Cross-Sectional Survey of Factors Contributing to COVID-19 Testing Hesitancy Among US Adults at Risk of Severe Outcomes from COVID-19.

INTRODUCTION: The United States Centers for Disease Control and Prevention (CDC) advises testing individuals for COVID-19 after exposure or if they display symptoms. However, a deeper understanding of demographic factors associated with testing hesitancy is necessary. METHODS: A US nationwide cross-sectional survey of adults with risk factors for developing severe COVID-19 ("high-risk" individuals) was conducted from August 18-September 5, 2023. Objectives included characterizing demographics and attitudes associated with COVID-19 testing. Inverse propensity weighting was used to weight the data to accurately reflect the high-risk adult US population as reflected in IQVIA medical claims data. We describe here the weighted results modeled to characterize demographic factors driving hesitancy. RESULTS: In the weighted sample of 5019 respondents at high risk for severe COVID-19, 58.2% were female, 37.8% were ≥ 65 years old, 77.1% were White, and 13.9% had a postgraduate degree. Overall, 67% were Non-testers (who indicated that they were unlikely or unsure of their likelihood of being tested within the next 6 months); these respondents were significantly more likely than Testers (who indicated a higher probability of testing within 6 months) to be female (60.2 vs. 54.1%; odds ratio [OR] [95% confidence interval (CI)], 1.3 [1.1‒1.4]), aged ≥ 65 years old (41.5 vs. 30.3%; OR [95% CI] compared with ages 18‒34 years, 0.6 [0.5‒0.7]), White (82.1 vs. 66.8%; OR [95% CI], 1.4 [1.1‒1.8]), and to identify as politically conservative (40.9 vs. 18.1%; OR [95% CI], 2.6 [2.3‒2.9]). In contrast, Testers were significantly more likely than Non-testers to have previous experience with COVID-19 testing, infection, or vaccination; greater knowledge regarding COVID-19 and testing; greater healthcare engagement; and concerns about COVID-19. CONCLUSIONS: Older, female, White, rural-dwelling, and politically conservative high-risk adults are the most likely individuals to experience COVID-19 testing hesitancy. Understanding these demographic factors will help guide strategies to improve US testing rates.

Large-scale deep learning analysis to identify adult patients at risk for combined and common variable immunodeficiencies.

BACKGROUND: Primary immunodeficiency (PI) is a group of heterogeneous disorders resulting from immune system defects. Over 70% of PI is undiagnosed, leading to increased mortality, co-morbidity and healthcare costs. Among PI disorders, combined immunodeficiencies (CID) are characterized by complex immune defects. Common variable immunodeficiency (CVID) is among the most common types of PI. In light of available treatments, it is critical to identify adult patients at risk for CID and CVID, before the development of serious morbidity and mortality. METHODS: We developed a deep learning-based method (named "TabMLPNet") to analyze clinical history from nationally representative medical claims from electronic health records (Optum® data, covering all US), evaluated in the setting of identifying CID/CVID in adults. Further, we revealed the most important CID/CVID-associated antecedent phenotype combinations. Four large cohorts were generated: a total of 47,660 PI cases and (1:1 matched) controls. RESULTS: The sensitivity/specificity of TabMLPNet modeling ranges from 0.82-0.88/0.82-0.85 across cohorts. Distinctive combinations of antecedent phenotypes associated with CID/CVID are identified, consisting of respiratory infections/conditions, genetic anomalies, cardiac defects, autoimmune diseases, blood disorders and malignancies, which can possibly be useful to systematize the identification of CID and CVID. CONCLUSIONS: We demonstrated an accurate method in terms of CID and CVID detection evaluated on large-scale medical claims data. Our predictive scheme can potentially lead to the development of new clinical insights and expanded guidelines for identification of adult patients at risk for CID and CVID as well as be used to improve patient outcomes on population level.

