ABSTRACT
INTRODUCTION: Randomized clinical trials (RCTs) have suggested that BTK inhibitors (BTKis) might increase infectious disease (ID) risk. Systematic analysis of this topic as derived from RCTs and clinical practice is needed. AREAS COVERED: An extensive Medline, Embase, and Cochrane search of peer-reviewed sources reporting on ID morbidity in patients on BTKis was performed (1 January 2014 - 31 December 2013). Contribution of intrinsic immune defects in indolent B-cell lymphomas to this morbidity was carefully considered. EXPERT OPINION: Patients with indolent B-cell lymphomas display a wide range of innate and adaptive immune defects. In addition, BTKi use is linked with an increased signal of upper respiratory tract infections (URTIs) and pneumonias, mainly grade 1-2. These agents also increase the risk of rare invasive fungal infections (IFIs), mainly due to Cryptococcus and Aspergillus spp. with a peak within several months after the start of therapy. More than half of these IFIs are fatal. Research suggests a similar ID risk across 1st, 2nd and 3rd generations of BTKis, all causing B-cell dysfunction due to BTK inhibition, along with off-target functional neutrophil/macrophage alterations. Expanding the knowledge base on ID morbidity in patients on BTKis would facilitate timely diagnosis and treatment, and improve clinical outcomes.
Subject(s)
Agammaglobulinaemia Tyrosine Kinase , Lymphoma, B-Cell , Protein Kinase Inhibitors , Humans , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Lymphoma, B-Cell/drug therapy , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Randomized Controlled Trials as Topic , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic useABSTRACT
INTRODUCTION: When examining health literacy and disease specific knowledge levels across ethnicities and communities, ethnic minority groups are known to be at a higher risk of being below the average health literacy threshold which is a factor linked to poor health status and higher mortality rates. This study examined disease specific knowledge levels, perceived severity, and perceived susceptibility surrounding anal cancer and HPV-related screening behaviors. METHODS: The following research questions were explored: (1) "What are the common themes and/or beliefs when asked about anal cancer, HPV, and preventive screening?" and (2) "What are the common themes and beliefs surrounding the severity and susceptibility of contracting anal cancer?". This study utilized a cross-sectional design to survey 26 individuals regarding their knowledge level and perspectives regarding anal cancer and HPV. An 8-question survey was developed de novo based on an application of the Health Belief Model (HBM) elements. This study employed thematic analysis to explore critical themes to construct a model to understand knowledge levels, attitudes, and risk perceptions regarding anal cancer and intention to participate in preventive screenings. The fundamental attitudes and themes related to anal cancer risk and intention to participate in preventative screenings were elicited using a qualitative descriptive technique. Coded data was utilized to analyze themes based on (1) knowledge and (2) perceived risk, both severity and susceptibility. RESULTS: Overall, the findings indicate very low levels of knowledge regarding screening, anal cancer, and HPV across all genders. The low levels of anal cancer and HPV knowledge were seen in 13 coded segments (50% of surveys) which showed no familiarity with or comprehension of HPV, and 4 coded segments indicated no familiarity with anal cancer. In addition, 15 respondents (57%) had low or no preventive or screening-related knowledge. While some respondents (46%) illustrated high perceived severity for anal cancer, only 23% indicated high perceived susceptibility for anal cancer. CONCLUSION: The results from this study may be used to inform practitioners, providers, and policymakers in developing interventions addressing low levels of understanding and disease specific knowledge surrounding anal cancer in support of creating a standardized health screening procedure.
