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1.
J Infect Dis ; 230(1): 45-54, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39052724

ABSTRACT

BACKGROUND: We assessed associations between binding antibody (bAb) concentration <5 days from symptom onset and testing positive for COVID-19 among patients in a test-negative study. METHODS: From October 2021 to June 2022, study sites in 7 states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain (RBD) and nucleocapsid antigens from the ancestral strain in standardized bAb units (BAU). Percentage change in odds of COVID-19 by increasing anti-RBD bAb was estimated via logistic regression as (1 - adjusted odds ratio of COVID-19) × 100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. RESULTS: Out of 2018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb levels were lower among COVID-19 cases than SARS-CoV-2 test-negative controls during the Delta-predominant period (112 vs 498 BAU/mL) and Omicron-predominant period (823 vs 1189 BAU/mL). Acute-phase ancestral spike RBD bAb levels associated with 50% lower odds of COVID-19 were 1968 BAU/mL against Delta and 3375 BAU/mL against Omicron; thresholds may differ in other laboratories. CONCLUSIONS: During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19.


Subject(s)
Antibodies, Viral , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , COVID-19/immunology , COVID-19/prevention & control , Antibodies, Viral/blood , SARS-CoV-2/immunology , Female , Male , Middle Aged , Adult , Aged , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Young Adult , Child , United States/epidemiology , Child, Preschool , COVID-19 Vaccines/immunology , Outpatients , Infant , Aged, 80 and over , Vaccine Efficacy , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage
2.
J Autoimmun ; : 103288, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39084998

ABSTRACT

Sarcoidosis is a multisystem granulomatous syndrome that arises from a persistent immune response to a triggering antigen(s). There is no "gold standard" test or algorithm for the diagnosis of sarcoidosis, making the diagnosis one of exclusion. The presentation of the disease varies substantially between individuals, in both the number of organs involved, and the manifestations seen in individual organs. These qualities dictate that health care providers diagnosing sarcoidosis must consider a wide range of possible alternative diagnoses, from across a range of presentations and medical specialties (infectious, inflammatory, cardiac, neurologic). Current guideline-based diagnosis of sarcoidosis recommends fulfillment of three criteria: 1) compatible clinical presentation and/or imaging 2) demonstration of granulomatous inflammation by biopsy (when possible) and, 3) exclusion of alternative causes, but do not provide guidance on standardized strategies for exclusion of alternative diagnoses. In this review, we provide a summary of the most common differential diagnoses for sarcoidosis involvement of lung, eye, skin, central nervous system, heart, liver, and kidney. We then propose a framework for testing to exclude alternative diagnoses based on pretest probability of sarcoidosis, defined as high (typical findings with sarcoidosis involvement confirmed in another organ), moderate (typical findings in a single organ), or low (atypical/findings suggesting of an alternative diagnosis). This work highlights the need for informed and careful exclusion of alternative diagnoses in sarcoidosis.

3.
Influenza Other Respir Viruses ; 18(7): e13339, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39012045

ABSTRACT

We describe humoral immune responses in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 Omicron variant infection. In dried blood spot (DBS) collected within 5 days of illness onset and during convalescence, we measured binding antibody (bAb) against ancestral spike protein receptor binding domain (RBD) and nucleocapsid (N) protein using a commercial multiplex bead assay. Geometric mean bAb concentrations against RBD increased by a factor of 2.5 from 1258 to 3189 units/mL and by a factor of 47 against N protein from 5.5 to 259 units/mL between acute illness and convalescence; lower concentrations were associated with greater geometric mean ratios. Paired DBS specimens may be used to evaluate humoral response to SARS-CoV-2 infection.


