Background: As hyperbaric oxygen therapy has been sporadically used in combination with antimicrobial treatment for refractory infections in patients with hematologic malignancies, data on its efficacy and outcomes are limited. Methods: We retrospectively analyzed 55 patients with hematologic malignancies treated with hyperbaric oxygen therapy over a 10-year period at a single tertiary care center and report on patients' clinical features, infection types, treatment responses, and survival outcomes. Results: The most common underlying hematologic malignancy diagnosis was acute myeloid leukemia (30 patients, 55%). The most common hyperbaric oxygen therapy indications were invasive mold disease (IMD) (35 patients, 64%), BK virus-associated cystitis (17 patients, 31%), and bacterial cellulitis (3 patients, 5%). Patients underwent a median of 10 hyperbaric oxygen therapy sessions (range, 1-45). In total, 54 (98%) of the 55 patients were evaluable for response, of whom 32 (59%) patients demonstrated a response, defined as either resolution or stabilization of the infection. Among the 35 patients with IMDs, we found that 11 patients (31%) achieved a complete response, 5 (14%) had a partial response, 6 (17%) had stable disease, and 13 (37%) patients experienced progression of their infection. In contrast, among the 17 patients with BK virus-associated cystitis, 9 patients (53%) had persistent or worsening hematuria. The two evaluable patients with bacterial cellulitis responded with resolution of the infection. We reviewed the status of the hematologic malignancies at the time of hyperbaric oxygen therapy treatment and found that the 21 patients whose hematologic malignancies were in remission tended to have a higher response rate of their infection compared to patients whose hematologic malignancies were not in remission (73% vs. 46% p = 0.057). Despite the response of infections, 1-year mortality in these patients remained high at 76%. Conclusions: Based on our experience, hyperbaric oxygen therapy, in conjunction with appropriate anti-infective therapy and debridement surgery, could benefit selected patients with hematologic malignancies, especially those whose underlying disease is controlled but experience recalcitrant bacterial or fungal infections.

Hepatic mucormycosis is a rare but often fatal opportunistic fungal infection, primarily affecting immunocompromised patients. Herein, we report such a case from MD Anderson Cancer Center (Houston, TX, USA) and systematically review published cases in patients ≥ 19 years of age to better characterize clinical presentation, diagnostic challenges, and treatment outcomes of hepatic mucormycosis. Among the 40 identified cases (including ours), hematologic malignancies (55%) and solid organ transplantation (30%) were the most common underlying conditions. Fever (70%) and abdominal pain (63%) were the predominant symptoms. Imaging revealed multiple hepatic lesions in 72% of cases. Diagnosis was primarily based on histopathology (73%), whereas culture positivity was low (36%), underscoring the difficulty of pathogen isolation. Mucorales-active antifungal therapy was often delayed but eventually used in 85% of cases (all amphotericin B +/- Mucorales-active triazoles), while 45% underwent additional surgical intervention. Despite treatment, 1-year all-cause mortality remained high at 46%, with a trend towards lower mortality for those who underwent surgery compared to non-surgical management (35% vs. 55%, p = 0.334). These findings highlight the aggressive nature of hepatic mucormycosis and the importance of early recognition as well as the need for non-culture-based diagnostics and multimodal treatment approaches. Improved awareness and further research into optimized management strategies are crucial to improve the outcomes of this challenging infection.

Patients with leukemia experience profound immunosuppression both from their underlying disease as well as chemotherapeutic treatment. Little is known about the prevalence and clinical presentation of nontuberculous mycobacteria (NTM) in this patient population. We identified six cases of NTM infection from 29,743 leukemia patients who had acid-fast bacilli (AFB) cultures. Four cases had bloodstream infections and five had disseminated disease, including one who presented with an unusual case of diffuse cellulitis/myositis. All patients were lymphopenic at time of diagnosis, and two patients ultimately died from their NTM infection. NTM infections are a rare, but potentially life-threatening infection in patients with leukemia. Sending AFB cultures early is important to direct appropriate antimicrobial therapy and allow for future leukemia-directed therapy.

