Digital cough monitoring - A potential predictive acoustic biomarker of clinical outcomes in hospitalized COVID-19 patients.

PURPOSE: Recent developments in the field of artificial intelligence and acoustics have made it possible to objectively monitor cough in clinical and ambulatory settings. We hypothesized that time patterns of objectively measured cough in COVID-19 patients could predict clinical prognosis and help rapidly identify patients at high risk of intubation or death. METHODS: One hundred and twenty-three patients hospitalized with COVID-19 were enrolled at University of Florida Health Shands and the Centre Hospitalier de l'Université de Montréal. Patients' cough was continuously monitored digitally along with clinical severity of disease until hospital discharge, intubation, or death. The natural history of cough in hospitalized COVID-19 disease was described and logistic models fitted on cough time patterns were used to predict clinical outcomes. RESULTS: In both cohorts, higher early coughing rates were associated with more favorable clinical outcomes. The transitional cough rate, or maximum cough per hour rate predicting unfavorable outcomes, was 3·40 and the AUC for cough frequency as a predictor of unfavorable outcomes was 0·761. The initial 6 h (0·792) and 24 h (0·719) post-enrolment observation periods confirmed this association and showed similar predictive value. INTERPRETATION: Digital cough monitoring could be used as a prognosis biomarker to predict unfavorable clinical outcomes in COVID-19 disease. With early sampling periods showing good predictive value, this digital biomarker could be combined with clinical and paraclinical evaluation and is well adapted for triaging patients in overwhelmed or resources-limited health programs.

A Personal View: Navigating conflicting claims of legality and women's safety at a volunteer medical clinic in Guatemala.

This paper examines the ethical considerations in a case of a 12-year-old girl seeking an abortion in Quetzaltenango, Guatemala in early 2020. The physician denied the girl care and did not refer her to a qualified provider, citing the illegality of such actions. Though abortion is illegal in Guatemala, enforcement of the law is sparse, and many abortions are performed every year. The physician would have taken on minimal personal risk by helping the girl. This case exemplifies a circumstance in which breaking the law to help a patient is ethically justified.

Primary Invasive Ductal Carcinoma of the Breast Occurring in a Patient With a History of Hepatocellular Carcinoma Developing From Focal Nodular Hyperplasia: A Case Report and Literature Review.

The risk of developing another primary malignancy after an initial liver cancer diagnosis is rare, and the management of multiple primary cancers is not typically discussed. Focal nodular hyperplasia (FNH) is considered a benign tumor, but there have been cases reported that describe hepatocellular carcinoma (HCC) arising from or within FNH. Here, we report a woman in her 70s who had a longstanding history of FNH, later found to be HCC upon resection, who also developed invasive ductal carcinoma. She had no family history of cancer and no genetic testing results were available. Each of her cancers was managed independently, hepatectomy for HCC and neoadjuvant therapy followed by mastectomy for her breast carcinoma. This case demonstrates that the diagnosis of FNH based on radiographic imaging may necessitate a biopsy to confirm diagnosis for a symptomatic patient or those with lesions suspicious for malignancy. It also showcases the importance of close follow-up after a primary cancer diagnosis for the possibility of another primary malignancy emerging. Fresh tissue biopsy for new lesions could help determine primary malignancy or metastasis. Genetic sequencing may help identify driver mutations or genetic alterations that can be targeted.

Bilateral primary breast Burkitt's lymphoma in pregnancy.

Pregnancy-associated cancer is defined as malignancy diagnosed during gestation or up to 1 year post partum. Treatment of cancer during pregnancy is complicated by the risk of harm to the fetus and limitations in safety data. Postpartum patients receiving chemotherapy, tyrosine-kinase inhibitors or hormonal agents should avoid breast feeding to avoid drug excretion in breast milk. Patients who will receive cytotoxic chemotherapy should be advised of the potential impact on their future fertility and offered fertility-preservation options. Breast cancer is the most common pregnancy-associated malignancy and is most frequently either invasive ductal or lobular carcinoma. Breast lymphoma is an exceedingly rare diagnosis that typically presents with unilateral disease in the seventh decade of life. Here, we present the case of a woman who presented with bilateral breast masses during the second trimester of pregnancy and was ultimately diagnosed with primary breast Burkitt's lymphoma.