Subject(s)
Antibodies, Viral , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Female , Adult , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Aged , Coronavirus Nucleocapsid Proteins/immunology , Young Adult , Immunity, Humoral , Antibody Formation
4.
Cureus ; 16(5): e61012, 2024 May.
Article in English | MEDLINE | ID: mdl-38910787

ABSTRACT

Neuroendocrine tumors (NETs) represent a heterogeneous group of neoplasms with diverse clinical presentations and prognoses. Accurate and timely diagnosis of these tumors is crucial for appropriate management and improved patient outcomes. In recent years, exciting advancements in artificial intelligence (AI) technologies have been revolutionizing medical diagnostics, particularly in the realm of detecting and characterizing pulmonary NETs, offering promising avenues for improved patient care. This article aims to provide a comprehensive overview of the role of AI in diagnosing lung NETs. We discuss the current challenges associated with conventional diagnostic approaches, including histopathological examination and imaging modalities. Despite advancements in these techniques, accurate diagnosis remains challenging due to the overlapping features with other pulmonary lesions and the subjective interpretation of imaging findings. AI-based approaches, including machine learning and deep learning algorithms, have demonstrated remarkable potential in addressing these challenges. By leveraging large datasets of radiological images, histopathological samples, and clinical data, AI models can extract complex patterns and features that may not be readily discernible to human observers. Moreover, AI algorithms can continuously learn and improve from new data, leading to enhanced diagnostic accuracy and efficiency over time. Specific AI applications in the diagnosis of lung NETs include computer-aided detection and classification of pulmonary nodules on CT scans, quantitative analysis of PET imaging for tumor characterization, and integration of multi-modal data for comprehensive diagnostic assessments. These AI-driven tools hold promise for facilitating early detection, risk stratification, and personalized treatment planning in patients with lung NETs.

5.
medRxiv ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38826353

ABSTRACT

Objective: Sarcoidosis is a granulomatous disease affecting the lungs in over 90% of patients. Qualitative assessment of chest CT by radiologists is standard clinical practice and reliable quantification of disease from CT would support ongoing efforts to identify sarcoidosis phenotypes. Standard imaging feature engineering techniques such as radiomics suffer from extreme sensitivity to image acquisition and processing, potentially impeding generalizability of research to clinical populations. In this work, we instead investigate approaches to engineering variogram-based features with the intent to identify a robust, generalizable pipeline for image quantification in the study of sarcoidosis. Approach: For a cohort of more than 300 individuals with sarcoidosis, we investigated 24 feature engineering pipelines differing by decisions for image registration to a template lung, empirical and model variogram estimation methods, and feature harmonization for CT scanner model, and subsequently 48 sets of phenotypes produced through unsupervised clustering. We then assessed sensitivity of engineered features, phenotypes produced through unsupervised clustering, and sarcoidosis disease signal strength to pipeline. Main results: We found that variogram features had low to mild association with scanner model and associations were reduced by image registration. For each feature type, features were also typically robust to all pipeline decisions except image registration. Strength of disease signal as measured by association with pulmonary function testing and some radiologist visual assessments was strong (optimistic AUC ≈ 0.9, p ≪ 0.0001 in models for architectural distortion, conglomerate mass, fibrotic abnormality, and traction bronchiectasis) and fairly consistent across engineering approaches regardless of registration and harmonization for CT scanner. Significance: Variogram-based features appear to be a suitable approach to image quantification in support of generalizable research in pulmonary sarcoidosis.

6.
Eur J Haematol ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890006

ABSTRACT

Diffuse large B-cell Lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL). The disease generally occurs in older patients. Although at a lower prevalence, the disease also occurs in the adolescent and young adult group (AYA). There is paucity of data in the literature on racial and ethnic disparities in the incidence and survival outcomes of DLBCL in the AYA group. The objective of our study is to demonstrate the disparities in these outcomes. Utilizing SEER, we obtained data on patient demographics, incidence, and survival from 2000 to 2020. We observed statistically significant reduced incidence of DLBCL in all racial groups, except the non-Hispanic Asian and Pacific Islander group (NHAPI). The non-Hispanic Black group (NHB) had one of the lowest survival despite showing the largest decrease in incidence in DLBCL. The differences in the survival could be secondary to socioeconomic factors, however other reasons need to be explored. The increased incidence among the NHAPI group mirrors that of large population-based studies in East Asian countries, however, underlying reasons have not been elucidated.

7.
PLOS Glob Public Health ; 4(4): e0003073, 2024.
Article in English | MEDLINE | ID: mdl-38568905

ABSTRACT

SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.