Background Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established. Methods An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: period 1 (before time-out: January 2007-June 2010) and period 2 (after time-out: July 2010-March/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1000 patient-days were also assessed. Results Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: -0.89 days (95% confidence interval [CI], -1.38 to -.41); linezolid: -0.89 days (95% CI, -1.27 to -.52); meropenem: -0.97 days (95% CI, -1.39 to -.56); tigecycline: -1.41 days (95% CI, -2.19 to -.63); P < .001 for each comparison. Days of therapy/1000 patient-days decreased significantly for meropenem (-43.49; 95% CI, -58.61 to -28.37; P < .001), tigecycline (-35.47; 95% CI, -44.94 to -26.00; P < .001), and daptomycin (-9.47; 95% CI, -15.25 to -3.68; P = .002). Discussion A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.

Burnout among health-care workers is highly prevalent and profoundly impacts the quality of patient care. In addition to affecting patient safety, burnout results in higher staff turnover, revenue deficits due to decreased productivity, financial risk, and diminished organization viability because of the impact on quality of care, patient satisfaction, and safety. Culmination of external and internal stressors in health-care worker populations is associated with a higher probability of burnout and workers who reported perceived low workplace flexibility. In addition, workplace flexibility is associated with reduced odds of experiencing burnout. Workplace flexibility plays a critical role in potentially reducing the occurrence of burnout in the health-care worker population. Individually focused solutions are important to mitigate burnout, however, comprehensive organizational change ensures durable and sustainable solutions. There is a correlation between a positive employee outlook and reduced stress when there is a perceived level of control over one’s work schedule. The goal of this article is to showcase the process of a successful implementation of a condensed work schedule for an advanced practice provider workforce in infectious diseases in response to burnout and workload shifts. This chronicles the steps of design, rationale, procuring buy-in by stakeholders, and operational implementation of the new schedules. Advanced practice provider satisfaction and burnout were measured by periodic surveys at timepoints along the way.

Background:In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries.Methods:We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers.Results:We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03).Conclusions:Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality.Funding:National Cancer Institute and National Institutes of Health.

Abstract Background Patients with COVID-19 and underlying malignancies, particularly those receiving immunosuppressive therapy, are at higher risk of severe COVID-19 disease. Our retrospective cohort study examines the outcomes of COVID-19 infection in patients with different underlying malignancies admitted to a 710- beds comprehensive cancer center during the first 2 years of the pandemic. Methods All patients with cancer admitted to MD Anderson Cancer Center with a positive PCR test for SARS-CoV-2 were included in a clinical case registry from 3/22/20 (first hospitalized COVID-19 patient) to 3/31/22. This clinical registry was approved at the beginning of the COVID-19 pandemic by the Quality Improvement Assessment Board at MDACC. Clinical information including type of malignancy, date of admission, length of stay, need for invasive mechanical ventilation (IMV), and in-hospital mortality was obtained from their electronic medical records. Statistical analysis was performed using a two-proportion z-test where p< 0.05 was considered significant. Results A total of 1748 patients with cancer and COVID-19 infection were admitted over a 2-year period (3.2% of total hospital admissions during the same period), 49% had hematological malignancies (HM) (see table). Patients with HM had significantly higher readmission rates (17.3% vs 9.1%, p< 0.0001), IMV rates (7.8% vs 4.4%, p=0.0029), and inpatient mortality rates (13.6% vs 7.1%, p< 0.0001). compared to patients with solid tumors (ST). Total mortality rate was 8.8% (154 patients), even higher in patients with different types of HM, such as lymphoma 18.1%, AML 14.2%, MM 8.4%, CML 7.1% while the mortality for ST was 7.1%. COVID-19 Hospitalized Patients at UT-MDACC (3/22/20-3/31/22) UT-MDACC: The University of Texas MD Anderson Cancer Center *p-value <0.01 for z-test of 2 proportions (one-tailed) Conclusion HM patients hospitalized with COVID-19 infection had more severe disease and worse outcomes based on readmissions, IMV, and mortality rates. Preventive measures, prompt diagnosis and early treatments should be considered on this patient population. Disclosures Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.

Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer. This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome composition was determined by sequencing the V3/V4 region of 16 s rDNA encoding gene. Differential abundance analyses were used to single out significant microbial features which differed across severity levels. On univariate analysis, factors associated with severe CDI included the presence of toxin A/B in stools (odds ratio [OR] 2.14 [1.05–4.36] p = 0.04 and prior 90-day metronidazole use (OR 2.66 [1.09–6.50] p = 0.03). Although alpha and beta diversity was similar between disease severity groups and toxin A/B in stools, increased abundance of Bacteroides uniformis, Ruminococcaceae, and Citrobacter koseri were associated with protection from severe CDI (p < 0.05) and depletion of anaerobes was higher in patients with prior metronidazole exposure. Use of metronidazole for non-CDI indications within 90 days prior to diagnosis and presence of toxin A/B in stools were associated with severe CDI. Findings provide valuable insights into risk factors for severe CDI in an underserved population with cancer that warrants further exploration.

Background and Objectives : Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. Methods : We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the quality of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. Results : Completeness of ID provider notes improved from a baseline of 77% to 100% (p<.0001) for antimicrobial recommendations, 75% to 97% (p<.0001) for follow-up recommendations, and 19% to 98% (p<.0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24% to 56% (p=.027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. Conclusions : Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.

Background Non-typhoidal Salmonella (NTS) infection is thought to be more severe in cancer patients, but this has not been studied since the development of new cancer therapies, increasing antibiotic resistance and the introduction of new antibiotics. We sought to describe the demographic characteristics, microbiological findings, clinical manifestations, and outcomes of NTS infections in cancer patients at our institution. Methods We reviewed microbiology laboratory records and identified patients who had cancer and from whom NTS organisms were recovered between January 1, 2000 and December 31, 2013, at a comprehensive cancer center in Houston, Texas. Descriptive statistics were used to summarize patient characteristics, clinical presentation and outcomes. Results We identified 110 isolates from 82 patients with 88 episodes of NTS infection (including five relapses [6%] in four patients, and two consecutive episodes in one patient). Fifty-five patients (67%) had hematologic malignancies. Most NTS isolates were susceptible to the commonly prescribed antimicrobials. Sixty-nine percent of patients had sepsis and one-third had severe sepsis or septic shock. Gastroenteritis, bacteremia, or both were present in 69% of patients, and the rest had focal infection. Mortality at 30 days was low (8%). Relapses occurred only in patients receiving ≤ 10 days of antibiotic therapy. Conclusions NTS affects predominantly patients with hematologic malignancies, followed by gastrointestinal and genitourinary cancers. Invasive disease, sepsis, and septic shock are common presentations among admitted patients. Antimicrobial prophylaxis may not prevent NTS infection. Thirty-day mortality and attributable mortality rates were low in our series compared to older case series. Early appropriate antibiotic therapy may have had a role in decreasing mortality. Relapses occurred in patients receiving ≤ 10 days of therapy, suggesting the need for longer duration of antibiotic therapy in cancer patients with uncomplicated NTS infections.

