Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.

In current practice, human immunodeficiency virus-infected (HIV(+) ) candidates with CD4 >200 cells/mm(3) are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm(3) among 38 anti-thymocyte globulin (ATG)-treated HIV-negative to HIV(+) kidney transplants performed at our center between 2006 and 2013. Median follow-up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm(3) ), however, was more common among patients with a baseline CD4 count 200-349 cells/mm(3) compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200-349 cells/mm(3) was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3-5.1) and 52 weeks (RR 14.3; 95% CI 2-100.4) after transplant. Patients with CD4 <200 cells/mm(3) at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log-rank p = 0.05). These findings suggest that ATG must be used with caution in HIV(+) kidney allograft recipients with a pretransplant CD4 count <350 cells/mm(3) .

Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function.

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi-center study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha- and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.3) and 1.36 (1.1-1.8), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

Case report: parenchymal pseudoaneurysm of a renal allograft after core needle biopsy: a rare cause of allograft injury.

There are multiple causes of worsening graft function after initial good function in cadaveric kidney transplant. In this report, we discuss a rare one: a traumatic pseudoaneurysm caused by a 14-gauge core needle biopsy in a 55-year-old woman. She had immediate graft function followed by rapid decline in the first postoperative week. Imaging studies showed an intraparenchymal 2-cm pulsatile mass with turbulent blood flow in the upper pole at the corticomedullary junction. Angiography the following morning confirmed the diagnosis of pseudoaneurysm. It was coiled successfully, with restoration of graft function. Although development of a pseudoaneurysm is a rare event, transplant centers must be cognizant of allograft injuries like this one.

Randomised clinical trial: a novel rabeprazole extended release 50 mg formulation vs. esomeprazole 40 mg in healing of moderate-to-severe erosive oesophagitis - the results of two double-blind studies.

BACKGROUND: Current PPIs may not achieve desired outcomes in some GERD patients due to limited duration of acid inhibition. AIM: To evaluate a novel rabeprazole extended release (ER), which provides longer duration of drug exposure and acid suppression, in healing and symptomatic resolution of moderate-severe erosive oesophagitis. METHODS: Patients with LA grade C or D oesophagitis were randomised to rabeprazole-ER 50 mg or esomeprazole 40 mg once daily in two identical 8-week double-blind trials (N = 2130). Two primary endpoints were tested sequentially: (1) healing by 8 weeks [hypothesis: rabeprazole-ER non-inferior to esomeprazole (non-inferiority margin = 8%)], (2) healing by 4 weeks [hypothesis: rabeprazole-ER superior to esomeprazole (P < 0.05)]. The secondary endpoint was sustained heartburn resolution at 4 weeks. RESULTS: Rabeprazole-ER was non-inferior to esomeprazole in week-8 healing (80.0% vs. 75.0%; 77.5% vs. 78.4%). Week-4 healing (54.8% vs. 50.3%; 50.9% vs. 50.7%) and sustained heartburn resolution (48.3% vs. 48.2%; 53.2% vs. 52.5%) were not significantly different. Post hoc combined results for grade D revealed rabeprazole-ER vs. esomeprazole differences in week-8 healing = 10.4% (95% CI: -1.4%, 22.2%) and week-4 healing = 12.0% (P = 0.048). CONCLUSIONS: Rabeprazole-ER is as effective as esomeprazole in healing moderate-severe oesophagitis and achieves similar rates of heartburn resolution. Subgroup analysis suggests the possibility of benefit in severe oesophagitis, but this requires further evaluation (ClinicalTrials.gov: NCT00658528 and NCT00658775).

Optimized technique in needle biopsy protocol shown to be of greater sensitivity and accuracy compared to wedge biopsy.