8.
Cureus ; 16(2): e54699, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38529429

ABSTRACT

Hypernatremia or high serum sodium levels can have many different causes, including insufficient free water intake, or excess free water losses. The management of hypernatremia focuses on resolving the underlying cause, replenishing free water deficit, and preventing further losses while closely monitoring serum sodium concentration. This systematic review was carried out using medical databases such as PubMed, PubMed Central, and Google Scholar for relevant medical literature. The identified articles were reviewed, eligibility criteria were applied, and seven research articles were identified. The effect of the rate of hypernatremia correction on both short- and long-term outcomes in volume-resuscitated patients was the focus of our search for randomized or observational studies. Based on our analysis of the clinical evidence, we concluded that the present recommendations for treating acute and chronic hypernatremia in resuscitated patients do not stem from high-quality research.

9.
Am J Trop Med Hyg ; 110(5): 989-993, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38531097

ABSTRACT

Many SARS-CoV-2 infections are asymptomatic, thus reported cases underestimate actual cases. To improve estimates, we conducted surveillance for SARS-CoV-2 seroprevalence among pregnant women attending their first antenatal care visit (ANC1) from June 2021 through May 2022. We administered a questionnaire to collect demographic, risk factors, and COVID-19 vaccine status information and tested dried blood spots for SARS-CoV-2 antibodies. Although <1% of ANC1 participants reported having had COVID-19, monthly SARS-CoV-2 seroprevalence increased from 15.4% (95% CI: 10.5-21.5) in June 2021 to 65.5% (95% CI: 55.5-73.7) in May 2022. Although COVID-19 vaccination was available in March 2021, uptake remained low, reaching a maximum of 9.5% (95% CI: 5.7-14.8) in May 2022. Results of ANC1 serosurveillance provided prevalence estimates helpful in understanding this population case burden that was available through self-report and national case reports. To improve vaccine uptake, efforts to address fears and misconceptions regarding COVID-19 vaccines are needed.


Subject(s)
COVID-19 Vaccines , COVID-19 , Pregnancy Complications, Infectious , Prenatal Care , SARS-CoV-2 , Humans , Female , Pregnancy , Seroepidemiologic Studies , COVID-19/prevention & control , COVID-19/epidemiology , Adult , COVID-19 Vaccines/administration & dosage , SARS-CoV-2/immunology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/epidemiology , Malawi/epidemiology , Young Adult , Antibodies, Viral/blood , Vaccination/statistics & numerical data , Adolescent , Pregnant Women
10.
Int J Biol Macromol ; 261(Pt 1): 129634, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38272413

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a major worldwide chronic disease and can lead to serious diabetic complications. Despite the availability of many anti-diabetic agents in the market, they are unable to meet the long-term treatment goals. Also, they cause many side effects which justify the need for novel class of anti-diabetic drugs with newer mechanism of action. Wnt signaling is one of such novel target pathways which can be explored for metabolic disorders. Many key components of the Wnt signaling are involved in the regulation of glucose homeostasis. Polymorphism in the Transcription factor 7-like 2 (TCF7L2) gene, and mutations in the LRP5 (LDL Receptor Related Protein 5) gene lead to disturbed glucose metabolism and obesity. Despite of several years of research in this field, there is no concrete proof of concept available on whether Wnt activation or Wnt inhibition is the beneficial approach for the treatment of T2DM. Here, we have summarized the conclusions of relevant published research studies to give structured insights into possibilities to explore Wnt modulation as a novel target pathway for the treatment of T2DM. The review also highlights the present challenges and future opportunities towards the development of anti-diabetic small molecules targeting the Wnt signaling pathway.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Wnt Signaling Pathway , Insulin/pharmacology , Homeostasis , Glucose/metabolism
11.
Lancet Respir Med ; 12(5): 409-418, 2024 May.
Article in English | MEDLINE | ID: mdl-38104579

ABSTRACT

One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis.


Subject(s)
Consensus , Delphi Technique , Phenotype , Sarcoidosis, Pulmonary , Tomography, X-Ray Computed , Humans , Sarcoidosis, Pulmonary/diagnostic imaging , Tomography, X-Ray Computed/methods , Lung/diagnostic imaging
12.
Cureus ; 15(11): e49016, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38111454