Abstract Background Given the limited collaborative international studies that evaluated COVID-19 in patients with cancer in comparison to patients without cancer, we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods We retrospectively collected de-identified data on cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, at 16 centers in Asia, Australia, Europe, North America, and South America. A logistic regression model was used to identify independent predictors of all-cause mortality within 30 days after COVID-19 diagnosis. Results Of the total 4015 COVID-19 confirmed patients entered, we analyzed 3966 patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were older than non-cancer patients (median age, 61 vs 50 years; p< 0.0001); more likely to be pancytopenic , had pulmonary disorders, hypertension, diabetes mellitus. In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms. By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to 6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who were on high flow oxygen (5.9% vs 17.6%; p=0.03). Patients transfused with convalescent plasma within 1 day of diagnosis had a lower 30-day mortality rate than those transfused later (1% vs 7%, p=0.04). Conclusion Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality, as well as convalescent plasma given early after COVID-19 diagnosis. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support) Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Monica Slavin, MBBS,MD, F2G (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Pfizer (Advisor or Review Panel member) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

Severe acute respiratory syndrome coronavirus 2 can lead to life-threatening coronavirus disease 2019 (COVID-19) infections in patients with hematologic malignancies, particularly among hematopoietic cell transplant (HCT) recipients. We describe two patients with COVID-19 during the pre-engraftment period after HCT and review previous reports of COVID-19 in HCT recipients. Because of significant mortality from COVID-19, primarily after allogeneic HCT, early, preemptive, and optimal directed therapy may improve outcomes and reduce the mortality rate but still needs to be established in clinical trials.

Background and objectives Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. Methods We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the completeness of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. Results Completeness of ID provider notes improved from a baseline of 77 to 100% ( p < .0001) for antimicrobial recommendations, 75 to 97% ( p < .0001) for follow-up recommendations, and 19 to 98% ( p < .0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24 to 56% ( p = .027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. Conclusions Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.

Background:COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP. Patients and Methods:Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed. Results:CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex. Conclusions:Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.

Introduction: Hyperbaric oxygen therapy (HBO) is approved for difficult-to-treat tissue injury. It also been used as a second-line treatment for refractory infection in hematologic malignancies. However, data on the efficacy of HBO in such population are limited. Here, we reviewed our single-center experience of HBO used in patients with hematologic malignancies. Methods: We identified patients undergoing HBO treatment by insurance authorization data between December 2012 and October 2019 at MD Anderson Cancer Center. Patients with a diagnosis of hematologic malignancies with or without history of stem-cell transplant were included. Clinical and demographic data were collected by retrospective chart review. Results: A total of 50 patients were included: 26 (52%) patients had Acute Myeloid Leukemia, 31 (62%) patients had received an SCT, and 34 (68%) patients had active disease, of whom 28 (56%) had relapsed/refractory disease. The most common infections were: 19 (38%) BK cystitis and 17 (34%) fungal sinusitis. Median number of HBO sessions was 5 (range 1–60), and median HBO duration was 17 days (range 0–109). All patients received initial HBO in the hospital; 25 (50%) patients were discharged from hospital at either completion of HBO or after transition to outpatient treatment. Sixteen (32%) patients were discharged to hospice, and 8 (16%) patients died during the hospitalization. Ninety-day and 1-year mortality were high at 52% and 78%, respectively. Median survival was 3.1 months. Patients with BK cystitis were less likely to respond to HBO (odds ratio 0.16, p=.004). Eight patients had response to HBO and achieved remission of infection at last follow-up. These patients had a higher proportion (50%) of underlying disease in remission, compared to 29% in rest of patients (n=42). The treatment indications in the responding group were 2 BK cystitis, 2 fungal sinusitis, 2 cellulitis, and 2 non-BK cystitis. Other patient characteristics were similar to the rest of the patients. Patients with response/infection remission had better survival with HR 0.18 (95% CI .063–.529, p=.002). Conclusion: A small subset of patients with hematologic malignancies, 16% in our study, had meaningful recovery from infection after HBO treatment. In our experience, patients whose underlying malignancy was in remission and patients with non-BK infection had better outcomes. Additional studies are needed to better identify the population who would benefit from HBO.

