Predictors of One Year Outcome in Lupus Nephritis: The Importance of Renal Biopsy

The short-term prognosis of lupus nephritis was evaluated byassessing serum creatinine 12 months after renal biopsy in 87patients with lupus nephritis. On univariate analysis, significantclinical and laboratory predictors of this outcome includedclinical signs of renal injury (serum creatinine, 24-hour urinaryprotein, prolonged renal disease, nephrotic syndrome, serumalbumin), as well as thrombocytopenia, older age, and coexistingillness or hypertension at the time of biopsy. On renal biopsy,diffuse proliferative nephritis, higher activity, chronicity,or tubulointerstitial scores, or subendothelial or subepithelialelectron dense deposits predicted a higher serum creatinine12 months after biopsy. A clinical predictive model was developed which included asindependent predictors serum creatinine, age, platelet countand 24-hour urinary protein. Any one of three biopsy variablesadded information to the clinical prediction model: a markedquantity of subendothelial deposits (p=0.02), a higher activityindex score (p=0.02), or the presence of diffuse proliferativelupus nephritis (p=0.05). However, the relative predictive accuracyof the clinical model did not improve with the addition of anyof the biopsy variables. The value of renal biopsy in lupus nephritis is discussed basedon the ability of biopsy information to confirm the prognosis,to add new predictive information for a group of subjects, andto improve predictive accuracy for individual patients.     

Infection or suspected infection after hip replacement surgery with autologous or homologous blood transfusions

Homologous blood transfusions have been associated in both animals and humans with an increased risk of acute postoperative infectious complications. Eighty-four patients who underwent hip replacement surgery and were transfused with 2 or 3 units of blood were analyzed to determine whether those receiving homologous transfusions had different outcomes than those receiving autologous blood only. Only patients free of other risks for postoperative infection were studied. Those receiving homologous blood had a 32 percent (16/50) rate of proven or suspected infections, which was significantly higher than the 3 percent (1/34) rate in patients receiving autologous blood (p = 0.0029). Wound infections accounted for only a minority (6/17) of the proven or suspected infections, which suggests that nonsurgical factors contributed to these complications. The patients identified as being infected required significantly more antibiotic therapy (mean, 7.6 days) and lengthier hospital stays (mean, 15.5 days) than the patients who remained free of evidence of infection (means: 2.3 days of antibiotics and 12.3 days in the hospital) (p = 0.0001 for each variable). Other potential risk factors for infection, such as duration of surgical procedure, advanced patient age, amount of blood loss, type of anesthesia, surgeon performing the operation, use of a cemented versus porous-coat prosthesis, leukocytopenia, anemia, and underlying medical diagnosis, did not account for the differences in infection rates seen in those receiving homologous and autologous transfusions. These results confirm previous reports of an increased risk of postoperative infection in patients receiving homologous transfusions. Homologous transfusion may contribute to an increased risk of infection by immunologic modulation of the recipient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mycobacterial Infections After Renal Transplantation

Mycobacterial infections occurred in 11 of 633 (1.7 per cent)recipients of successful renal transplants. There were no casesof tuberculosis in patients receiving chemoprophylaxis, butamongst those who did not receive prophylaxis disease occurredin six of the 27 (22 per cent) high-risk patients. The majorcause of morbidity during treatment was renal allograft rejection,largely due to reduction in immunosuppressive drug therapy.     

Fluoxetine in orthostatic hypotension of Parkinson's disease: A clinical and experimental pilot study

