Risk of infectious complications in patients taking glucocorticosteroids

The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials. The overall rate of infectious complications was 12.7% in the 2,111 patients randomly allocated to systemic corticosteroids and 8.0% in the 2,087 controls (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3-1.9; P less than .001). The risk of infection was particularly high in patients with neurologic diseases (RR, 2.8; 95% CI, 1.9-4.3; P less than .001) and less pronounced in patients with intestinal (RR, 1.4; 95% CI, 1.1-1.7; P = .02), hepatic (RR, 1.4; 95% CI, 0.9-2.3; P = .25), and renal (RR greater than 1; P = .03) diseases. The rate was not increased in patients given a daily dose of less than 10 mg or a cumulative dose of less than 700 mg of prednisone. With increasing doses the rate of occurrence of infectious complications increased in patients given corticosteroids as well as in patients given placebo, a finding suggesting that not only the corticosteroid but also the underlying disease state account for the steroid-associated infectious complications observed in clinical practice.     

Irinotecan-involved regimens for advanced gastric cancer: a pooled-analysis of clinical trials

AIM:To assess the efficiency and toxicities of irinotecan (CPT-11)-involved regimens in patients with advanced gastric cancer.METHODS:Randomized phases Ⅱ and Ⅲ clinical trials on chemotherapy for advanced gastric cancer were searched from MEDLINE,EMbase,Cochrane Controlled Trials Register,and EBSCO.Relevant abstracts were manually searched.A total of 657 patients were analyzed for their overall response rate (ORR),time to treatment failure (TTF),overall survival (OS) rate,and toxicities.Overall survival rate,reported as hazard ratio (HR) with 95% CI,was used as the primary outcome measure.RESULTS:Four randomized controlled trials on chemotherapy for advanced gastric cancer were detected.The CPT-11-containing combination chemotherapy was not significantly advantageous over the non CPT-11containing combination chemotherapy for OS rate (HR =1.12,95% CI:0.92-1.36,P=0.266) and ORR [risk ratio (RR)=1.23,95% CI:0.71-2.14,P=0.458].However,the CPT-11-containing combination chemotherapy was significantly advantageous over the non CPT-11-containing combination chemotherapy for TTF (HR=1.35,95% CI:1.12-1.64,P=0.002).Grade 3/4 haematological toxicity (thrombocytopenia:RR=0.20,95% CI:0.09-0.48;P < 0.001) and gastrointestinal toxicity (diarrhea:RR=4.09,95% CI:2.42-6.93,P < 0.001) were lower in patients with advanced gastric cancer after CPT11-containing combination chemotherapy than after non CPT-11-containing combination chemotherapy.CONCLUSION:CPT-11-containing combination chemotherapy is advantageous over non CPT-11-containing combination chemotherapy for TTF with no significant toxicity.CPT-11-containing combination chemotherapy can be used in treatment of advanced gastric cancer.     

Annual incidence and risk factors for nosocomial bacterial infections in an acute care geriatric unit

PURPOSE: Elderly inpatients are particularly exposed to the risk of nosocomial infections, thus the study of their risk factors and consequences is of interest. METHODS: Among 1,565 subjects referred to a short-term geriatric unit, patients hospitalised for a year for an acute event and unable to move themselves were followed up for the occurrence of nosocomial infections. RESULTS: Among these 402 immobilised patients (age: 86.3 +/- 7.6 years), 102 nosocomial infections occurred in 91 patients (22.6%), whereas the estimation of the incidence in the total hospitalised population (1,565 subjects, age: 85.1 +/- 6.2 years) was 9.4% (95% confidence interval [CI] 8.3-11.2). Forty-seven point seven percent of nosocomial infections were urinary tract nosocomial infections, 27.5% were lower respiratory nosocomial infections, 9.2% were cutaneous nosocomial infections, 7.3% were septicaemia and 8.2% were of unknown origin. The relative risk (RR) of NI linked to functional dependency for mobility was 5.5 (95% CI: 3.93-7.7, P < 0.001). Other risk factors were: for all nosocomial infections: cancer diagnosis (RR 1.1, 95% CI: 1.1-1.2, P = 0.01); and respectively for urinary tract NI: bladder indwelling (RR 4.8, 95% CI: 2.9-7.7, P < 0.001), pulmonary NI: swallowing disorders (RR 5.4, 95% CI: 2.8-10.5, P < 0.001); and septicaemia: venous catheter (RR 5.4, 95% CI: 1.3-23.3, P = 0.002). NI were associated with an increased length of stay (22.1 +/- 11.7 days in infected patients vs 16.3 +/- 9.5 days in immobilised non-infected subjects, P < 0.001). The mean length of stay for the 1,565 subjects was 10.3 +/- 7.6 days. Death was attributed to nosocomial infections in 13 subjects. In conclusion, functional dependency for mobility, bladder indwelling, venous catheter, swallowing disorders and diagnosis of cancer were risk factors for nosocomial infections in hospitalised elderly subjects in an acutecare setting.     

