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Objectives To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). Methods This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). Results We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115; 69.7%), 1 mg/kg/week (18; 10.9%), 3 mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL; P Conclusions One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.

Invasive fungal diseases (IFDs) are common in patients with acute myeloid leukemia (AML), but no recent data on incidence without antifungal prophylaxis are available. We evaluated the incidence of IFDs in patients with AML undergoing induction chemotherapy at Stanford University Hospital from 2012 to 2017, for up to 12 weeks after induction. We also analyzed factors associated with IFD development. Thirty-six of 240 patients (13%) developed at least one proven or probable IFD. Seventy-eight percent of the proven or probable IFDs were due toiCandida/ioriAspergillus/ispecies. Infection due toiFusarium/iandiMucorales/iwas uncommon. Absolute neutrophil count (ANC) oflt;500 µL/L at the start of induction was associated with an increased risk of IFD. One hundred and eighty-seven patients (78%) were started on systemic antifungal drugs, even without microbiologic evidence of an IFD. IFDs remain frequent in AML patients undergoing induction chemotherapy without antifungal prophylaxis.

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count

Background Fungal prostatitis is exceedingly rare with mostly case reports. Methods Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years. Results Seven cases were identified from 105 600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable. Conclusion Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.

Bronchiolitis obliterans syndrome (BOS)-chronic graft-versus-host disease (cGVHD) affecting the lungs-is an uncommon complication of allogeneic hematopoietic cell transplant (HCT). The epidemiology and complications of lower respiratory tract infections (LRTIs) and community-acquired respiratory viruses (CARVs) in these patients are poorly understood.We aim to characterize the epidemiology of LRTIs in patients with BOS complicating HCT. We also aim to explore the association of LRTIs and CARV detection on lung function in BOS patients.Adult patients with BOS at Stanford Health Care between January 2010 and December 2019 were included in this retrospective cohort study. LRTI diagnosis was based on combined clinical, microbiologic, and radiographic criteria, using consensus criteria where available.Fifty-five patients with BOS were included. BOS was diagnosed at a median of 19.2 (IQR 12.5-24.7) months after HCT, and patients were followed for a median of 29.3 (IQR 9.9-53.2) months from BOS diagnosis. Twenty-two (40%) patients died after BOS diagnosis; 17 patients died from complications of cGVHD (including respiratory failure and infection) and 5 died from relapsed disease. Thirty-four (61.8%) patients developed at least one LRTI. Viral LRTIs were most common, occurring in 29 (52.7%) patients, primarily due to rhinovirus. Bacterial LRTIs-excluding Nocardia and non-tuberculous mycobacteria (NTM)-were the second most common, occurring in 21 (38.2%) patients, mostly due to Pseudomonas aeruginosa. Fungal LRTIs, NTM, and nocardiosis occurred in 14 (25.5%), 10 (18.2%), and 4 (7.3%) patients, respectively. Median time to development of the first LRTI after BOS diagnosis was 15.3 (4.7-44.7) months. Twenty-six (76.5%) of the 34 patients who developed LRTIs had infections due to more than one type of organism-fungi, viruses, Nocardia, NTM, and other bacteria-over the observation period. Patients with at least one LRTI had significantly lower forced expiratory volume in one second percent predicted (FEVLRTIs are common in BOS and associated with lower FEV

BACKGROUND: The role of lung resection in patients with pulmonary aspergillosis is generally reserved for those with localized disease who fail medical management. We used a national database to investigate the influence of preoperative patient comorbidities on inpatient mortality and need for surgery. METHODS: Patients admitted with pulmonary aspergillosis between 2007 to 2015 were identified in the National Inpatient Sample dataset. Inpatient mortality rates were compared between patients treated medically and surgically. Predictors of mortality, surgical intervention, and non-elective admission were evaluated using multivariable logistic regression. RESULTS: Among a population estimate of 112,998 patients with pulmonary aspergillosis, 107,606 (95.2%) underwent medical management alone and 5,392 (4.8%) underwent surgical resection. Positive predictors for surgery included hemoptysis, and history of lung cancer or chronic pulmonary diseases. Surgically treated patients had a lower inpatient mortality when compared to those treated medically (11.5% vs. 15.1%, P

