Hepatitis B Vaccine Compliance, Serologic Response, and Durability in Adult Thoracic Organ Transplant Recipients.

INTRODUCTION: Hepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients. METHODS: We conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Conventional recombinant hepatitis B vaccine (Recombivax HB) was used before 2020, and Heplisav-B was preferred after 2020. HBV seroprotection was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L. Furthermore, we compared characteristics between recipients who maintained HBV seroprotection and those who lost HBV seroprotection (HBsAb < 10 IU/L) at 30 days posttransplantation (D30). RESULTS: Among 922 candidates who were eligible for HBV vaccination, 430 (47%) completed the HBV vaccine series. Patients receiving Heplisav-B were more likely to complete the series than Recombivax HB (81% vs. 60%, p < 0.001) and Heplisav-B had a higher seroprotection rate than Recombivax HB (75% vs. 64%, p = 0.023). Multivariate logistic regression analysis identified receiving Heplisav-B as an independent predictor for HBV seroprotection (adjusted odds ratio [aOR] 1.723; 95% confidence interval [CI] 1.056-2.810; p = 0.029). A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. Loss of HBV seroprotection occurred in 38 (26%) patients at D30. Multivariate logistic regression analysis identified two predictors for HBV seroprotection loss at D30: age ≥ 60 years (aOR, 2.503; 95% CI 1.026-6.107; p = 0.044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI 5.211-66.209; p < 0.001). CONCLUSIONS: Although less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav-B provided a higher vaccine completion rate and seroprotection than the 3-dose Recombivax HB. Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L. Assessment of seroprotection after HBV vaccination should be prioritized during the pretransplant period.

Analysis of Indeterminate QuantiFERON Assay Results in Solid Organ Transplant Candidates and Proposed Management Algorithm.

BACKGROUND: Identification and treatment of latent tuberculosis infection (LTBI) mitigate the risk of tuberculosis (TB) reactivation after transplantation. TB reactivation is higher in those with indeterminate QuantiFERON (QFT) than those with negative results. Management of indeterminate QFT results in the pretransplant period remains unclear. METHODS: We conducted a retrospective study of solid organ transplant (SOT) recipients, 18 y and older, who were screened with QFT assay pretransplantation at Mayo Clinic between January 2010 and June 2023. We examined the frequency of indeterminate QFT results, results of repeat LTBI screening, treatment decisions, and rate of posttransplant TB infection. RESULTS: Of 13 008 patients screened for LTBI before SOT, 736 (6%) patients had indeterminate QFT results. Among these, 247 (34%) underwent a second LTBI screening test, and 39 (5%) received LTBI treatment. Among 247 patients with a repeat LTBI screening test, 185 (75%), 48 (19%), and 14 (6%) were tested by QFT, T-SPOT.TB, or TST, respectively. The repeat QFT remained indeterminate in 160 (86%) patients, whereas all T-SPOT.TB results were negative. Posttransplant TB infection occurred in 2 (0.3%) patients; neither had a second TB screening test pretransplant nor received LTBI treatment. CONCLUSIONS: In SOT recipients with indeterminate QFT results at pretransplant evaluation, opting for T-SPOT.TB as a second test may be preferable over repeat QFT. TB infection after transplantation in patients with a pretransplant indeterminate QFT result was rare. Patient management and LTBI treatment in those with indeterminate QFT pretransplant should account for epidemiological risk factors, and shared decision-making is recommended.

Hepatitis B Virus Reactivation in Non-Liver Solid Organ Transplantation: Incidence and Risk Analysis.

