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Aim: The faecal immunochemical test (FIT) is now widely used in English primary care to triage people who exhibit signs or symptoms of colorectal cancer (CRC). National guidelines for FIT implementation were based on data that acknowledged limitations. This study examines FIT accuracy in primary care patients with low‐ and high‐risk symptoms of CRC. Methods: This study describes a retrospective cohort study in South Yorkshire, UK (n = 2029). Consecutive symptomatic adult patients in primary care undergoing a FIT between 01/04/2021 and 30/04/2021 were assessed. A threshold > 10 μg Hb/g was defined as a positive FIT result. Lower gastrointestinal tract (LGI) investigations were the reference standard. Follow‐up over 24 months was used to identify serious colorectal diseases (CRC, high‐risk polyps and inflammatory bowel disease [IBD]). Results: Five hundred and fifteen (25.4%) patients had a positive FIT. The CRC prevalence was 1.2% (24/2029). Nineteen (79.1%) of the 24 CRC cases had NG12 symptoms, with two (8.3%) having a negative FIT. For CRC detection, FIT showed 91.7% sensitivity (95% CI: 71.5%–98.5%), 75.4% specificity (95% CI: 73.4%–77.2%), 4.3% positive predictive value (PPV) (95% CI: 2.8%–6.5%) and 99.9% negative predictive value (NPV) (95% CI: 99.5%–99.97%). Combining CRC, high‐risk polyps and IBD increased PPV and specificity but decreased sensitivity and NPV. Conclusions: In primary care, FIT safely triages patients having at‐risk CRC risk symptoms. Negative FIT results indicate a low likelihood of CRC and supports safety‐netting interventions. [ABSTRACT FROM AUTHOR]

Background: Botulism is a rare and life-threatening disease caused by the potent botulinum neurotoxin (BoNT), which can be produced by Clostridium botulinum (C. botulinum) and related bacteria. Clinical manifestations, which include a symmetrical, descending muscular paralysis, generalized hypotonia, and potentially respiratory failure, are non-specific and diagnosis is challenging, especially when anamnesis does not reveal any typical risk factor, like honey consumption. Case Presentation: We present what is, to the best of our knowledge, the first documented case of infant botulism (IB) in Sicily and discuss its peculiarities and the challenges faced in the diagnostic-therapeutic process. The infant was exclusively breastfed and no history of consumption of possibly contaminated foods, like honey, was found. The signs observed at presentation included poor suction, hypotonia, and hyporeactivity. A detailed anamnesis motivated the suspicion of botulism, due to the occurrence of constipation and exposure to dust from home renovation works during the days before the onset of symptoms. The botulinum antitoxin was administered and the diagnosis was confirmed through fecal examination, detecting toxin-producing C. botulinum. Conclusion: IB should be considered in every infant with rapidly progressing hypotonia and a history of constipation. However rarely, transmission could occur through inhalation of dust particles containing the toxin, therefore it is important to explore all possible sources of exposure. In the case described, timely diagnosis and treatment determined the successful outcome, which highlights the importance of early intervention in managing IB. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation. Summary: AIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter. Splenectomy, which is still a good option for young/fit wAIHA, is contraindicated in CAD, and classic immunosuppressants are moving to further lines. Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan). Clinically, AIHAs are highly heterogeneous, from mild/compensated to life-threatening/fulminant, and may be primary or associated with infections, neoplasms, autoimmune diseases, transplants, immunodeficiencies, and drugs. Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging. Key Messages: This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) has a "pre‐RA" period in which multiple autoantibodies, including antibodies to citrullinated (cit) proteins (ACPA), rheumatoid factor (RF), anti–peptidyl arginine deiminase (anti‐PAD), among others, have been described; however, few studies have tested all autoantibodies in a single pre‐RA cohort. This study aims to evaluate the prevalence of multiple autoantibodies in pre‐RA and potentially identify an autoantibody profile in pre‐RA that indicates imminent onset of clinical RA. Methods: We evaluated 148 individuals with two pre‐ and one post‐RA diagnosis samples available from the Department of Defense Serum Repository and matched controls. Samples were tested for immuglobulin (Ig) G anti–cyclic cit peptide‐3 (anti‐CCP3), five ACPA fine specificities, five anti‐PAD isoforms, as well as RF IgA and RF IgM using commercial platforms; cutoffs were determined using levels present in <1% of controls. Results: Positivity of anti‐CCP3, RF IgA and RF IgM, anti‐PAD1, anti–cit‐vimentin 2, anti–cit‐fibrinogen, and anti–cit‐histone 1 increased over time in pre‐RA, although anti‐PAD and ACPA fine specificities were predominately present within anti‐CCP3–positive individuals. Within anti‐CCP3–positive samples from the pre‐RA period, positivity for RFs as well as anti‐PAD and ACPA fine specificities classified samples as being closer to the time of RA diagnosis. Conclusion: Multiple autoantibodies are present in pre‐RA and increase in positivity as the time of RA diagnosis approaches. These results confirm previous findings predicting imminent RA and provide a pathway using commercial‐grade assays to assess the risk for and timing of development of clinical RA. [ABSTRACT FROM AUTHOR]

