Breakthrough Pneumocystis jirovecii Pneumonia in an Allogeneic Hematopoietic Stem Cell Transplant Recipient.

Pneumocystis carinii pneumonia (PCP), which is currently referred to as Pneumocystis jirovecii pneumonia, is an opportunistic fungal infection that commonly affects immunocompromised patients, and it is potentially fatal. Individuals at risk include those whose host immunity has been altered by underlying disease states, such as HIV and cancer patients, as well as transplant recipients and those taking immunosuppressive medications. Here, we present a case of a breakthrough PCP infection of an adult allogeneic hematopoietic stem cell transplant patient who was infected despite prophylaxis with inhaled pentamidine. The patient's transplant course was complicated by acute graft-versus-host disease (GVHD), which was treated with tacrolimus, prednisone, beclomethasone, and budesonide. Treatments for GVHD, which include immunosuppressive therapies, are a risk factor for PCP. Thus, the patient was on prophylactic treatment with inhaled pentamidine. The case presents challenges that immunocompromised patients face, particularly those undergoing allogeneic hematopoietic stem cell transplantation. While the patient received prophylactic treatment, there was still a breakthrough PCP infection. We highlight the risks this infection can cause and the need to promptly address these infections to prevent complications and optimize prophylactic regimens.

Real-world Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels.

Background: Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with subtherapeutic concentrations with the newer delayed-release tablet formulation. Methods: In this retrospective, single-center cohort study at a national comprehensive cancer center, all oncology patients receiving delayed-release posaconazole at standard dosing of 300 mg orally per day from 06/2021 to 07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical, and laboratory data were evaluated to identify risk factors associated with subtherapeutic drug levels at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Results: Of 110 patients identified, 98 met criteria for inclusion in the study. The median time from initiation of posaconazole to drug level assessment was 13 days, and the median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis, 5 (22.7%) failed to achieve concentrations ≥0.7 µg/mL, and of 76 patients receiving posaconazole for treatment, 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multivariable analysis, albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with subtherapeutic levels. For a higher target of ≥1.8 µg/mL, only albumin ≤3 g/dL was associated with subtherapeutic levels for the variables evaluated. Conclusions: A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole, particularly for the treatment of invasive fungal infection, could be considered.

Chemotherapy Extravasation Causing Soft-Tissue Necrosis Mimicking Infection: A Longitudinal Case Study.

Extravasation injuries are uncommon, underreported, and often misdiagnosed in patients. The signs and symptoms of extravasation injuries vary from simple pain and tenderness to tissue necrosis and potentially fatal secondary infections. Extravasation may progress to more severe conditions such as necrotizing fasciitis (NF) or cellulitis, so special care is needed by physicians to identify and treat these injuries correctly. Here, we explore a case study on extravasation injuries mimicking NF leading to infectious complications and discuss the proper diagnosis and treatment of extravasation injuries as well as other NF-mimicking diseases. We present a case of a 44-year-old Hispanic male with a history of B-cell acute lymphoblastic leukemia who underwent inpatient chemotherapy treatment via a chest port.

Safety and Outcomes With Combination Therapy With Sarilumab and Baricitinib for Severe COVID-19 Respiratory Infection in Cancer Patients.

