS: This prospective study of autism spectrum disorders (ASD) examined development using the Mullen Scales of Early Learning (MSEL) in 87 infants tested at target ages 6, 14, and 24 months. Participants came from infants at high risk (siblings of children with autism) and low risk (no family history of autism) groups. Based on language test scores, Autism Diagnostic Observation Schedule, and clinical judgment at 24 months of age, participants were categorized as: unaffected, ASD, or language delayed (LD). Longitudinal linear regression and ANOVA models were applied to MSEL raw scores, and estimates were compared between the three diagnostic groups. RESULTS: No statistically significant group differences were detected at 6 months. By 14 months of age, the ASD group performed significantly worse than the unaffected group on all scales except Visual Reception. By 24 months of age, the ASD group performed significantly worse than the unaffected group in all domains, and worse than the language delayed group in Gross Motor, Fine Motor, and Receptive Language. The developmental trajectory of the ASD group was slower than the other groups', and showed a significant decrease in development between the first and second birthdays. CONCLUSIONS: Variations from typical and language delayed development are detectable in many children with ASD using a measure of general development by 24 months of age. Unusual slowing in performance occurred between 14 and 24 months of age in ASD.

Algorithms↗

PubMed2006

The continual reassessment method for dose-finding studies: a tutorial.

The Continual Reassessment Method (CRM), along with other adaptive dose-finding study designs, has gained popularity since its proposal by O'Quigley. Several of the reasons it has been embraced by clinical trialists is that it tends to incur fewer toxic events, and more accurately estimate the maximum tolerated dose as compared to the standard Phase I dose escalation designs. Many variations have been published and discussed in the statistical literature, but there has not been as much practical advice for choosing design parameters and implementing the CRM. As a result, the CRM has not been as widely utilized as it could be for dose-finding studies. The goal of this paper is to provide a tutorial for those unfamiliar with the CRM who are either statisticians considering using the CRM for the first time, or investigators with some statistical background. This paper presents the original CRM, and then some of its modified versions. It also explains the specifications that define a CRM design, along with simulated examples of CRMs and standard designs, for illustration.

Clinical Trials, Phase I as Topic↗

PubMed2005

Phase I study of low-dose interleukin-2, fludarabine, and cyclophosphamide for previously untreated indolent lymphoma and chronic lymphocytic leukemia.

PURPOSE: Fludarabine and cyclophosphamide is an effective combination but increases the risk of opportunistic infections due to depressed lymphocyte counts. In an attempt to preserve CD4 counts, we conducted a phase I, double-blind, placebo-controlled trial of recombinant interleukin-2 (IL-2) added to fludarabine and cyclophosphamide in patients with treatment-naive indolent lymphomas or chronic lymphocytic leukemia. EXPERIMENTAL DESIGN: Subcutaneous IL-2 (days 1-21 of each 28-day cycle) was combined with cyclophosphamide (600 mg/m2, day 8) and fludarabine (20 mg/m2, days 8-12) at four dose levels: 0.8, 1.0, 1.2, and 1.4 x 10(6) IU/m2/d. IL-2 dose was escalated in cohorts of four to six patients, with one patient per cohort receiving placebo. RESULTS: Twenty-three patients, median age 50, were enrolled, of whom 30% had chronic lymphocytic leukemia/small lymphocytic lymphoma and 52% had follicular lymphomas. The combination was generally well tolerated, with mainly hematologic toxicities. CD4 counts typically declined substantially during the early weeks of treatment and remained suppressed for months afterward. In the 18 evaluable patients who received IL-2, the mean absolute CD4 count was 999 cells/microL (range, 97-3,776) pretreatment, 379 cells/microL (range, 54-2,599) at day 14, and 98 cells/microL (range, 17-291) at end of treatment. In longitudinal linear models, the changes in CD4 counts were not significantly different across IL-2 dose levels. CONCLUSIONS: The addition of low-dose IL-2 to fludarabine and cyclophosphamide does not seem immunoprotective. New approaches are needed to reduce the cellular immunosuppression and infectious complications associated with purine analogues.

Adult↗

PubMed2005

Loss of polycystin-1 or polycystin-2 results in dysregulated apolipoprotein expression in murine tissues via alterations in nuclear hormone receptors.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of PKD1 and PKD2. Murine gene targeting studies have shown that these genes play an essential role in development, with homozygous inactivation resulting in embryonic lethality. Recently, Pkd1-/- lethality has been linked to placental insufficiency. In this study, the placenta was used as a model to identify factors involved in these developmental abnormalities. Microarray analysis of Pkd1-/- placentae showed upregulation of a set of apolipoprotein-related genes. These changes were validated and were found to be associated with increased quantities of apolipoproteins in the amniotic fluid. Increased apolipoprotein gene expression was also observed in Pkd2-/-placentae and in cystic kidneys of Pkd1cond/-; Meox2cre/+ mice. Using chromatin immunoprecipitation assays, we determined that the activity of HNF-4alpha, a major regulator of apolipoprotein gene expression, was also increased in these organs. These findings suggest a potential role for dysregulation of nuclear hormone receptors in the pathogenesis of ADPKD.