Primary immunodeficiencies (PI) are disorders that weaken the immune system, increasing the incident of life-threatening infections, organ damage and the development of cancer and autoimmune diseases. Although PI is estimated to affect 1-2% of the global population, 70-90% of these patients remain undiagnosed. Many patients are diagnosed during adulthood, after other serious diseases have already developed. We developed a computational method to analyze the clinical history from a large group of people with and without PI. We focused on combined (CID) and common variable immunodeficiency (CVID), which are among the least studied and most common PI subtypes, respectively. We could identify people with CID or CVID and combinations of diseases and symptoms which could make it easier to identify CID or CVID. Our method could be used to more readily identify adults at risk of CID or CVID, enabling treatment to start earlier and their long-term health to be improved.

Real-World Evidence of the Top 100 Prescribed Drugs in the USA and Their Potential for Drug Interactions with Nirmatrelvir; Ritonavir.

Nirmatrelvir (coadministered with ritonavir as PAXLOVIDTM) reduces the risk of COVID-19-related hospitalizations and all-cause death in individuals with mild-to-moderate COVID-19 at high risk of progression to severe disease. Ritonavir is coadministered as a pharmacokinetic enhancer. However, ritonavir may cause drug-drug interactions (DDIs) due to its interactions with various drug-metabolizing enzymes and transporters, including cytochrome P450 (CYP) 3A, CYP2D6, and P-glycoprotein transporters. To better understand the extent of DDIs (or lack thereof) of nirmatrelvir; ritonavir in a clinical setting, this study used real-world evidence (RWE) from the Optum Clinformatics Data Mart database to identify the top 100 drugs most commonly prescribed to US patients at high risk of progression to severe COVID-19 disease. The top 100 drugs were identified based on total counts associated with drugs prescribed to high-risk patients (i.e., ≥ 1 medical condition associated with an increased risk of severe COVID-19) who were continuously enrolled in the database throughout 2019 and had ≥ 1 prescription claim. Each of the 100 drugs was then assessed for DDI risk based on their metabolism, excretion, and transport pathways identified from available US prescribing and medical literature sources. Seventy drugs identified were not expected to have DDIs with nirmatrelvir; ritonavir, including many cardiovascular agents, anti-infectives, antidiabetic agents, and antidepressants. Conversely, 30 drugs, including corticosteroids, narcotic analgesics, anticoagulants, statins, and sedatives/hypnotics, were expected to cause DDIs with nirmatrelvir; ritonavir. This RWE analysis is complementary to the prescribing information and other DDI management tools for guiding healthcare providers in managing DDIs.

Three metachronous primary lung cancers in a chronic smoker: A case report and review of the literature.

RATIONALE: Lung cancer is a leading cause of cancer-related deaths. Smoking is major risk factor for initial and subsequent lung cancer especially in active smokers. Treatment of subsequent lung cancer depends on whether it is synchronous or metachronous. We report a rare case of triple metachronous lung cancer and review of literature of patients with triple metachronous cancers. This will be the second case reported of triple metachronous lung cancer. PATIENT CONCERNS: A 60-year-old male, active smoker with diabetes mellitus, chronic obstructive pulmonary disease (COPD) and peripheral arterial disease presented with cough and hemoptysis. Initial computed tomography (CT) scan showed right upper lobe spiculated mass. DIAGNOSIS: He underwent transthoracic needle biopsy for right upper lobe mass, showing primary lung adenocarcinoma (ADC)-Stage-IIIA. He continued to smoke and 9-years later had new left upper lobe spiculated nodule, which on surgical resection showed squamous cell carcinoma (SCC)-Stage-IA1. Despite counselling on smoking cessation, he was unable to quit. Six months later, he presented with shortness of breath and CT chest showing right hilar adenopathy in right upper and lower lobes. He underwent transbronchial biopsies of lesion which showed small cell lung carcinoma (SCLC). INTERVENTIONS: His initial lung ADC-Stage-IIIA, was treated with chemotherapy, weekly thoracic radiation and additional chemotherapy cycles. Nine years later, his left upper lobe mass showing SCC-Stage-IA1 was deemed curative after apical resection and he was kept on surveillance. Six months later, after diagnosis of SCLC in right upper and lower lobe, patient was not a candidate for systemic chemotherapy due to poor performance status and opted for hospice care. OUTCOMES: His initial lung ADC-Stage-IIIA showed complete radiological response with chemotherapy and radiation. Subsequent SCC-Stage-IA1 was deemed curative after resection. Due to his poor performance status, he was not a candidate for chemotherapy for SCLC and patient opted for hospice care. LESSONS: Smoking is a major risk factor for developing lung cancer and with continued smoking, patients are at higher risk for developing subsequent primary lung cancers. We recommend, patients with lung cancer must quit smoking, and those who do not, should remain on long-term surveillance.

