Mechanism of dilutional anemia in massive splenomegaly.

Twenty patients with anemia and massive splenomegaly were studied in order to elucidate the mechanism by which splenomegaly results in plasma volume expansion. In 18 patients, increased plasma volume accounted for most of the anemia. Fourteen patients had an exaggerated renin response to standing, mean 1967 +/- 613 (SE) ng angiotensin ll/100 ml plasma (p less than 0.05). The mean resting forearm blood flow was increased 3.47 +/- 0.32 (SE) ml/100 ml forearm tissue (p less than 0.001). The venous capacitance was normal, as contrasted to a marked decrease in venous capacitance in patients with anemia of comparable degree without splenomegaly. Cardiac indices were increased in 10 of 11 patients (range 4.1-8.1 liters/min/sq m). In nine of ten patients oxygen consumption was increased (range 147-231 ml/min/sq m). Splenectomy was performed on 14 patients. Splenic blood flow was elevated in four of four patients (range 750-2000 ml/min). Splenic A-V oxygen difference was exaggerated in seven of seven patients and in three of three patients splenic indocyanine-green dye dilution curve failed to show an early peak suggestive of A-V shunting in the spleen. Free portal pressure was elevated in 12 of 12 patients and decreased immediately after splenectomy. The intravascular albumin mass decreased in ten patients, was unchanged in three at 2-4 mo after splenectomy, and was accompanied by a rise in the plasma albumin concentration in nine. These data suggest that a flow-induced portal hypertension with expansion of the portal vascular space is an important early hemodynamic change. This finding, together with a decreased peripheral resistance, probably results in a decrease in effective intravascular volume, resulting in stimulation of the renin-angiotensin-aldosterone system and other renal hemodynamic changes necessary for salt and water retention. Splenectomy usually accomplishes a complete reversal of these abnormalities and correction of the anemia.     

Peripheral arterial disease: identification and implications

Peripheral arterial disease (PAD) is most commonly a manifestation of systemic atherosclerosis in which the arterial lumen of the lower extremities becomes progressively occluded by atherosclerotic plaque. Patients with PAD are at triple the risk of all-cause mortality and at more than 6 times the risk of death from coronary heart disease as those without the disease, yet PAD is probably the most underdiagnosed and least aggressively managed atherosclerotic disease. In the diagnosis of PAD, a detailed history and physical examination are extremely important, although limited by a lack of consistent sensitivity and specificity. Other office-based noninvasive tests, including the ankle-brachial index, can be easily performed to confirm the diagnosis and help stratify the risk. The ankle-brachial index correlates well with disease severity and functional symptoms and can also be used to assess disease progression and to predict cardiovascular and cerebrovascular mortality. Once diagnosed, risk factor modification, symptomatic relief, and secondary prevention strategies with antiplatelet agents form the core of medical management of PAD.     

Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1-3)IGF-I in rats

Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 degrees C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1-3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1-3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1-3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4.59, 1.20 and 1.34 ml/min per kg respectively. The mean steady-state volume of distribution was larger for des(1-3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1-3)IGF-I greater than IGF-I greater than IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo.     

Frailty Assessment Predicts Acute Outcomes in Patients Undergoing Screening Colonoscopy

Background

Colonoscopy is associated with multiple adverse outcomes. With an aging population undergoing colorectal cancer screening, few modalities exist to assess the patient risk prior to colonoscopy. Frailty, the age-related decline in reserve and function across multiple organ systems, predicts poor surgical outcomes, but its role in endoscopy is unclear.

Aims

This prospective cohort study assesses the efficacy of frailty in predicting acute colonoscopy outcomes.

Methods

Participants aged ≥?50 years undergoing screening colonoscopy at a tertiary care center were recruited over 2 months ending in July 2017. Frailty was assessed using a validated 20-s upper-extremity frailty test, which measures the capacity of muscle performance. Demographic data, American Society of Anesthesiologists (ASA) status, and Charlson comorbidity index (CCI) were evaluated. Procedure-related adverse events and cardiopulmonary changes during and in the immediate post-procedure period were recorded. Adverse events were stratified into minor and major events. Chi-square and ANCOVA models were used in the analysis.

Results

Ninety-nine adults (mean age 62.8 years) were enrolled, among which 49 were non-frail and 50 were pre-frail/frail; 50 were female. Overall, 55 participants experienced a total of 87 adverse events. Frailty and ASA status were significantly associated with colonoscopy adverse events (p?=?0.01 and p?=?0.02, respectively). Age and CCI did not predict colonoscopy outcomes.

Conclusions

Compared to age and CCI, frailty status better predicts colonoscopy outcomes in older adults. Among adults undergoing colonoscopy, routine frailty screening should be considered for risk stratification. Additional prospective studies evaluating frailty measurements in endoscopy will further clarify its role in forecasting adverse events.

     

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor- risk ALs.     

Patient-health care provider communication among patients with newly diagnosed prostate cancer: Findings from a population-based survey

Objective

To examine the multidimensional concept of patient-health care provider (HCP) communication, its effects on patient satisfaction with oncology care services, and related racial differences.

Methods

The current analysis draws from a population-based survey sample of 1011 African American and 1034 Caucasian American men with newly diagnosed prostate cancer. The variables of satisfaction with health care services, interpersonal treatment, contextual knowledge of the patient, and prostate cancer communication were analyzed using multiple-group structural equation modeling.

Results

Regardless of race, patient-HCP communication was related positively to interpersonal treatment by the HCP, HCP's contextual knowledge of the patient, and prostate cancer communication. More positive patient-HCP communication was related to more satisfaction with health care services. Racial differences were significant in the relationships between patient-HCP communication and prostate cancer communication.

Conclusion

Content and interpersonal relationships are important aspects of patient-HCP communication and affect patient satisfaction with oncologic care for prostate cancer.

Practice implications

HCPs need to integrate the transfer of information with emotional support and interpersonal connection when they communicate with men with newly diagnosed prostate cancer.