Identification of prognostic factors for plerixafor-based hematopoietic stem cell mobilization

The introduction of plerixafor has enabled successful collection of stem cells in the majority of patients with lymphoma or myeloma in whom previous attempts at mobilization have failed. However, a proportion of patients have been shown to be resistant to this mobilization regimen. To identify the factors that impair stem cell mobilization and collection with plerixafor, we reviewed the data for 197 patients who had undergone mobilization with plerixafor and granulocyte-colony stimulating factor in Central Europe. Predictors of mobilization failure were evaluated using logistic regression analysis. Among the 197 patients mobilized, the target of ≥2.0 × 10(6) CD34+ cells/kg was collected from 133 (67.5%). Our analysis revealed that previous treatment with lenalidomide, bortezomib, melphalan, radiotherapy, or autologous stem cell transplantation and regimen of plerixafor use in combination with chemotherapy had no significant effect on the efficiency of collection. In contrast, an age ≥65 years (odds ratio 0.331, 95% CI: 0.112-0.977, P < 0.05), a diagnosis of non-Hodgkin's lymphoma (odds ratio 0.277, 95% CI: 0.124-0.622, P < 0.01), and treatment with ≥ four chemotherapy regimens (odds ratio 0.366, 95% CI: 0.167-0.799, P < 0.05) were associated significantly with failed mobilization. The rate of successful mobilizations was decreased in patients treated with purine analogues (odds ratio 0.323, 95% CI: 0.096-1.094, P = 0.07) but increased in female patients (odds ratio 1.961, CI: 0.943-4.080, P = 0.07). Patients who are characterized by the above negative features could benefit potentially from further improvement in the mobilization strategy.     

Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation

Infectious complications remain a major problem contributing to significant mortality after hematopoietic allogeneic stem cell transplantation (HSCT). Few studies have previously analyzed mortality due to late infections. Forty-four patients dying from an infectious complication were identified from a cohort of 688 consecutive patients surviving more than 6 months without relapse. A control group of 162 patients was selected using the year of HSCT as the matching criterion. Out of 44 patients, 30 (68%) died from pneumonia, 7/44 (16%) from sepsis, 5/44 (11%) from central nervous system infection and 2/44 (4.5%) from disseminated varicella. The cumulative incidences of different types of infection were 1.6% for viral, 1.5% for bacterial and 1.3% for fungal infections and 0.15% for Pneumocystis jirovecii pneumonia. The majority (66%) of the lethal infections occurred within 18 months after HSCT. Acute GVHD (relative risk (RR): 7.19, P<0.0001), chronic GVHD (RR: 6.49, P<0.001), CMV infection (RR: 4.69, P=0.001), mismatched or unrelated donor (RR: 3.86, P=0.004) and TBI (RR: 2.65, P=0.047) were independent risk factors of dying from a late infection. In conclusion, infections occurring later than 6 months after HSCT are important contributors to late non-relapse mortality after HSCT. CMV infection or acute GVHD markedly increase the risk.     