Introduction: The lack of cognitive awareness, anosognosia, is a clinical deficit in Alzheimer's disease (AD) dementia. However, an increased awareness of cognitive function, hypernosognosia, may serve as a marker in the preclinical stage. Subjective cognitive decline (SCD) might correspond to the initial symptom in the dynamic trajectory of awareness, but SCD might be absent along with low awareness of actual cognitive performance in the preclinical stage. We hypothesized that distinct meta-cognitive profiles, both hypernosognosia and anosognosia, might be identified in preclinical-AD. This research evaluated the association between cerebrospinal fluid (CSF) AD biomarkers and the awareness of episodic memory, further exploring dyadic (participant-partner) SCD reports, in the preclinical Alzheimer's continuum. Methods: We analyzed 314 cognitively unimpaired (CU) middle-aged individuals (mean age: 60, SD: 4) from the ALFA+ cohort study. Episodic memory was evaluated with the delayed recall from the Memory Binding Test (MBT). Awareness of episodic memory, meta-memory, was defined as the normalized discrepancy between objective and subjective performance. SCD was defined using self-report, and dyadic SCD profiles incorporated the study partner's report using parallel SCD-Questionnaires. The relationship between CSF Ab42/40 and CSF p-tau181 with meta-memory was evaluated with multivariable regression models. The role of SCD and the dyadic contingency was explored with the corresponding stratified analysis. Results: CSF Ab42/40 was non-linearly associated with meta-memory, showing an increased awareness up to Ab-positivity and a decreased awareness beyond this threshold. In the non-SCD subset, the non-linear association between CSF Ab42/40 and meta-memory persisted. In the SCD subset, higher Ab-pathology was linearly associated with increased awareness. Individuals presenting only study partner's SCD, defined as unaware decliners, exhibited higher levels of CSF p-tau181 correlated with lower meta-memory performance. Discussion: These results suggested that distinct meta-cognitive profiles can be identified in preclinical-AD. While most individuals might experience an increased awareness associated with the entrance in the AD continuum, hypernosognosia, some might be already losing insight and stepping into the anosognosic trajectory. This research reinforced that an early anosognosic profile, although at increased risk of AD-related decline, might be currently overlooked considering actual diagnostic criteria, and therefore its medical attention delayed. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in _4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Objectives Inflammatory arthritis (IA) is considered the last stage of a disease continuum, where features of systemic autoimmunity can appear years before clinical synovitis. Time to progression to IA varies considerably between at-risk individuals, therefore the identification of biomarkers predictive of progression is of major importance. We previously reported on the value of three CD4+T cell subsets as biomarkers of progression. Here, we aim to establish the value of 18 lymphocyte subsets (LS) for predicting progression to IA. Methods Participants were recruited based on a new musculoskeletal complaint and being positive for anti-citrullinated-peptide antibody. Progression (over 10 years) was defined as the development of clinical synovitis. LS analysis was performed for lymphocyte lineages, naive/memory subsets, inflammation-related cells (IRC) and regulatory cells (Treg/B-reg). Modelling used logistic/Cox regressions. Results Of 210 patients included, 93 (44%) progressed to IA, 41/93 (44%) within 12 months (rapid progressors). A total of 5/18 LS were associated with progression [Treg/CD4-naïve/IRC (adjusted P  < 0.0001), CD8 (P  = 0.021), B-reg (P  = 0.015)] and three trends (NK-cells/memory-B-cells/plasmablasts). Unsupervised hierarchical clustering using these eight subsets segregated three clusters of patients, one cluster being enriched [63/109(58%)] and one poor [10/45(22%)] in progressors. Combining all clinical and LS variables, forward logistic regression predicted progression with accuracy = 85.7% and AUC = 0.911, selecting smoking/rheumatoid-factor/HLA-shared-epitope/tender-joint-count-78 and Treg/CD4-naive/CD8/NK-cells/B-reg/plasmablasts. To predict rapid progression, a Cox regression was performed resulting in a model combining smoking/rheumatoid factor and IRC/CD4-naive/Treg/NK-cells/CD8+T cells (AUC = 0.794). Conclusion Overall, progression was predicted by specific LS, suggesting potential triggers for events leading to the development of IA, while rapid progression was associated with a different set of subsets. [ABSTRACT FROM AUTHOR]