Sweet syndrome (SS) is an inflammatory disorder characterized by sudden onset of fever and tender erythematous skin lesions commonly localized on the face, neck, upper trunk and extremities.1-4 Malignancy-associated SS (MASS) can be observed with acute myeloid leukaemia (AML). Although SS normally presents as erythematous skin lesions, here we present three rare, atypical cases of necrotizing SS, which can be mistaken for other forms of dermatologic disease leading to inappropriate therapy and mortality. Awareness of this unique cutaneous presentation is important for accurate diagnosis and prompt treatment. A 26-year-old man with newly diagnosed AML had left lower leg cellulitis progressing to a large bullous lesion over 4–5 days despite broad-spectrum anti-infective therapy (BSAI). Skin biopsy showed dense dermal neutrophilic infiltrate negative for infection, suggestive of pyoderma gangrenosum or atypical SS (Fig 1). Methylprednisolone 2 mg/kg intravenous (IV) daily was started with improvement of the cutaneous lesions over the next seven days without surgical intervention (Fig 2A–C). Bone marrow (BM) showed AML with fibrosis (MF-2/3) with trisomy 8 and mutations in STAT5A, U2AF1 and CBL genes. Upon improvement of the lower extremity lesion on day 6, induction chemotherapy was started. On day 7, bullous lesions appeared closed, crusted and healing following steroid taper. Post-induction BM was hypocellular, but subsequently showed 2% blasts with negative minimal residual disease (MRD). After count recovery, the patient had complete resolution of his skin lesions with minimal scarring. A 57-year-old woman transferred for suspicion of acute leukaemia had ulcerative lesions on the right arm and non-pruritic rash on her scalp and left inner thigh without resolution after a week of steroids. Skin biopsy was done and empiric BSAI and prednisone 40 mg daily were started (Fig 2D–F). Right axilla tissue culture showed methicillin-resistant Staphylococcus aureus (MRSA) treated with daptomycin. On day 5, pathology results of right arm skin biopsy confirmed SS with extensive dermal neutrophilic infiltrate and focal necrosis. BM biopsy revealed myelodysplastic syndrome (MDS) with 5% blasts, deletion 20q, CEBPA, NRAS, RUNX1 and U2AF1 mutations. She began investigational therapy for MDS along with a slow steroid taper over four weeks. Upon completion, new erythema on the lower extremity, progressive erythema on the left upper extremity and pain with oedema on the posterior arms were noted. Additional small asymptomatic erythematous lesions were found on her knees, left arm and dorsal hand. Prednisone 20 mg daily (tapered over two weeks) with dapsone 25 mg daily was initiated. Upon completion, new erythematous areas appeared on the lower extremities. A new prednisone taper over four weeks with dapsone 50 mg and intralesional triamcinolone began. After three months, she had two well-healed scars on her right forearm and scattered erythematous papules treated with topical clobetasol. She is currently seven months post allogenic stem cell transplant with resolution of her cutaneous lesions. A 61-year-old woman presented with a one-week history of fever, fatigue and forearm cellulitis with deep ulceration, consistent with her history of a recent burn wound (Fig 2G–I). Laboratory values revealed leukocytosis with 88% blasts, anaemia and thrombocytopenia. BM biopsy revealed AML with t(6;9)(p23;q34), NRAS and U2AF1 mutations. A right arm punch biopsy showed extensive dermal neutrophilic inflammatory infiltrate and a tissue culture was negative for infection. She began AML-directed therapy and prednisone 40 mg daily for five days with improvement of the right upper extremity ulceration. On day 7, she developed painful swelling and tenderness on her upper extremity at the (IV)-line removal site. Imaging revealed soft tissue oedema without fluid collection. A repeat skin biopsy was negative for infection but had mixed inflammatory infiltrate with neutrophils and histiocytes, suggestive of necrotizing SS. Aggressive management with methylprednisolone 2 mg/kg/day IV for five days followed by a slow taper, IV immunoglobulin (IVIG) daily for three days, and dapsone 100 mg daily was initiated. This led to improvement of upper extremity pain, swelling and ulceration. Day 28 BM biopsy showed 1% blasts and negative MRD. After a four-week steroid taper, she had complete resolution of her skin lesions. Although the pathogenesis of SS,1, 2, 5 diagnosed by clinical and pathologic features6 (Table I), is not well understood, potential mechanisms include genetic susceptibility and cytokine dysregulation secondary to infection, inflammation, drugs or malignancy, such as in the cases presented here. MASS accounts for approximately 15–20% of SS cases that can portend or co-occur with the malignancy.3 The mechanisms of neutrophilic dermatosis in MDS/AML remain unclear; however, leukaemia-driven inflammasome activation and production of pro-inflammatory cytokines may play a role in the cutaneous infiltration.7 Molecular and cytogenetic aberrations, such as del(5q), FLT3 and IDH1 mutations, have been linked to SS.7-9 Although patients with MASS often present with well-recognized erythematous lesions, here we present three cases with rare necrotizing and ulcerating skin lesions. Necrotizing SS, or necrotizing neutrophilic dermatosis (NND) is an infrequent entity10-14 that can mimic pyoderma gangrenosum or necrotizing fasciitis (NF). The latter is a potentially fatal skin infection that can present with painful erythema, vesicles, or necrosis but histopathologic findings are negative for neutrophilic infiltration. Unlike in necrotizing SS, treatment of NF consists of early wound debridement and anti-infectives tailored to isolated specimen. Glucocorticoids, systemic or topical, along with treatment of the underlying disease, are the mainstay of SS therapy, including NND, and can lead to rapid resolution of symptoms. High-dose steroids may be required to treat severe cases with taper based on resolution of symptoms. In MASS, prompt and effective initiation of anti-leukaemic therapy is also important. Early surgical evaluation and empiric BSAI may be indicated if there is marked necrosis or suspicion of infection, but cannot alone treat SS. Salvage SS therapies, such as potassium iodide, dapsone, IVIG or colchicine could potentially be effective if steroid use is insufficient or contraindicated.15 In conclusion, our case series underscores the importance of proper identification of rare forms of SS such as NND and its distinction from other necrotizing skin disorders. As in our series, prompt initiation of steroid and anti-leukaemic treatment can lead to adequate resolution of these lesions and minimize the morbidity and mortality associated with uncontrolled necrotizing dermatoses. All authors equally contributed in collecting the data, writing and editing the manuscript. This research is supported in part by the M. D. Anderson Cancer Center Support Grant P30 CA016672 and the SagerStrong Foundation.