INTRODUCTION: Hepatitis B virus reactivation (HBVr) can occur in solid organ transplant (SOT) recipients with previously inactive hepatitis B virus (HBV) infection. Previous studies have reported that HBVr is generally less than 10% in nonliver SOT recipients with past HBV infection. METHODS: We conducted a retrospective study from January 2018 to August 2023 at Mayo Clinic sites in Arizona, Florida, and Minnesota. We examined the antiviral prophylaxis strategy used and the characteristics of HBVr in hepatitis B core antibody-positive (HBcAb +) nonliver SOT adult recipients. Past HBV infection was defined as HBcAb + / hepatitis B surface antigen (HBsAg) -. Chronic HBV infection was defined as HBcAb + / HBsAg +. RESULTS: A total of 180 nonliver SOT recipients were identified during the study period. Indefinite antiviral prophylaxis was utilized in 77 recipients, and none developed HBVr after transplantation. In 103 recipients without antiviral prophylaxis, the incidence of HBVr was 12% (12/97) and 33% (2/6) in those with past HBV infection and chronic HBV infection. The incidence of HBVr in patients with past HBV infection is 16% (8/50), 15% (3/20), and 5% (1/22) in kidney, heart, and lungs, respectively. HBVr was more frequent in those who received alemtuzumab. Among 14 recipients with HBVr, none had HBV-associated liver failure or death. CONCLUSIONS: Our study observed a higher rate of HBVr (12%) in nonliver SOT recipients with past HBV infection compared to the previous studies. Further studies are needed to identify predictors of HBVr in nonliver SOT recipients and optimize antiviral prophylaxis guidance.

The Cascade of Care in Management of Solid Organ Transplant Candidates With Latent Tuberculosis Infection.

Background: Solid organ transplant (SOT) candidates should be screened and treated for latent tuberculosis infection (LTBI) to prevent tuberculosis (TB) reactivation after transplantation. We aimed to assess the steps from positive QuantiFERON (QFT) through LTBI treatment (cascade of care) in the SOT population. Methods: We conducted a retrospective study of SOT recipients older than 18 y with a positive QFT during pretransplant evaluation at the Mayo Clinic from January 2010 to June 2023. We analyzed each cascade step to determine associated drop-out factors for LTBI management. Results: Of 629 patients who had positive QFT results, 587 (93%) were evaluated by an infectious disease (ID) specialist, 478 (76%) were recommended to start LTBI treatment, 473 (75%) initiated LTBI treatment, and 457 (73%) completed LTBI treatment. LTBI treatment was not recommended in 109 patients evaluated by infectious disease, most of whom had previously received either LTBI (n = 72) or TB (n = 14) treatment. LTBI treatment was initiated before or after transplantation for 45% and 55% of patients, respectively. Isoniazid monotherapy was the most common regimen (92%), and adverse events were rare (7%). Seven patients developed active TB infection posttransplantation under various circumstances (3 without LTBI treatment, 1 during LTBI treatment, and 3 after completing LTBI treatment). Conclusions: Our findings demonstrate the variability of LTBI management in SOT recipients with positive QFT. When recommended, most patients completed LTBI treatment successfully. Nonetheless, active TB was noted regardless of whether patients received LTBI treatment. This study highlights the importance of optimizing LTBI management in this population.

Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections.

Ruxolitinib, a selective inhibitor of Janus kinases, is a standard treatment for intermediate/high-risk myelofibrosis (MF) but is associated with a predisposition to opportunistic infections, especially herpes zoster. However, the incidence and characteristics of invasive fungal infections (IFIs) in these patients remain uncertain. In this report, we present the case of a 59-year-old woman with MF who developed disseminated histoplasmosis after seven months of ruxolitinib use. The patient clinically improved after ten weeks of combined amphotericin B and azole therapy, and ruxolitinib was discontinued. Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. We also reviewed the literature on published cases of proven IFIs in patients with MF who received ruxolitinib. Including ours, we identified 28 such cases, most commonly due to Cryptococcus species (46%). IFIs were most commonly disseminated (39%), followed by localized lung (21%) infections. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies.

False-Reactive Fourth-Generation Human Immunodeficiency Virus Testing in Cancer Patients.

BACKGROUND: The fourth-generation (4th-gen) human immunodeficiency virus (HIV)-1/2 antibody/antigen (Ab/Ag) combination immunoassay currently used for HIV screening offers greater sensitivity than previous assays, but false-reactive results occur in up to 20% of patients. Large-scale observations in cancer patients are lacking. METHODS: We conducted a retrospective study of cancer patients seen at the University of Texas MD Anderson Cancer Center (March 2016-January 2023) who had reactive 4th-gen ARCHITECT HIV-1/2 Ab/Ag combination immunoassay results. We analyzed characteristics of patients with true-reactive and false-reactive results, defined based on Centers for Disease Control and Prevention criteria. RESULTS: A total of 43 637 patients underwent 4th-gen HIV screening, and 293 had reactive 4th-gen HIV test results. Twenty-one patients were excluded because they did not have cancer. Among the remaining 272 patients, 78 (29%) had false-reactive results. None of these patients experienced delays in their cancer treatment, but 26% experienced mental distress. Multivariate logistic regression analysis identified 5 predictors of having false-reactive results: age >60 years (adjusted odds ratio [aOR], 6.983; P < .0001), female sex (aOR, 6.060; P < .0001), race/ethnicity (Black: aOR, 0.274; Hispanic: aOR, 0.236; P = .002), syphilis coinfection (aOR, 0.046; P = .038), and plant alkaloids therapy (aOR, 2.870; P = .013). CONCLUSIONS: False-reactive 4th-gen HIV test results occur in almost one-third of cancer patients. Physicians should be aware of the high rates of false-reactive HIV screening results in this patient population. These findings may have implications for counseling regarding testing, especially among those at low risk for HIV infection.

