Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study.

BACKGROUND: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. METHODS: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. RESULTS: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. CONCLUSIONS: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.

High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients.

OBJECTIVE: Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. METHODS: Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 µg/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome. RESULTS: Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104-335) and 331 (140-476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment. CONCLUSION: Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ.

Regional Anesthesia in a Patient With Shprintzen-Goldberg Syndrome: A Case Report.

Shprintzen-Goldberg syndrome (SGS) is a rare condition characterized by craniofacial, cardiac, and neurologic alterations that can challenge an anesthesiologist. There are a few case reports of pediatric patients with SGS receiving general anesthesia but none about other techniques. A patient with SGS and insufficient dura mater was once reported, and this has caused some anesthesiologists to be wary of regional anesthesia. However, the link between SGS and insufficient dura mater remains unclear. We report the case of a 19-year-old patient with SGS who safely underwent an open cholecystectomy with regional anesthesia.

Liver metastases of colorectal adenocarcinoma with intrahepatic biliary spread pattern: clinical manifestation and importance of immunohistochemical analysis.

Liver metastases of colorectal carcinoma (LMCC) with macroscopic intrabiliary ductal involvement are a rare entity that can clinically and radiologically mimic a cholangiocarcinoma. However, a thorough anatomopathologic and immunohistochemical study of biliary ductal involvement is required because of its distinctive clinical features and relatively indolent biological behavior, reflecting a better prognosis and long-term survival. We present the case of a patient who debuted with LMCC with intrahepatic biliary ductal involvement, whose definitive diagnosis was established by immunohistochemical analysis, showing a characteristic CK7 - /CK20 + pattern.

Does Experiencing Racialized Aggressions on Social Media Influence Perceptions About the Campus Racial Climate?

The purpose of this study was to use structural equation modeling to examine how the experience of racialized aggressions on social media influenced the perceptions of campus racial climate for undergraduate students of color (n = 771). Findings suggest that students who experienced racialized aggressions on social media did report less positive perceptions of campus diversity climate. Given that in-person and online environments are growing evermore seamless for students, this has implications for campus climate and diversity programming.

Risk factors for relapse after complete remission with high-dose therapy for multiple myeloma.

Complete remission (CR) is an important surrogate for long-term survival for patients with multiple myeloma. However, most patients achieving CR eventually relapse and die from their disease. To better define the predictors of relapse, we conducted a retrospective review of outcomes for patients who achieved CR after autografting at our institution. From January 1990 to December 2002, among >400 patients transplanted, 81 (54 males and 27 females) achieved CR. With a median follow up of 58 months for all surviving patients, the 5-year progression-free survival (PFS) was 33% [95% confidence interval (CI) = 23 - 44] and 5-year overall survival (OS) was 67% (95% CI = 54 - 77). Median PFS was 37 months and median OS has not yet been reached. On multivariate analysis, high tumor mass at diagnosis emerged as a predictor of poor outcome. We conclude that high tumor mass at diagnosis predicts a significantly shorter remission duration for myeloma patients undergoing autografting.

Autologous and allogeneic stem cell transplantation in Waldenstrom's macroglobulinemia: review of the literature and future directions.

Waldenstrom's macroglobulinemia (WM) is a chronic lymphoproliferative disorder characterized by lymphoplasmacytic infiltrate and a monoclonal IgM serum peak. Treatment includes cytotoxic chemotherapy with alkylators, or purine nucleoside analogues and monoclonal anti-CD20 antibody. The role of stem cell transplantation (SCT) in WM has not been established. We identified 24 published cases of WM treated with high-dose chemotherapy (HDC) followed by autologous SCT (ASCT). The median age was 50 years; half of the patients had refractory disease and received a variety of preparative regimens. Nine complete and 14 partial responses were observed, with one early death. Fifteen patients were alive and well at follow-ups ranging from 1 to 132 months. Six additional patients, with a median age of 45 years (range, 30 to 62), who received allogeneic SCT have been reported. All were heavily pretreated with refractory or relapsed disease. Median time from diagnosis to transplant was 3.1 years (range, 1.3 to 7). Two patients died of complications of the procedure while one died of disease progression. Three patients were alive and well between 5 and 112 months post-transplant. The small number of reported patients precludes any significant conclusion except that SCT is feasible in WM and long-term disease control can be achieved in selected patients with autologous or allogeneic SCT, even in those with refractory disease.