Abstract Background Our objective was to describe the clinical course, risk factors and outcomes of patients infected with COVID-19 around the globe comparing cancer to non-cancer patients. Methods We conducted a retrospective cohort study of COVID-19 confirmed cases through an international multicenter collaboration including 17 centers around the world including the United States of America, Brazil, Europe, Far East, Middle East and Australia from January to date. We evaluated the patients’ clinical characteristics, clinical course of the disease, hospitalization and outcome. Death was considered to be COVID-associated if it occurred within 30 days from the time of diagnosis. Results Preliminary data on 571 patients included 186 cancer patients and 385 non-cancer patients. Cancer patients were more likely to have COPD and received steroids but were less likely to have COVID-related symptoms compared to non-cancer patients (84% vs 97%, p< 0.0001). The rate of pneumonia with hypoxia, non-invasive ventilation and mechanical ventilation were similar in both groups. Despite the fact that hospital admissions were significantly higher in non-cancer patients (70% vs 56%, p< 0.001), promising antiviral and immune-related therapy including remdesivir, convalescent plasma and immunomodulators were more commonly used in cancer patients compared to non-cancer patients (P=0.04). Cancer patients had a higher COVID-associated mortality rate compared to non-cancer patients (20% vs 11%, p=0.006). Conclusion Despite the fact that cancer patients received more frequent antiviral and immune-related therapy, the mortality rate among cancer patients was significantly higher than non-cancer patients. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix (Consultant, Research Grant or Support)Clinigen (Consultant)Merck (Consultant, Research Grant or Support)Novartis (Research Grant or Support)Oxford Immunotec (Consultant, Research Grant or Support)Shire/Takeda (Research Grant or Support)Viracor (Research Grant or Support) Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