Prior radiation and/or chemotherapy has no effect on the outcome of metal stent placement for oesophagogastric carcinoma

OBJECTIVE: It is still unclear whether prior radiation and/or chemotherapy (RTCT) increases the risk of complications after the placement of self-expanding metal stents in patients with inoperable oesophagogastric carcinoma. We evaluated the influence of prior RTCT on the outcome of stent placement in a large group of patients. METHODS: From October 1994 to December 2000, 200 patients underwent placement of self-expanding metal stents for malignant dysphagia, and were followed prospectively. Forty-nine of these patients had received prior RTCT (chemotherapy n = 35, radiation therapy n = 8, or both n = 6). RESULTS: At 4 weeks after stenting, the dysphagia score had improved similarly in patients with or without prior RTCT, from a median of 3 to 0 (P < 0.001). The occurrence of major complications (bleeding, perforation, fistula formation, fever and severe pain) was not different between patients with or without prior RTCT (29% vs 21%; relative risk (RR) = 1.15 (95% CI 0.54-2.46; P = 0.72)), as was the occurrence of recurrent dysphagia due to tumour overgrowth, stent migration, or impaction of a food bolus (35% vs 27%; RR = 1.49 (95% CI 0.71-3.13; P = 0.29)). Median survival of both patient groups after stent placement was similar (110 vs 93 days; RR = 0.90 (95% CI 0.60-1.34; P = 0.60) for prior RTCT versus no prior treatment). Only minor complications (mainly mild retrosternal pain) occurred more frequently in patients with prior RTCT (41% vs 15%; RR = 2.12 (95% CI 1.06-4.25; P = 0.035)). CONCLUSIONS: Both the incidence of life-threatening complications and survival after placement of self-expanding metal stents for oesophagogastric carcinoma are not affected by prior RTCT, but retrosternal pain occurs more frequently in patients who had previously undergone RTCT.     

Double high-dose therapy for Hodgkin's disease with dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP) prior to high-dose melphalan and autologous stem cell transplantation

We previously reported a 50% (95% CI = 33-76%) 5 year event-free survival (EFS) rate for 23 patients with Hodgkin's disease (HD) who received salvage therapy with single agent high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). Predictors of poor outcome included bulky disease and initial remission <1 year. Since 1995, similar poor prognosis patients have been treated with double high-dose therapy consisting of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP) for tumor cytoreduction and stem cell mobilization followed by HDM/ASCT. The purpose of the present study is to determine if the use of DICEP is associated with improved event-free (EFS) and overall survival (OAS) for patients treated with HDM/ASCT. From February 1981 to June 1999, 46 consecutive patients received HDM/ASCT for relapsed (n = 35) or refractory (n = 11) HD. DICEP re-induction and blood stem cell mobilization was used for 21 patients. Factors considered for univariate and multivariate analyses included age at transplant, number of failed chemotherapy regimens, prior radiotherapy, length of initial remission, relapsed or refractory disease status, extranodal relapse, B symptoms at relapse, bulk, post-ASCT radiotherapy, and DICEP re-induction therapy. Cox proportional hazards models were constructed for both event and death. DICEP and HDM were well tolerated with no early treatment-related mortality or toxicity requiring life-sustaining measures. For all 46 patients, the projected 5 year EFS was 52% (95% CI = 38-72%) and OAS was 57% (95% CI = 40-82). Factors independently associated with relapse in multivariate analysis included bulk >5 cm (RR = 6.38, P = 0.002), prior radiotherapy (RR = 3.59, P = 0.027), and not using DICEP (RR = 5.29, P = 0.005). Factors independently associated with death included bulk >5 cm (RR = 5.13, P = 0.009), > or =3 prior chemotherapy regimens (RR = 4.72, P = 0.019), and not using DICEP (RR = 7.49, P = 0.015). This study demonstrates that DICEP re-induction prior to HDM/ASCT is feasible. The preliminary data are sufficiently encouraging to warrant a multicenter phase II or a phase III trial evaluating DICEP followed by HDM/ASCT as salvage therapy for HD.     

Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients

Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and assigned to receive high-dose chemotherapy and peripheral stem-cell reinfusion were evaluated. Median catheter dwell time was 25 days (range 1-141). Catheter-related infections were seen in 28.3% of patients (11 infections per 1000 catheter-days). Coagulase-negative staphylococci were found in 104 of 186 positive blood cultures (56%). No systemic fungal infections occurred. Cox regression analysis showed that duration of neutropenia >10 days (P=0.04), using the catheter for both stem-cell apheresis and high-dose chemotherapy (P= <0.01), and use of total parenteral nutrition (TPN, P=0.04) were predictive for catheter-related infections. In conclusion, a high incidence of catheter-related infections after high-dose chemotherapy was seen related to duration of neutropenia, use of the catheter for both stem-cell apheresis and high-dose chemotherapy, and use of TPN. Selective use and choice of catheters could lead to a substantial reduction of catheter-related infectious complications.     

Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections,organ dysfunctions,and mortality in critically ill surgical patients: a prospective,stratified, randomized,double-blind,placebo-controlled clinical trial

We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and stratified according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 x 400 mg of intravenous ciprofloxacin for 4 days, together with a mixture of topical gentamicin and polymyxin applied to the nostrils, mouth, and stomach throughout their ICU stay or to receive intravenous and topical placebo. When receiving prophylaxis, significantly fewer patients acquired infections (p = 0.001, risk ratio [RR], 0.477; 95% confidence interval [CI], 0.367-0.620), especially pneumonias (6 versus 29, p = 0.007), other lower respiratory tract infections (39 versus 70, p = 0.007), bloodstream infections (14 versus 36, p = 0.007), or urinary tract infections (36 versus 60, p = 0.042). Also, significantly fewer patients acquired severe organ dysfunctions (63 versus 96 patients, p = 0.0051; RR, 0.636; 95% CI, 0.463-0.874), especially renal dysfunctions (17 versus 38; p = 0.018). Within 5 days after admission, 24 patients died in each group, whereas 28 patients receiving prophylaxis and 51 receiving placebo died in the ICU thereafter (p = 0.0589; RR, 0.640; 95% CI, 0.402-1.017). The overall ICU mortality was not statistically different (52 versus 75 fatalities), but the mortality was significantly reduced for 237 patients of the midrange stratum with APACHE-II scores of 20-29 on admission (20 versus 38 fatalities, p = 0.0147; RR, 0.508; 95% CI, 0.295-0.875); there was still a favorable trend after 1 year (51 versus 60 fatalities; p = 0.0844; RR, 0.720; 95% CI, 0.496-1.046). Surveillance cultures from tracheobronchial, oropharyngeal, and gastric secretions and from rectal swabs did not show any evidence for the selection of resistant microorganisms in the patients receiving prophylaxis.     

Screening for peripheral arterial disease by means of the ankle-brachial index in newly diagnosed Type 2 diabetic patients.

AIM: To evaluate the prevalence of peripheral arterial disease (PAD) with the ankle-brachial index (ABI) in newly diagnosed Type 2 diabetic subjects. METHODS: Between autumn 2002 and spring 2003, 2559 newly diagnosed Type 2 diabetic subjects (about 15% of the cases/year in Italy) were enrolled in 265 diabetology centres. Family history of diabetes, smoking, height, weight, waistline, fasting glycaemia, glycosylated haemoglobin, total and HDL-cholesterol and triglyceride values were collected. Claudication, cyanosis, cold foot, foot hair anomalies, skin thinning and femoral, popliteal, posterior tibial and dorsalis pedis pulses were assessed. The ABI was measured with a portable Doppler continuous-wave instrument. RESULTS: An ABI < 0.9 was found in 539 (21.1%) patients. Claudication was present in 187 (7.3%). Femoral pulse was absent in 218 (8.5%), popliteal in 316 (12.3%), tibial in 563 (22.0%) and dorsalis pedis in 578 (22.6%). Foot cyanosis was observed in 88 (3.4%), cold foot in 359 (13.9%), skin thinning in 468 (18.3%) and hair anomalies in 857 (33.5%). Multivariate analysis of the variables associated with ABI < 0.9 in the univariate analysis confirmed the independent role of age [relative risk (RR) 1.02, P < 0.001, confidence interval (CI) 1.01, 1.04], claudication (RR 4.53, P < 0.001, CI 2.97, 6.93), absence of tibial pulse (RR 3.45, P < or = 0.001. CI 2.54, 4.68) and pedis pulse (RR 1.96, P < or = 0.001, CI 1.4, 2.68). CONCLUSIONS: PAD, as represented by ABI < 0.9, is common in newly diagnosed Type 2 diabetic patients.     

