Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis.

Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.

Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis.

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.

Antibiotic modification versus withhold in febrile patients without evidence of bacterial infection, unresponsive to initial empiric regimen: a multicentre retrospective study conducted in Israel.

Prescribing antibiotics for febrile patients without proof of bacterial infection contributes to antimicrobial resistance. Lack of clinical response in these patients often leads to antibiotic escalation, although data supporting this strategy are scarce. This study compared outcomes of modifying, withholding, or continuing the same antibiotic regimen for such patients. Febrile or hypothermic stable patients with suspected infection, unresponsive to empiric antibiotic treatment, admitted to one of 15 internal medicine departments in three hospitals during a 5-year study period, were included. Patients with a definitive clinical or microbiological bacterial infection, malignancy, immunodeficiency, altered mental status, or need for mechanical ventilation were excluded. Participants were divided into groups based on treatment strategy determined 72 h after antibiotic initiation: antibiotic modified, withheld or continued. Outcomes measured included in-hospital and 30-day post-discharge-mortality rates, length of hospital stay (LOS) and days of antimicrobial therapy (DOT). A total of 486 patients met the inclusion criteria: 124 in the Antibiotic modified group, 67 in the Antibiotic withheld group and 295 in the Initial antibiotic continued group. Patient characteristics were similar among groups with no differences in mortality rates in-hospital (23% vs. 25% vs. 20%, p = 0.58) and within 30 days after discharge (5% vs. 3% vs. 4%, p = 0.83). Changing antibiotics led to longer LOS (9.0 ± 6.8 vs. 6.2 ± 5.6 days, p = 0.003) and more DOT (8.6 ± 6.0 vs. 3.2 ± 1.0 days, p < 0.001) compared to withholding treatment. Withholding as compared to modifying antibiotics, in febrile patients with no clear evidence of bacterial infection, is a safe strategy associated with decreased LOS and DOT.

The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients: A decision analytic model.

PURPOSE: Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. METHODS: A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. RESULTS: The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. DISCUSSION: Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

Postimplantation Syndrome Is Not Associated with Myocardial Injury after Noncardiac Surgery after Endovascular Aneurysm Repair.

BACKGROUND: Postimplantation syndrome (PIS) is the clinical and biochemical expression of an inflammatory response following endovascular aneurysm repair (EVAR), with a reported incidence ranging from 2% to 100%. Although generally benign, some studies report an association between PIS and postoperative major adverse cardiovascular events (MACEs). Nonetheless, the role of PIS in postoperative myocardial injury after noncardiac surgery (MINS) is unknown. This work aims to evaluate the relationship between PIS and MINS in a subset of EVAR patients, as well as assess the impact of PIS in all-cause mortality. METHODS: All patients undergoing elective standard EVAR between January 2008 and June 2017, and with at least one measurement of contemporary (cTnI) or high sensitivity troponin I (hSTnI) in the first 48h after surgery, were retrospectively analyzed. PIS was defined as the presence of fever and leukocytosis in the postoperative period in the absence of infectious complications. MINS was defined as the value exceeding the 99th percentile of a normal reference population with a coefficient of variation <10%, which was >0.032 ng/mL for cTnI and 0.0114 (female) and 0.027 ng/mL (male) for hSTnI. Patients' demographics, comorbidities, medication, access, and anesthesia were also evaluated. RESULTS: One hundred thirty-three consecutive patients were included (95.5% male; mean age 75.66 ± 7.13 years). Mean follow-up was 46.35 months. Survival rate was 86.5%, 80.5%, and 57.6% at 1, 3, and 5 years of follow-up, with 2 fatalities at 30 days of follow-up. The prevalence of PIS was 11.4%. MACE occurred in 2.3% of the patients, while MINS was reported in 16.5% of the patients. No association was found between PIS and patients' gender, comorbidities, type of anesthesia, or transfusional support. The type of graft used significantly affected the prevalence of PIS, with all cases reported when polyester grafts were used (P = 0.031). MACE occurred in 2.3% of the patients, while MINS was reported in 16.5% of the patients. PIS was found to be significantly associated with postoperative MACE (P = 0.001), but not MINS. Survival analysis revealed no differences between patients with or without PIS regarding 30-day mortality as well as long-term all-cause mortality. American Society of Anesthesiologists score (hazard ratio [HR] 2.157, 95% confidence interval [CI] 1.07-4.33, P = 0.031) and heart failure (HR 2.284, 95% CI 1.25-4.18, P = 0.008) were found to be independently associated with increased long-term all-cause mortality in this cohort of patients. CONCLUSIONS: PIS is a common complication after EVAR, occurring in 11.4% of the patients from this cohort. Graft type seems to significantly affect the risk of PIS, since all reported cases occurred when polyester grafts were used. PIS did not influence 30-day or long-term survival and was found to be significantly associated with postoperative MACE but not MINS, suggesting the involvement of different pathophysiological mechanisms.