BACKGROUND: Kidney biopsy is an important tool in determining allograft suitability for transplantation. Most deceased-donor renal biopsies performed today in the United States are wedge biopsies (WBs), with core needle biopsies being performed only by a minority of organ procurement organizations (OPOs). The lack of a gold standard in tissue sampling and tissue evaluation has prompted our OPO to find a more sensitive biopsy method as well as a more accurate pathology evaluation protocol to reassess expanded-criteria donor kidneys. METHODS: Between the months of March 2007 and June 2008, the New York Organ Donor Network OPO imported 226 kidneys. These kidneys had been previously biopsied by the originating OPOs utilizing the WB method. All 226 kidneys were rebiopsied by our preservation team using the optimized needle biopsy technique (ONBT) and then evaluated by the pathologists of the Transplant Pathology Laboratory of the Mount Sinai Hospital. RESULTS: Histologic findings from both types of biopsies were compared in the following parameters: glomerular yield, percentage of obsolete glomeruli, tubular interstitial scarring, arterial intimal fibrosis and acute tubular necrosis. Difference in glomerular yield between WB and ONBT was not statistically significant (P = .1736). ONBT detected more tubular interstitial scarring and arterial intimal fibrous narrowing than WB (P = .00). No statistical difference was found between the two biopsy methods in identifying acute tubular necrosis. CONCLUSION: The data suggest that there were no statistical differences in sample reliability between ONBT and WB. However, ONBT was found to be significantly more sensitive in identifying allograft tubular interstitial scarring as well as intimal fibrous narrowing. Overall this study provides proof that ONBT is a more reliable and accurate method compared to WB in identifying important parameters of renal allograft.

Recombinant tissue-type plasminogen activator in the treatment of acute renal artery thrombosis after kidney transplantation.

Acute arterial thrombosis is an uncommon but potentially devastating consequence of kidney transplantation. Early recognition followed by thrombectomy may salvage the graft. We present a case of acute renal artery thrombosis after a living-related kidney transplant with successful treatment with operative thrombectomy and intraarterial infusion of recombinant tissue-type plasminogen activator.

Hypothermic machine preservation in human liver transplantation: the first clinical series.

Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.

A case of human intramuscular adrenal gland transplantation as a cure for chronic adrenal insufficiency.

Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm(3) segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineral-corticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency.

Treatment of Strongyloides stercoralis hyperinfection-associated septic shock and acute respiratory distress syndrome with drotrecogin alfa (activated) in a renal transplant recipient.

We report a case of Strongyloides stercoralis hyperinfection syndrome in a renal transplant recipient complicated by septic shock, acute respiratory distress syndrome, and Klebsiella pneumoniae superinfection. The patient was treated successfully with drotrecogin alfa (activated), parenteral ivermectin, albendazole, and piperacillin/tazobactam. This outcome suggests that drotrecogin alfa (activated) may be useful therapy for transplant recipients who develop severe sepsis or septic shock secondary to potentially lethal opportunistic infections.

Manipulating the host response to autologous tumour vaccines.

From our way of thinking the problem facing vaccine strategies for cancer is not that we do not have "enough" tumour antigens. The problem is we cannot induce an immune response that is sufficient to mediate tumour regression. The normal "checks and balances" found in the body prevent the sustained expansion and subsequent persistence of immune killer cells. If vaccine strategies are going to become effective treatments for cancer patients, they will need to overcome this substantial roadblock. Recent developments in immunology have provided insights into the mechanisms that regulate the expansion and persistence of T cells. This has allowed investigators to reinterpret decades-old observations suggesting that chemotherapy administered before vaccination often led to a stronger immune response. This manuscript will review experiments that offer an explanation for these observations and present pre-clinical data from our laboratory that describes an innovative new approach to combining chemotherapy and vaccination. This approach is readily translatable to the clinic and is broadly applicable to any vaccine strategy for advanced cancer.

Family transactions and relapse in bipolar disorder.

This study examined whether patient symptoms and relatives' affective behavior, when expressed during directly observed family interactions, are associated with the short-term course of bipolar disorder. Twenty-seven bipolar patients and their relatives participated in two 10-minute family interactions when patients were discharged after a manic episode. Results indicated that patients who showed high levels of odd and grandiose thinking during the interactions were more likely to relapse during a 9-month followup period than patients who did not show these symptoms during the family discussions. Relapse was also associated with high rates of harshly critical and directly supportive statements by relatives. Patients' odd thinking and relatives' harsh criticism were significantly more likely to be correlated when patients relapsed (r = .53) than when they did not relapse (r = .12). Results suggest that bipolar patients who show increased signs of residual symptomatology during family transactions during the post-hospital period are at increased relapse risk. The data also suggest that relatives of relapsing patients cope with these symptoms by increasing both positive and negative affective behaviors. Moreover, a bidirectional, interactional relationship between patients' symptoms and relatives' coping style seems to capture best the role of the family in predicting relapse in bipolar disorder.

Neurocognitive vulnerability, interpersonal criticism, and the emergence of unusual thinking by schizophrenic patients during family transactions.