Summary Objectives To compare the effectiveness and tolerability of micafungin versus posaconazole during chemotherapy-induced neutropenia in acute leukemia (AL) and myelodysplastic syndrome (MDS). Methods Patients with AL or MDS undergoing chemotherapy were randomized to open-label micafungin 100 mg intravenously daily or posaconazole suspension 400 mg orally twice daily until neutrophil recovery, up to 28 days. Patients were followed for 12 weeks. The primary endpoint was prophylaxis failure (premature discontinuation due to infection, intolerance, adverse event, or death). Time to failure and survival were calculated by Kaplan–Meier analysis. Results From March 2011 to May 2016, 113 patients who received at least 2 doses of prophylaxis were analyzed (58 patients randomized to micafungin and 55 to posaconazole). Prophylaxis failure occurred in 34.5% and 52.7% of patients on micafungin and posaconazole, respectively (P = 0.0118). The median number of days on prophylaxis was 16 [interquartile range (IQR) 12–20] for micafungin and 13 [IQR 6–16] for posaconazole (P = 0.01). Micafungin failures were largely due to antifungal treatment; posaconazole failures were mostly due to gastrointestinal intolerance or adverse effects. IFI incidence and survival were similar between study arms. Conclusions Our data support micafungin as alternative antifungal prophylaxis in patients with AL and MDS.

Hematopoietic cell transplantation (HCT) is potentially curative for patients with hematologic disorders, but carries significant risks of infection-related morbidity and mortality. Infectious diseases are the second most common cause of death in HCT recipients, surpassed only by progression of underlying disease. Many infectious diseases are difficult to diagnose and treat, and may only be first identified by autopsy. However, autopsy rates are decreasing despite their value. The clinical and autopsy records of adult HCT recipients at our center who underwent autopsy between 1 January 2000 and 31 December 2017 were reviewed. Discrepancies between premortem clinical diagnoses and postmortem autopsy diagnoses were evaluated. Of 185 patients who underwent autopsy, 35 patients (18.8%) had a total of 41 missed infections. Five patients (2.7%) had >1 missed infection. Of the 41 missed infections, 18 (43.9%) were viral, 16 (39.0%) were fungal, 5 (12.2%) were bacterial, and 2 (4.9%) were parasitic. According to the Goldman criteria, 31 discrepancies (75.6%) were class I, 5 (12.2%) were class II, 1 (2.4%) was class III, and 4 (9.8%) were class IV. Autopsies of HCT recipients frequently identify clinically significant infectious diseases that were not suspected premortem. Had these infections been suspected, a change in management might have improved patient survival in many of these cases. Autopsy is underutilized and should be performed regularly to help improve infection-related morbidity and mortality. Illustrative cases are presented and the lessons learned from them are also discussed.

Antifungal prophylaxis is the standard of care for patients undergoing intensive chemotherapy for haematological malignancy or haematopoietic cell transplantation (HCT). Prophylaxis with azoles reduces invasive fungal infections and may reduce mortality. However, breakthrough infections still occur, and the use of azoles is sometimes complicated by pharmacokinetic variability, drug interactions, adverse events and other issues. Echinocandins are highly active against Candida species, including some organisms resistant to azoles, and have some clinical activity against Aspergillus species as well. Although currently approved echinocandins require daily intravenous administration, the drugs have a favourable safety profile and more predictable pharmacokinetics than mould-active azoles. Clinical data support the efficacy and safety of echinocandins for antifungal prophylaxis in haematology and HCT patients, though data are less robust than for azoles. Notably, sparse evidence exists supporting the use of echinocandins as antifungal prophylaxis for patients with significant graft-versus-host disease (GvHD) after HCT. Two drugs that target (1,3)-β-d-glucan are in development, including an oral glucan synthase inhibitor and an echinocandin with unique pharmacokinetics permitting subcutaneous and weekly administration. Echinocandins are a reasonable alternative to azoles and other agents for antifungal prophylaxis in patients undergoing intensive chemotherapy for haematological malignancy or those receiving HCT, excluding those with significant GvHD.

