Real world results of venetoclax combined with hypomethylating agents in relapsed/refractory AML.

OBJECTIVE: Relapsed/refractory AML cases are much more resistant to chemotherapy. Venetoclax is a highly sensitive BCL-2 inhibitor. It was aimed to evaluate the effects of venetoclax therapy on real-world R/R AML survival outcomes, the effects of the cytogenetic characteristics of the patients and previous clinical applications on treatment response, and venetoclax treatment toxicity. PATIENTS AND METHODS: The study included patients who only received a venetoclax-based salvage on R/R AML patients from Turkey. The study included a total of 62 patients from 6 different centers in Turkey. Response to 2 cycles of venetoclax treatment was assessed by bone marrow blast rate. The demographic data, cytogenetic characteristics, AML type, MDS type, response rates and overall survival of the patients after venetoclax combination treatment were assessed. Median age of the patients was 65 (19-85). Mean number of prior treatments was 2.67 ±1.75. RESULTS: 13 patients (21%) had a history of allogenic stem cell transplantation. 58 (93.5%) had received HMA therapy before venetoclax. 36 patients (58.1%) had de-novo AML, and 25 (40.3%) previously had MDS. Treatment response was evaluated as complete remission (n = 21, 33.9%), partial response (n = 17, 27.4%), and treatment failure (n = 24, 38.7%). Patients in the TF group were significantly more likely to have poor cytogenetic and to have received allogeneic transplants. The mean estimated overall survival after the venetoclax treatment was 9.13 ± 0.75 months. CONCLUSIONS: The study population consisted of a group of patients who had relapsed or primary refractory disease with poor prognosis, despite numerous rounds of chemotherapy. It is our belief that the high response rates obtained with the combination of venetoclax/HMA, and having obtained positive results with poor risk patients, indicated a promising perspective for R/R AML patients.

Proteolysis of insulin-like growth factor-binding protein-3 is increased in urine from patients with diabetic nephropathy.

The insulin-like growth factor (IGF) system has been implicated in the development of experimental diabetic nephropathy. IGF-binding protein-3 (IGFBP-3) modulates IGF actions, and proteolysis decreases its binding affinity for IGFs. The aim of this study was to explore the possibility that proteolysis of IGFBP-3 may be altered in diabetic nephropathy and may therefore modify the intrarenal effects of IGFs. IGFBP-3 proteolysis in urine from diabetic patients with normo- [albumin excretion rate (AER), <20 microg/min], micro- (AER, 20-200 microg/min), and macroalbuminuria (AER, >200 microg/min) was studied in 34 patients with noninsulin-dependent diabetes mellitus (NIDDM), 14 patients with insulin-dependent diabetes mellitus, and 9 controls. Urine samples were analyzed by Western ligand blotting and IGFBP-3 immunoblotting. Protease activity was quantitated using [125I]IGFBP-3 as a substrate. WLB showed three main bands (40-46, 35, and 26 kDa) in control urine and a fainter 18-kDa band. All but the 35-kDa band were immunoreactive with the IGFBP-3 antiserum. The same pattern of IGFBPs was seen in urine from normoalbuminuric diabetic patients. However, the urine of diabetic patients with micro- and macroalbuminuria contained little or no intact 40- to 46-kDa IGFBP-3. In patients with noninsulin-dependent diabetes mellitus, urinary IGFBP-3 protease activity in micro- (n = 13) and macroalbuminuric patients (n = 12; mean +/- SD[SCAP], 75 +/- 25% and 84 +/- 24%) was significantly higher than that in normoalbuminuric patients (29 +/- 9%; P = 0.0001). Similar results were observed in patients with insulin-dependent diabetes mellitus. Proteolytic activity in diabetic urine was due to a serine protease. In conclusion, diabetic nephropathy was associated with IGFBP-3 proteolysis in urine. As similar changes were not observed in patients' sera, this is likely to reflect changes in the kidney or urinary tract, resulting in increased local IGF bioavailability, and therefore may contribute to the structural changes of diabetic nephropathy.

The results of surgical treatment and percutaneous drainage of hepatic hydatid disease.

BACKGROUND: Hydatid disease of the liver remains an important and challenging problem in rural areas. Although, surgery is considered the treatment of choice for hydatid disease of the liver, percutaneous drainage is an alternative treatment method for selected cases. The purpose of this study was to evaluate the results of percutaneous drainage and surgery. METHODS: A total of 66 patients underwent surgery; 36 cases had percutaneous drainage and were evaluated preoperatively for treatment choice according to localization, multiplicity, echographic type and size of the cysts in the liver. The patients were also evaluated postoperatively for systemic complications, e.g. fistula formation, infection of residual cyst, recurrence and hospitalization period for each group. RESULTS: Two groups, those with multiple cysts and cysts bigger than 5 cm, were treated by surgery. At the end of two treatment modalities, systemic complications, biliary fistulizations, recurrence and infection of cyst's cavity were seen more frequently in the surgery group and caused a longer hospital stay. CONCLUSIONS: Percutaneous drainage plus medical treatment can be successfully done for type I, type II and some selected type III hydatid cysts of the liver giving less complications, lower recurrence and shorter hospitalization periods. But, surgery is the primary treatment for big, multiple, complicated and recurrent hydatid cysts of the liver.

Detection of microalbuminuria in diabetic patients by urinary dipstick.