ABSTRACT

Miller-Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome, characterized by ataxia, areflexia, ophthalmoplegia, and possible facial, swallowing and limb weakness alongside respiratory failure. Variations within MFS may include respiratory and limb weakness and Bickerstaff brainstem encephalitis (BBE), marked by altered consciousness, ataxia, ophthalmoparesis, and paradoxical hyperreflexia. MFS can emerge in both children and adults, often following bacterial or viral illness. While autoimmune-driven nerve damage occurs, most MFS patients recover within six months without specific treatment, with a low risk of lasting neurological deficits or relapses. Rarely fatal, MFS's co-occurrence with cholangiocarcinoma (CCA) presents unique management challenges. CCA, primarily affecting bile ducts, has a bleak prognosis; surgical resection offers limited cure potential due to late-stage detection and high recurrence rates. Advances in CCA's molecular understanding have led to novel diagnostic and therapeutic approaches, requiring a comprehensive interdisciplinary care approach for optimal MFS and CCA management outcomes. Herein, we present a 50-year-old male with a complex medical history who was admitted to the hospital due to abdominal discomfort, nausea, vomiting, and ascites. Imaging revealed pneumonia and secondary bacterial peritonitis. Later, he developed neurological symptoms, including weakness, gait abnormalities, and brainstem symptoms, leading to the diagnosis of MFS. Despite treatment efforts, his condition deteriorated, leading to acute liver failure and unexplained anasarca. N-acetyl cysteine was initiated for liver issues. Neurologically, he showed quadriparesis and areflexia. Intravenous immunoglobulin (IVIG) treatment improved his neurological symptoms but worsened gastrointestinal issues, including ileus and elevated CA19-9 levels, suggesting a potential carcinoma. A liver biopsy was performed. After IVIG treatment, he experienced widespread discomfort, emotional unresponsiveness, swallowing difficulties, and aspiration risk, ultimately leading to his demise.

13.
medRxiv ; 2023 Nov 18.
Article in English | MEDLINE | ID: mdl-38014151

ABSTRACT

To describe humoral immune responses to symptomatic SARS-CoV-2 infection, we assessed immunoglobulin G binding antibody levels using a commercial multiplex bead assay against SARS-CoV-2 ancestral spike protein receptor binding domain (RBD) and nucleocapsid protein (N). We measured binding antibody units per mL (BAU/mL) during acute illness within 5 days of illness onset and during convalescence in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 infection with Omicron variant viruses. Comparing acute- to convalescent phase antibody concentrations, geometric mean anti-N antibody concentrations increased 47-fold from 5.5 to 259 BAU/mL. Anti-RBD antibody concentrations increased 2.5-fold from 1258 to 3189 BAU/mL.

14.
medRxiv ; 2023 Sep 23.
Article in English | MEDLINE | ID: mdl-37790578

ABSTRACT

Background: We assessed the association between antibody concentration ≤5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative study. Methods: From October 2021-June 2022, study sites in seven states enrolled and tested respiratory specimens from patients of all ages presenting with acute respiratory illness for SARS-CoV-2 infection using rRT-PCR. In blood specimens, we measured concentration of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent reduction in odds of symptomatic COVID-19 by anti-RBD antibody was estimated using logistic regression modeled as (1-adjusted odds ratio of COVID-19)×100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure. Results: A total of 662 (33%) of 2,018 symptomatic patients tested positive for acute SARS-CoV-2 infection. During the Omicron-predominant period, geometric mean anti-RBD binding antibody concentrations measured 823 BAU/mL (95%CI:690-981) among COVID-19 case-patients versus 1,189 BAU/mL (95%CI:1,050-1,347) among SARS-CoV-2 test-negative patients. In the adjusted logistic regression, increasing levels of anti-RBD antibodies were associated with reduced odds of COVID-19 for both Delta and Omicron infections. Conclusion: Higher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants.

15.
Cureus ; 15(8): e44464, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37791211

ABSTRACT

Gitelman syndrome (GS) is a rare autosomal recessive salt-losing renal tubular disorder associated with a mutation of SLC12A3 or CLCNKB genes which encodes the thiazide-sensitive sodium-chloride co-transporter (NCCT) in the distal renal tubule. It is inherited as an autosomal recessive disorder. Hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation are characteristics of GS. GS is often misdiagnosed or underdiagnosed owing to its low incidence and lack of awareness. Its prevalence is estimated to be around 1-10 per 40,000 people. We report a case of cardiac arrest secondary to torsade de pointes (TdP) because of GS-induced hypomagnesemia. Our case highlights the importance of clinicians being aware of the potential electrolyte abnormalities and complications associated with GS, as it can lead to catastrophic consequences if not identified and corrected earlier.