The article discusses the case of a patient with severe trismus leading to the diagnosis of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Topics discussed include magnetic resonance imaging revealing inflammation of masticatory muscles, the mutation in exon 3 of the UBA 1 gene, and the resolution of clinical symptoms following corticosteroid therapy with prednisone.

Objectives: Fecal immunochemical testing (FIT) is an effective screening tool for colorectal cancer. If an FIT is abnormal, a follow-up colonoscopy is necessary to remove polyps or find cancers. We sought to develop a usable risk prediction model to identify patients unlikely to complete a colonoscopy following an abnormal FIT test. Methods: We recalibrated and then redeveloped a prediction model in federally qualified health centers (FQHCs), using a retrospective cohort of patients aged 50–75 with an abnormal FIT test and clinical data. Logistic and Cox regressions were used to recalibrate and then redevelop the model. Results: The initial risk model used data from eight FQHCs (26 clinics) including 1723 patients. When we applied the model to a single large FQHC (34 clinics, 884 eligible patients), the model did not recalibrate successfully (c-statistic dropped more than 0.05, from 0.66 to 0.61). The model was redeveloped in the same FQHC in a cohort of 1401 patients with a c-statistic of 0.65. Conclusions: The original model developed in a group of FQHCs did not adequately recalibrate in the single large FQHC. Health system, patient characteristics or data differences may have led to the inability to recalibrate the model. However, the redeveloped model provides an adequate model for the single FQHC. [ABSTRACT FROM AUTHOR]

Objectives: This study examines the associations of active matrix metalloproteinase‐8 (aMMP‐8) point‐of‐care immunotest (Periosafe) outcomes with oral health of patients with haemato‐oncologic diseases. Methods: Adult patients diagnosed with haematological diseases aimed to be treated with haematopoietic stem cell transplantation (HSCT) between 2018 and 2019 were included in the study. Clinical and radiological dental examination were taken immediately prior to transplantation. The presence of oral foci of infections, caries or periodontitis was examined and compared with the outcomes of aMMP‐8 immunotest. Results: Acute oral infection foci were present in 11.9%, chronic in 44.1% and periodontitis in 42.0% of the 143 subjects. aMMP‐8 immunotest was positive in 13.3% of all the 143 subjects. Among subjects with periodontitis (n = 60), the aMMP‐8 immunotest was also positive in 13.3% of these subjects. However, the subjects with positive aMMP‐8 immunotest (n = 19) had more often acute or chronic infection foci and more than one of the examined dental treatment needs compared with subjects with negative immunotest (all p < 0.05). There were no differences in age, sex, hyposalivation, DMFT‐index values nor with plasma levels of leukocytes, neutrophils or C‐reactive protein between subjects with positive or negative aMMP‐8 immunotest. Conclusions: aMMP‐8 immunotest accuracy might be reduced, in relation to periodontitis, in haemato‐oncologic patients. [ABSTRACT FROM AUTHOR]

Nonlinear curve fitting is an important process in laboratory medicine, particularly with the increased use of highly sensitive antibody-based assays. Although the process is often automated in commercially available software, it is important that clinical scientists and physicians recognize the limitations of the various approaches used and are able to select the most appropriate model. This article summarizes the key nonlinear functions and demonstrates their application to common laboratory data. Following this, a basic overview of the statistical comparison of models is presented and then a discussion of important algorithms used in nonlinear curve fitting. An accompanying Microsoft Excel workbook is available that can be used to explore the content of this article. [ABSTRACT FROM AUTHOR]

The progression of cancer involves a critical step in which malignant cells escape from control by the immune system. Antineoplastic agents are particularly efficient when they succeed in restoring such control (immunosurveillance) or at least establish an equilibrium state that slows down disease progression. This is true not only for immunotherapies, such as immune checkpoint inhibitors (ICIs), but also for conventional chemotherapy, targeted anticancer agents, and radiation therapy. Thus, therapeutics that stress and kill cancer cells while provoking a tumor-targeting immune response, referred to as immunogenic cell death, are particularly useful in combination with ICIs. Modern oncology regimens are increasingly using such combinations, which are referred to as chemoimmunotherapy, as well as combinations of multiple ICIs. However, the latter are generally associated with severe side effects compared with single-agent ICIs. Of note, the success of these combinatorial strategies against locally advanced or metastatic cancers is now spurring successful attempts to move them past the postoperative (adjuvant) setting to the preoperative (neoadjuvant) setting, even for patients with operable cancers. Here, the authors critically discuss the importance of immunosurveillance in modern clinical cancer management. [ABSTRACT FROM AUTHOR]