Paradoxical Stress Fracture in a Patient With Multiple Myeloma and Bisphosphonate Use.

Multiple myeloma (MM) is a plasma cell disorder with related organ dysfunction, including hypercalcemia, renal insufficiency, anemia, and bone disease. Osteolytic bone lesions that result in pain and pathologic fractures are a major source of morbidity and the use of bisphosphonates is generally safe and effective treatment in reducing myeloma-related skeletal fractures and associated morbidity. We present a 73-year-old African American woman with MM in remission and on intravenous (IV) bisphosphonate therapy in the past five years who reported gradually worsening bilateral thigh pain of six months duration. A bone survey showed no neoplastic focus, and bilateral hip X-rays showed incomplete insufficiency stress fractures with characteristic features suspicious for bisphosphonate-related atypical femoral fracture (AFF). Increasingly reported in the literature, bilateral AFF is a unique and serious adverse effect for patients on bisphosphonates. Our case illustrates the distinct challenges in managing a patient with MM on long-term bisphosphonate therapy who suffered bilateral atypical femoral fractures, an uncommon presentation of a relatively rare phenomenon. It is important to balance the established benefits of bisphosphonate therapy with potential fracture risk and be particularly vigilant about adverse effect monitoring and timely intervention.

Leukostasis in Chronic Lymphocytic Leukemia.

BACKGROUND Chronic lymphocytic leukemia (CLL) is a mature B cell lymphocytic neoplasm that has an indolent clinical course. Therefore, not all patients with CLL require treatment at the time of diagnosis. Hyperleukocytosis (white blood cell count, >100×109/L) is present in a large proportion of patients with CLL. However, symptomatic hyperleukocytosis (leukostasis) is an extremely uncommon presentation of CLL. Leukostasis frequently presents with the clinical manifestation of respiratory, neurological, or renal system problems. This is secondary to the decreased tissue perfusion due to the intravascular accumulation of large aggregates of leukemic cells. Leukostasis is a medical emergency requiring intensive care unit (ICU) admission and its management includes aggressive hydration, prevention and treatment of tumor lysis syndrome, cytoreduction, and leukapheresis. CASE REPORT We report a case of a 77-year-old woman with a long history of untreated CLL who presented with respiratory symptoms with hyperleukocytosis. Her condition rapidly deteriorated, requiring intubation. She required induction chemotherapy with chlorambucil as well as 2 sessions of leukapheresis, to which she responded well. In most reported leukostasis cases in the literature, the white blood cell (WBC) count was >1000×109/L. We present a case of a patient with leukostasis with WBC count 524×109/L who responded to chlorambucil and leukapheresis, with good recovery. CONCLUSIONS Leukostasis, although extremely rare, is a life-threatening complication in patients with CLL. It should be strongly considered in the differential diagnosis of patients with CLL who present with hyperleukocytosis and acute pulmonary symptoms. Clinicians should be aware of this medical emergency, as delayed treatment can increase morbidity and mortality.

Clinical Characteristics and Outcomes of Caribbean Patients With Adult T-Cell Lymphoma/Leukemia at Two Affiliated New York City Hospitals.