OBJECTIVES: This study aims to describe the clinical outcomes of combination therapy with sarilumab and baricitinib for severe novel Coronavirus-19 (COVID-19) infection in cancer patients. With this study, we aim to evaluate the role of expanded immunotherapy for severely ill patients with COVID-19 respiratory infections with limited options. The secondary objective is to assess the safety of combination therapy with sarilumab and baricitinib for severe COVID-19 infection. METHODS: This was a retrospective cohort study of patients admitted to Moffitt Cancer Center with COVID-19 infection between January 2020 and April 2022. Our research received a waiver to sign consent by the patients according to our institutional IRB because it was free of any risk for the patients and respected the patient's privacy. Following the Institutional IRB approval and relevant Equator guidelines, we collected information on patients with severe COVID-19 infection and received sarilumab and baricitinib. We evaluated the survival rate and safety of combination therapy. All the patient's information was de-identified to protect their information according to Health Insurance Portability and Accountability Act (HIPAA). RESULTS: Four patients were included in the data analysis. Two survived, and two of them died (Table 1). All the patients that survived were previously vaccinated. Among the two patients who died, one was vaccinated, and the other was unvaccinated. All the patients tolerated the combination therapy well, and none of the patients who survived developed secondary infections or COVID-19-associated complications beyond 12 months of discharge. CONCLUSION: Our study explores the potential safe combination use of different immune modulators targeting multiple pathways of the inflammatory cascade for severe and refractory COVID-19 respiratory infections in high-risk oncology patients. The small number of patients in our observational study was a limitation. A larger sample of patients will be needed to conclude more precisely the efficacy of the combination therapy of sarilumab and baricitinib for refractory cases of severe COVID-19 respiratory infection. Moreover, exploring other cytokine release signaling pathway targets may be the key to significantly reducing inflammation and further pulmonary fibrosis with chronic unbearable respiratory sequela.

Intestinal Coccidian Infections in Cancer Patients: A Case Series.

Introduction Coccidian protozoa and microsporidian fungi are opportunistic pathogens increasingly implicated in infections in immunosuppressed individuals. These parasites typically infect the intestinal epithelium, resulting in secretory diarrhea and malabsorption. The disease burden and timeline are both greater and longer among immunosuppressed patients. Therapeutic options for immunocompromised individuals are limited. As a result, we wanted to better characterize the disease course and treatment efficacy of these parasitic gastrointestinal infections. Methods We performed a single-center, retrospective MedMined (BD Healthsight Analytics, Birmingham, AL, USA) chart review of patients between January 2012 and June 2022 diagnosed with coccidian or microsporidian infections. Relevant data were collected from Cerner's PowerChart (Oracle Cerner, Austin, TX, USA). Descriptive analysis was performed with IBM SPSS Statistics (IBM Corp., Armonk, NY, USA), and Microsoft Excel (Microsoft, Redmond, WA, USA) was used to generate graphs and tables. Results In these 10 years, there were 17 patients with Cryptosporidium infections, four with Cyclospora infections, and no positive cultures for Cystoisospora belli or microsporidian infections. In both infections, the majority of patients experienced diarrhea, fatigue, and nausea, with vomiting, abdominal pain, appetite loss, weight loss, and fever occurring to a lesser degree. Nitazoxanide was the most common treatment for Cryptosporidium, while trimethoprim-sulfamethoxazole or ciprofloxacin were the treatments of choice for Cyclospora. Of the Cryptosporidium infections, three received combination therapy with azithromycin, immunoreconstitution, or IV immunoglobulins. Among the four Cyclospora-infected patients, one received combination therapy of ciprofloxacin and trimethoprim-sulfamethoxazole. Treatment lasted around two weeks, and 88% of Cryptosporidium patients and 75% of Cyclospora patients had a resolution of symptoms. Conclusion The most detected coccidian infection was Cryptosporidium, followed by Cyclospora, with the lack of Cystoisospora or microsporidian infections likely due to diagnostic limitations and prevalence. Cryptosporidium and Cyclospora likely caused their associated symptoms in most cases, with other possible etiologies, including graft-versus-host disease, medications, and feeding tubes. The small number of patients receiving combination therapy prohibited a comparison with monotherapy. In our patient population, though, there was a clinical response to treatment despite immunosuppression. While promising, additional randomized control experiments are required to fully understand the efficacy of parasitic treatments.

The epidemiology, mechanisms, diagnosis and treatment of cardiovascular disease in adult patients with HIV.