The emergence and spread of 2019 novel coronavirus have led to an unprecedented public health crisis around the globe, threatening the lives of millions of people. We report a severe case of COVID-19 in a patient with chronic lymphocytic leukemia and describe primarily the clinical presentation and the challenges encountered in the COVID-19 diagnosis, treatment, and specimens sampling pitfalls. This case highlights the importance of a comprehensive diagnostic approach of pneumonia in immunocompromised hosts, including timely and safe bronchoscopy, because of the broad differential diagnosis, more challenging with the current outbreak of COVID-19.

Background. Patients with cancer are particularly vulnerable to Clostridioides difficile infection (CDI). Guidelines recommend a two-step diagnostic algorithm to differentiate carriers from CDI; however, there are limited data for this approach while including other confounding risk factors for diarrhea such as radiation, cytotoxic chemotherapy, and adoptive cell based therapies. Methods. We conducted a prospective, non-interventional, single center, cohort study of cancer patients with acute diarrhea and C. difficile, identified in stools by nucleic acid amplification tests (NAAT) and culture. Fecal toxin A/B was detected by enzyme immunoassay (EIA) and isolates were ribotyped using 16s rRNA fluorescent sequencing. Patients were followed for 90 days to compare outcomes according to malignancy type, infecting ribotype, and EIA status. Results. We followed 227 patients with a positive NAAT. Of these, 87% were hospitalized and 83% had an active malignancy. EIA was confirmed positive in 80/227 (35%) of patients. Those with EIA+ were older (60 +/- 18 years vs 54 +/- 19 years., P = .01), more likely to fail therapy [24/80 (30%) vs 26/147 (18%), P= .04] and experience recurrence [20/80 (25%) vs 21/147(14%), P < .05]. We found a low prevalence (22%) of ribotypes historically associated with poor outcomes (002, 018, 027, 56, F078-126, 244) but their presence were associated with treatment failure [17/50 (34%) vs 33/177 (19%), P = .02]. Conclusions. When compared to cancer patients with fecal NAAT+/EIA-, patients with NAAT+/EIA+ CDI are less likely to respond to therapy and more likely to experience recurrence, particularly when due to ribotypes associated with poor outcomes.