Nonmyeloablative reduced-intensity transplantation in multiple myeloma.

Reduced-intensity conditioning (RIC) allogeneic transplants are being performed more frequently in a variety of hematologic malignancies. The aim is to exploit the graft-versus-tumor (GVT) effect seen after allografting without the toxicities of myeloablative conditioning. RIC regimens are being extensively explored for salvage therapy of myeloma. Although nonrelapse mortality rates are acceptable, relapse remains the most common cause of treatment failure. New combinations and novel therapies need to be explored to improve outcomes. This strategy should also be employed earlier in the course of the disease.

High-dose topotecan, melphalan and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of multiple myeloma.

The goal of this trial was to assess the toxicity and potential efficacy of high-dose topotecan, melphalan and cyclophosphamide as a preparative regimen for patients with multiple myeloma undergoing autologous stem cell transplantation. Eighteen patients were treated, 8 for first remission consolidation, 4 with relapse sensitive disease, 3 primary refractory and 3 relapsed refractory. The median age was 56 (38 - 65) and the median number of prior regimens was 3 (1 - 8). Patients received cyclophosphamide 1 g/m2/d on days -6, -5, -4; melphalan 70 mg/m2 on days -3, -2 and topotecan 3.0 to 3.5 mg/m2/d on days -6 to -2. Peripheral blood stem cells were infused on day 0. Toxicity (Bearman Toxicity Criteria) was mostly limited to grade 1 - 2 mucositis and grade 1 diarrhea. There were no transplant-related deaths. The overall response rate at 3 months post transplantation was 89% with 17% CR, 2 of those in refractory patients. The overall response rate in refractory patients was 67%. With a median follow up of 12.3 months, 89% of patients are alive. The TMC regimen is well tolerated and produces high response rates. Further evaluation of TMC to fully assess response and survival is ongoing.

Anaphylactoid reaction caused by moxifloxacin.

We report on a patient who suffered an anaphylactoid reaction because of moxifloxacin.

Symptoms and quality of life in diverse patients undergoing hematopoietic stem cell transplantation.

CONTEXT: Symptoms and quality of life (QOL) are critically important in hematopoietic stem cell transplantation (HSCT). However, few studies have examined these factors by transplant type among diverse cultures. OBJECTIVES: To identify and compare QOL and symptom severity and prevalence by transplant type in a diverse population having HSCT. METHODS: The M. D. Anderson Symptom Inventory Blood and Marrow Transplantation (MDASI-BMT) module measured symptom severity and its impact. The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) measured QOL. RESULTS: Symptom data were collected from 164 patients at eight points (pretransplant to 100 days post-transplant) and QOL data at four times. Over time, symptom severity was significantly correlated with QOL and patients who had allogeneic transplants with myeloablative regimens showed more severe sleep disturbance and poorer QOL than patients having autologous transplants. Male patients reported less fatigue than female patients. However, ethnicity was not significant. Patients whose functional status was good had fewer of the five worst symptoms and higher QOL than patients with a poor functional status. Patients with acute graft-versus-host disease had more severe symptoms than those who did not. CONCLUSION: Type of transplant and preparative regimen are the most important aspects to consider when managing symptoms and QOL. This information is important for providing anticipatory guidance and support needed during the transplantation experience, to explore in future research the mechanisms involved in symptoms after HSCT, and to develop additional effective interventions.

Symptom burden after autologous stem cell transplantation for multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is the most common indication for high-dose chemotherapy with autologous stem cell transplantation (ASCT) in the U.S. and can be associated with substantial morbidity. Thorough assessment and understanding of symptoms and risk factors for symptom development after ASCT are logical first steps toward developing strategies aimed at reducing the symptom burden associated with this procedure. METHODS: The authors performed a prospective evaluation of symptom burden among 64 patients with myeloma who underwent ASCT. Symptom data were collected using the M. D. Anderson Symptom Inventory (MDASI) at 4 time points: baseline, the day of stem cell infusion (Day 0), nadir of counts, and Day 30. Univariate analysis was performed to correlate pretransplantation variables with post-transplantation symptom burden at these time points. RESULTS: MDASI scores increased significantly throughout transplantation, with most patients returning to baseline by Day 30 after the procedure. Patients with the highest MDASI scores at baseline had the highest MDASI scores at nadir (P= .02). Patients with prolonged time to transplantation and women had a trend toward higher nadir global symptom severity scores. These groups, as well as patients aged >60 years, had a trend toward higher nadir interference scores. CONCLUSIONS: ASCT for MM was associated with significant but reversible symptom burden during the first 30 days, and the baseline symptom burden was the most important predictor of symptom burden after transplantation. The MDASI was useful as a tool for following the symptom burden associated with ASCT and may be used to evaluate interventions aimed at reducing transplantation-related morbidity in these patients.