A 39-year-old man presented to the Bellevue Hospital emergency department in November with 1 week of fevers and cough. On the previous day, he had been assaulted, developing right buttock and thigh pain. His medical history was notable for alcohol use disorder treated with the opioid antagonist

Background While invasive fungal infections (IFIs) are common in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy, little current data exist on the epidemiology of IFIs in this patient population given widespread use of antifungal prophylaxis. Because our institution does not administer antifungal prophylaxis, we are in a unique position to study the natural history of IFIs in these patients. Methods We evaluated the incidence of IFIs using established definitions in adults with AML undergoing induction chemotherapy at Stanford Health Care from 2012 to 2017. We also analyzed incidence of antifungal treatment, impact of IFI diagnosis on survival, and risk factors for IFI development. Patients were followed for up to 12 weeks after beginning induction chemotherapy. Results Of 488 patients analyzed, 243 were eligible for inclusion. The median age was 57 (interquartile range 45–65). Men composed 134 (55%) of the patients and 157 (65%) where white. Fifty-four (22%) had antecedent myelodysplastic syndrome; most received a “7 + 3” regimen involving cytarabine and an anthracycline. Thirty-one (13%) developed a proven or probable IFI; 104 (43%) developed a proven, probable, or possible IFI. Most IFIs were due to lower respiratory tract disease. Eighteen identified organisms were Candida, including six C. albicans. Eight organisms were mold, including four Aspergillus isolates (all but one A. fumigatus) and one isolate each of Fusarium solani, Rhizomucor, Rhizopus, and Scedosporium apiospermum/Pseudallescheria boydii. One hundred ninety patients (78%) received antifungals during their initial admission and 99 (46%) of patients surviving their initial admission were discharged on antifungals. Only 66.7% of patients with a proven or probable IFI survived through 12 weeks, compared with 92.2% of those without (P = 0.007). Baseline absolute neutrophil count ≤500 cells/μL and longer duration of neutropenia were significantly associated with development of proven or probable IFIs. Conclusion Among patients receiving induction chemotherapy for AML, IFIs due to Candida and mold remain frequent absent antifungal prophylaxis and are associated with worse survival. Our findings support the use of antifungal prophylaxis in this patient population. Disclosures All authors: No reported disclosures.

Eremothecium coryli is a dimorphic fungus of the Saccharomycetes class. While species within this class are known to cause human infection, Eremothecium species have previously only been known as phytopathogens and never been isolated from a human sample. Here, we report the first known case of human E. coryli infection.

Solid organ transplant recipients are at an increased risk of tuberculosis and transplant candidates should be screened early in their evaluation with a detailed history, tuberculin skin test or tuberculosis interferon-gamma release assay, and chest radiograph. For latent tuberculosis treatment, isoniazid and rifamycin-based regimens have advantages and disadvantages; treatment decisions should be customized. Tuberculosis after solid organ transplantation generally occurs after months or years; early infections should raise the possibility of donor-derived infections. Tuberculosis diagnosis and treatment in solid organ transplant recipients may be complicated by protean manifestations, drug interactions, and adverse drug reactions.

Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.

Background: Tuberculosis (TB) is a common infection with challenges in diagnosis and treatment. Management of TB in solid organ transplant (SOT) candidates and recipients poses unique challenges not seen in other populations. Questions and recommendations: Latent TB infection (LTBI) is important to diagnose pre-transplant through history, physical examination, imaging, and laboratory tests. Tuberculin skin tests and interferon-gamma release assays are important tools but not sufficiently sensitive nor specific to diagnose LTBI alone. Active TB is more likely to present as a disseminated or extrapulmonary infection. Donor-derived infections occur infrequently though can be serious; these can sometimes be prevented through LTBI treatment of the donor or recipient. Treatment of active or latent TB is similar to that in other populations with particular attention to drug interactions and adverse drug reactions. Conclusions: LTBI and TB are important infections in SOT candidates and recipients with unique challenges though substantial literature and experience have emerged to guide providers.

Background Hematopoietic cell transplantation (HCT) is a potentially curative treatment option for patients with hematologic malignancies and other diseases but carries a significant risk of infection-related morbidity and mortality. Many of these infections are difficult to diagnose and treat. It is not infrequent that HCT recipients die from infection despite extensive investigations and broad-spectrum antimicrobial therapy. Autopsy is the gold standard for establishing the cause of death but rates of performing autopsies are decreasing despite their immense value. We present the most recent case series of infectious diseases found on autopsy in HCT recipients at our high-volume academic transplant center. Methods We retrospectively reviewed the medical charts and autopsy records of 131 HCT recipients who underwent autopsy between January 1, 2000 and December 31, 2016. The premortem clinical diagnoses as documented by the clinical teams were compared with autopsy findings. Discrepancies were identified and classified according to the Goldman Criteria (NEJM 1983; 308:1000–5). Results A total of 4,072 patients received 4,395 transplants between January 1, 2000 and December 31, 2016. Of the 1,937 patients who died, 131 (7%) had an autopsy performed. Of these 131 patients, 24 (18%) patients had a total of 29 infections that were identified only postmortem; 4 (3%) patients had >1 such infection. Of these 29 infections, 15 (52%) were viral, 9 (31%) were fungal, 3 (10%) were bacterial, and 2 (7%) were parasitic; no mycobacterial infections were found. According to the Goldman Criteria, 22 (76%) had class I discrepancies (“major diagnoses for which detection before death would in all probability have led to a change in management that might have resulted in cure or prolonged survival”). Illustrative cases of each infection type will be presented to highlight the challenges of infection management in HCT. Conclusion Autopsies of HCT recipients frequently identify clinically significant infections which were not suspected pre-mortem. Our study reinforces the educational value of the autopsy, which is underutilized but can be employed to help prevent future similar infectious complications and improve patient outcomes. Disclosures All authors: No reported disclosures.