Risk factors for severe hemorrhagic cystitis following BMT

Hemorrhagic cystitis (HC) is a common toxicity of preparative regimens for bone marrow transplantation (BMT). Severe HC often requires prolonged and expensive hospitalization, and occasionally can result in death. To investigate the risk factors for severe HC, we conducted a retrospective study among 1908 patients who received BMTs at the University of Minnesota during 1974 to 1993. A previous report from our institution reported on 977 of these patients. We identified all patients with genitourinary complication within 100 days post-BMT from the BMT database. Medical charts for these patients were reviewed to determine whether the patient had HC and also the grade of HC. A total of 208 HC cases were identified during the study period. Of them, 92 patients had severe HC, an incidence of 5% (95% CI = 4-6%). We found that grade II-IV graft-versus-host disease (RR = 2.56; 95% CI = 1.43-4.56), use of busulfan (RR = 2.69; 95% CI = 1.35-5.35), and age at transplant (RR = 2.20; 95% CI = 1.27-3.81, for age of 10-30 compared to age of 0-9) were related to an increased risk of HC. In contrast, transplant year was inversely associated with the risk of HC (trend test, P < 0.01). We did not find any significant difference in HC with the use of prophylactic Mesna.     

Does maternity care improve pregnancy outcomes in women with previous complications? A study from Zimbabwe

To determine the utilization of maternal health care services and pregnancy outcomes for women with a history of complications in previous pregnancy, we analysed the pregnancy records of multiparous women (parity > or =1) who booked and completed follow-up in Gutu district, Zimbabwe between January 1995 and June 1998. Women with previous uncomplicated pregnancies (n = 6140) were classified as low risk, whereas those with complications of previous pregnancy (n = 1077) were classified high risk. At enrolment, there was no difference in maternal age and parity between low- and high-risk women. A higher proportion of high-risk women had more than five antenatal visits (32% versus 21%; P<0.001) and gave birth in hospital (47% versus 18%; P<0.001). The risk of antenatal (relative risk [RR] 1.57; 95% confidence interval [CI] 1.32-1.88), labour/delivery (RR 1.98; 95% CI 1.75-2.25) and neonatal (RR 1.83; 95% CI 1.44-2.34) complications was elevated in high-risk women. There was increased risk for perinatal death in high-risk women, but this did not reach statistical significance (RR 1.56; 95% CI 0.98-2.49). The recurrence ratio for most complications was low and the sensitivity of historical risk markers in predicting women likely to develop further complicated pregnancies was only 23%. Most women with previous pregnancy complications can safely give birth in the rural health centre. We concluded that high-risk women had an elevated risk of complications in the index pregnancy and that better utilization of maternal health care, especially for delivery, reduced adverse perinatal outcomes.     

Sequential or concomitant chemotherapy with hypofractionated radiotherapy for locally advanced non-small cell lung cancer: a meta-analysis of randomized trials

BackgroundFor patients with locally advanced non-small cell lung cancer (NSCLC), the standard treatment is concurrent or sequential chemotherapy with radiotherapy. Most treatment schedules use radiotherapy with conventional fractionation; however, the application of hypofractionated radiotherapy (HYPO-RT) regimens is rising. A meta-analysis was performed to assess the efficacy and safety of chemotherapy combined with HYPO-RT and indirectly compare with the outcomes from previous studies employing concomitant conventional radiotherapy (CONV-RT).MethodsRandomized controlled trials (RCTs) were identified on the electronic database sources through June 2020. Following the PRISMA guidelines, a meta-analysis was performed to assess if there were significant differences in the overall mortality (OM), local failure (LF), and disease progression (DP), comparing HYPO-RT-C vs. sequential chemotherapy followed HYPO-RT (HYPO-RT-S). To establish an indirect comparison with the current standard treatment, we calculate the risk ratio (RR) of the OM from RCTs using conventional chemoradiation, concurrent (CONV-RT-C), and sequential (CONV-RT-S), and compared with HYPO-RT. A P value <0.05 was considered significant.ResultsTwo RCTs with a total of 288 patients were included. The RR for the OM, DP and LF at 3 year comparing HYPO-RT-C vs. HYPO-RT-S were 1.09 (95% CI: 0.96–1.28, P=0.17), 1.06 (95% CI: 0.82–1.23, P=0.610), and 1.06 (95% CI: 0.86–1.29, P=0.490), respectively. The late grade 3 pneumonitis and esophagitis had no significant difference between HYPO-RT groups. In the indirect comparison of RCTs using CONV-RT, the RR for the OM at 3 years was 1.03 (95% CI: 0.96–1.10, P=0.36) with no significant difference for the HYPO-RT arms 1.09 (95% CI: 0.96–1.28, P=0.17).DiscussionHYPO-RT given with chemotherapy provides satisfactory OM, LF, and DP in locally advanced NSCLC with similar rates to the CONV-RT. These findings support HYPO-RT inclusion in future clinical trials as an experimental arm in addition to the incorporation of new strategies, such as immunotherapy.     

