Ehrlichia-induced hemophagocytic lymphohistiocytosis after autologous stem cell transplant.

Hemophagocytic lymphohistiocytosis (HLH) causes multiorgan failure due to the release of multiple cytokines mediating widespread inflammation. We present a patient with multiple myeloma on maintenance chemotherapy with the anti-CD38 monoclonal antibody daratumumab after autologous stem cell transplant (ASCT) who developed fatal HLH secondary to Ehrlichiosis.

Bacteremias following autologous stem cell transplantation for multiple myeloma: Risk factors and outcomes.

BACKGROUND: Autologous stem cell transplantation (ASCT) is a commonly used treatment for multiple myeloma (MM). This retrospective cohort study characterizes the risk factors and outcomes associated with bacteremia following ASCT at a single center. METHODS: We conducted a retrospective analysis in subjects who underwent ASCT for multiple myeloma and other malignancies from May 2014 to March 2015 at a single center. The control cohort included all subjects undergoing ASCT in the same time period who did not develop bacteremia. RESULTS: During the study period, 363 ASCTs were completed in 282 discrete patients. Bacteremia was documented in 13% of all transplants. Enterococcus faecium was the most frequent species overall (14/62, 23%). Vancomycin resistance was present in 93% of E faecium isolates. Bacteremia was associated with a significantly decreased survival in patients who received their transplant after the first year of myeloma treatment. Overall survival (OS) was not significantly different in the two cohorts among patients undergoing ASCT within the first year of myeloma treatment. Survival analysis showed a significantly decreased OS in patients who developed Enterococcus bacteremia as compared to the non-bacteremia cohort. Enterococcal bacteremia was associated with significantly longer duration of neutropenia (mean 14 vs 9.7 days, P = 0.01), hospitalization (mean 61.7 vs 20.4 days, P = 0.0006), and higher mortality (69% vs 25%, P = 0.01) as compared to other bacteremias. CONCLUSION: We found a high incidence of E faecium and a low incidence of MRSA and Pseudomonas bacteremias following ASCT in our patient population. Survival analysis in our cohort suggests that the effect of underlying disease status and cumulative chemotherapy is critically important in determining outcomes related to bacteremia. Enterococcal bacteremias following ASCT were associated with significantly higher morbidity and mortality than non-enterococcal bacteremias.

Psychological and demographic factors associated with fatigue and social adjustment in young people with severe chronic fatigue syndrome/myalgic encephalomyelitis: a preliminary mixed-methods study.

This mixed-methods study investigated factors associated with fatigue, disability and school attendance in young people with severe CFS/ME. Participants' illness experiences were also explored. Questionnaires were completed at baseline (T1) and approximately 5 months later (T2). There were 51 participants aged between 12 and 25, with a mean age of 18.8 years (SD 3.4). At T1, participants reported severe fatigue and poor social adjustment. Stronger fear avoidance beliefs at T1 were associated with higher fatigue at T2, and with worse social adjustment at T1 and T2. Female gender was associated with lower work/school attendance at T1 and T2 but not with higher fatigue or worse social adjustment. Having accessed treatment was associated with reporting lower levels of work/school attendance at T1 and T2. Multivariate analyses of key outcomes identified significant associations between stronger fear avoidance beliefs and worse social adjustment at T2, and between female gender and lower work/school attendance at T2. It was clear from the qualitative data that severe CFS/ME negatively impacted on many aspects of young people's lives. Fearful beliefs about activity could be targeted using cognitive-behavioural interventions.

Genome-Based Comparison of Clostridioides difficile: Average Amino Acid Identity Analysis of Core Genomes.

Infections due to Clostridioides difficile (previously known as Clostridium difficile) are a major problem in hospitals, where cases can be caused by community-acquired strains as well as by nosocomial spread. Whole genome sequences from clinical samples contain a lot of information but that needs to be analyzed and compared in such a way that the outcome is useful for clinicians or epidemiologists. Here, we compare 663 public available complete genome sequences of C. difficile using average amino acid identity (AAI) scores. This analysis revealed that most of these genomes (640, 96.5%) clearly belong to the same species, while the remaining 23 genomes produce four distinct clusters within the Clostridioides genus. The main C. difficile cluster can be further divided into sub-clusters, depending on the chosen cutoff. We demonstrate that MLST, either based on partial or full gene-length, results in biased estimates of genetic differences and does not capture the true degree of similarity or differences of complete genomes. Presence of genes coding for C. difficile toxins A and B (ToxA/B), as well as the binary C. difficile toxin (CDT), was deduced from their unique PfamA domain architectures. Out of the 663 C. difficile genomes, 535 (80.7%) contained at least one copy of ToxA or ToxB, while these genes were missing from 128 genomes. Although some clusters were enriched for toxin presence, these genes are variably present in a given genetic background. The CDT genes were found in 191 genomes, which were restricted to a few clusters only, and only one cluster lacked the toxin A/B genes consistently. A total of 310 genomes contained ToxA/B without CDT (47%). Further, published metagenomic data from stools were used to assess the presence of C. difficile sequences in blinded cases of C. difficile infection (CDI) and controls, to test if metagenomic analysis is sensitive enough to detect the pathogen, and to establish strain relationships between cases from the same hospital. We conclude that metagenomics can contribute to the identification of CDI and can assist in characterization of the most probable causative strain in CDI patients.