Invasive mucorales sinusitis in a young patient with Emberger syndrome and newly diagnosed AML: A case report and literature review of invasive fungal infections in GATA2 deficiency.

Germline pathogenic variants (PVs) in the gene encoding the GATA2 transcription factor can result in profound reductions of monocytes, dendritic cells, natural killer cells and B cells. GATA2 PVs are associated with an increased risk of myeloid malignancies and a predisposition to nontuberculous mycobacterial and human papillomavirus infections. Additionally, invasive fungal infections (IFIs) have been reported in individuals with GATA2 PVs, even in the absence of myeloid malignancies. In this report, we present the case of a 40-year-old man with Emberger syndrome (GATA2 mutation, recently diagnosed acute myeloid leukaemia [AML] and history of lymphedema with hearing loss) who developed Mucorales sinusitis while receiving his first course of remission induction chemotherapy. Additionally, we review the literature on all published cases of proven IFIs in patients with GATA2 PVs. Clinicians should be aware that patients with GATA2 PVs could be vulnerable to opportunistic IFIs, even in the absence of AML and antineoplastic therapy. Furthermore, the distinctly unusual occurrence of mucormycosis during the first course of induction chemotherapy for AML in our patient indicates that patients with germline GATA2 PVs receiving induction chemotherapy for AML might be at high risk for early onset of IFIs due to aggressive, opportunistic moulds.

Hepatitis B Virus Reactivation in Patients Receiving Bruton Tyrosine Kinase Inhibitors.

BACKGROUND: Bruton tyrosine kinase (BTK) inhibitors are used to treat B-cell hematologic malignancies. Ibrutinib has been associated with hepatitis B virus (HBV) reactivation. We sought to identify patients with hematologic malignancies who developed HBV reactivation after receiving first-generation (ibrutinib) or second-generation (acalabrutinib and zanubrutinib) BTK inhibitors. METHODS: We retrospectively studied all consecutive patients with hematologic malignancies with past HBV infection (HBV surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) or chronic HBV infection (HBsAg positive and anti-HBc positive) treated with BTK inhibitors at our institution from November 1, 2015, through November 1, 2022. RESULTS: Of 82 patients initially identified, 53 were excluded (11 because of false-positive anti-HBc results, and 42 because they were receiving anti-HBV prophylaxis owing to recent receipt of anti-CD20 monoclonal antibodies). The 29 remaining patients were further analyzed and 3 (10%; 2/28 with past and 1/1 with chronic HBV infection) were found to have HBV reactivation. One patient received ibrutinib, and 2 received acalabrutinib. All developed HBV-associated hepatitis requiring anti-HBV therapy and survived. One patient continued receiving acalarutinib. Among the patients with past HBV infection, 13 received ibrutinib and 1 (8%) had HBV reactivation; 14 received acalabrutinib and 1 (7%) had HBV reactivation (P = 1.0). CONCLUSIONS: HBV reactivation risk is intermediate in patients with past HBV infection who receive BTK inhibitors. For patients with past HBV infection who received BTK inhibitors, data are insufficient to recommend universal anti-HBV prophylaxis, but monitoring for HBV reactivation is warranted.