Results of a retrospective single institution analysis of targeted skeletal radiotherapy with (166)Holmium-DOTMP as conditioning regimen for autologous stem cell transplant for patients with multiple myeloma. Impact on transplant outcomes.

(166)Holmium-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high-dose radiation to the bone marrow. Phase I/II trials showed feasibility and tolerability when combined with high-dose melphalan with or without total-body irradiation (TBI) in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). The purpose of this study was to define the potential impact of (166)Holmium-DOTMP on outcomes in patients with MM undergoing ASCT. Retrospective review of transplant outcomes among patients with MM who received an ASCT between January 1998 to December 2001 with either melphalan 200 mg/m(2) or a (166)Holmium-DOTMP containing regimen as part of their initial therapy. Univariate analysis was performed for response, overall survival (OS), and event free survival (EFS). One hundred four patients were identified, of which 41 received a (166)Holmium-DOTMP containing regimen and 63 received melphalan alone. The (166)Holmium-DOTMP patients were divided into 2 groups according to the dose received (<2400 mCi versus > or = 2400 mCi). The (166)Holmium-DOTMP group had a trend towards a higher complete remission (CR) rate compared to patients receiving melphalan alone (51% versus 32%). The median EFS for the low-dose (166)Holmium-DOTMP, the high-dose (166)Holmium-DOTMP, and melphalan alone was 30, 23, and 19 months, respectively; the OS rate at 5 years for the 3 groups was 61%, 40%, and 43%, respectively. (166)Holmium-DOTMP, in combination with high-dose melphalan, can result in higher CR rates when given in optimal doses (<2400 mCi) when compared to melphalan alone, and should be further tested in phase III trials in patients with MM undergoing ASCT.

Transplant-associated microangiopathy in patients receiving tacrolimus following allogeneic stem cell transplantation: risk factors and response to treatment.

Transplant-associated microangiopathy (TAM) is a life-threatening complication after allogeneic HSCT, particularly with the use of calcineurin inhibitors as post-transplantation immunosuppressive therapy. We report our experience with TAM after HSCT with tacrolimus-based GVHD prophylaxis in a single-center study. Sixty-six of 1219 transplant recipients developed TAM with a cumulative incidence of 5.9%. Risk factors for TAM were female gender, lymphoid malignancy, receipt of a matched unrelated donor, and grade II-IV aGVHD. Most patients had infection and/or active GVHD at the diagnosis of TAM (82%). In the absence of renal dysfunction or encephalopathy, tacrolimus was generally continued, maintaining blood levels within the lower therapeutic range. Sixty-three patients were treated with plasma exchange. The cumulative incidence of response of TAM was 60%. Only 1 patient had a response of TAM without resolution of concomitant infections or GVHD. Six-month survivals were 0% and 50% for TAM nonresponders and responders, respectively. In conclusion, TAM is a common, life-threatening complication of allogeneic hematopoietic transplantation using tacrolimus prophylaxis. Control of TAM generally requires response of associated infections and GVHD. TMA response may occur despite continuation of tacrolimus treatment.

Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma.