Infection at diagnosis-a unique challenge in acute myeloid leukemia treatment in developing world.

PURPOSE: A large number of AML patients present with infection at the time of initial presentation in Indian settings. There is lack of published data on the proportion of patients with infection at initial presentation and its impact on induction mortality. METHODS: A retrospective audit of patients with newly diagnosed AML more than 14 years of age, who underwent standard induction chemotherapy between the periods of January 2011 to December 2018, was done. Infection at presentation if any was documented. Induction mortality was defined as death happening within 28 days of starting induction chemotherapy. RESULTS: Among a total of 315 cases of AML, 96 (30%) patients underwent induction chemotherapy with 7 + 3 regimen. Documented infection at baseline was present in 30 (31%) of patients. Another 10 patients had fever at the time of presentation but without any documented infection focus. Fifteen patients died within 4 weeks of induction amounting to induction mortality of 15.6%. Induction mortality was 28% among patients with infection at baseline compared with 7% without baseline infections (P = 0.01). CONCLUSION: Around 40% of patients had fever at the time of presentation, and 31% had documented infections. Baseline infections led to increase in induction mortality. We would like to propose that infection at baseline is to be considered as one of the potential variables in the predictive scoring system for induction mortality in developing countries.

Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) occurs in neonates with disseminated infection of herpes simplex virus (HSV). Little has been reported on the control of rapid HLH progression. We studied the cytokine profile and genetic basis of two index cases with divergent outcomes after early treatment of type 2 HSV infection. One survivor had fever and elevated serum levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), interferon (IFN)-ß, and IFN-γ at diagnosis. The other neonate had no fever or TNF-α production, but significant IL-6 or IFN responses during the treatment course, and died 19 days after birth. Among 16 reported cases of neonatal HSV-HLH including index cases, eight deceased neonates experienced significantly less fever at presentation (p = 0.028), lower platelet counts (p = 0.019), and lower ratios of soluble IL-2 receptor (sIL-2R) to ferritin levels (p = 0.044) than eight survivors. The 100-day overall survival rates were significantly higher in patients with fever (p = 0.004), > 100 × 109/L of platelet counts (p = 0.035) or > 20 of sIL-2R/ferritin ratio at diagnosis (p = 0.004). The first febrile and cytokine responses to HSV infection predict the early outcome of neonatal HSV-HLH.

Association Between Postoperative Body Temperature and All-Cause Mortality After Off-Pump Coronary Artery Bypass Graft Surgery: A Retrospective Observational Study.

BACKGROUND: Inadvertent perioperative hypothermia is common in patients undergoing off-pump coronary artery bypass grafting (OPCAB). We investigated the association between early postoperative body temperature and all-cause mortality in patients undergoing OPCAB. METHODS: We reviewed the electronic medical records of 1714 patients who underwent OPCAB (median duration of follow-up, 47 months). Patients were divided into 4 groups based on body temperature at the time of intensive care unit admission after surgery (moderate-to-severe hypothermia, <35.5°C; mild hypothermia, 35.5°C-36.5°C; normothermia, 36.5°C-37.5°C; and hyperthermia, ≥37.5°C). Cox proportional hazards models were used to assess the association between body temperature and all-cause mortality. The association between early postoperative changes in body temperature and all-cause mortality was also assessed by dividing the patients into 4 categories according to the body temperature measured at postoperative intensive care unit admission and the average body temperature during the first 3 postoperative days. RESULTS: Compared to the normothermia group, the adjusted hazard ratios of all-cause mortality were 2.030 (95% confidence interval, 1.407-2.930) in the moderate-to-severe hypothermia group and 1.445 (95% confidence interval, 1.113-1.874) in the mild hypothermia group. Patients who were hypothermic at postoperative intensive care unit admission but attained normothermia thereafter were at a lower risk of all-cause mortality compared to patients who did not regain normothermia (adjusted hazard ratio, 0.631; 95% confidence interval, 0.453-0.878), while they were still at a higher risk of all-cause mortality than those who were consistently normothermic (adjusted hazard ratio, 1.435; 95% confidence interval, 1.090-1.890). CONCLUSIONS: Even mild early postoperative hypothermia was associated with all-cause mortality after OPCAB. Patients who regained normothermia postoperatively were at lower risk of all-cause mortality compared to those who did not.