PURPOSE: Adult T-cell lymphoma/leukemia (ATL) is a rare and aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus-1 infection, which occurs in areas of high prevalence, predominantly in Japan and the Caribbean basin. Most ATL literature is derived from Japan and little is published about Caribbean patients. We describe the clinicopathologic characteristics and treatment outcomes of our Caribbean patients who have ATL at the State University of New York Downstate Medical Center and Kings County Hospital. PATIENTS AND METHODS: We conducted a retrospective analysis of our patients with ATL who were diagnosed between 2005 and 2017. Medical records were reviewed for clinicopathologic data and treatment outcomes. The final analysis included acute and lymphomatous subtypes only. For the univariable analysis, outcomes were calculated by using a log-rank test, and survival curves were estimated by the Kaplan-Meier method. RESULTS: We identified 63 patients with acute (55%) and lymphomatous (45%) subtypes, 95% of whom had Ann Arbor stage III to IV disease. The median age was 54 years, and the study population was predominantly female (65%). Most patients (82%) received first-line etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone (EPOCH) or cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) chemotherapy (10%) with an overall response rate of 46%. The median overall survival was 5.5 months, and the median progression-free survival was 4 months. Incidence of atypical immunophenotype (32%) was higher than previously reported in the Japanese literature and was associated with worse survival (P = .04). Abnormal cytogenetics correlated with shorter progression-free survival (P < .05). CONCLUSION: We describe here the clinicopathologic characteristics and treatment outcomes of our Caribbean patients with aggressive ATL, which is largely chemotherapy resistant, and the challenges of treating a population with unmet medical needs.

Refractory Renal Cell Cancer with Gastro-renal Fistula: A Rare Complication.

Metastatic renal cell cancer is treated with systemic therapy, and cytoreductive nephrectomy can be offered in selected patients. The systemic therapy treatment options for kidney cancer have now expanded to include tyrosine kinase inhibitors, monoclonal antibodies, immunotherapy, and combinations thereof. Cytoreductive nephrectomy is considered a safe surgery in most patients. Patients with advanced kidney cancer are known to develop several paraneoplastic syndromes and malignant cachexia. We present the case of a patient with renal cell cancer who was treated with tyrosine kinase inhibitors and despite treatment her disease progressed with subsequent increase in the renal cancer, which led to the development of a fistula between the renal mass and the stomach.

Acute Immune-Mediated Thrombocytopenia due to Oxaliplatin and Irinotecan Therapy.

We describe a case of a 63-year-old woman with advanced colon cancer and liver metastases who was treated with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and cetuximab chemotherapy. She tolerated 13 cycles of chemotherapy without any significant hematological side effects, but after the 14th cycle, she developed melena and was admitted for severe thrombocytopenia. After supportive care, the platelet counts rapidly improved to 76,000/µL. Upon initiation of FOLFIRI and cetuximab chemotherapy, she again developed rectal bleeding and severe thrombocytopenia with a platelet count of 6000/µL. Lab testing was positive for oxaliplatin and irinotecan drug-dependent platelet antibodies on flow cytometry assay. Drug-induced thrombocytopenia (DITP) is associated with several classes of drugs with several proposed underlying mechanisms. Prospective studies are needed to further address different mechanisms of drug-induced thrombocytopenia.

Hydroxyurea-induced Tongue Hypermelanosis and Transverse Melanonychia.

Hydroxyurea (HU) is a commonly used medication for myeloproliferative neoplasm (MPN) and is usually well tolerated. Cutaneous toxicity of HU is well known and can be seen in several manifestations. We report a case of a man with MPL gene mutation associated with essential thrombocytosis, who had a rare mucocutaneous toxicity with diffuse tongue, skin and nail discoloration. Mucocutaneous toxicity is usually a benign condition and self-resolves after discontinuation of the medication. It can lead to patient anxiety and medication discontinuation. The mechanism for development of HU-induced mucocutaneous hyperpigmentation is poorly understood.

Findings of Multiple Myeloma in Afro-Caribbean Patients in the United States.

