Quantifying infection risks in incompatible living donor kidney transplant recipients

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.771.40_2.56,P = .3) and moderately (wIRR = _0.881.35_2.06,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.332.22_3.72,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.623.57_4.88, P < .001) and death-censored graft loss (wHR = _1.154.01_13.95,P = .03). Post–KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.     

Cytopathologic analysis of paraspinal masses: a study of 59 cases with clinicoradiologic correlation

Paraspinal masses (PSM) are uncommon and present a wide spectrum of differential diagnoses on fine-needle aspiration (FNA). We analyzed 59 cases of PSM on FNA in a 15-yr period, in the context of clinicoradiologic correlation. Radiologic findings, clinical data, and tissue biopsies were reviewed. Patients were 14-83 yr of age (mean 54.7) with a M:F ratio of 1.36:1. Of the 59 cases, 39 (66%) were deemed diagnostic. Of these, 8 (21%) revealed nonneoplastic lesions and 31 (79%) yielded neoplasms: 2 (6%) benign and 29 (94%) malignant. Of the malignant cases, 22 (76%) were metastatic tumors from various sites, while 7 (24%) were cancers from local spread, which included non-Hodgkin's lymphoma (NHL, 5) and myeloma (2). Benign neoplasms were nerve sheath tumors. Metastatic tumors consisted of adenocarcinoma, 9; squamous-cell carcinoma, 3; renal-cell carcinoma, 1; and non-small-cell carcinoma/not otherwise specified (NOS), 9. Twenty-four (41%) cases received further studies: immunoperoxidase (IPOX) alone, 17 (71%); special stains for microorganisms, 2 (8%); IPOX/other special stains, 4 (17%); and flow cytometry analysis, 1 (4%). Eight (14%) cases received follow-up biopsies. Half of these biopsies added information to previously "nondiagnostic" FNAs. Of the previously "diagnostic" FNAs, tissue biopsy yielded no additional information. Cytopathologic diagnoses were consistent with the pre-FNA radiology analyses in 13 (39%) cases. In instances of radiologic and cytopathologic discrepancy (4 cases, 12%), diagnoses made by FNA reversed the initial radiologic impression of neoplasm to infection, and vice versa. PSMs are rare lesions (0.26% of total FNAs done in 15 yr at our institution). The most common lesion encountered is metastatic adenocarcinoma, followed by NHL. Ancillary studies are helpful in difficult cases. In cases of radiologic/cytopathologic discrepancy, FNA diagnoses are more accurate and decisive for patient management. The sensitivity and specificity of a PSM FNA are 88% and 75% respectively.     

Effects of two stressors on behaviour in the elevated X-maze: preliminary investigation of their interaction with 8-OH-DPAT

Effects of water deprivation and restraint were compared in the rat elevated X-maze. Water deprivation for 12–48 h increased corticosterone and had a duration-dependent anxiolytic effect in the elevated X-maze, increasing the ratio of open/total arm entries (OTR) and the proportion of time spent on the open arms (% time) without affecting total entries. Brain 5HIAA/5HT was increased only after 24 or 48 h deprivation. Restraint for 15 min also increased plasma corticosterone and brain 5HIAA/5HT but had no effect on behaviour in the elevated X-maze when rats were tested immediately afterwards. However, 1 h restraint was anxiogenic in the elevated X-maze immediately after release, reducing OTR and % time, but with a less consistent reduction in total entries; reductions in OTR and % time were still present 24 h later. The 5HT_1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.1–0.2 mg/kg), administered 10 min before testing in the elevated X-maze, had anxiogenic actions in non-stressed rats. The effect of 0.1 mg/kg 8-OH-DPAT was not significantly altered by 24 or 48 h water deprivation but was abolished by restraint for 1 h immediately beforehand, despite the anxiogenic effect of restraint alone. Similar mutual antagonism of 8-OH-DPAT and restraint occurred when the dose of 8-OH-DPAT was increased to 0.2 mg/kg. Twenty-four hours after restraint, restrained rats which had received 8-OH-DPAT (0.1–0.2 mg/kg) still did not show any significant anxiogenic effect compared with non-restrained vehicle treated controls. Restraint-induced deficits in elevated X-maze exploration may prove a useful model with which to study the pharmacology of depression-related anxiety. However, the effects of the stressors examined, and their interaction with 8-OH-DPAT in the elevated X-maze, appear to depend on the nature of the stressor.     