Incidence of Pneumocystis Pneumonia in Immunocompromised Patients without Human Immunodeficiency Virus on Intravenous Pentamidine Prophylaxis: A Systematic Review and Meta-Analysis.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is a first-line Pneumocystis pneumonia (PCP) prophylaxis agent, but monthly intravenous pentamidine (IVP) is used in immunocompromised hosts without human immunodeficiency virus (HIV) infection because IVP is not associated with cytopenia and delayed engraftment. METHOD: We performed a systematic review and meta-analysis to estimate breakthrough PCP incidence and adverse reactions in HIV-uninfected immunocompromised patients receiving IVP. MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from their inception until 15 December 2022. RESULTS: The pooled incidence of breakthrough PCP with IVP was 0.7% (95% CI, 0.3-1.4%, 16 studies, 3025 patients) and was similar when used as first-line prophylaxis (0.5%; 95% CI, 0.2-1.4%, 7 studies, 752 patients). The pooled incidence of adverse reactions was 11.3% (95% CI, 6.7-18.6%, 14 studies, 2068 patients). The pooled adverse event-related discontinuation was 3.7% (95% CI, 1.8-7.3%, 11 studies, 1802 patients), but was lower in patients receiving IVP monthly (2.0%; 95% CI 0.7-5.7%, 7 studies, 1182 patients). CONCLUSION: Monthly IVP is an appropriate second-line agent for PCP prophylaxis in certain non-HIV immunocompromised hosts, especially in patients with hematologic malignancies and hematopoietic stem cell transplant recipients. Using IVP for PCP prophylaxis as an alternative to oral TMP-SMX while patients are unable to tolerate enteral medication administration is feasible.

Evaluating the Nephrotoxicity of Area-under-the-Curve-Based Dosing of Vancomycin with Concomitant Antipseudomonal Beta-Lactam Antibiotics: A Systematic Review and Meta-Analysis.

Background and Objectives: Vancomycin combined with piperacillin/tazobactam (vancomycin + piperacillin/tazobactam) has a higher risk of acute kidney injury (AKI) than vancomycin combined with cefepime or meropenem. However, it is uncertain if applying area under the curve (AUC)-based vancomycin dosing has less nephrotoxicity than trough-based dosing in these combinations. Materials and Methods: We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to December 2022. We examined the odds ratio (OR) of AKI between vancomycin + piperacillin/tazobactam and the control group. The control group was defined as vancomycin combined with antipseudomonal beta-lactam antibiotics, except for piperacillin-tazobactam. Results: The OR for AKI is significantly higher in vancomycin + piperacillin/tazobactam compared with the control group (3 studies, 866 patients, OR of 3.861, 95% confidence interval of 2.165 to 6.887, p < 0.05). In the sample population of patients who received vancomycin + piperacillin/tazobactam (2 studies, 536 patients), the risk of AKI (OR of 0.715, 95% CI of 0.439 to 1.163, p = 0.177) and daily vancomycin dose (standard mean difference-0.139, 95% CI-0.458 to 0.179; p = 0.392) are lower by AUC-based dosing than trough-based dosing, although it is not statistically significant. Conclusions: Nephrotoxicity is higher when combined with piperacillin/tazobactam than other antipseudomonal beta-lactam antibiotics (cefepime or meropenem) using the AUC-based dosing. However, applying the AUC-based dosing did not eliminate the risk of AKI or significantly reduce thedaily vancomycin dose compared with the trough-based dosing in the available literature.

Undetectable JC virus CSF PCR in patients with JC virus-induced progressive multifocal leukoencephalopathy.

The diagnosis of progressive multifocal leukoencephalopathy (PML) is based on a combination of clinical, radiographic, and laboratory findings. However, negative JC polyomavirus (JCPyV) PCR in CSF does not always rule out JCPyV-related PML. In this narrative review, we sought to examine the characteristic of biopsy-proven PML in patients with undetectable JCPyV CSF PCR and provide alternative approaches in this scenario.

Streptococcus gordonii empyema: A case report and literature review.

Empyema is often caused by Streptococcus anginous species, followed by Streptococcus pneumoniae. The organism Streptococcus gordonii belongs to the Streptococcus mitis group, which rarely causes empyema. We report the case of a 59-year-old man who presented with exertional dyspnea and chest pain on the right side. The image obtained showed effusion on the right side. Streptococcus gordonii was recovered from purulent pleural effusion culture. The patient underwent video-assisted thoracoscopic surgery with decortication, pneumolysis and received antibiotics for 13 days. A total of seven cases were analyzed after combining six cases in the literature and our presented case. The majority of Streptococcus gordonii empyema patients were male (six patients, 86%) and empyema on the right side (five patients, 71%). Common risk factors included poor dental hygiene or recent dental procedure (three patients, 43%), diabetes mellitus (three patients, 43%), and smoking (three patients, 43%). Only a few cases developed empyema-related complications, including bacteremia (one patient, 14%) and spleen abscesses (one patient, 14%). Most patients underwent chest tube insertion (seven patients, 100%) and survived without recurrent empyema (six patients, 86%).