Possible Transfusion-Transmitted Babesia divergens-like/MO-1 Infection in an Arkansas Patient.

A patient with asplenia and multiple red blood cell transfusions acquired babesiosis infection with Babesia divergens-like/MO-1 organisms and not Babesia microti, the common United States species. He had no known tick exposure. This is believed to be the first transfusion-transmitted case and the fifth documented case of B. divergens-like/MO-1 infection.

Skin lesion in a patient with acute myeloid leukemia.

We present the case of a 51-year-old man with acute myeloid leukemia who developed fevers with a skin lesion following the first cycle of induction chemotherapy. Skin biopsy showed evidence of invasive fungal infection. Cultures remained negative, but polymerase chain reaction on tissue detected Rhizopus oryzae complex. The patient was started on liposomal amphotericin B and underwent surgical debridement. He was switched to posaconazole, with plans for allogeneic hematopoetic stem cell transplant in the future.

Cytomegalovirus appendicitis after hematopoietic stem cell transplantation.

We present the case of a young man with acute lymphoblastic leukemia who developed cytomegalovirus (CMV) appendicitis after receiving alemtuzumab for acute refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT). CMV appendicitis is a rare complication; and we are reporting the first case to our knowledge of CMV appendicitis following HSCT. Our case highlights the importance of recognition of CMV viral reactivation following the use of alemtuzumab. Using a preemptive strategy of checking CMV PCR, with initiation of early effective treatment on detection of CMV replication, may be appropriate following use of alemtuzumab in hematologic malignancies in patients after HSCT.

Guided Self-Help for Patients with Chronic Fatigue Syndrome Prior to Starting Cognitive Behavioural Therapy: a Cohort Study.

BACKGROUND: Previous research suggests that minimal interventions such as self-help guidance can improve outcomes in patients with fatigue or chronic fatigue syndrome (CFS). AIMS: The aim of the current study was to investigate whether self-help guidance could improve physical functioning, social adjustment and fatigue in a group of patients with CFS who were awaiting CBT at a clinic in secondary care. METHOD: Patients completed questionnaires at their initial assessment (baseline), immediately before beginning CBT (pre-treatment), and after their last session of CBT (end of treatment). The primary outcome was physical functioning, and the secondary outcomes were social adjustment and fatigue. Multi-level linear models were used to assess change over time after adjustment for gender and age. RESULTS: Multi-level models revealed that from baseline to pre-treatment, patients showed statistically significant improvements in physical functioning, but there were no statistically significant improvements in fatigue or social adjustment. However, all the primary and secondary outcomes showed statistically significant changes after CBT. CONCLUSIONS: The findings of this study indicate that self-help guidance may be beneficial for patients with CFS who are awaiting CBT treatment or those who are unable to access specialist treatment in their local area.

To eat or not to eat-international experiences with eating during hemodialysis treatment.

Providing food or nutrition supplements during hemodialysis (HD) may be associated with improved nutritional status and reduced mortality; however, despite these potential benefits, eating practices vary across countries, regions, and clinics. Understanding present clinic practices and clinician experiences with eating during HD may help outline best practices in this controversial area. Therefore, the objective of this study was to examine clinical practices and experiences related to eating during HD treatment. We surveyed clinicians about their clinic practices during the 2014 International Society of Renal Nutrition and Metabolism Conference. We received 73 responses from six continents. Respondents were primarily dietitians (71%) working at units housed in a hospital (63%). Sixty-one clinics (85%) allowed patients to eat during treatment, with 47 of these patients (65%) actively encouraging eating. Fifty-three clinics (73%) provided food during HD. None of the nine clinics from North America, however, provided food during treatment. The majority (47 clinics; 64%) provided supplements during treatment. Clinics in the hospital setting were more likely to provide food during treatment, whereas outpatient clinics were less likely to provide nutrition supplements (P≤ 0.05 for both). We also asked clinicians about their experience with six commonly cited reasons to restrict eating during treatment using a four-point scale. Clinicians responded they observed the following conditions "rarely" or "never": choking (98%), reduced Kt/V (98%), infection control issues (96%), spills or pests (83%), gastrointestinal issues (71%), and hypotension (62%). Our results indicate that while eating is common during treatment in some areas, disparities may exist in global practices, and most of the proposed negative sequelae of eating during HD are not frequently observed in clinical practice. Whether these disparities in practice can explain global differences in albumin warrants further research to help inform decisions regarding eating during HD.