More than 1.2 million people in the United States have Human Immunodeficiency Virus (HIV) infections but 13% of these people are unaware of their HIV infection. Current combination antiretroviral therapy (ART) does not cure HIV infection but rather suppresses the infection with the virus persisting indefinitely in latent reservoirs in the body. As a consequence of ART, HIV infection has changed from a fatal disease in the past to a chronic disease today. Currently in the United States, more than 45% of HIV+ individuals are greater than 50 years of age and 25% will be greater than 65 years of age by 2030. Atherosclerotic cardiovascular disease (CVD), including myocardial infarction, stroke, and cardiomyopathy, is now the major cause of death in HIV+ individuals. Novel risk factors, including chronic immune activation and inflammation in the body, antiretroviral therapy, and traditional CVD risk factors, such as tobacco and illicit drug use, hyperlipidemia, the metabolic syndrome, diabetes mellitus, hypertension, and chronic renal disease, contribute to cardiovascular atherosclerosis. This article discusses the complex interactions involving HIV infection, the novel and traditional risk factors for CVD, and the antiretroviral HIV therapies which can contribute to CVD in HIV-infected people. In addition, the treatment of HIV+ patients with acute myocardial infarction, stroke, and cardiomyopathy/heart failure are discussed. Current recommended ART and their major side effects are summarized in table format. All medical personnel must be aware of the increasing incidence of CVD on the morbidity and mortality in HIV infected patients and must be watchful for the presence of CVD in their patients with HIV.

ExPeCT: a randomised trial examining the impact of exercise on quality of life in men with metastatic prostate cancer.

PURPOSE: All patients living with cancer, including those with metastatic cancer, are encouraged to be physically active. This paper examines the secondary endpoints of an aerobic exercise intervention for men with metastatic prostate cancer. METHODS: ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells), was a multi-centre randomised control trial with a 6-month aerobic exercise intervention arm or a standard care control arm. Exercise adherence data was collected via heart rate monitors. Quality of life (FACT-P) and physical activity (self-administered questionnaire) assessments were completed at baseline, at 3 months and at 6 months. RESULTS: A total of 61 patients were included (69.4 ± 7.3 yr, body mass index 29.2 ± 5.8 kg/m2). The median time since diagnosis was 34 months (IQR 7-54). A total of 35 (55%) of participants had > 1 region affected by metastatic disease. No adverse events were reported by participants. There was no effect of exercise on quality of life (Cohen's d = - 0.082). Overall adherence to the supervised sessions was 83% (329 out of 396 possible sessions attended by participants). Overall adherence to the non-supervised home exercise sessions was 72% (months 1-3) and 67% (months 3-6). Modelling results for overall physical activity scores showed no significant main effect for the group (p-value = 0.25) or for time (p-value = 0.24). CONCLUSION: In a group of patients with a high burden of metastatic prostate cancer, a 6-month aerobic exercise intervention did not lead to change in quality of life. Further exercise studies examining the role of exercise for people living with metastatic prostate cancer are needed. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT02453139) on May 25th 2015.

Neurological update: structural and functional imaging in epilepsy surgery.

Structural and functional imaging prior to surgery in drug-resistant focal epilepsy, has an important role to play alongside electroencephalography (EEG) techniques, in planning the surgical approach and predicting post-operative outcome. This paper reviews the role of structural and functional imaging of the brain, namely computed tomography (CT), magnetic resonance imaging (MRI), functional MRI (fMRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging in the preoperative work-up of people with medically refractory epilepsy. In MRI-negative patients, the precise localisation of the epileptogenic zone may be established by demonstrating hypometabolism on PET imaging or hyperperfusion on SPECT imaging in the area surrounding the seizure focus. These imaging modalities are far less invasive than intracranial EEG, which is the gold standard but requires surgical placement of electrodes or recording grids. Even when intracranial EEG is needed, PET or SPECT imaging can assist in the planning of EEG electrode placement, due to its' limited spatial sampling. Multimodal imaging techniques now allow the multidisciplinary epilepsy surgery team to identify and better characterise focal pathology, determine its' relationship to eloquent areas of the brain and the degree of interconnectedness within both physiological and pathological networks, as well as improve planning and surgical outcomes for patients. This paper will update the reader on this whole field and provide them with a practical guide, to aid them in the selection of appropriate investigations, interpretation of the findings and facilitating patient discussions in individuals with drug-resistant focal epilepsy.