Pneumocystis jirovecii pneumonia in a patient treated with trastuzumab-deruxtecan.

Trastuzumab-deruxtecan (T-DXd) is a novel antibody drug conjugate that has improved treatment outcomes in patients with ERBB2-positive cancer, including locally advanced or metastatic gastric and gastro-oesophageal junction adenocarcinoma. One of the reported side effects of this medication is drug-induced pneumonitis. We present in this case report, a diagnostic dilemma of a patient presenting with clinical and radiographical features of drug-induced pneumonitis but was found to have pneumocystis jirovecii pneumonia (PJP). Our case is the first of PJP in a patient treated with T-DXd, highlighting the increasing incidence of this opportunistic infection in patients with solid malignancy. It also highlights the clinical and radiographical similarities between the PJP and drug-induced pneumonitis.

Clinical characteristics, prognostic factors, and long-term outcomes associated with epithelial malignancies of the thymus: A 20-year single-institution experience.

BACKGROUND: Thymic epithelial tumors are rare and include thymomas and thymic carcinomas. There is scarce literature characterizing prognostic factors and long-term outcomes in these tumors. AIMS: This review aims to describe disease features of thymomas and thymic carcinomas and to report clinical differences among thymoma histological subtypes. METHODS AND RESULTS: A retrospective chart review was performed at the University of Florida Shands Hospital, a tertiary care academic medical center in Gainesville, Florida, USA. The review included clinical data of adults with thymic epithelial tumors diagnosed between 2001 and 2021. Significant associations among demographics, histology, stage, and outcomes were investigated. Thymoma subgroup analysis was performed using histological subtype and sex. Forty patients with thymoma and seven patients with thymic carcinoma were included in the final analysis. Among those with thymomas, patients with subtype B1, B2, or B3 tumors were younger, had larger tumors, and presented with higher stage disease when compared to those with subtypes A or AB. Tumor recurrence was most common in subtype B2 and B3 tumors (50.0% and 16.7% vs. 0%; p < .01). However, there was no significant difference in overall survival between histologic subtypes. Compared to females, males with thymomas had superior overall survival (103.0 vs. 62.9 months; p = .021) despite presenting with larger tumors (9.8 vs. 5.8 cm; p = .041). Concomitant myasthenia gravis was associated with increased recurrence but not worsened mortality. Compared to thymomas, patients with thymic carcinoma presented with higher-stage disease and had poorer 5-year survival (50.0% vs. 93.1%; p < .01). CONCLUSION: This study affirmed pathologic stage and resectability as prognostic factors for thymic epithelial tumors. New findings include inferior overall survival in female patients and higher recurrence rates in those with thymomas and concomitant myasthenia gravis.

Pericardial Effusion: A Novel Presentation of Aplastic Anemia.

Pericardial effusion is defined as the accumulation of fluid between the visceral and parietal pericardium. The underlying etiology varies as any pathology that causes pericarditis or involves the pericardium can cause effusion. In practice, the majority of pericarditis cases are idiopathic, although these are assumed to be secondary to occult viral infection or inflammatory phenomena. Malignancy, particularly the metastatic spread of noncardiac primary tumors, has been implicated as a differential in the diagnosis of pericardial effusion. Though commonly seen in solid malignancies, effusion has been reported in hematologic malignancies such as myelodysplastic syndrome (MDS), acute leukemia, and lymphoma. Nonetheless, pericardial effusions associated with hematologic conditions are extremely rare with only one case report published describing pericardial effusion secondary to immune thrombocytopenia (ITP). We herein report the first documented case, to our knowledge, of pericardial effusion as an initial clinical manifestation of aplastic anemia in a middle-aged male presenting with pancytopenia.