Shock and Early Death in Hematologic Patients with Febrile Neutropenia.

Empirical antibiotic therapy with a beta-lactam is the standard of care in febrile neutropenia (FN) and is given to prevent early death. The addition of vancomycin is recommended in certain circumstances, but the quality of evidence is low, reflecting the lack of clinical data. In order to characterize the epidemiology of early death and shock in FN, we reviewed all episodes of FN from 2003 to 2017 at University Hospital, Federal University of Rio de Janeiro, and looked at factors associated with shock at first fever and early death (within 3 days from first fever) by univariate and multivariate analyses. Among 1,305 episodes of FN, shock occurred in 42 episodes (3.2%) and early death in 15 (1.1%). Predictors of shock were bacteremia due to Escherichia coli (odds ratio [OR], 8.47; 95% confidence interval [95% CI], 4.08 to 17.55; P < 0.001), Enterobacter sp. (OR, 7.53; 95% CI, 1.60 to 35.33; P = 0.01), and Acinetobacter sp. (OR, 6.95; 95% CI, 1.49 to 32.36; P = 0.01). Factors associated with early death were non-Hodgkin's lymphoma (OR, 3.57; 95% CI, 1.18 to 10.73; P = 0.02), pneumonia (OR, 21.36; 95% CI, 5.72 to 79.72; P < 0.001), shock (OR, 11.64: 95% CI, 2.77 to 48.86; P = 0.01), and bacteremia due to Klebsiella pneumoniae (OR, 5.91; 95% CI, 1.11 to 31.47; P = 0.03). Adequate empirical antibiotic therapy was protective (OR, 0.23; 95% CI, 0.07 to 0.81; P = 0.02). Shock or early death was not associated with Gram-positive bacteremia; catheter-related, skin, or soft tissue infection; or inadequate Gram-positive coverage. These data challenge guideline recommendations for the empirical use of vancomycin at first fever in neutropenic patients.

Work-up for Fever During Neutropenia for Both the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient.

Fever is a common complication in patients with underlying neutropenia and is associated with significant mortality in neutropenic patients with acute myelogenous leukemia or hematopoietic cell transplant. Fever may be the only sign of infection and requires further clinical assessment, including a history, a physical examination, and additional laboratory and radiographic testing. National and international guidelines recommend initiation of empiric antimicrobial therapy in patients with fever during neutropenia. Stepwise escalation of antibacterial therapy, followed by antifungal therapy for patients with persistent fever, generally is recommended. Consideration should also be given to de-escalation of antimicrobial therapy in the appropriate clinical settings.

Clinical characteristics and prognosis of idiopathic pulmonary hemosiderosis in pediatric patients.

OBJECTIVE: This study aimed to analyze the clinical characteristics and prognosis of pediatric idiopathic pulmonary hemosiderosis (IPH). METHODS: Pediatric IPH cases that were diagnosed at West China Second University Hospital, Sichuan University between 1996 and 2017 were reviewed. Follow-up data from 34 patients were collected. RESULTS: A total of 107 patients were included (42 boys and 65 girls). The median age was 6 years at diagnosis. The main manifestations of the patients were as follows: anemia (n = 100, 93.45%), cough (n = 68, 63.55%), hemoptysis (n = 61, 57%), fever (n = 23, 21.5%), and dyspnea (n = 23, 21.5%). There were relatively few pulmonary signs. The positive rates of hemosiderin-laden macrophages in sputum, gastric lavage fluid, and bronchoalveolar lavage fluid were 91.66%, 98.21%, and 100%, respectively. Seventy-nine patients were misdiagnosed. A total of 105 patients were initially treated with glucocorticoids, among whom 102 survived and three died. Among the followed up patients, two died and 32 survived, among whom 10 presented with recurrent episodes. CONCLUSIONS: The classic triad of pediatric IPH is not always present. The rates of misdiagnosis and recurrence of IPH are high. Early recognition and adequate immunosuppressive therapy are imperative for improving prognosis of IPH.