Amniotic Fluid↗

PubMed2005

Pharmacologic and toxicologic evaluation of C. novyi-NT spores.

Clostridium novyi-NT (C. novyi-NT) spores have been shown to be potent therapeutic agents in experimental tumors of mice and rabbits. In the present study, pharmacologic and toxicologic studies were performed to better understand the factors influencing the efficacy and toxicity of this form of therapy. We found that spores were rapidly cleared from the circulation by the reticuloendothelial system. Even after large doses were administered, no clinical toxicity was observed in healthy mice or rabbits. The spores were also not toxic in mice harboring poorly vascularized non-neoplastic lesions, including myocardial infarcts. In tumor-bearing mice, toxicity appeared related to tumor size and spore dose, as expected with any bacterial infection. However, there was no laboratory or histopathologic evidence of sepsis, and the toxicity could be effectively controlled by simple hydration.

Animals↗

PubMed2005

Outcomes of autologous and allogeneic blood or marrow transplantation for mantle cell lymphoma.

To evaluate high-dose therapy and autologous or allogeneic blood or marrow transplantation (BMT) for mantle cell lymphoma, patients receiving BMT for newly diagnosed or relapsed mantle cell lymphoma were identified through the registry at Johns Hopkins. The pathologic diagnostic criteria were reviewed, and details of the presentation, transplant procedure, and survival outcomes were determined. Fifty-eight patients were identified, of whom 64% underwent transplantation in first remission and 12% had primary induction failure. Nineteen patients (one third) received an allograft. Preparative regimens consisted of cyclophosphamide in combination with either busulfan or total body irradiation. On multiple regression analysis, transplantation after 1 or more relapses (hazard ratio, 2.98; P = .02), primary induction failure (hazard ratio, 5.39; P = .002), and allogeneic transplantation (hazard ratio, 3.03; P = .007) were associated with an inferior event-free survival (EFS). However, EFS curves were not statistically different for autologous and allogeneic BMT performed in first remission, with an estimated 3-year EFS approaching or equaling 70%. Primary induction failure and residual bone marrow involvement were the only statistically significant predictors of relapse on multiple regression analysis. At 3 years, the estimated EFS for the entire cohort after BMT was 51%, the probability of relapse was 31%, and the overall survival was 59%. The benefit of autologous or allogeneic BMT for mantle cell lymphoma is thus most apparent when transplantation is performed in first remission. Whether allogeneic BMT ultimately confers an advantage because of a graft-versus-lymphoma effect remains to be determined.

Adult↗

PubMed2005

25-hydroxyvitamin D deficiency is a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy.

BACKGROUND: Patients with primary hyperparathyroidism who undergo minimally invasive parathyroidectomy (MIP) may have postoperative symptoms of hypocalcemia or secondary hyperparathyroidism. This study sought to identify factors predictive of these events. METHODS: Between 1998 and 2004, 190 patients with primary hyperparathyroidism underwent MIP with excision of a single adenoma. Age, gender, race, prior head and neck surgery, use of preoperative thyroid hormone or calcium-channel blockers, preoperative levels of calcium, 25-hydroxyvitamin D (25[OH]D) and intact parathyroid hormone (iPTH), the presence of osteopenia or osteoporosis, intraoperative iPTH levels, and adenoma weight were evaluated by univariate analysis as predictors of postoperative symptoms of hypocalcemia and secondary hyperparathyroidism. RESULTS: None of the following were predictors of postoperative symptoms of hypocalcemia: age, gender, race, prior head and neck surgery, preoperative medications, preoperative calcium and iPTH levels, osteopenia or osteoporosis, intraoperative iPTH levels, or adenoma weight. However, patients with postoperative symptoms of hypocalcemia had significantly lower preoperative 25[OH]D levels (P = .01). Further, higher preoperative iPTH levels (P < .01) and lower preoperative 25[OH]D levels (P = .05) were associated with secondary hyperparathyroidism postoperatively. CONCLUSIONS: A low preoperative 25[OH]D level is associated with postoperative symptoms of hypocalcemia and secondary hyperparathyroidism in patients undergoing MIP. One might consider instituting empiric calcium supplementation postoperatively in patients with low 25[OH]D levels.

Adenoma↗