Subject(s)
Anus Neoplasms , Papillomavirus Infections , Humans , Male , Female , Human Papillomavirus Viruses , Ethnicity , Papillomavirus Infections/complications , Papillomavirus Infections/prevention & control , Cross-Sectional Studies , Minority Groups , Anus Neoplasms/prevention & control , Health Knowledge, Attitudes, PracticeABSTRACT
Cavitary pulmonary coccidioidomycosis is rare diagnosis with an incidence of 13% to 15% of pulmonary coccidioidomycosis cases. High clinical suspicion is necessary in the setting of geographical location endemicity. We present a 49-year-old male who has lived in the Coachella Valley of California for several years, with a medical history of uncontrolled type 2 diabetes who noted 1 week of right-sided chest pain with shortness of breath, fever, chills, night sweats, and weight loss. A chest X-ray revealed a 4- to 5-cm mass in the right lung. Initial workup revealed negative sputum cultures (aerobic/anaerobic, acid-fast bacilli). However, dedicated fungal cultures (samples from sputum, lymph nodes, lung right lower lobe bronchial swabs), bronchial washings, and surgical tissue biopsy of the right lower lobe revealed mold. The patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection for both diagnostic (lung specimen) and therapeutic (removing necrotic lung tissue, source control) purposes. Finally, serum Coccidioides antigens were positive and antibody titers were positive at 1:8; surgical biopsy of the right lower lobe grew mold that came back positive for Coccidioides posadasii. Targeted pharmacotherapy was commenced using intravenous fluconazole and then oral fluconazole for 3 months was prescribed upon discharge. The patient had gradual improvement of his shortness of breath and was instructed to follow-up at an infectious disease clinic.
Subject(s)
Coccidioidomycosis , Diabetes Mellitus, Type 2 , Male , Humans , Middle Aged , Coccidioidomycosis/complications , Coccidioidomycosis/diagnosis , Coccidioidomycosis/drug therapy , Fluconazole/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Lung/diagnostic imaging , Lung/pathology , Dyspnea , BacteriaABSTRACT
INTRODUCTION: Zanubrutinib is a second generation, irreversible small-molecule Bruton tyrosine kinase inhibitor (BTK) approved for the treatment of Waldenström's macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. As a class, BTKs have been linked with an increased risk of respiratory infections in clinical trials. CASE REPORT: We describe a 75-year-old patient who presented with generalized weakness, fevers, dyspnea, and dry cough four months after starting zanubrutinib therapy for Waldenström's macroglobulinemia. He was subsequently diagnosed with pneumonia. Septic work-up led to diagnosis of disseminated cryptococcal infection, complicated by fungal pneumonia and meningitis. MANAGEMENT AND OUTCOME: Zanubrutinib was held on admission, and the patient was started on combination oral and intravenous antifungal therapy. Despite clearance of fungemia, aggressive resuscitation, and appropriate antimicrobial therapy, respiratory status deteriorated requiring intubation. His condition progressed to septic shock, multiorgan failure, and demise. DISCUSSION/CONCLUSION: We report herein a case of fatal disseminated cryptococcosis in the setting of zanubrutinib use for Waldenström's macroglobulinemia. At the time of diagnosis, his Waldenström's macroglobulinemia was in a partial response. The mechanism by which Bruton tyrosine kinase inhibitors (BTKs) lead to invasive fungal infections in these patients remains to be explored. T- and B-cell immune defects accompanying low-grade B-cell lymphomas may contribute to the severity of these infections.
Subject(s)
Cryptococcosis , Lymphoma, B-Cell , Waldenstrom Macroglobulinemia , Male , Humans , Adult , Aged , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/complications , Cryptococcosis/drug therapyABSTRACT
We present a rare case of a healthy, non-pregnant, middle-aged and immunocompetent woman who underwent laparoscopic cholecystectomy for acute cholecystitis with a post-operative course complicated by herpes simplex virus type 1 (HSV-1) hepatitis secondary to post-surgical inflammation. Her initial post-operative course was complicated by intermittent fevers, leukocytosis, jaundice, elevated transaminases, and right upper quadrant abdominal pain, and she was subsequently placed on broad-spectrum antibiotics with no improvement. During her hospital course, the patient developed herpes labialis, and HSV-1 hepatitis was confirmed by serology and HSV-1 polymerase chain reaction (PCR), in lieu of a liver biopsy. After this was discovered, the patient was placed on valacyclovir and had a successful response. The importance of this case is to emphasize the possibility of herpes simplex virus (HSV) hepatitis as a post-operative complication and the benefit of early empiric antiviral treatment.