Methotrexate intoxication: Beyond the adverse events.

AIM: Methotrexate (MTX) is the first-line disease-modifying antirheumatic drug in rheumatoid arthritis (RA). However, this anchor may cause some side effects that may range from nausea to mortality. The clinical features of MTX toxicity are under-researched. In this study, we aimed to find out the potential predisposing factors and outcomes of the MTX toxicity (n = 31). METHODS: The data were collected from 31 patients whose ages ranged from 25 to 81 years, who were suffering from immune-mediated inflammatory diseases and major MTX-related toxicity. RESULTS: Out of 31 patients, six (19.4%) used MTX every day, and 13 (41.9%) patients had renal insufficiency who were admitted to the hospital because of mucositis (90.3%) and fever (71%). While using MTX, 27 patients (87.1%) were discharged after the treatment and four patients (12.9%) died. CONCLUSIONS: Although MTX has high efficacy for the toxicity ratio, wrong use and dosage of MTX may be harmful to patients. Thus, patients should be informed about the proper use of MTX.

Febrile events in acute lymphoblastic leukemia: a prospective observational multicentric SEIFEM study (SEIFEM-2012/B ALL).

The purpose of the present study is to estimate the current incidence of febrile events (FEs) and infectious episodes in acute lymphoblastic leukemia (ALL) and evaluate the outcome. We analyzed data on all FEs in a cohort of patients affected by ALL admitted to 20 Italian hematologic centers during 21 months of observation from April 1, 2012 to December 31, 2013. Data about treatment phase, steroids, neutropenia, type and site of infection, and outcome of infection were collected. The population comprehended 271 ALL adult patients. Median age was 46 years old (range 19-75), M/F 1.1:1. We collected 179 FEs occurring during 395 different phases of treatment in 127 patients (45.3% incidence): remission induction treatment 53.1%, consolidation/maintenance 35.7%, treatment for a first or second relapse 44.3%, and refractory disease 85.7%. The incidence of FUO (fever of unknown origin) was 55/395 (13.9%). In the remaining cases, bacteria caused 92 FEs (23.2%), fungi 17 (4.3%), viruses 5 (1%). Mixed infections occurred in 10 cases mainly fungal+bacterial (9/10 cases). Neutropenia was mostly present at onset of FE (89.9% of FEs). Mortality rate was 11.7% (21/179) while 16 deaths occurred with evidence of infection (8.9%). Age > 60 years, neutropenia, poor performance status, steroids, refractory disease, and mixed infections significantly correlated with infection-related mortality. A statistically significant association with mortality was observed also for pulmonary localization and bacteremia. Our study describes the real-life epidemiological scenario of infections in ALL and identifies a subset of patients who are at higher risk for infection-related mortality.

Patterns of infectious complications in acute myeloid leukemia and myelodysplastic syndromes patients treated with 10-day decitabine regimen.

Decitabine has been explored as a reduced-intensity therapy for older or unfit patients with acute myeloid leukemia (AML). To better understand the risk of infections during decitabine treatment, we retrospectively examined the culture results from each infection-related serious adverse event that occurred among 85 AML and myelodysplastic syndromes (MDS) patients treated in a prospective clinical study using 10-day cycles of decitabine at Washington University School of Medicine. Culture results were available for 163 infection-related complications that occurred in 70 patients: 90 (55.2%) events were culture-negative, 32 (19.6%) were gram-positive bacteria, 20 (12.3%) were gram-negative bacteria, 12 (7.4%) were mixed, 6 (3.7%) were viral, 2 (1.2%) were fungal, and 1 (0.6%) was mycobacterial. Infection-related mortality occurred in 3/24 (13%) of gram-negative events, and 0/51 gram-positive events. On average, nearly one third of patients experienced an infection-related complication with each cycle, and the incidence did not decrease during later cycles. In summary, in patients receiving 10-day decitabine, infectious complications are common and may occur during any cycle of therapy. Although febrile events are commonly culture-negative, gram-positive infections are the most frequent source of culture-positive infections, but gram-negative infections represent a significant risk of mortality in AML and MDS patients treated with decitabine.