Effect of alcohol, cigarette smoking, and diabetes on occurrence of hepatocellular carcinoma in patients with transfusion-acquired hepatitis C virus infection who develop cirrhosis

AIM: Alcohol drinking, cigarette smoking, and diabetes have been claimed as risk factors for hepatocellular carcinoma in case-control studies. The aim of this study was to define the impact of these risk factors on the development of hepatocellular carcinoma in hepatitis C virus-related liver cirrhosis. METHODS: A historical cohort of 138 patients with posttransfusion hepatitis C virus-related cirrhosis was selected by reviewing all files of patients referred to our liver unit. Sixty-three of them (46%) developed hepatocellular carcinoma. RESULTS: At univariate analysis, risk factors for hepatocellular carcinoma were observed in patients aged above 59 years [P=0.004; relative risk (RR): 2.08, 95% confidence interval (CI): 1.19-3.68], male sex (P<0.001; RR: 2.48, 95% CI: 1.59-3.87), habit of alcohol drinking (P=0.001; RR: 1.89, 95% CI: 1.24-2.88), and duration of alcohol consumption of more than 30 years (P=0.02; RR: 2.08, 95% CI: 0.98-4.40). At Cox regression analysis, only male sex was an independent predictive factor (beta=0.86; P=0.002; hazard ratio=2.4, 95% CI: 1.3-4.1). CONCLUSION: Diabetes, smoking, and alcohol drinking were not independently related to the risk of developing hepatocellular carcinoma in hepatitis C virus-related cirrhosis.     

Infections following peripheral blood progenitor cell transplantation for lymphoproliferative malignancies: etiology and potential risk factors

PURPOSE: We sought to describe the infections that occur after large-dose chemotherapy, which was followed by autologous peripheral blood progenitor cell transplantation, and to determine their risk factors. PATIENTS AND METHODS: We retrospectively analyzed the occurrence and the characteristics of infections in 277 consecutive patients who received intensive chemotherapy for non-Hodgkin's lymphoma (n = 207), Hodgkin's disease (n = 27), or multiple myeloma (n = 43) in a single institution. Conditioning regimens included total body irradiation in 47% of the cases. Infections occurring within the 30 days after transplant were defined as early infections, whereas infections after that time in patients who had achieved a neutrophil count greater than 1.0 x 10(9)/L (1,000 per microL) were considered as late infections. RESULTS: Within the first 30 days, 172 patients had unexplained fever (62%); infections were documented in 83 patients (30%), most commonly bacteremia (57 patients). Late infections occurred in 64 (26%) of 244 evaluable patients and consisted mainly of varicella zoster virus infections (n = 36) and pneumonia (n = 16). Administration of total body irradiation [odds ratio (OR) = 2.50; 95% confidence interval (CI) 1.4 to 4.5; P = 0.002) and previous use of fludarabine (OR 2.5; CI 1.2 to 5.2; P = 0.02) and a diagnosis of myeloma (OR 2.6; CI 1.2 to 5.6; P = 0.04) were significantly associated with late infections. CONCLUSIONS: This study confirms that infectious toxicity after peripheral blood progenitor cell transplantation is usually moderate, although bacteremia remains a serious problem. Late infections are encountered in about 25% of patients and are more common in those with myeloma, or those who received total body irradiation or fludarabine.     