Results of a pilot program to improve phosphorus outcomes in hemodialysis patients.

OBJECTIVE: End-stage renal disease causes dysregulation of bone and mineral metabolism, including increased serum phosphorus levels. Kidney Foundation Kidney Disease Outcome Quality Initiative 2003 guidelines recommend maintaining phosphorus levels between 3.5 and 5.5 mg/dL in dialysis patients. We examined the effects of a focused phosphorus management pilot program designed to improve the percentage of hemodialysis patients achieving phosphorus levels <5.5 mg/dL. DESIGN, SETTING, SUBJECTS, AND INTERVENTION: We conducted a prospective, multicenter, single-arm study at 8 geographically diverse at-risk facilities (n = 702 hemodialysis patients) in a large U.S. dialysis organization. The focused phosphorus management program provided in-service training to staff members, and provided patients with diet and phosphorus management through in-center, 1:1 education and support, direct-to-patient adherence communications, benefit management assistance, and adherence support specific to lanthanum carbonate over a 6-month period. MAIN OUTCOME MEASURE: Facility-level markers of bone and mineral metabolism (phosphorus, parathyroid hormone, corrected calcium) and nutritional status (serum albumin, normalized protein catabolic rate) were assessed before and after program implementation. RESULTS: There was a significant increase in the percentage of patients per facility achieving phosphorus levels <5.5 mg/dL (mean ± SD at baseline = 61.6% ± 5.2%; month 6 = 71.3% ± 9.0%; P < .01) and parathyroid hormone (150 to 300 pg/mL; mean ± SD at baseline = 39.1% ± 2.4%; month 6 = 44.5% ± 7.0%; P = .04). During the course of the evaluation, mean calcium, albumin, and normalized protein catabolic rate levels did not change significantly. CONCLUSIONS: These results show proof-of-concept that a focused phosphorus management program targeting both staff members and patients can significantly improve patient outcomes without compromising nutritional status.

Cognitive behaviour therapy for chronic fatigue syndrome in adults: face to face versus telephone treatment: a randomized controlled trial.

BACKGROUND: Previous research has shown that face to face cognitive behaviour therapy (CBT) is an effective treatment for chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME). However, some patients are unable to travel to the hospital for a number of reasons. AIMS: The aim of this study was to assess whether face to face CBT was more effective than telephone CBT (with face to face assessment and discharge appointment) for patients with CFS. METHOD: Patients aged 18-65 were recruited from consecutive referrals to the Chronic Fatigue Syndrome (CFS) Research and Treatment Unit at The South London and Maudsley NHS Trust in London. Participants were randomly allocated to either face to face CBT or telephone CBT by a departmental administrator. Blinding of participants and care givers was inappropriate for this trial. A parallel-groups randomised controlled trial was used to compare the two treatments. The primary outcomes were physical functioning and fatigue. RESULTS: Significant improvements in the primary outcomes of physical functioning and fatigue occurred and were maintained to one year follow-up after discharge from treatment. Improvements in social adjustment and global outcome were noted and patient satisfaction was similar in both groups. CONCLUSIONS: Results from this study indicate that telephone CBT with two face to face appointments is a mild to moderately effective treatment for CFS and may be offered to patients where face to face treatment is not a viable option. Despite these encouraging conclusions, dropout was relatively high and therapists should be aware of this potential problem.

Investigation of a Prolonged and Large Outbreak of Healthcare-Associated Mucormycosis Cases in an Acute Care Hospital-Arkansas, June 2019-May 2021.

Background: Outbreaks of healthcare-associated mucormycosis (HCM), a life-threatening fungal infection, have been attributed to multiple sources, including contaminated healthcare linens. In 2020, staff at Hospital A in Arkansas alerted public health officials of a potential HCM outbreak. Methods: We collected data on patients at Hospital A who had invasive mucormycosis during January 2017-June 2021 and calculated annual incidence of HCM (defined as mucormycosis diagnosed within ≥7 days after hospital admission). We performed targeted environmental assessments, including linen sampling at the hospital, to identify potential sources of infection. Results: During the outbreak period (June 2019-June 2021), 16 patients had HCM; clinical features were similar between HCM patients and non-HCM patients. Hospital-wide HCM incidence (per 100 000 patient-days) increased from 0 in 2018 to 3 in 2019 and 6 in 2020. For the 16 HCM patients, the most common underlying medical conditions were hematologic malignancy (56%) and recent traumatic injury (38%); 38% of HCM patients died in-hospital. Healthcare-associated mucormycosis cases were not epidemiologically linked by common procedures, products, units, or rooms. At Hospital A and its contracted offsite laundry provider, suboptimal handling of laundered linens and inadequate environmental controls to prevent mucormycete contamination were observed. We detected Rhizopus on 9 (9%) of 98 linens sampled at the hospital, including on linens that had just arrived from the laundry facility. Conclusions: We describe the largest, single-center, HCM outbreak reported to date. Our findings underscore the importance of hospital-based monitoring for HCM and increased attention to the safe handling of laundered linens.