Clinical presentation and neurovascular manifestations of cardiac myxomas and papillary fibroelastomas: a retrospective single-institution cohort study.

Background: Primary cardiac tumors are often benign and commonly present as cardiac myxomas (CMs) or papillary fibroelastomas (CPFEs). There is a paucity of prognostic indicators for tumor burden or potential for embolic cerebrovascular events (CVEs). This study was performed to address these gaps. Methods: Medical records at the University of Florida Health Shands Hospital between 1996 and 2021 were screened to identify patients with CMs or CPFEs. Clinical features, echocardiographic reports, and CVE outcomes were quantitatively assessed. Results: A total of 55 patients were included in the study: 28 CM (50.9%) and 27 CPFE (49.1%) patients. Baseline patient characteristics were similar among patients. The neutrophil-lymphocyte ratio was correlated (p < 0.005 in all cases) to three metrics of tumor size in both CM (r = 64-67%) and CPFE (r = 56-59%). CVEs were the presenting symptom in 30 (54.5%) patients. CVE recurrence was high; the 5-year CVE recurrence rate in patients with tumor resection was 24.0% compared to 60.0% without resection. No baseline patient characteristics or tumor features were associated with an initial presentation of CVEs compared to any other indication. Univariate analysis indicated that prolonged duration to surgical resection, left atrial enlargement, male sex, and a neutrophil-lymphocyte ratio >3.0 at the follow-up were significantly associated with 5-year CVE recurrence. Left atrial enlargement and a neutrophil-lymphocyte ratio >3.0 at the follow-up remained significantly associated with 5-year CVE recurrence in multivariate analysis. Conclusion: The neutrophil-lymphocyte ratio may prognosticate tumor size and recurrence of neurologic events. An increased risk of CVE within 5 years of mass resection is almost exclusive to patients initially presenting with CVEs.

Impact of Institutional Universal Microsatellite-Instability (MSI) Reflex Testing on Molecular Profiling Differences Between Younger and Older Patients with Colorectal Cancer.

INTRODUCTION: DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC) is found in about 15% of early-stage diseases and 5% of metastatic diseases. We reviewed a large, single-institutional database after implementation of universal reflex dMMR/MSI-H testing in CRC to compare profiles of younger (≤50) and older (>50) patients. PATIENTS AND METHODS: Between 2009 and 2017, all patients diagnosed with CRC at the University of Florida underwent reflex somatic tumor testing for dMMR by immunohistochemistry (MLH1, PMS2, MSH2, MSH6), MSI by PCR, and Next-Generation Sequencing. Statistical analysis was conducted with 2-sample comparison tests and logistic regression models. RESULTS: There were 375 patients included in the final analysis. Patients were grouped as younger (ages ≤50 years-old; n = 80) or older (>50 years-old; n = 295). Compared to tumors from older patients, tumors from younger patients were less likely to be dMMR/MSI-H (12.5% vs. 21.4%, P = .013) and less likely to have a BRAF mutation (1.5% vs. 16.1%, P = .002). BRAF mutation status was highly associated with MMR status; BRAF-mutated tumors were 29.7 times more likely than BRAF-WT tumors to be dMMR/MSI-H (P = < .001, 95% CI 11.3-78.3). CONCLUSIONS: Tumors of younger patients were less likely than tumors of older patients to have a dMMR/MSI-H or BRAF mutation. Universal MMR/MSI testing in our dataset identified a relatively large population of older patients with sporadic CRC who were eligible for immunotherapy.

Adherence to guideline-directed hepatocellular carcinoma screening: A single-center US experience.