Neutropenic Fever.

Fever is a common presenting complaint among adult or pediatric patients in the emergency department setting. Although fever in healthy individuals does not necessarily indicate severe illness, fever in patients with neutropenia may herald a life-threatening infection. Therefore, prompt recognition of patients with neutropenic fever is imperative. Serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients. Neutropenic fever should trigger the initiation of a rapid work-up and the administration of empiric systemic antibiotic therapy to attenuate or avoid the progression along the spectrum of sepsis, severe sepsis, septic shock syndrome, and death.

Granulocyte transfusion experience in pediatric neutropenic fever: Splitted product can be an alternative?

The granulocyte transfusion (GTX) has been used for a long time due to uncontrolled neutropenic fever with antimicrobial agents. In some cases, the product needs to be splitted for using in the next 12 hours. The aim of this study is to evaluate the efficacy of splitted product and clinical response to GTX. In this study, 15 patients with malignancy with 19 neutropenic fever, who had received 56 GTX, were included. Seventeen of 56 GTX were splitted and used in maximum 12 hours during infections which did not respond to antibacterial and antifungal therapy in 7 days. The patients were divided in to response groups as a complete, partial and progressive. The predictive factors for response group were evaluated. GTX were well tolerated in all patients. The median granulocyte dose was 1.26 (0.38-5.22) × 10(9)/kg. Total response rate was 89.5%. The infection-related mortality rate was 10.5%. Although the granulocyte doses are the same in both of the product groups, an hour later ANC increment of primer product was higher than that of splitted product (p = 0.001). Among the products, 48.7% of primer product and 17.6% of splitted product had induced ≥ 1000/mm(3) ANC increment after an hour (p = 0.039). Granulocyte transfusion is safe and effective in controlling the febrile neutropenia attack. GTX should be applied in a short time to provide effective ANC increment. For now, main granulocyte product instead of splitted product should be preferred in case of uncontrolled neutropenic fever with antibacterial/antifungal agents.

Effects of lethal dose of γ-radiation and partial body hyperthermia on Wistar rats.

PURPOSE: The radioprotectors currently available are generally poorly tolerated in human beings; thus, their use has been restricted due to their side effects and their limited clinical tolerance. In a search for fewerand/or without side effects agents, the radioprotective effects of partial body hyperthermia (PBH) were tested on Wistar rats of both sexes at different ages. MATERIALS AND METHODS: PBH (43 °C, 1 h) was carried out by immersion of each animal's lower parts and legs in a thermostatically controlled water bath 20 h prior to irradiation with a lethal single exposure dose of 9 Gy of gamma irradiation. Irradiated PBH pretreated animals were monitored for 30 days post-irradiation and survival percentages were calculated. RESULTS: The data obtained provide evidence that PBH treatment prolonged the irradiated rats' lifespans and the mortality rates varied significantly with animal age and sex. In addition, PBH treatment significantly enhanced bone marrow recovery of irradiated rats of both genders. CONCLUSIONS: Partial body hyperthermia prior to radiation proved to have beneficial effects on gamma irradiated rats.

Fever, infection, and rejection after kidney transplant failure.

BACKGROUND: Patients returning to dialysis therapy after renal transplant failure have high morbidity and retransplant rates. After observing frequent hospitalizations with fever after failure, it was hypothesized that maintaining immunosuppression for the failed allograft increases the risk of infection, while weaning immunosuppression can lead to symptomatic rejection mimicking infection. METHODS: One hundred eighty-six patients with failed kidney transplants were analyzed for rates of hospitalization with fever within 6 months of allograft failure. Patients were stratified by the presence of full immunosuppression versus minimal (low-dose prednisone) or no immunosuppression, before hospital admission. Subsequent rates of documented infection and nephrectomy, as well as patient survival, were ascertained. RESULTS: Hospitalization with fever within 6 months of allograft failure was common, occurring in 44% of patients overall. However, among febrile hospitalized patients who had been weaned off of immunosuppression before admission, only 38% had documented infection. In contrast, 88% of patients maintained on immunosuppression had documented infection (P<0.001). In both groups, dialysis catheter-related infections were the most common infection source. Allograft nephrectomy was performed in 81% of hospitalized patients with no infection, compared to 30% of patients with documented infection (P<0.001). Mortality risk was significantly higher in patients with concurrent pancreas transplants or who were hospitalized with documented infection. CONCLUSIONS: Maintenance immunosuppression after kidney allograft failure was associated with a greater incidence of infection, while weaning of immunosuppression commonly resulted in symptomatic rejection with fever mimicking infection on presentation. Management of the failed allograft should include planning to avoid both infection and sensitizing events.