16.
J Patient Saf ; 19(8): 532-538, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37883056

ABSTRACT

OBJECTIVES: Computed tomographic pulmonary angiography (CT-PA) is associated with significant cost, contrast, and radiation exposure. Clinical decision rules (CDRs) reduce the need for diagnostic imaging; however, their utility in the medical intensive care unit (MICU) remains unknown. We explored the diagnostic yield and complications associated with CT-PA (radiation exposure and contrast-induced acute kidney injury [AKI]) while investigating the efficacy of CDRs to reduce unnecessary testing. METHODS: All CT-PAs performed in an academic MICU for 4 years were retrospectively reviewed. The Wells and revised Geneva scores (CDRs) and radiation dose per CT-PA were calculated, and the incidence of post-CT-PA AKI was recorded. RESULTS: A total of 439 studies were analyzed; the diagnostic yield was 11% (48 PEs). Positive CT-PAs were associated with a higher Wells score (5.8 versus 3.2, P < 0.001), but similar revised Geneva scores (6.4 versus 6.0, P = 0.32). A Wells score of ≥4 had a positive likelihood ratio of 2.1 with a negative predictive value of 98.2. More than half (88.9%) of patients with a Wells score of ≤4 developed an AKI, with 55.6% of those having recovery of renal function. CONCLUSIONS: There is overutilization of CT-PA in the MICU. The Wells score retains its negative predictive value in critically ill adult patients and may aid to limit radiation exposure and contrast-induced AKI in MICU.


Subject(s)
Acute Kidney Injury , Pulmonary Embolism , Radiation Exposure , Adult , Humans , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/etiology , Clinical Decision Rules , Retrospective Studies , Angiography/adverse effects , Tomography, X-Ray Computed/adverse effects , Radiation Exposure/adverse effects , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis
17.
Cureus ; 15(8): e43429, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37706116

ABSTRACT

In melanoma patients, distant metastases frequently manifest in the skin, lung, brain, liver, bone, and intestine. Notably, bone metastasis predominantly occurs within the axial skeleton, with the lumbar and thoracic spines being the most affected regions. Conversely, prostate cancer often disseminates to the bone, lung, liver, pleura, and adrenal glands. The spinal column, particularly the lumbar region, frequently harbors metastases in prostate cancer cases. Given the proximity of axial lesions to the spinal cord, patients commonly experience pain, weakness, and urinary dysfunction. This article presents a compelling case report of a patient initially diagnosed with metastatic prostate cancer, who later exhibited a metastatic lesion in the thoracic spine, subsequently identified as originating from acral melanoma on the plantar surface of the right foot. Histopathological examination confirmed the presence of acral melanoma in both the spine and the right foot. The patient received comprehensive treatment for advanced melanoma from a multidisciplinary team comprising medical and radiation oncologists. Considering the overlapping pathophysiology of prostate cancer and melanoma, simultaneous screening for both diseases in cases where one is detected could yield significant benefits, including enhanced morbidity and mortality outcomes and the facilitation of early detection for secondary malignancies.

18.
Front Immunol ; 14: 1151422, 2023.
Article in English | MEDLINE | ID: mdl-37767091

ABSTRACT

Introduction: While cystic fibrosis (CF) lung disease is characterized by persistent inflammation and infections and chronic inflammatory diseases are often accompanied by autoimmunity, autoimmune reactivity in CF has not been studied in depth. Methods: In this work we undertook an unbiased approach to explore the systemic autoantibody repertoire in CF using autoantibody microarrays. Results and discussion: Our results show higher levels of several new autoantibodies in the blood of people with CF (PwCF) compared to control subjects. Some of these are IgA autoantibodies targeting neutrophil components or autoantigens linked to neutrophil-mediated tissue damage in CF. We also found that people with CF with higher systemic IgM autoantibody levels have lower prevalence of S. aureus infection. On the other hand, IgM autoantibody levels in S. aureus-infected PwCF correlate with lung disease severity. Diabetic PwCF have significantly higher levels of IgA autoantibodies in their circulation compared to nondiabetic PwCF and several of their IgM autoantibodies associate with worse lung disease. In contrast, in nondiabetic PwCF blood levels of IgA autoantibodies correlate with lung disease. We have also identified other autoantibodies in CF that associate with P. aeruginosa airway infection. In summary, we have identified several new autoantibodies and associations of autoantibody signatures with specific clinical features in CF.