BACKGROUND: Multiple myeloma (MM) is the second most common malignancy in the United States and has a higher incidence in the black and Afro-Caribbean population. There remain limited data on disease presentation and clinical characteristics in this patient group in the United States. The clinical profile of MM in this underrepresented patient group is described here. METHODS: This retrospective study was conducted at Kings County Hospital, an urban New York City hospital in a majority Afro-Caribbean neighborhood. Data from patients diagnosed with MM from 2000 through 2013 were collected from the institution's tumor registry. Clinical and demographic characteristics of these patients were then analyzed. RESULTS: Patients with a diagnosis of MM were identified (N = 287). Data were available for 231 patients and of these, 97% self-identified as black. 55% were female, and there was a male-to-female ratio of 1:1.2. The mean age of female patients was 64 years; that of male patients was 63 years. Of the 231 patients, 81% had anemia, 68% had bone lesions, 47% had renal impairment, and 29% had hypercalcemia. Low levels of monoclonal protein were present in 27% of patients and 57% had disease of International Staging System stages I and II. Women had higher BMI than men. CONCLUSION: The mean age of presentation of MM in Afro-Caribbean patients is similar to that in the standard population; however, unlike the general US population, there was a higher incidence in women; mean BMI of women also was higher than that of male patients. A sizeable percentage of Afro-Caribbean patients with MM presented with low levels of monoclonal protein in the presence of multiorgan involvement and damage, suggesting the need for early and aggressive diagnostic testing.

Cryoglobulinemia in a patient with chronic lymphocytic leukemia - A case report and review of literature of renal involvement in CLL.

The incidence of glomerulonephritis, as a manifestation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), has always been considered low. Though renal infiltration is usually detected at post-mortem, it does not often interfere with kidney function [1]. Though immunoglobulin (Ig) levels in most CLL patients are subnormal, small monoclonal Ig peaks are occasionally detected in serum. They were present in a number of reported CLL nephropathy patients, and not all were cryoglobulins; serum and glomerular staining were concordant for Ig type [2,3,4]. Myeloma, which secretes monoclonal light chains, causes nephropathy in 25% of patients. But the little presumably secreted by small plasma cell clones, without myeloma, may also be nephrotoxic. The same is true of the low secretory CLL cells, which may occasionally be associated with cryoglobulins and other nephrotoxic Igs [5]. We report a patient with early stage CLL (Rai stage 0) with cryoglobulins, which led to membranoproliferative glomerulonephritis (MPGN), and death. We located reports of 51 patients with CLL-associated nephrotic syndrome or nephropathy, mostly from MPGN related to local Ig deposits. In those patients screened for cryoglobulins, about half tested positive. Many were early stage cases, where MPGN developed long after CLL presentation, and responded to its treatment. As early diagnosis and treatment CLL-related nephropathy may be curative, we propose a prospective study to determine the incidence of hyperalbuminuria development after presentation.

Attributes of brain metastases from breast and lung cancer.

BACKGROUND: Most brain metastases arise from breast and lung cancers. Few studies compare the brain regions they involve, their numbers and intrinsic attributes. METHODS: Records of all patients referred to Radiation Oncology for treatment of symptomatic brain metastases were obtained. Computed tomography (n = 56) or magnetic resonance imaging (n = 72) brain scans were reviewed. RESULTS: Data from 68 breast and 62 lung cancer patients were compared. Brain metastases presented earlier in the course of the lung than of the breast cancer patients (p = 0.001). There were more metastases in the cerebral hemispheres of the breast than of the lung cancer patients (p = 0.014). More breast than lung cancer patients had cerebellar metastases (p = 0.001). The number of cerebral hemisphere metastases and presence of cerebellar metastases were positively correlated (p = 0.001). The prevalence of at least one metastasis surrounded with >2 cm of edema was greater for the lung than for the breast patients (p = 0.019). The primary tumor type, rather than the scanning method, correlated with differences between these variables. CONCLUSIONS: Brain metastases from lung occur earlier, are more edematous, but fewer in number than those from breast cancers. Cerebellar brain metastases are more frequent in breast cancer.