Magnesium prophylaxis for arrhythmias after cardiac surgery: a meta-analysis of randomized controlled trials

BACKGROUND: Magnesium supplementation may reduce the incidence of arrhythmias, which often occur after cardiac surgery; however, recent findings of the effectiveness of magnesium prophylaxis have yielded discrepant results. METHODS: We searched electronic databases for randomized controlled trials of magnesium for the prevention of arrhythmias after cardiac surgery. The primary outcomes comprised the incidence of supraventricular and ventricular arrhythmias, and the secondary outcomes comprised serum magnesium concentration, length of hospital stay, myocardial infarction, and mortality. Effect sizes were estimated using a random-effects model. RESULTS: Seventeen trials (n=2069 patients) met the inclusion criteria. Pooled serum magnesium concentration at 24 hours after surgery in the treatment group was significantly higher than that in the control group (weighted mean difference=0.45 mmol/L [1.1 mg/dL]; 95% confidence interval [CI]: 0.30 to 0.59 mmol/L [0.7 to 1.4 mg/dL]; P <0.001). Magnesium supplementation reduced the risk of supraventricular arrhythmias (relative risk [RR]=0.77; 95% CI: 0.63 to 0.93; P=0.002) and ventricular arrhythmias (RR = 0.52; 95% CI: 0.31 to 0.87; P <0.0001), but had no effect on the length of hospital stay (weighted mean difference=-0.28 days; 95% CI: -0.70 to 1.27 days; P=0.48), the incidence of perioperative myocardial infarction (RR=1.03; 95% CI: 0.52 to 2.05; P = 0.99), or mortality (RR=0.97; 95% CI: 0.43 to 2.20; P=0.94). CONCLUSION: Administration of prophylactic magnesium reduced the risk of supraventricular arrhythmias after cardiac surgery by 23% (atrial fibrillation by 29%) and of ventricular arrhythmias by 48%. Supplementation had no notable benefit with respect to length of hospitalization, incidence of myocardial infarction, or mortality.     

Risk and determinants of developing severe liver toxicity during therapy with nevirapine-and efavirenz-containing regimens in HIV-infected patients

We examined the risk and determinants of developing severe liver toxicity in 108 HIV-infected patients showing adherence to nevirapine- and efavirenz-containing regimens. Between January 1997 and December 2000, 70 patients were treated with nevirapine- and 38 patients with efavirenz-containing regimens, for a median period of 127 days (interquartile range 65-240). Severe liver toxicity was defined as grade 3-4 elevations (>5 x upper limit of normal) of aminotransferases AST or ALT. A total of 22 (20%) patients showed severe liver toxicity, 17 of them were treated with nevirapine- and five with efavirenz-containing regimens (relative risk [RR]: 1.85, 95% confidence intervals [CIs] 0.74-4.61; P=not significant). Multivariate analysis showed the association of severe liver toxicity with hepatitis C antibody positive (RR 7.64; 95% CI: 1.48-39.52; P=0.01), nevirapine- or efavirenz-containing regimens combined with a protease inhibitor (RR: 3.07, 95% CI: 1.01-9.32, P=0.04) and alcohol intake greater than 40 g per day (RR: 3.09, 95% CI: 1.27-7.54, P=0.01). These findings have potential implications for selecting and monitoring antiretroviral therapy in HIV-infected patients with hepatitis C virus coinfection and for avoiding alcohol intake during antiretroviral therapy.     