The emergence of novel coronavirus disease 2019 (COVID-19) has led to a global pandemic and has threatened the lives of millions of people. This disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in respiratory failure, multiple organ dysfunction, and death.1Wu Z. McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention.JAMA. 2020; 323: 1239-1242Crossref PubMed Scopus (12457) Google Scholar Little is known about the spectrum of clinical presentations of COVID-19 in cancer patients.2Liang W. Guan W. Chen R. et al.Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China.Lancet Oncol. 2020; 21: 335-337Abstract Full Text Full Text PDF PubMed Scopus (3239) Google Scholar Herein, we present a patient with chronic lymphocytic leukemia (CLL) who developed organizing pneumonia (OP) as a late manifestation of COVID-19 after an initial improvement who was successfully treated with corticosteroids. A 62-year-old woman with CLL, hypertension, and type 2 diabetes mellitus presented with low-grade fever, cough, and shortness of breath of 1-week duration. Her CLL was treated with rituximab initially that was switched to ibrutinib 3 months earlier but was discontinued a few days before her hospitalization due to palpitations and arthralgia. On admission, she was hypoxic, requiring supplemental oxygen at 2 L/min to maintain oxygen saturation, SpO2 > 93%, and in atrial fibrillation with no hemodynamic instability. Laboratory studies were significant only for elevated C-reactive protein at 74 mg/L (normal <10 mg/L). Nasopharyngeal swab specimen for reverse transcriptase-polymerase chain reaction for SARS-CoV-2 was positive, but negative for other respiratory viruses. Computed tomography scan of the chest showed bilateral ground-glass opacities (Figure A). The patient was enrolled in the Mayo Clinic COVID-19 expanded access program for convalescent plasma (CCP) on day 9 of her illness and received one dose of CCP. The patient's respiratory status rapidly improved the day following CCP transfusion, maintaining SpO2 on room air. After 3 days, the patient developed daily low-grade fevers and increasing shortness of breath requiring supplemental oxygen via nasal cannula. Infectious disease workup including blood cultures and fungal serum markers were negative. A repeat chest computed tomography, on day 17 of illness (Figure B), revealed new and migratory ground-glass opacities in both lungs that were consistent with an OP pattern. The patient was started on intravenous methylprednisolone at 1 mg/kg/d, which resulted in improvement in oxygenation and resolution of fever. She was discharged in stable condition after 7 days of corticosteroids. Our case may present a rare clinical course of COVID-19. Given the radiological appearance of migratory lung infiltrates and rapid improvement with corticosteroids, we hypothesize that this is OP due to the associated hyper-inflammation phase commonly seen in the later stages of COVID-19.3Wu Y. Xie Y. Wang X. Longitudinal CT findings in COVID-19 pneumonia: case presenting organizing pneumonia pattern.Radiol Cardiothorac Imaging. 2020; 2: e200031Crossref Scopus (51) Google Scholar Moreover, acute fibrinous and OP (a subtype of OP) are described in COVID-19, which could be the case in our patient, although it cannot be confirmed without a tissue biopsy.4Copin M.-C. Parmentier E. Duburcq T. et al.Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection.Intensive Care Med. 2020; (Epub ahead of print https://doi.org/10.1007/s00134-020-06057-8)Crossref PubMed Scopus (197) Google Scholar Although we conjecture that this is likely the explanation in our case, other plausible mechanisms of OP in our patient are 1) an immune activation-like phenomenon following cessation of ibrutinib or 2) augmentation of immune response by convalescent plasma.5Shaz B. Dunbar C. Hillyer C. COVID-19 and Convalescent Plasma: Frequently Asked Questions. American Society of Hematology.https://www.hematology.org/covid-19/covid-19-and-convalescent-plasma.2020Google Scholar Bruton's tyrosine kinase inhibitors are involved in toll-like receptor–mediated signaling and triggering of inflammatory cytokine and chemokine release.6Treon S.P. Castillo J. Skarbnik A.P. et al.The BTK-inhibitor ibrutinib may protect against pulmonary injury in COVID-19 infected patients.Blood. 2020; 135: 1912-1915Crossref PubMed Google Scholar Ibrutinib, a highly potent inhibitor of Bruton's tyrosine kinase, is considered to protect against lung injury in COVID-19.6Treon S.P. Castillo J. Skarbnik A.P. et al.The BTK-inhibitor ibrutinib may protect against pulmonary injury in COVID-19 infected patients.Blood. 2020; 135: 1912-1915Crossref PubMed Google Scholar Corticosteroids are not currently recommended in the management of hospitalized patients with COVID-19 unless there is a separate indication such as asthma or chronic obstructive pulmonary disease or in intubated patients with acute respiratory distress syndrome.7Bhimraj A. Morgan R.L. Shumaker A.H. et al.Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19.Clin Infect Dis. 2020; (Epub ahead of print https://doi.org/10.1093/cid/ciaa478)Google Scholar Organizing pneumonia as a delayed presentation of COVID-19 for which corticosteroids have significant benefit should be considered. Moreover, given the increasing use of convalescent plasma, OP as a possible downstream consequence should be investigated.