BACKGROUND: Most patients undergoing high-dose therapy and autologous transplant for multiple myeloma eventually develop a disease recurrence. However, to the authors' knowledge, the optimal salvage treatment for these patients is not well defined. Both autologous and allogeneic hematopoietic stem cell transplantations have been used for salvage therapy. The outcomes of salvage autologous or allogeneic transplants were analyzed retrospectively in patients relapsing after an autograft. METHODS: Fourteen patients (median age, 52 yrs) received a second autograft for salvage, whereas 26 patients (median age, 51 yrs) underwent a reduced-intensity allogeneic transplantation (related in 18 patients and unrelated in 8 patients). The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The two groups were evenly matched with regard to other disease characteristics. RESULTS: After a median follow-up of 18 months for the autologous group and 30 months for the allogeneic group, the median progression-free survival (PFS) and overall survival (OS) in the 2 groups were 6.8 months versus 7.3 months and 29 months versus 13 months, respectively. Acute and chronic graft versus host disease (15%) was the most common cause of non-recurrence mortality in the allogeneic group and infections (14%) in the autologous group. On univariate analysis, an interval of > 1 year between the first and the salvage transplant predicted a better OS in the allogeneic group. CONCLUSIONS: Both autografting and allografting are feasible as salvage therapy for myeloma patients who develop disease recurrence after the first autograft, although disease progression remains the major cause of failure. Better approaches are needed for salvage therapy in patients developing disease recurrence after an autograft.

Comparison of high-dose melphalan with a more intensive regimen of thiotepa, busulfan, and cyclophosphamide for patients with multiple myeloma.

BACKGROUND: High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) as part of the initial treatment regimen improves progression-free survival (PFS) and overall survival (OS) for patients with multiple myeloma. The optimal preparative regimen for patients with multiple myeloma has yet to be defined. In the current study, the authors compared the outcomes associated with high-dose melphalan (HDM) and a more intensive regimen of thiotepa, busulfan, and cyclophosphamide (TBC) in patients with multiple myeloma. METHODS: One hundred eighty-six patients with newly diagnosed multiple myeloma (median age, 51 years) received HDC with ASCT for consolidation of first remission (n = 108) or for treatment of primary refractory disease (n = 78). Seventy patients had a large tumor mass at the time of diagnosis. The preparative regimen consisted of TBC for 97 patients and HDM for 89 patients. Patients in the TBC group were younger and had more advanced disease stage at diagnosis and at the time of ASCT compared with patients in the HDM group. RESULTS: The response rates (complete response [CR] and partial response [PR]) were similar in the TBC group (overall response rate, 66%; CR rate, 17%; PR rate, 49%) and the HDM group (overall response rate, 69%; CR rate, 28%; PR rate, 41%). PFS and OS were similar in both groups. A proportional hazards regression model revealed that Durie-Salmon disease stage at diagnosis and having received three or more previous treatment regimens were the only factors that predicted PFS; the type of preparative regimen did not influence outcome. CONCLUSIONS: The results of the current study indicate that the use of a more intensive regimen did not improve results compared with HDM in patients with multiple myeloma. HDM should continue to be considered the standard preparative regimen for patients with myeloma.

Allergy to kiwi: a double-blind, placebo-controlled food challenge study in patients from a birch-free area.

BACKGROUND: Allergy to kiwi fruit is being increasingly reported, but it has never been evaluated by means of a double-blind, placebo-controlled food challenge (DBPCFC) study. OBJECTIVE: We sought to assess kiwi allergy on the basis of a DBPCFC and identify the patterns of allergen recognition in sensitized patients from a birch-free area. METHODS: Forty-three patients with allergy symptoms who were sensitized to kiwi were evaluated by means of clinical history, skin tests, IgE determinations, and DBPCFCs. The pattern of allergen recognition was assessed by means of IgE immunoblotting. Sequence analysis of IgE-binding bands was performed by using Edman degradation. RESULTS: DBPCFCs were performed in 33 patients; 4 patients had experienced severe anaphylaxis, and 6 patients declined informed consent. DBPCFC results were positive in 23 patients and negative in 10 patients. The most frequent clinical manifestation was oral allergy syndrome. Twenty-one percent of the patients were not allergic to pollen. Forty-six percent of patients experienced systemic symptoms, and this happened with higher frequency in patients not allergic to pollen (100%). Twenty-eight percent of the patients were sensitized to latex. The IgE-binding bands in kiwi extract more frequently recognized by patient sera were those of 30, 24, 66, and 12 kd, and they could not be associated with any pattern of kiwi-induced allergic reactions. CONCLUSION: The results provide evidence that kiwi allergy is not a homogeneous disorder because several clinical subgroups can be established. No definite allergen-recognition pattern was associated with the type of allergic reactions to kiwi. One of 5 patients with kiwi allergy was not allergic to pollen, and these patients had the highest risk of systemic reactions to kiwi.