The prognostic value of the derived neutrophil-to-lymphocyte ratio (dNLR) in patients treated with immune checkpoint inhibitors.

BACKGROUND: The (derived) neutrophil-to-lymphocyte ratio (dNLR) is a potential predictive biomarker in the era of checkpoint inhibitors (CPI). An elevated dNLR is associated with worse outcomes across several malignancies. However, there is no clearly defined cut-off in the clinical setting. AIM: To compare outcomes in patients prescribed CPI with a baseline dNLR0 > 3 and dNLR0 ≤ 3. The dNLR6 was measured 6 weeks later to determine its impact on patient overall survival (OS). METHODS: Prospectively maintained pharmacy databases in a regional cancer centre were interrogated for patients who were prescribed CPI in the advanced setting between January 2017 and May 2020. RESULTS: There were 121 patients with advanced cancer and a median age of 68 (range 30 to 88) years. Forty-four percent (n = 53) received prior systemic therapy. Patients with an initial dNLR0 > 3 when compared with a dNLR0 ≤ 3 had significantly shorter median progression-free survival (PFS), 3 vs. 14 months (p = 0.001) and median OS, 6.4 vs. 30.2 months (p = 0.001). Patients with an initial dNLR0 > 3 and increased dNLR at 6 weeks (dNLR6) had significantly reduced median PFS (3.5 vs. 14.7 months, p = 0.03) and OS (5.7 vs. 16.3, p = 0.03) when compared with those whose dNLR decreased. In the dNLR0 ≤ 3 cohort, any increased dNLR when compared with decreased dNLR after 6 weeks of CPI had significantly reduced PFS (8.4 months vs. NR, p = 0.01) and OS (24.2 months vs. NR, p = 0.02). CONCLUSIONS: Lower pre-CPI treatment dNLR is associated with improved OS. A decrease in dNLR during treatment confers improved OS.

Malignant pleural disease.

Malignant pleural disease represents a growing healthcare burden. Malignant pleural effusion affects approximately 1 million people globally per year, causes disabling breathlessness and indicates a shortened life expectancy. Timely diagnosis is imperative to relieve symptoms and optimise quality of life, and should give consideration to individual patient factors. This review aims to provide an overview of epidemiology, pathogenesis and suggested diagnostic pathways in malignant pleural disease, to outline management options for malignant pleural effusion and malignant pleural mesothelioma, highlighting the need for a holistic approach, and to discuss potential challenges including non-expandable lung and septated effusions.

Uncommon presentations of common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder that causes decreased immunity and increased susceptibility to infections. It affects B lymphocyte differentiation, resulting in predominantly bacterial and less frequently viral, fungal, and protozoal infections. The respiratory and gastrointestinal tracts where antibody defences are essential are usually affected. Individuals with CVID are also predisposed to developing lymphoid and gastrointestinal malignancies. We present two cases with rare infectious and oncological complications of CVID, including a patient with Mycobacterium avium complex-intracellular infection and ovarian cancer, and another patient with group B Streptococcus empyema of the lung with acute myeloid leukaemia. The main objective of this study is to highlight how CVID-induced hypogammaglobulinaemia can lead to rare infections and malignancies. The management of these complications can vary according to severity, but an awareness of their existence is crucial to diagnose them promptly in an already immunocompromised CVID patient.

Nocardia niwae Disseminated Nocardiosis: A Novel Species Presenting Concurrently With Lung Adenocarcinoma.