Hepatitis E Virus Infection in Cancer Patients.

Hepatitis E virus (HEV) infection in immunocompetent patients can lead to chronic hepatitis and liver failure. However, the burden of HEV infection in cancer patients is largely unknown. We studied the characteristics of HEV infection in patients at a tertiary care cancer center in the United States. This retrospective study included adult cancer patients with HEV infection diagnosed between September 2011 to September 2021. A total of 405 patients were tested for HEV, and 63 (16%) had detectable HEV IgG. Thirty-three patients (52%) were male, 43 were born in America (68%), 46 (73%) were screened for HEV because of pre-existing liver conditions, and 22 (35%) had hematological malignancies. Only 2 patients had detectable HEV RNA. The first patient had myelodysplastic syndrome and underwent allogeneic stem cell transplantation (HSCT). He developed elevated liver enzymes with HEV RNA 14,000 IU/mL (4.2 log IU/mL) 13 months after HSCT. After reducing immunosuppression, his HEV viremia resolved. The second patient had diffuse large B-cell lymphoma and underwent anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. She had elevated liver enzymes with HEV RNA 4,560,000 IU/mL (6.7 log IU/mL) 12 months after CAR T-cell therapy. She developed chronic HEV infection, and ribavirin treatment failed. Now she is being considered for salvage treatment with peginterferon alfa-2a and ribavirin. This study is the first report of chronic HEV infection in patients who received CAR T-cell therapy. HEV infection in cancer patients appears to be at least as common as in the general population. Cancer patients with hematologic malignancies may be at risk for HEV viremia and chronic infection refractory to antiviral treatment.

Telemedicine experience of NYC Internal Medicine residents during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic challenged the resilience of public health, including diagnostic testing, antiviral development and transmission prevention. In addition, it also affected the medical education of many residents and learners throughout the country. Historically, physicians undergoing their residency training were not involved in telemedicine. However, in response to the challenges faced due to COVID-19, the Accreditation Council for Graduate Medical Education (ACGME) released a provision in May 2020 to allow residents to participate in telemedicine. METHOD: Lincoln Medical Center, located in the South Bronx of New York City, currently has 115 Internal Medicine residents, and telemedicine clinic visits have been conducted by residents since June 2020. An anonymous 25-question survey was sent to all Internal Medicine residents between August 8, 2020 to August 14, 2020. RESULT: Of 115 residents, 95 (82.6% of the residents) replied to this questionnaire. Residents revealed feeling less confident in managing chronic diseases through telemedicine visits. The survey also shows that 83.1% of respondents prefer in-person visits during their training, 65.3% feel that the telemedicine experience will affect their future career choice, and 67.4% would prefer less than 50% of visits to be telemedicine in their future careers. OUTCOME: The purpose of the new ACGME rules allowing telemedicine was to prevent the undertraining of residents and maintain health care for the patient during the COVID-19 pandemic. This affects residency training and the experiences of residents, which in turn can influence their future career plans.

Austrian syndrome followed by severe cutaneous adverse reactions in a HIV patient.

Invasive pneumococcal infection, defined as the combination of pneumonia with endocarditis and meningitis, was described as Austrian syndrome in the 1800s. We report the case of a 63-year-old woman with underlying human immunodeficiency virus who presented with fever and altered mental status. Subsequent workup supported a diagnosis of Austrian syndrome. During the 5-week course of ceftriaxone treatment, she developed fever, pruritus and follicular accentuation throughout the body. Labs were significant for eosinophilia, which along with systemic symptoms, supported the diagnosis of a drug reaction. Coagulase negative staphylococcus bacteremia was discovered when the patient developed septic shock. Subsequently, diffuse desquamative eruption with rapidly progressing sloughing appeared and biopsy proved toxic epidermal necrolysis. Patient eventually succumbed to multiorgan failure.