BACKGROUND: This study examined whether the combination of patients' neurocognitive deficits and criticism by others would predict the emergence of patients' unusual thinking during stressful family transactions. METHODS: When clinically stable, 41 patients with recent-onset schizophrenia completed 2 versions of a visual vigilance task, the Continuous Performance Test (CPT). One CPT emphasized early perceptual processing, while the other stressed immediate, working memory. On a separate occasion, patients and family members participated in a 20-minute interaction in which the number of relatives' criticisms and patients' unusual thoughts was assessed. RESULTS: In a hierarchical regression model, after entering performance on the CPT demanding immediate, working memory, and the number of criticisms by family members, the interaction of CPT performance and criticism significantly predicted the number of patients' unusual thoughts during the family session (r(2) change = 0.09; P =.03). Post hoc analyses revealed that the number of criticisms and odd thoughts correlated significantly (r = 0.59, P =. 03) for patients who had poor memory-load CPT performance, but were unrelated (r = -0.07) for patients who did well on the memory-load CPT. The CPT emphasizing early visual processing, either alone or in combination with interpersonal criticism, did not predict the number of patients' unusual thoughts during the interaction. CONCLUSION: The results suggest that the combination of patients' working memory deficits and interpersonal criticism jointly predicts psychotic thinking, consistent with a model of schizophrenia that emphasizes the interaction of neurocognitive vulnerability and psychosocial stress factors. Arch Gen Psychiatry. 2000;57:1174-1179.

A comparison of psychiatric symptoms between Anglo-Americans and Mexican-Americans with schizophrenia.

Culture is widely thought to influence the form, content, and extent of symptoms experienced and expressed by the mentally ill. However, little is known about how specific cultural groups differ in their symptomatic presentation of mental illness. Using data derived from the Present State Exam, the current study compared 63 Anglo-American and 53 Mexican-American patients with schizophrenia on ten psychiatric symptoms. A series of logistic regressions offered several interesting findings. For instance, as hypothesized, Mexican-American patients were more likely to report physical symptoms than their Anglo-American counterparts. Also in line with expectations, Anglo-American patients reported experiencing a greater frequency of several psychiatric symptoms such as persecutory delusions, nervous tension, and blunted affect. Results from this study suggest that the presentation of even a very biologically determined disorder such as schizophrenia can be shaped by sociocultural factors. Specific aspects of Anglo-American and Latino cultures that may influence symptom patterns in patients suffering from schizophrenia are discussed.

Difficulty in implementing a family intervention for bipolar disorder: the predictive role of patient and family attributes.

Family affect was examined as a predictor of difficulty implementing a 9-month, manual-based, psychoeducational family therapy for recently manic bipolar patients. Prior to therapy, family members were administered measures to assess both their expressed emotion and affective behavior during a family interaction task. Following family treatment, both therapists and independent observers rated the overall difficulty of treating the family, and therapists also rated each participant's problem behaviors during treatment, in the areas of affect, communication, and resistance. Therapists regarded affective problems among relatives and resistance among patients as central in determining the overall difficulty of treating the family. Relatives' critical behavior toward patients during the pretreatment interaction task predicted both independent observers' ratings of overall treatment difficulty and therapists' perceptions of relatives' affective problems during treatment. Moreover, patients' residual symptoms predicted independent observers' ratings of overall difficulty and therapists' perceptions of patients' resistance to the family intervention. Results suggest that difficulties in conducting a manual-based family intervention can be predicted from systematic, pretreatment family and clinical assessment.

Controllability perceptions and reactions to symptoms of schizophrenia: a within-family comparison of relatives with high and low expressed emotion.

In a sample of 35 family members of patients with recent-onset schizophrenia, attributions of control and the content of critical comments were compared for 2 relatives of the same household who held discrepant expressed emotion (EE) attitudes (1 high and 1 low) toward their mentally ill family member. Attributions and the content of critical comments were also compared for low-EE relatives from low-EE homes versus low-EE relatives from high-EE homes. Our results indicate that high-EE relatives tend to attribute more control over behavior to patients than do low-EE relatives of the same patient. In addition, low-EE relatives from high-EE homes attribute more behavioral control to patients than do low-EE relatives from low-EE homes. These findings suggest that EE status is linked to attributions of control over behaviors, but additional patient factors or influences among family members may also affect EE attitudes.

Early detection and intervention in schizophrenia.