Correlation between the proportion of breast volume involved by locally advanced tumors and invasion of the skin and posterior structures.

AIM: To evaluate any differences between the percentages of involved breast volume, pathologic attributes, and tumor marker expression of T3 and T4a-c tumors in locally advanced breast cancers (BC). METHODS: All patients with T3N > 0 and T4a-c BC without evidence of distant metastasis (M0), presenting to the Breast Clinic from 1980 to 2010, were examined to determine whether their BC's involved ≥ 50% of their breast volumes, defined by gross replacement of at least one hemisphere. Core needle biopsy or post-mastectomy specimens from tumors involving a known percent of breast volume were evaluated for: (1) pathological grades and lympho-vascular invasion (LVI); (2) hormone receptor (ER/PR) expression > 0; and (3) epidermoid growth factor 2 (her2) over-expression (3+) by immune-histochemical staining or fluorescent in situ hybridization. RESULTS: The data base included 98 patients with T3N> 0 M0 and 120 with T4a-c, any N disease, M0 disease. T3 tumor masses involved 50% or more of the breast in 23/98 (24%), and T4a-c tumors 65/120 (54%) (P < 0.001). Only 1% of T3 tumors and 23% of T4a-c tumors presented with total breast replacement. There were no significant differences between the pathological attributes and marker expression of the T3 and T4a-c tumors. CONCLUSION: These data suggest that erosion of the overlying skin or underlying chest wall by some BC may be due to neglect and delay, rather than inherent biological aggressiveness.

Fine needle aspiration (FNA) cytology for diagnosis of cervical lymphadenopathy.

Patients with cervical adenopathy suspicious for malignancy are often referred to the Otolaryngology Service for tissue diagnosis. Confirmation of nodal involvement by upper aero-digestive tract tumors (UADT) is best obtained by fine needle aspiration (FNA). Reported studies of FNA for lymphoma diagnosis have yielded conflicting results. Retrospective review of charts and pathology of 161 patients diagnosed with lymphomas yielded 53 patients with cervical adenopathy without apparent UADT. FNA's were performed on 28, and were repeated nine times, for a total of 37. Eleven had Hodgkin's disease and 17 other types of lymphomas. Seven of 37 specimens contained only blood; 15 contained lymphoid cells, nine of which were designated "reactive." Lymphoid cells designated as "atypical" or "suspicious for lymphoma" were found in 13 of the 37 aspirates. Two were diagnostic of lymphoma. Lymphoma was confirmed by histopathologic specimens in all patients, obtained 0-941 days (median 15, mean 73 days) after initial FNA. In lymphoma patients with cervical lymphadenopathy, FNA does not usually suffice for, and often leads to significant delays in diagnosis.

Rising incidence of tumorectomies without breast radiation in patients treated for invasive breast cancer in Caribbean nations.

BACKGROUND: Tumorectomy for invasive breast cancer (BC) is followed by local recurrence in 30% of patients who do not receive radiotherapy. In the United States 88% of tumorectomy patients receive radiation therapy. Many Caribbean nations lack radiation facilities and access to existing facilities is limited. METHODS: The charts of the 95 breast clinic patients treated in Caribbean nations for primary BC between 1980 and 2008 were reviewed. The nation of origin, original treatments, reported physician recommendations, and status at presentation to our clinic were recorded. RESULTS: Mastectomies (MCT) had been performed on 51 patients and tumorectomies (TCT) on 39. The ratio of TCT to MCT from 1980 to 1991 was 0.19, and then rose to 0.94, with a slight increase since. Only 6 of the 33 (18%) TCT patients had received radiation therapy. Patient accounts of why they had not been irradiated were available for 20 of 33: 12 denied referral for radiation, 4 refused it, and 4 had not been able to obtain it in their nation or region. At presentation to our clinic, 22 of the 51 MCT patients (43%) and 23 of the 33 TCT patients (70%) had locally recurrent BC. CONCLUSIONS: TCT entails significant risk of local relapse in nations without, or with insufficient radiotherapy facilities for their populations.