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.

New-Onset Cervical Lymphadenopathy in a Patient Undergoing Treatment of Pulmonary Mycobacterium avium Complex Infection: Toxoplasmosis Lymphadenitis.

Immunocompetent hosts with toxoplasmosis are usually asymptomatic. However, T. gondii can present as an acute systemic infection. Symptomatic patients usually have a benign, self-limited course that typically lasts from a few weeks to months. Herein, we present a 66-year-old immunocompetent female who developed dysphagia and new-onset cervical lymphadenopathy during pulmonary Mycobacterium avium complex treatment.

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Induced by Long-Term Use of Citalopram and Short-Term Use of Naproxen.

BACKGROUND Use of selective serotonin reuptake inhibitors (SSRIs) has been reported to be associated with the syndrome of inappropriate antidiuretic hormone (SIADH), although it is uncommon. Nonsteroidal anti-inflammatory drugs (NSAIDs), as a sole agent, are an even rarer cause of SIADH. Despite being documented in the literature, the understanding of the mechanism of both agents is limited. Here, we report a case of a patient taking both of these medications, a dangerous combination that led to the development of SIADH. CASE REPORT An 88-year-old woman with a history of asymptomatic chronic hyponatremia presented to our facility with symptomatic acute-on-chronic hyponatremia after she started using naproxen in addition to her daily citalopram. Her hyponatremia symptoms resolved after discontinuing these 2 offending agents, along with administration of fluid restriction and oral sodium supplements. CONCLUSIONS Naproxen is commonly prescribed and is often taken by elderly patients to control long-term or short-term pain. SSRIs, on the other hand, are a first-line treatment for depression and are usually prescribe by a psychiatrist. Hyponatremia is a rare medication adverse effect that should be kept in mind when treating these patients with either of these medications, and should especially be considered when combining them. Medication reconciliation should be done carefully by the provider to avoid adverse effects and drug interactions. When hyponatremia is encountered, options for future medication prescriptions include rechallenging with the same medication, switching to a different medication with the same mechanism of action, or using a medication from another class altogether. Monitoring of serum sodium level is warranted when titrating the offending agent.

Quality assessment of weekend discharge: a systematic review and meta-analysis.

PURPOSE: Hospital bed utility and length of stay affect the healthcare budget and quality of patient care. Prior studies already show admission and operation on weekends have higher mortality rates compared with weekdays, which has been identified as the 'weekend effect.' However, discharges on weekends are also linked with quality of care, and have been evaluated in the recent decade with different dimensions. This meta-analysis aims to discuss weekend discharges associated with 30-day readmission, 30-day mortality, 30-day emergency department visits and 14-day follow-up visits compared with weekday discharges. DATA SOURCES: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched from January 2000 to November 2019. STUDY SELECTION: Preferred reporting items for systematic reviews and meta-analyses guidelines were followed. Only studies published in English were reviewed. The random-effects model was applied to assess the effects of heterogeneity among the selected studies. DATA EXTRACTION: Year of publication, country, sample size, number of weekday/weekend discharges, 30-day readmission, 30-day mortality, 30-day ED visits and 14-day appointment follow-up rate. RESULTS OF DATA SYNTHESIS: There are 20 studies from seven countries, including 13 articles from America, in the present meta-analysis. There was no significant difference in odds ratio (OR) in 30-day readmission, 30-day mortality, 30-day ED visit, and 14-day follow-up between weekday and weekend. However, the OR for 30-day readmission was significantly higher among patients in the USA, including studies with high heterogeneity. CONCLUSION: In the USA, the 30-day readmission rate was higher in patients who had been discharged on the weekend compared with the weekday. However, interpretation should be cautious because of data limitation and high heterogeneity. Further intervention should be conducted to eliminate any healthcare inequality within the healthcare system and to improve the quality of patient care.