Subject(s)
Cystic Fibrosis , Cysts , Diabetes Mellitus , Humans , Cystic Fibrosis/complications , Staphylococcus aureus , Autoantibodies , Lung , Immunoglobulin A , Immunoglobulin M
19.
Reg Anesth Pain Med ; 2023 Sep 24.
Article in English | MEDLINE | ID: mdl-37748801

ABSTRACT

INTRODUCTION: Preclinical research demonstrated water-cooled radiofrequency (CRF) ablations have a significant impact on structural and functional changes compared to standard radiofrequency (SRF) ablations. Clinical procedures utilizing RF to treat chronic pain conditions also show sustained functional outcomes. We hypothesize that the design of the RF probes plays an important role in interventional procedure success, but it remains unclear which specific design features. METHODS: RF ablations were performed in male Lewis rats (n=51) using multiple-sized probes for CRF (17 Ga/2 mm and 17Ga/4 mm) and SRF (22Ga/5 mm, 18Ga/10 mm and 16Ga/10 mm) to evaluate generator energy output, lesion length, axon damage by histology and nerve function analysis via electromyography. To exclude probe design variables beyond size and remain objective, we tested cooled probes with and without water circulation, which resulted in the CRF probe performing like an SRF probe. RESULTS: Consistent with our previous findings in smaller probes, CRF large probes delivered more energy (p<0.01) and generated multiple zones of thermal damage in sciatic nerves. When the water-circulating feature was turned off, however, energy output (p<0.001) and lesion length (p<0.05) was significantly reduced. CRF probes with the water circulation also featured significantly more axonal disruption, than larger sized SRF probes (p<0.0001). CONCLUSIONS: Overall, this data confirms that CRF's water-circulating technology has a greater impact on energy deposition, lesion length and axon damage compared with SRF ablations. Moreover, results suggest that the structural differences between RF modalities cannot be solely attributed to probe size, and it may shed light on its differences in clinical outcomes.

20.
Mod Pathol ; 36(12): 100347, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37769995

ABSTRACT

It is not widely recognized that iron (ferrous sulfate) pill aspiration causes airway damage. Clinical diagnosis is challenging because patients are often unaware that they have aspirated a pill. The literature on this entity consists mainly of case reports. The aim of this study is to describe the clinical and pathologic features of iron pill aspiration in a series of 11 patients. A retrospective review of our pathology archives was performed to identify cases of iron pill aspiration (2013-2023). All available histologic and cytologic material was rereviewed. Clinical information was collected from the electronic medical record, and imaging studies were rereviewed. Eighteen endobronchial biopsies were identified from 11 patients (7 women and 4 men; mean age, 70 years; range, 44-82 years). Eight patients had corresponding cytology (20 specimens). Medication history was available in 9 of 11 patients, all of whom were taking iron sulfate pills. Two patients reported possible aspiration episodes; 4 had risk factors for aspiration. The diagnosis of iron pill aspiration was suspected prior to biopsy in only 1 case. Histologically, iron pill particles were yellow, golden brown, or gray, were elongated and crystal or fiber like, and stained strongly with an iron stain. Common histologic findings included mucosal ulceration, acute and/or chronic inflammation, fibrosis, and squamous metaplasia. Iron pill particles were also identified in 11 cytology specimens from 6 patients. On Papanicolaou staining, iron pill particles were yellow to golden, fiber like, refractile, and crystalline. Reactive epithelial cells, squamous metaplasia, and acute inflammation were common. The combination of iron pill intake and discolored mucosa on bronchoscopy is a potential clue to the diagnosis of iron pill aspiration. Pathologists should familiarize themselves with the appearance of iron pill particles in endobronchial biopsies and cytology specimens from the respiratory tract as this diagnosis is seldom suspected on clinical grounds, and most patients lack a history of aspiration.


Subject(s)
Inflammation , Iron , Male , Humans , Female , Aged , Iron/adverse effects , Metaplasia , Sulfates
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