BACKGROUND: The American Association for the Study of Liver Disease recommends screening patients with cirrhosis for hepatocellular carcinoma (HCC) using imaging with or without alpha-fetoprotein every six months. Unfortunately, screening rates remain inadequate. AIM: To assess root causes of screening failure in a subspecialty hepatology clinic. METHODS: The authors identified patients with cirrhosis seen in a subspecialty hepatology clinic and determined whether they underwent appropriate screening, defined as two cross-sectional images between five and seven months apart. The authors characterized the primary driver of screening failure. Finally, other hepatologists were surveyed to determine provider perceptions of screening failure causes. RESULTS: 1034 patients were identified with an average age of 61 years and a mean MELD of 8.1 ± 3.8. Hepatitis C virus was the most common cirrhosis etiology. 489 (47%) underwent appropriate screening. No demographic or clinical differences were detected between those who underwent appropriate screening and those who did not. The most common etiologies of screening failure, in descending order, were: radiology unable to schedule timely imaging, provider did not order imaging, patient canceled follow up appointment, appointments scheduled too far apart, lost to follow up, no-show to radiology appointment, and provider canceled appointment. Hepatologists surveyed believed the most common cause of screening failure was no-show to radiology. CONCLUSION: Rates of screening were poor even in a subspecialty hepatology clinic. Screening failure was mostly due to systemic factors such as radiology availability and time between hepatology appointments rather than individual error.

Impact of genotype on clinical course in sickle cell disease and the utility of neutrophil-lymphocyte ratio: a ten-year single-institution experience.

BACKGROUND: Sickle cell disease (SCD) is a diverse group of blood disorders with significant global disease burden. Contemporary interest in the underlying inflammatory paradigm of SCD has emphasized the role of the neutrophil-lymphocyte ratio (NLR) as a prognostic inflammatory marker. METHODS: We retrospectively reviewed 268 hospitalized patients with SCDs of different genotypes (HbSS, HbSß0 thalassemia, HbSß+ thalassemia, and HbSC), totaling 3329 hospital admissions over a 10-year period. Patients were stratified into SS/Sß0 and Sß+/SC groups for statistical analysis of parameters collected at steady state and at hospital admission. RESULTS: At steady state, per unit increase of hemoglobin values was associated with reduced odds of ≥ 2 hospital admissions per year in SS/Sß0 and Sß+/SC groups; per unit increase in platelet count and white blood cell count was associated with increased odds only in the SS/Sß0 group. The NLR had no association in either group. During admission, a cutoff of NLR = 3.5 discerned infection with a sensitivity of 60% and specificity of 57%. Performance improved when excluding patients on outpatient hydroxyurea therapy (cutoff of NLR = 3.5; sensitivity of 68% and specificity of 64%). CONCLUSION: This study supports the utility of NLR as an accessible adjunctive clinical tool in SCD prognostication.

Importance of carbohydrate antigen (CA 19-9) and carcinoembrionic antigen (CEA) in the prognosis of patients with duodenal adenocarcinoma: a retrospective single-institution cohort study.

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare malignancy without validated tumor markers. In practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) are often used in the management of DA, though their prognostic value is unknown. MATERIALS AND METHODS: A single-institution retrospective review included patients diagnosed with biopsy-confirmed adenocarcinoma of the duodenum between 2006 and 2021. Peri-ampullary tumors were excluded. Levels of CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal Ca 19-9 <35 U/ml; CEA <3 ng/ml). Survival analysis was conducted using Kaplan Meier curves, log-rank test and Cox proportional hazards model. RESULTS: There were 68 patients included in the final analysis. Median age was 67 years old and median follow-up time was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. A concomitant elevation of both tumor markers was associated with worsened OS (HR 2.140, 95% CI: 1.114-4.112; p = 0.019). After controlling for age and sex on multivariate analysis, elevation in both CA 19-9 ≥35 and CEA ≥3.0 remained significantly associated with increased mortality (HR 2.278, 95% CI: 1.162-4.466; p = 0.016). CONCLUSIONS: In summary, CA 19-9 and, to a lesser extent, CEA, show promise as prognostic markers in DA. Larger studies are needed to validate their use and to evaluate their performance as markers of recurrence.

Diffuse hepatocellular carcinoma secondary to cardiac cirrhosis in heterotaxy syndrome.