During the course of schizophrenia, symptoms tend to increase at the highest rate during the first 5 years of the disease. Moreover, 10% of suicides by schizophrenic patients occur within the first 10 years of schizophrenia being diagnosed. These facts emphasize the importance of early intervention to improve the course of the disease before further deterioration. The use of psychosocial interventions and drug management programmes, in addition to maintenance antipsychotic medication, reduces the risk of psychotic relapse. Continuity of care from inpatient to outpatient treatment also significantly improves outcome, largely as a result of better drug compliance. It appears, however, that the addition of a behavioural family intervention alone to a standard programme offers little additional benefit. The benefits of intervention programmes last only as long as the programme, and patients should continue with such intensive treatment strategies for at least the duration of the critical phase. Under these circumstances, very mild psychotic complaints may be recognized at an early stage so that treatment can begin even earlier, further increasing the chance of an optimal long-term outcome. Further studies of early intervention and relapse prevention are required to support these findings.

Expressed emotion, attributions, and schizophrenia symptom dimensions.

Using a sample of 40 Anglo American family members of schizophrenic patients, the present study replicates and lends cross-cultural support for an attribution-affect model of expressed emotion (EE). Consistent with attribution theory, the authors found that highly critical relatives (high-EE) viewed the illness and associated symptoms as residing more within the patient's personal control as compared with less critical relatives (low-EE). A content analysis classified the types of behaviors and symptoms most frequently criticized by relatives. Symptoms reflecting behavioral deficits (e.g., poor hygiene) were found to be criticized more often than symptoms reflecting behavioral excesses (e.g., hallucinations). In line with an attribution-affect framework, relatives may be less tolerant of behavioral deficits because they are viewed as intentional, whereas behavioral excesses are easily recognized as core symptoms of mental illness.

Depressive symptoms in the early course of schizophrenia: relationship to familial psychiatric illness.

OBJECTIVE: This study examined the relation between the presence of depressive symptoms in schizophrenic patients with a recent first psychotic episode and affective disorders among their relatives. METHOD: Data on depressive symptoms in 70 patients with schizophrenia diagnosed according to the DSM-III-R criteria, who had had a recent first psychotic episode, and psychiatric diagnostic information on 293 of their first-degree and 674 of their second-degree relatives were collected. Depressive symptoms in the schizophrenic probands were examined at the index psychotic episode (at study entry) and systematically over a 1-year follow-through period. The majority of first-degree family members were interviewed in person with the use of semistructured diagnostic interviews. RESULTS: The linear regression findings confirmed the hypothesis that depressive symptoms in the early course of schizophrenia are associated with a family history of unipolar affective illness. CONCLUSIONS: Because depression in the patients was associated with a family history of depression, this suggests that depression in schizophrenia is not solely either a reaction to having had a psychotic episode or part of the recovery process. The findings are consistent with a model in which a familial genetic liability to affective disorder, when present, is viewed a s exerting a modifying influence on the patient's schizophrenic illness to increase expression of depressive symptoms.

Children with schizophrenia-spectrum disorders: thought disorder and communication problems in a family interactional context.

Thought disorder and communication patterns during an interactional task were examined in families of children with schizophrenia-spectrum disorders (schizophrenia and schizotypal personality disorder), depressed children, and normal controls. Children with schizophrenia-spectrum disorders showed significantly more thought disorder than their normal peers; levels of thought disorder among depressed children fell between those observed in the other two groups but did not differ significantly from either of them. Similarly, mothers of children with schizophrenia-spectrum disorders showed more thought disorder than mothers of normal control children but did not differ from mothers of depressed children. Children with schizotypal personality disorder did not differ from children with schizophrenia. These findings demonstrate that the thought disorder present in childhood-onset schizophrenia and schizotypal personality disorders is manifest in an important social context, the family.

Relatives' expressed emotion and non-verbal signs of subclinical psychopathology in schizophrenic patients.

BACKGROUND: Previous research has generally found that variations in relatives' affective attitudes (expressed emotion; EE) towards a schizophrenic family member could not be accounted for by differences in the severity or form of the patient's symptomatology. These findings have been based on clinicians' ratings of psychopathology in patients. METHOD: To approach the question from a different perspective, videotaped interactions between a patient and family members, obtained four to five weeks after hospital discharge, were coded for subclinical signs of psychopathology expressed by the patient. The Behavioral Subclinical Rating Scale (BSRS) was developed to compare subclinical levels of non-verbal and paralinguistic symptoms expressed by patients from both high- and low-EE families. RESULTS: Highly significant differences were found in the BSRS data. Patients from high-EE families showed more hostile and unusual behaviour with relatives than those from low-EE homes, who, in contrast, showed more anxious behaviour. CONCLUSION: These data suggest that a complex transactional model is necessary to understand how family attitudes evolve during the course of a relatives' schizophrenic disorder.