Rotating platform spinouts with cruciate-retaining mobile-bearing knees.

Spinout or dislocation is a complication of mobile-bearing total knee arthroplasty. We have observed this complication in 7 of 1255 cruciate-retaining mobile-bearing total knees (0.56%). Patient factors associated with a spinout included female sex, obesity, and preoperative valgus deformity. Operative treatment was generally successful, but significant complications occurred in 3 of the 7 patients.

Mucormycosis in Hematopoietic Cell Transplant Recipients and in Patients With Hematological Malignancies in the Era of New Antifungal Agents.

BACKGROUND: The survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined. METHODS: This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America. RESULTS: Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following: lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, P = .136). CONCLUSIONS: Long-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.

Home-based family focused rehabilitation for adolescents with severe Chronic Fatigue Syndrome.

AIMS:: The purpose of this article is to describe and evaluate a home based, family focused rehabilitative approach for severely affected housebound adolescents with Chronic Fatigue Syndrome (CFS). The main aims were to facilitate a return to school, improve physical functioning, reduce fatigue and assess any adverse effects of the intervention. METHODS:: Six housebound adolescents aged 11-18, diagnosed with CFS by a paediatrician, were assessed and treated at home by an experienced cognitive behaviour therapist. Outcomes were assessed 12 months after discharge from treatment. RESULTS:: At 12 months follow-up all patients had returned to either school or college, and physical functioning had improved in most of the patients. Fatigue had reduced in some. No adverse effects of the intervention were reported. CONCLUSION:: Severely affected adolescents with CFS showed improved physical functioning and social adjustment after a home-based rehabilitative approach. Although several patients showed improvements in physical functioning, they did not all show substantial improvements in fatigue. At this crucial stage of development, it is important to offer young people and their parents hope by stating that improvement is possible.

The role of next generation sequencing in infection prevention in human parainfluenza virus 3 infections in immunocompromised patients.

BACKGROUND: Respiratory viral infections are a significant problem in patients with hematologic malignancies. We report a cluster of HPIV 3 infections in our myeloma patients, and describe the utility of next generation sequencing (NGS) to identify transmission linkages which can assist in infection prevention. OBJECTIVES: To evaluate the utility of NGS to track respiratory viral infection outbreaks and delineate between community acquired and nosocomial infections in our cancer units. STUDY DESIGN: Retrospective chart review conducted at a single site. All patients diagnosed with multiple myeloma who developed symptoms suggestive of upper respiratory tract infection (URTI) or lower respiratory tract infection (LRTI) along with a respiratory viral panel (RVP) test positive for HPIV 3 between April 1, 2016, to June 30, 2016, were included. Sequencing was performed on the Illumina MiSeq™. To gain understanding regarding community strains of HPIV 3 during the same season, we also performed NGS on HPIV3 strains isolated from pediatric cases. RESULTS: We saw a cluster of 13 cases of HPIV3 infections in the myeloma unit. Using standard epidemiologic criteria, 3 cases were considered community acquired, 7 cases developed infection during treatment in the cancer infusion center, while an additional 3 developed infections during hospital stay. Seven patients required hospitalization for a median duration of 20days. NGS enabled sensitive discrimination of the relatedness of the isolates obtained during the outbreak and provided evidence for source of transmission. Two hospital onset infections could be tracked to an index case; the genome sequences of HPIV 3 strains from these 3 patients only differed by a single nucleotide. CONCLUSIONS: NGS offers a significantly higher discriminatory value as an epidemiologic tool, and can be used to gather real-time information and identification of transmission linkages to assist in infection prevention in immunocompromised patients.

Response to the editorial by Dr Geraghty.

This article is written in response to the linked editorial by Dr Geraghty about the adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation (PACE) trial, which we led, implemented and published. The PACE trial compared four treatments for people diagnosed with chronic fatigue syndrome. All participants in the trial received specialist medical care. The trial found that adding cognitive behaviour therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. In this article, we suggest that Dr Geraghty's views are based on misunderstandings and misrepresentations of the PACE trial; these are corrected.