Nocardia includes over 90 species of filamentous gram-positive bacilli that may cause disease in immunocompromised or immunocompetent hosts. Presentations may include pulmonary, 4, cutaneous, or disseminated infections. Tissue diagnosis may be required as it may mimic alternative etiologies. There is a paucity of data regarding rarer species of Nocardia. Intraspecies variability in antimicrobial susceptibility limits many treatment regimens to in-vitro activity data and treatment regimens often must be tailored to individual patients based on microbiologic cultures. We describe the case of a 63-year-old female who presented with disseminated Nocardia niwae, a species that was previously first identified in Florida for which little clinical data is known, along with concurrent lung adenocarcinoma with pulmonary and central nervous system lesions. Typical susceptibility patterns are discussed along with potential side effects of antimicrobial therapy.

Multidisciplinary approach in diagnosis and treatment of COVID-19-associated mucormycosis: a description of current reports.

Background: We reviewed the epidemiology, risk factors, pathophysiology, and clinical presentations of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM), then discussed the importance of rapid diagnosis and treatment facilitated by multidisciplinary approach. Main body: India has reported world's highest number of CAM cases where Rhizopus arrhizus was the most predominant etiology. CAM caused by Rhizopus microsporus was the most common from the rest of the world. Multiple risk factors for CAM were identified including diabetes mellitus, inappropriate corticosteroid use, COVID-19-related hypoxia, and lung damage.Rhino-orbito-cerebral mucormycosis (ROCM) accounted for almost 90% of CAM in India while 64% of global cases were ROCM. Less than 10% of CAM from India were pulmonary while the rest of the world reported 21% of pulmonary CAM.CAM is diagnosed by confirmed SARS-CoV2 infection along with clinical, radiological, histopathological, and/or microbiological evidence of mucormycosis. In patients with risks of CAM and associated symptoms, CT or MRI are recommended. If ROCM is suspected, endoscopy and biopsy are recommended. If pulmonary CAM is suspected, tissue biopsies, nasal samples, or bronchoalveolar lavage is recommended with histopathological exams.Early diagnosis, surgical, and pharmaceutical interventions are key to treat mucormycosis. Upon diagnosis, antifungal therapy with liposomal amphotericin B (IV) is considered first-line of therapy. Alternatively, posaconazole (PO/IV) or isavuconazole (PO/IV) can be used. Conclusion: Treating CAM requires a multidisciplinary approach for early diagnosis and prompt initiation of interventions to maximize patient's chance of survival.

Infectious Complications of DiGeorge Syndrome in the Setting of Malignancy.

This report describes a case of a young man with DiGeorge Syndrome, repaired Tetralogy of Fallot, relapsed metastatic Hodgkin's Lymphoma, immunodeficiency, and a history of recurrent and severe infections. A review of the literature indicates that patients with DiGeorge Syndrome are at greater risk for infection, malignancy, and cardiac events due to anatomic and immunologic complications resulting from a deletion in the 22q11.2 chromosome. As an increased number of patients with DiGeorge Syndrome are surviving into adulthood, it is important to understand the progression of the disease and the long-term implications associated with variable degrees of thymic hypoplasia and immune deficiency.

Bacillus Cereus bacteremia complicated by brain abscess in a severely immunocompromised patient: Addressing importance of early recognition and challenges in diagnosis.

Bacillus cereus (B. cereus) is a known cause of a food poisoning in the general population. However, it can cause life-threatening sepsis and shock in severely immunocompromised patients with hematologic malignancies, which frequently lead to central nervous system (CNS) infections associated with high mortality and morbidity. In this case report, we describe a patient with a newly diagnosed acute myeloid leukemia that underwent induction chemotherapy and developed B. cereus infection that was associated with septic shock and brain abscesses. Definitive diagnosis of multiple brain abscesses was not manifested with routine microbiological investigation but required the use of 16S ribosomal (rRNA) gene polymerase chain reaction (PCR) sequencing of the resected brain lesion. The patient was eventually treated with 8-week course of intravenous vancomycin and high-dose ciprofloxacin which led to a full recovery. This report highlights the significant risk posed by B. cereus infection in neutropenic patients, the use of 16S rRNA PCR sequencing test for definitive diagnosis and use of combination therapy for successful treatment of B. Cereus CNS infection.