Destruction of WiDr multicellular tumor spheroids with the novel thymidylate synthase inhibitor 1843U89 at physiological thymidine concentrations

The activity of a novel thymidylate synthase inhibitor, 1843U89, against WiDr human colon carcinoma multicellular tumor spheroids was investigated. Continuous exposure of the spheroids to 3 nM 1843U89 for 10 days resulted in spheroid disruption, whereas 100 nM methotrexate (MTX) was required for similar effects. Short-term treatment experiments demonstrated that a 3-day exposure to 100 nM 1843U89 caused spheroid disruption 9 days after drug removal. A 4-day exposure to 10 nM 1843U89 caused spheroid disruption 8 days after drug removal. In contrast, treatment with 10 or 100 nM 1843U89 for 6–48 h or treatment with 1 nM 1843U89 for up to 5 days caused only growth delay. Continuous exposure of spheroids to 30 nM 1843U89 in the presence of 0.05–0.3 M thymidine was as effective in causing spheroid disruption as treatment in the absence of thymidine, but treatment in the presence of 0.7–3.0 M thymidine caused partial reversal of spheroid disruption. The results of these experiments suggest that 1843U89 should have potent solid tumor activity in humans but should be less effective in mice due to differences in circulating thymidine levels (0.1 vs 1 M, respectively).     

Quality assurance in a children's psychiatric hospital

The use of short-term isolation (STI) in a children's psychiatric hospital was examined using the Joint Commission on Accreditation of Hospitals (JCAH) quality assurance mode. A Clinical Care Evaluation addressed two questions: Are we providing quality use of STI? And are we adequately documenting its use? A medical record audit of 78 discharged patients and a review of unit records provided hospital staff with utilization and demographic statistics; structured interviews with staff and inpatients were conducted that provided information about their opinions of STI. The data gathered served as the basis for recommendations that led to planned, informed program changes.     

Recruit,screen, and hire: Staff selection and the decision-making process

This article focuses on the role of the clinician-manager in staff selection. The duties of the clinician-manager in a mental health center include those tasks described as recruit, screen, and hire but little or no guidance on the steps involved in this sequence of events is available. The how of hiring is transmitted by word of mouth, by following another's example, or by trial and error. This article examines the component parts of staff selection from the assimilation of procedures, rules, and regulation of the public authority under which a particular mental health center operates, to the compilation of a short list of those to be screened and finally the risk taking and decision-making process by the clinician-manager who makes the choice. Some speculation on the emotional impact it has on the clinician-manager is examined. The impact of personal value judgments of the selector are considered. Recommendations are made for the inclusion of training in staff selection by academic programs for mental health administrators.Sheila Melville, A.C.S.W., is the Director, Partial Hospitalization, Mt. Vernon Center for Community Mental Health, 8119 Holland Road, Alexandria, Virginia 22306.     

Utilization of acute inpatient psychiatric services: “Heavy users” in New York State

The severely and persistently mentally ill (SPMI) population are often forced to rely on emergency/acute inpatient services. The authors analyze Medicaid expenditures and state hospital utilization data to identify and describe the characteristics of heavy users of these services. Also described is New York State's intensive case management (ICM) initiative targeted at this heavy user group. It is postulated that ICM will alter the utilization patterns of participants from over-reliance on the most costly services and more effectively and efficiently serve the SPMI population, specifically the heavy user subpopulation.     

Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction.

Individuals with cytological atypia in sputum may be at increased risk for lung cancer. We conducted a longitudinal analysis of the association between lung cancer incidence and cytological atypia in sputum samples collected prospectively from an ongoing cohort of adults at high risk for lung cancer. Cohort members had a smoking history of > or = 30 pack-years and chronic obstructive pulmonary disease documented by pulmonary airflow testing. Sputum samples collected at baseline and periodically thereafter were examined by standard cytological methods. From the cohort of 2,006 people, there were 83 incident lung cancers over 4,469 person-years of observation. At baseline, the association between personal and behavioral characteristics, and sputum cytological atypia was assessed by multiple logistic regression. The association between sputum cytological atypia and incident lung cancer was then assessed by hazard ratios using proportional hazards regression analysis, adjusting for potential confounding factors. Cytological atypia graded as moderate or worse was associated with continuing cigarette smoking (adjusted odds ratio, 2.5; 95% confidence interval, 1.5-4.1), and with lower levels of intake of fruits and vegetables (P for trend = 0.04). Atypia was not associated with several other factors, including the degree of airflow obstruction, the use of vitamin supplements, nonsteroidal anti-inflammatory drugs, or metered-dose steroid inhalers. Incident lung cancer was increased among those with moderate or worse cytological atypia (adjusted hazards ratio, 2.8; 95% confidence interval, 1.4-5.5). This association was not confounded by other risk factors. We conclude that in this high-risk cohort, cytological atypia is associated with continuing smoking and low intake of fruits and vegetables, but that independent of these and other factors, the risk of incident lung cancer is increased among those with moderate or worse grades of cytological atypia in their sputum.     

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patient was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m ² per minute). Results from the 120 mU/m ² per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 ± 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 ± 1.1, patients with CF = 10.2 ± 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance ( r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes. (J Pediatr 1997;130:948-56)