Summary— Recent clinical studies have reported a beneficial effect of fluoxetine, a serotonin reuptake inhibitor, in patients with severe refractory orthostatic hypotension. The present study was undertaken to investigate the effect of fluoxetine in orthostatic hypotension occurring during Parkinson's disease on both blood pressure values and number of clinical symptoms during orthostatic procedure evaluated using a validated clinical rating scale. In a pilot study performed in fourteen patients with idiopathic Parkinson's disease plus orthostatic hypotension, fluoxetine hydrochloride (20 mg orally daily during one month) significantly reduced the fall in systolic blood pressure [-33 ± 21 (SD) mmHg before fluoxetine vs -22 ± 19 mmHg after fluoxetine, P = 0.03] elicited by standing without modifying heart rate. The drug also significantly reduced the number of postural symptoms occurring during the orthostatic procedure [2.9 ± 1.5 (SD) before fluoxetine vs 1.2 ± 1.3 after fluoxetine, P = 0.006]. A similar pattern of response was obtained in an experimental model of neurogenic orthostatic hypotension obtained in chronically sino-aortic denervated dogs submitted to an 80° head-up tilt test procedure under chloralose anaesthesia. Fluoxetine did not change plasma noradrenaline levels. This pilot study suggests a slight but clinically significant effect of fluoxetine on both hemodynamic parameters and clinical symptoms in parkinsonian patients suffering from orthostatic hypotension.     

Smac Mimetic Bypasses Apoptosis Resistance in FADD- or Caspase-8-Deficient Cells by Priming for Tumor Necrosis Factor ��-Induced Necroptosis

Searching for new strategies to bypass apoptosis resistance, we investigated the potential of the Smac mimetic BV6 in Jurkat leukemia cells deficient in key molecules of the death receptor pathway. Here, we demonstrate for the first time that Smac mimetic primes apoptosis-resistant, FADD- or caspase-8-deficient leukemia cells for TNFα-induced necroptosis in a synergistic manner. In contrast to TNFα, Smac mimetic significantly enhances CD95-induced apoptosis in wild-type but not in FADD-deficient cells. Interestingly, Smac mimetic- and TNFα-mediated cell death occurs without characteristic features of apoptosis (i.e., caspase activation, DNA fragmentation) in FADD-deficient cells. By comparison, Smac mimetic and TNFα trigger activation of caspase-8, -9, and -3 and DNA fragmentation in wild-type cells. Consistently, the caspase inhibitor zVAD.fmk fails to block Smac mimetic- and TNFα-triggered cell death in FADD- or caspase-8-deficient cells, while it confers protection in wild-type cells. By comparison, necrostatin-1, an RIP1 kinase inhibitor, abolishes Smac mimetic- and TNFα-induced cell death in FADD- or caspase-8-deficient. Thus, Smac mimetic enhances TNFα-induced cell death in leukemia cells via two distinct pathways in a context-dependent manner: it primes apoptosis-resistant cells lacking FADD or caspase-8 to TNFα-induced, RIP1-dependent and caspase-independent necroptosis, whereas it sensitizes apoptosis-proficient cells to TNFα-mediated, caspase-dependent apoptosis. These findings have important implications for the therapeutic exploitation of necroptosis as an alternative cell death program to overcome apoptosis resistance.     

Early recognition of heart failure in patients with diabetes type 2 in primary care. A prospective diagnostic efficiency study. (UHFO-DM2)

Background  

We hypothesize that the prevalence of unknown heart failure in diabetic patients aged 60 years and over is relatively high (15% or more) and that a cost-effective strategy can be developed to detect heart failure in these patients. The strategy is expected to include some signs and symptoms (such as dyspnoea, orthopnoea, pulmonary crepitations and laterally displaced apical beat), natriuretic peptide measurements (Amino-terminal B-type natriuretic peptide) and possibly electrocardiography. In a subset of patients straightforward echocardiography may show to be cost-effective. With information from our study the detection of previously unknown heart failure in diabetic patients could be improved and enable the physician to initiate beneficial morbidity and mortality reducing heart failure treatment more timely.     

Regional radiotherapy versus an axillary lymph node dissection after lumpectomy: a safe alternative for an axillary lymph node dissection in a clinically uninvolved axilla in breast cancer. A case control study with 10 years follow up

Background

To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy.

Methods

36 patients were studied pre- and post-radiotherapy with¹⁸FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy.

Results

There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 ± 32.7% vs 47.1 ± 26.1% respectively, p = 0.03)

Conclusion

Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.