Zoonotic Bacterial Respiratory Infections Associated With Cats and Dogs: A Case Series and Literature Review.

Cats and dogs make up an essential part of the household for families in the United States. Close contact with pets can carry a risk of potential infectious disease transmission. This case series outlines causes of zoonotic pneumonia associated with cats and dogs, with a particular focus on the three cases presented of respiratory infection with Bordetella (B.) bronchiseptica and Pasteurella (P.) multocida in patients with an underlying malignancy. B. bronchiseptica is a rare bacterial pathogen in humans that can cause disease in immunocompromised individuals. Interpreting the significance of B. bronchiseptica as a pathogenic agent can be challenging given that this microbe often accompanies other organisms in culture. P. multocida is another important pathogen known to cause severe respiratory infection in immunocompromised populations or those with certain underlying comorbidities. A broadened differential for other bacterial etiologies of zoonotic respiratory infection acquired from dogs or cats includes Francisella tularensis, Yersinia pestis, Coxiella burnetii, and Bartonella henselae. These pathogens should be considered in the correct clinical context. Pets also play a role as reservoirs for the transmission of resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus intermedius group (SIG), and extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae. Immunocompromised individuals must be educated on the potential for household transmission of zoonotic disease and how to limit certain types of close contact with pets. This report also highlights the importance of flea and tick control in pets for the prevention of zoonotic disease spread.

Rosacea Granulomatosis in a Neutropenic Leukemic Patient.

Rosacea granulomatosis is a common, chronic skin disorder that primarily affects the central face, namely the cheek, nose, chin, and central forehead. Although rosacea is mainly a disorder of innate and adaptive immunity, a variety of endogenous and exogenous triggers such as Demodex may stimulate it. Often found as commensal organisms in human skin, Demodex ​​​​​​​can be parasitic if there is a change in the host's cutaneous environment. This is especially relevant for immunosuppressed patients, who need prompt treatment to prevent further complications. We review the literature regarding rosacea granulomatosis in immunosuppression and present an acute myelogenous leukemia patient with severe neutropenia, which may have promoted the development of rosacea due to Demodex ​​​​​​​mite proliferation. This local proliferation of the ectoparasite on the face can cause an atypical skin rash that mimics severe infections in the setting of neutropenia.

Targeting OXPHOS and the electron transport chain in cancer; Molecular and therapeutic implications.

Oxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought to be reduced in tumours and that glycolysis was the critical pathway for generation of ATP but it is now clear that OXPHOS, at least in many tumour types, plays a critical role in delivering the bioenergetic and macromolecular anabolic requirements of cancer cells. There is now great interest in targeting the OXPHOS and the electron transport chain for cancer therapy and in this review article we describe current therapeutic approaches and challenges.

First Case of Infective Endocarditis With Streptococcus equinus in an Immunocompetent Patient in North America: A Case Report and Review of Literature.

Infective endocarditis (IE) can be caused by bacterial or fungal infections invading the endocardial surface of the heart, such as its valves and chambers. Staphylococcus and Streptococcus species are mainly responsible for IE. Streptococcus equinus (S. equinus) has been rarely noted to cause IE. We present a case of a 69-year-old white male with a past medical history of severe aortic regurgitation, who during an elective aortic heart valve replacement surgery was noted to have multiple plaque-like vegetations at the base of the mitral valve that were positive for S. equinus. To date, there are only four cases of S. equinus endocarditis reported worldwide, with a high possibility of our case being the first reported in North America.