Lymphocytopenia is associated with an increased risk of severe infections in patients with multiple myeloma treated with bortezomib-based regimens

Bortezomib is a proteasome inhibitor with potent antimyeloma activity in relapsed/refractory multiple myeloma (MM) patients. We evaluated the types and factors affecting the onset of infectious complications and mortality owing to infection in MM patients treated with bortezomib-based regimens. We reviewed 139 patients with MM treated with regimens containing bortezomib in order to assess the types and factors affecting the development of severe infections. Infections occurred in 56 (40.3 %) of 139 patients and 83 (7.8 %) cases of the 1,069 evaluable cycles. Severe infections developed in 43 (30.9 %) patients and ten patients (7.1 %) died during bortezomib-based treatment. Multivariate analysis determined lymphocytopenia grade 3–4 (OR 3.17, 95 % CI 1.38–7.31, P = 0.007) and number of cycles ≤8 (OR 3.91, 95 % CI 1.39–11.02, P = 0.010) as risk factors associated with increased severe infection. This study showed that MM patients who received bortezomib-based regimens are at a higher risk of severe infections within eight cycles of treatment during especially severe lymphocytopenic periods. MM patients treated with bortezomib-based regimens should be closely monitored for the development of infectious complications during lymphocytopenia.     

Minimally invasive spleen-preserving distal pancreatectomy: Does splenic vessel preservation have better postoperative outcomes? A systematic review and meta-analysis

BACKGROUND: Minimally invasive spleen-preserving distal pancreatectomy(SPDP) can be performed with either splenic vessel preservation(SVP) or resection [Warshaw procedure(WP)]. The aim of this study was to evaluate the postoperative clinical outcomes of patients undergoing both methods.DATA SOURCES: Database search of PubM ed, Embase, Scopus,Cochrane, and Google Scholar was performed(2000-2014); key bibliographies were reviewed. Qualified studies comparing patients undergoing SPDP with either SVP or WP, and assessing postoperative complications were included. Calculated pooled risk ratio(RR) with the corresponding 95% confidence interval(CI) by random effects methods were used in the meta-analyses. RESULTS: The search yielded 215 studies, of which only 14 observational studies met our selection criteria. The studies included 943 patients in total; 652(69%) underwent SVP and 291(31%) underwent WP. Overall, there was a lower incidence of splenic infarction(RR=0.17; 95% CI: 0.09-0.33; P0.001),gastric varices(RR=0.16; 95% CI: 0.05-0.51; P=0.002), and intra/postoperative splenectomy(RR=0.20; 95% CI: 0.08-0.49; P0.001) in the SVP group. There was no difference in incidence of pancreatic fistula(WP vs SVP, 23.6% vs 22.9%;P=0.37), length of hospital stay, operative time or blood loss. There was moderate cross-study heterogeneity.CONCLUSIONS: SVP is a safe, efficient and feasible technique that may be used to preserve the spleen. WP may be more suitable for large tumors close to the splenic hilum or those associated with splenomegaly. Randomized clinical trials are justified to examine the long-term benefits of SVP-SPDP.     

Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study

Although numerous reports indicate that patients receiving autotransplants for lymphoma are at increased risk for myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), the separate contributions of pretransplantation- and transplantation-related therapy are not well characterized. We conducted a case-control study of 56 patients with MDS/AML and 168 matched controls within a cohort of 2 739 patients receiving autotransplants for Hodgkin disease or non-Hodgkin lymphoma at 12 institutions (1989-1995). Detailed abstraction of medical records was undertaken to determine all pre- and posttransplantation therapy, and transplantation-related procedures. In multivariate analyses, risks of MDS/AML significantly increased with the intensity of pretransplantation chemotherapy with mechlorethamine (relative risks [RRs] = 2.0 and 4.3 for cumulative doses < 50 mg/m2 and > or = 50 mg/m,2 respectively; trend over dose categories, P =.04) or chlorambucil (RRs = 3.8 and 8.4 for duration < 10 months or > or = 10 months, respectively; trend, P =.009), compared with cyclophosphamide-based therapy. Transplantation-conditioning regimens including total-body irradiation (TBI) at doses 12 Gy or less did not appear to elevate leukemia risk (RR = 1.3; P =.48) compared with non-TBI regimens; however, a statistically significant increased risk was found for TBI doses of 13.2 Gy (RR = 4.6; P =.03). Peripheral blood stem cells were associated with a nonsignificant increased risk of MDS/AML (RR = 1.8; P =.12) compared with bone marrow grafts. Our data show that type and intensity of pretransplantation chemotherapy with alkylating agents are important risk factors of MDS/AML following autotransplantation. Transplantation-related factors may also modulate this risk; however, the apparent contribution of high-dose TBI requires confirmation.