Euthermic endocarditis.

BACKGROUND: Most patients with infective endocarditis (IE) manifest fever. Comparison of endocarditis patients with and without fever, and whether the lack of fever in IE is a marker for poorer outcomes, such as demonstrated in other severe infectious diseases, have not been defined. METHODS AND RESULTS: Cases from the Mayo Clinic, Rochester, Minnesota, Division of Infectious Diseases IE registry, a single-center database that contains all cases of IE treated at our center. Diagnosis date between 1970 and 2006, which met the modified Duke criteria for definite endocarditis, without fever was included. There were 240 euthermic endocarditis cases included in this analysis, with 282 febrile controls selected by frequency matching on gender and decade of diagnosis. Euthermic patients had a median age of 63.6 years (± 16.1) as compared to 59.0 years (± 16.4) in the febrile control group (p=0.001). Median (IQR) symptom duration prior to diagnosis was 4.0 (1.0, 12.0) weeks in the euthermic group compared to 3.0 (1.0, 8.0) weeks in the febrile controls (p= 0.006). From unadjusted analyses, survival rates were 87% in euthermic cases versus 83% in febrile controls across 28-day follow-up (p=0.164), and 72% in euthermic group cases versus 69% in febrile controls across 1-year follow-up (p=0.345). Also unadjusted, the 1-year cumulative incidence rate of valve surgery was higher in euthermic cases versus febrile controls (50% vs. 39%, p= 0.004). CONCLUSIONS: Patients with euthermic endocarditis are older, and lack of fever was associated with longer symptom duration and delayed diagnosis prior to IE diagnosis. Despite a higher unadjusted rate of valve surgery in euthermic patients, the result was not significant when adjusting for baseline confounders. Differences in survival rates at both 28-days and 365-days were not statistically significant between the two groups.

Iatrogenia institucional y muerte materna: semmelweis y la fiebre puerperal / Institutional iatrogeny and maternal death: semmelweis and puerperal fever

La fiebre puerperal es una enfermedad que asume carácter epidémico en el siglo XVIII como consecuencia de dos factores: las masas trabajadoras urbanas generadas por la revolución industrial, y la progresiva hegemonización y medicalización de la atención del parto en grandes hospitales públicos. La mortalidad materna institucionalizada alcanza cifras superiores al 30%, en tanto con la atención por parteras es menor al 2%. Semmelweis, médico húngaro, postula que los médicos contaminaban a las parturientas por insuficiente higiene luego de realizar necropsias, e implanta medidas profilácticas en el Hospital de Viena, las cuales reducen dramáticamente la mortalidad, pero sus ideas son rechazadas por que afectan el proceso de institucionalización de la medicina basado en el altruismo y honor, por los que supuestamente era imposible que causen daño a sus pacientes. Es obligado a retirarse del Hospital de Viena, y continua su lucha en Budapest, pero el rechazo y la incomprensión de sus colegas por su doctrina afecta su salud mental. Muere en un asilo, pocos años antes que Pasteur y Koch demuestren las bacterias causantes de enfermedades como la fiebre puerperal.

Puerperal fever is a disease that becomes epidemic in the eighteenth century as a result of two factors: the urban working masses generated by the industrial revolution and the progressive hegemonization and medicalization of birth care in large public hospitals. Institutionalized maternal death reached figures above 30%, while in the case of birth care provided by midwives, it was than 2%. Semmelweis, an Hungarian physician, sustained that physicians contaminated women in labor due to insufficient hygiene after performing necropsies and established prophylactic measures in the Vienna Hospital that reduced mortality dramatically. However, his ideas were rejected because they affected the institutionalization process of medicine, based on altruism and honor, which would make it impossible to cause harm to patients. He was forced to leave Vienna Hospital and he continued his struggle in Budapest, but the rejection and disagreement of his peers with his doctrine affected his mental health. He died in an asylum, a few years before Pasteur and Koch proved the existence of the bacteria that caused diseases such as puerperal fever.