Physiological processes responsible for ecosystem carbon and nitrogen cycling may vary across hill slopes and be controlled by watershed hydrology and the associated nutrient transport. Mass transport of nutrients down slope and into water tracks may increase nutrient delivery to plant roots, nutrient uptake, and perhaps photosynthetic activity. Small arctic watersheds are commonly characterized by increased biomass, particularly of woody deciduous shrubs, both down slope and in water tracks. We ask if photosynthetic physiology varies with hill slope position and if it is correlated to observed changes in above ground biomass. Chlorophyll fluorescence surveys from six common species reveal that maximum photosynthetic electron transport decreased significantly (by as much as 85%) down slope in 4 species. Leaf nitrogen concentrations varied from 1 to 2.5% across all leaves sampled, but show little trend with hill slope position, and as a result are not well correlated with photosynthetic electron t...

Toxoplasma encephalitis is a well recognized complication of acquired immune deficiency syndrome, solid organ transplantation, and allogeneic hematopoietic stem cell transplantation (HSCT). However, patients with hematologic malignancies not treated with allogeneic HSCT may also develop this condition, which requires high clinical suspicion and consideration for prophylactic therapy.

Gilligan and Krehbiel (1989) analyze bipartisanship in committees through a model in which committee ideal points are exactly symmetric about the floor’s ideal point. This article has three objectives: it shows that the Gilligan and Krehbiel equilibrium does not generalize to asymmetric committee members; it proves that a similar equilibrium can be supported when the majority party committee member has gatekeeping power; and it compares this equilibrium to the one-signaler case to show that when partisan differences over policy are small, or when the uncertainty associated with a policy area is large, bipartsianship will be preferred to partisan policy making.

The acromioclavicular joint is comprised of the articulation between the distal end of the clavicle and the acromion. It functions to anchor the clavicle to the scapula and to the shoulder girdle. The subcutaneous location of this joint makes it vulnerable to injury. It comprises approximately 9% of all injuries to the shoulder girdle. The majority of these injuries occur in males with a male to female ratio of approximately 5:1, and the most common age group affected are those in their 20s. Injuries to the acromioclavicular joint are prevalent in football, rugby, and other contact sports. Given the high incidence of acromioclavicular injuries, it is common for orthopedists, emergency physicians, and physical therapists to recognize and initiate treatment for the full spectrum of this type of injury. The current literature outlines joint biomechanics, various methods of fixation, and outcomes of both nonoperative and operative therapy. This article reviews the anatomy, biomechanics, classification of injury, fixation techniques, and outcomes. Language: en

Nine principal components were extracted from the scores of 26 homosexual and 26 heterosexual males matched on age, education, occupation status, and sampling frame on Adjective Check List, Bem Sex Role Inventory, Chapin Social Insight Test, Experience Inventory, and Sixteen Personality Factor Questionnaire scales selected to represent a variety of "masculine" and "feminine" sex role attributes. The four most general varimax factors, accounting for 48% of the total variance, were: I) "Feminine Openness," II) "Masculine Boldness," III) "Reflection," and IV) "Novelty Seeking." Factor scores were constructed and indicated that the homosexual sample was significantly more identified with Factor I (p < .00l; 17% of total variance). There was no significant difference between the samples on Factor II, nor on the remaining two general factors which were not sex typed.

Excerpt Coumarin skin necrosis is an uncommon but well recognized complication of oral anticoagulant therapy (1). We have discovered that a patient with coumarin penile necrosis whose case was prev...