Heterotaxy syndrome is a rare congenital defect of left-right laterality of major visceral organs, often categorised by the presence of symmetric left or right atrial heart chambers with a single effective ventricle. Known as left or right atrial isomerism, these conditions may present with a distinct pattern of extracardiac anomalies. Heterotaxy is often palliated with the Fontan procedure and is suggested to be subject to similar long-term sequelae of congestive hepatopathy and ischaemia, increasing the risk for hepatocellular carcinoma. Few works document primary, localised hepatocellular carcinoma in patients with heterotaxy syndrome. We present a case of diffuse, multifocal metastatic hepatocellular carcinoma in a young patient with left atrial isomerism and dextrocardia. We also review suggested guidelines of surveillance for liver disease and hepatocellular carcinoma in this patient population.

Management of adrenal insufficiency in the setting of chronic HIV and advanced extra-adrenal Hodgkin lymphoma.

Adrenal insufficiency is one of the most common endocrine disorders that presents in patients with HIV. Aetiologies of adrenal dysfunction include opportunistic infection, malignancy, such as lymphoma or Kaposi sarcoma, and chronic cytokine-mediated disruption of the hypothalamic-pituitary-adrenal axis. In the case of lymphoma, the manifestation of adrenal insufficiency is most often via primary neoplastic infiltration. However, a spectrum of associated cytokine-mediated abnormal immune responses and coagulopathies may independently contribute to adrenal insufficiency. Literature regarding the presence of the endocrine disorder in patients with both HIV and lymphoma is scarce. We report a case of adrenal insufficiency in a patient with well-controlled HIV and advanced Hodgkin lymphoma without primary adrenal involvement with suboptimal response to corticosteroids who exhibited improvement following initiation of chemotherapy, demonstrating that chemotherapy should not be delayed until adrenal insufficiency resolves and in fact may aid in resolution of adrenal dysfunction.

DiGeorge syndrome: consider the diagnosis.

DiGeorge syndrome (DGS) is caused by a chromosomal microdeletion at 22q11.2 that results in impaired development of the pharyngeal pouch system. Patients with DGS may have developmental abnormalities of craniofacial structures, parathyroid glands, thymus and cardiac outflow tract. Doctors have been routinely testing for DGS in newborns with conotruncal cardiac anomalies since the late 1990s; before then, however, they relied on complex diagnostic criteria and the disease was often missed. Adults born with conotruncal defects before the late 1990s may have undiagnosed DGS. We present one such case: a 35-year-old woman with a cardiac diagnosis of tetralogy of Fallot and unilateral absence of a pulmonary arter who was found to have DGS. Identifying DGS in adults is important both for disease management and genetic counselling. Our case emphasises the importance of screening for DGS in adults who were born with conotruncal cardiac abnormalities before widespread neonatal testing became common.

Metastatic malignant peripheral nerve sheath tumour in a patient with neurofibromatosis 1 and review of contemporary systemic treatments.

Malignant peripheral nerve sheath tumours are rare soft tissue sarcomas commonly seen in patients with neurofibromatosis type 1. They typically manifest in the fibrous sheaths of major nerve trunks in the extremities or in an axial location. Presenting symptoms are generally non-specific, including pain and weakness, and survival is dependent on size and location of the tumour. Surgical resection is the primary treatment modality followed by radiotherapy or chemotherapy; however, prognosis is poor. Medications such as tyrosine kinase inhibitors and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway inhibitors are increasingly being recognised as potentially effective therapy for these malignancies. We report a case of a patient with neurofibromatosis type 1 presenting with a malignant peripheral nerve sheath tumour along the tibial nerve that was initially diagnosed as a muscle strain. We discuss the utility of diagnostic imaging and pathology in correctly identifying this aggressive tumour as well as review the drugs used in her care.

Extremely delayed-onset post-transplant lymphoproliferative disorder in a renal transplant patient.