The present study was undertaken to determine the usefulness of a new, sensitive urinary dipstick, Micral-Test II (Boehringer-Mannheim, Mannheim, Germany) for the detection of microalbuminuria (urinary albumin concentration: 20-200 mg/l) in diabetic patients. four hundred and eleven consecutive outpatients with diabetes were screened for microalbuminuria. The diagnostic accuracy of Micral-Test II for the detection of urinary albumin excretion > 20 mg/l was assessed by comparing the urinary albumin concentration determined by Micral-Test II with radioimmunoassay (RIA). In comparison with radioimmunoassay, Micral-Test II had an overall sensitivity of 93%, specificity of 93% and positive predictive value of 89%. False negative results were found in 7% and false positives were obtained in 7% of specimens. These findings suggest that Micral-Test II may be a useful method for the screening of microalbuminuria. However, it should not be regarded as a diagnostic test and a positive result should be followed by measuring AER by a laboratory based method.

Effects of liver transplantation and resection on lipid parameters: a longitudinal study.

BACKGROUND: The liver plays a vital role in the production and clearance of a large number of lipoproteins and is an important determinant of the plasma levels of various lipids including cholesterol, as well as apoproteins such as apoprotein (a). METHODS: To explore the role of the liver in the regulation of lipids and apoprotein concentrations, a serial prospective study measuring lipid parameters and apoprotein (a) levels over 6 months was performed in individuals undergoing hepatic resection for isolated hepatic metastases, transplantation for end-stage liver disease and in individuals undergoing colorectal surgery for malignancy. RESULTS: In the group with hepatic resection, there was a rapid decrease in total, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in the immediate postoperative period. However, these changes could be explained by fasting and surgical intervention as a similar phenomenon was observed in the control subjects. In patients undergoing liver transplantation, total cholesterol decreased over the the immediate postoperative period but had fully recovered by day 40. Apoprotein (a) was low pre-operatively, remained low over the first week but had risen by day 10. Apoprotein (a) at day 40 correlated with the apoprotein (a) level of the donor (r = 0.80, P < 0.01) but not of the recipient's pre-operative level and this correlation persisted 6 months after hepatic transplantation. CONCLUSIONS: The liver has a large reserve and is able to maintain lipoprotein production and removal despite greater than 50% removal. The major cause of reduced plasma lipid concentrations in the postoperative period relates to other factors such as fasting and handling of the gut during surgery. In liver transplantation, apoprotein (a) levels resemble those of the donor within 2 weeks of organ donation, consistent with the liver being the major site of production of this apoprotein.

Relationship of progressively increasing albuminuria to apoprotein(a) and blood pressure in type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetic patients.

This study has explored the temporal relationship between apoprotein(a), blood pressure and albuminuria over a mean interval of 11 years in a cohort of 107 diabetic patients of whom 26 (14 Type 2 (non-insulin-dependent), 12 Type 1 (insulin-dependent) had progressively increasing albuminuria ('progressors'). In Type 2 diabetic patients, no significant differences were noted for HbA1, blood pressure, creatinine clearance or serum lipids between progressors and non-progressors. In Type 1 diabetic patients, final systolic and diastolic blood pressures were higher in progressors compared with non-progressors and progressors showed impairment of renal function in association with a rise in blood pressure at the macroalbuminuric stage. Initial apoprotein(a) levels were similar in progressors and non-progressors of either diabetes type. Apoprotein(a) levels increased exponentially with time in 12 of 14 Type 2 progressors but only in 5 of 12 Type 1 progressors (p < 0.01). In Type 2 diabetic patients, the annual increase in apoprotein(a) levels was 9.1 +/- 2.4%, which was significantly greater than in non-progressors, 2.0 +/- 1.2% (p < 0.01) and also exceeded the rates of increase of apoprotein(a) in progressors with Type 1 diabetes, 4.0 +/- 1.4%, (p < 0.05). Apoprotein(a) levels correlated significantly with albuminuria in 8 of 14 Type 2 progressors but only in 3 of 12 Type 1 progressors (p < 0.05). The rate of increase of apoprotein(a) levels was not related to mean HbA1, creatinine or creatinine clearance levels, or to albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Semi-quantitative determination of microalbuminuria by urinary dipstick.

Microalbuminuria predicts subsequent clinical nephropathy and mortality in diabetic patients. This study was undertaken to determine the usefulness of a new immunochemical urinary dipstick test (Micral-Test, Boehringer Mannheim, GmbH Mannheim, Germany) in identifying urinary albumin concentrations within the microalbuminuric range (urinary albumin concentration 20-200 mg/L). Twenty-four hour urine specimens were collected from 298 consecutive diabetic outpatients. Micral-Test was performed by two laboratory scientists blinded to each other's results and those of radioimmunoassay (RIA) and immunoturbidimetry on the same specimen. When compared with RIA, Micral-Test had an overall sensitivity of 92.2%, specificity of 92.3% and positive predictive value of 86.4%. However, at the threshold value of 20 mg/1 Micral-Test showed false positive results in 37.8% of samples when compared with RIA. Similar results were obtained when Micral-Test was compared with immunoturbidimetry. We conclude that Micral-Test is a useful screening method for the detection of microalbuminuria. We suggest that positive tests be confirmed by a timed urine collection using established methodology and that patients whose Micral-Test is negative be subjected to annual retesting.