Post-transplant lymphoproliferative disorder (PTLD) is a rare condition that occurs in patients who have undergone solid organ transplantation. Symptoms at presentation depend on the organs involved. PTLD most commonly occurs in the first year after transplant (early onset) or around 5 years after transplant (late onset). Herein, we report a rare presentation of central nervous system PTLD in an adult who presented with seizures 17 years after renal transplantation. After extensive infectious and transplant-related workup, brain biopsy confirmed the diagnosis of PTLD. The patient was treated with rituximab and high-dose methotrexate. Eighteen months later, the patient had no signs of recurrence. Very late-onset (>10 years) PTLD is rare, but is likely to become more common with more long-term survivors of solid organ transplant. Data are limited but show that the factors associated with very late-onset PTLD are different from early or late-onset PTLD.

Synchronous Recto-Sigmoid Colorectal Carcinomas With Microsatellite Instability and an Activating PIK3CA Mutation.

Synchronous colorectal cancer is a rare subtype of colorectal carcinoma defined by the presence of 2 or more primary tumors simultaneously or within 6 months of initial detection. The overall impact of a synchronous presentation on prognosis is not yet clear. Surgical resection is the primary treatment. However, higher rates of local recurrence and metastasis in synchronous colorectal cancer demand greater exploration of the role of adjuvant therapy. The increased frequency of microsatellite instability observed in synchronous colorectal cancer also affects therapy selection. Similarly, activating PIK3CA mutations are regularly noted in colorectal cancer, but their role in a synchronous presentation has not yet been described. We report a case of a young patient with a synchronous recto-sigmoid colorectal carcinoma complicated by microsatellite instability and an activating PIK3CA mutation-a presentation as of yet unreported in literature. We also review the impact of these molecular events on the efficacy of several chemotherapies and targeted therapies.

Analysis of the Diagnosis of Burkitt-Like Lymphoma in a Patient With Atypical Cytogenetics and Molecular Markers.

The World Health Organization (WHO) criteria for diagnosis of hematopoietic and lymphoid cancers serve as a useful t-ool for distinguishing between malignant conditions based on phenotypic, morphologic, and/or cytogenetic presentations, but their utility is limited in patients whose diseases contain elements of multiple diagnoses. We present a case of a 59-year-old male with enlargement of muscular and soft tissues of the left hip and an intraconal soft tissue mass surrounding the left optic nerve, who was treated for Burkitt-like lymphoma (BLL). Cytogenetics revealed the absence of an MYC rearrangement involving chromosomes 2, 14, or 22, normally found in Burkitt lymphoma, or the classic telomeric losses and proximal gains observed in BLL. Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) and high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS) were also considered as possible diagnoses. The persistence of ambiguous lymphoma diagnoses demonstrates the need for both continued research in the area and regular revision of the WHO criteria. Physicians working with patients with poorly defined lymphomas should defer to diagnostic algorithms where applicable, many of which have been proposed in the literature.

Hepatocellular Carcinoma in Patients With Liver Cirrhosis Secondary to Autoimmune Hepatitis: A Case Series and Literature Review.

Autoimmune hepatitis (AIH) is a known risk factor for the development of hepatocellular carcinoma (HCC). However, the current clinical guidelines do not offer a systematic approach to the surveillance and follow-up of patients with AIH to help with the diagnosis and treatment of HCC in this patient population. In this case series, we describe the clinical presentation and management of eight patients who were diagnosed with HCC secondary to underlying AIH at the University of Florida Health Shands Hospital. Throughout their treatment course, all eight patients were identified to have either histological or radiological evidence of liver cirrhosis. Furthermore, all of them tested negative for chronic viral hepatitis serologies and denied any history of excessive alcohol consumption. The median time interval between AIH diagnosis and HCC development in this cohort was 48 months. All demographic, clinical, and laboratory findings were summarized and compared to the relevant data in the existing literature. Our findings suggest that patients diagnosed with AIH would benefit from liver cirrhosis screening and, if present, they should adhere to a regular HCC surveillance schedule.