Simple Summary: Receptor tyrosine kinases (RTKs) are a family of transmembrane proteins that play crucial roles in regulating various cellular processes. The introduction of ImmunoPET targeting RTKs by specific monoclonal antibodies (mAbs) or antibody fragments is regarded as a promising tool for imaging treatment efficacy and developing anticancer drugs. Herein, we review the current clinical research on ImmunoPET targeting RTKs, with particular interest in the epidermal growth factor family, or HER family, and vascular endothelial-derived growth factor/receptor. Receptor tyrosine kinases, or RTKs, are one large family of cell surface receptors involved in signal transduction, which represent an integral part of the signaling pathways. They play a crucial role in most important cellular processes, starting with the cell cycle, proliferation and differentiation, as well as cell migration, metabolism and survival. The introduction of ImmunoPET evaluating the expression of RTKs by specific monoclonal antibodies (mAbs) or antibody fragments is regarded as a promising tool for imaging treatment efficacy and developing anticancer therapeutics. Our review focuses mainly on the current clinical research regarding ImmunoPET targeting RTKs, with particular interest in the epidermal growth factor family, or HER family, and vascular endothelial-derived growth factor/receptor. [ABSTRACT FROM AUTHOR]

Objective: Allergic rhinitis is a common disease all over the world and allergy tests play an important role in the diagnostic process. Inhalant allergen susceptibility varies by region. We aimed to assess the distribution of aero-allergens in adult patients with allergic rhinitis in Van province. Materials and Methods: We included 583 adult allergic rhinitis patients with compatible history, physical examination, and an allergy test. We evaluated the demographic features and allergy test results in addition to clinical and laboratory findings on patients with allergic rhinitis. The characteristics of the patients allocated into two groups with moderate/severe and mild allergic rhinitis were compared. Results: Seventy-four percent of the patients were female and the median age of the patients was 29 years. The most common allergic comorbidities were allergic conjunctivitis (28%) and asthma (22%) while the non-allergic comorbidity was chronic rhinosinusitis (23%). The most frequent inhalant allergen sensitization was the grass mix (n=382, 65%), followed by cereal mix (n=308, 52%), dermatophagoides farinae (n=258, 44%), dermatophagoides pteronyssinus (n=256, 43%), english plantain (n=118, 20%), wall pellitory (n=54, 9%), olive tree (n=37, 6%), ragweed (n=21, 3%), birch (n=14, 2%), alternaria alternata (n=15, 2%), cat (n=13, 2%), aspergillus fumigatus (n=4, 0.6%), bird (n=3, 0.5%), and dog (n=1, 0.1%). Moderate/severe allergic rhinitis was associated with older age, longer disease duration and the presence of a family history of an allergic disease (p=0.003, p<0.001, p=0.004, respectively). Additionally, polysensitization was found to be higher in patients with moderate/severe allergic rhinitis while asthma and chronic rhinosinusitis were more common in patients with moderate/severe allergic rhinitis (p<0.001, p=0.009, p<0.001, respectively). Conclusion: This study showed that pollen is the most common in the distribution of allergens in the sensitization of patients with adult allergic rhinitis in Van province. This study will guide physicians in the management of allergic rhinitis especially in terms of allergen immunotherapy. [ABSTRACT FROM AUTHOR]

Consuming plant sprouts as part of the daily human diet is slowly on the increase, and the health benefits are now of interest in several disciplines. The aim of this investigation was to evaluate the chemical compositions of dried broccoli or dried green pea sprouts and the subsequent effects on the biological, biochemical and immunological parameters of male albino rats supplemented with acrylamide as a toxic material. Chemical constituents, mineral contents, total phenols and total flavonoid of tested vegetable sprouts were analyzed. Thirty male albino rats weighting 160± 5 g. were separated into 6 groups. The negative control group was first, and then the second group was given acrylamide 2.5 μg/kg/day. Groups (3, 4) and (5,6) were given treatment of the same toxic material and received 5 and 10 g dried broccoli and pea sprouts per 100 g basal diet, respectively. Feed intake, body weight gain, FER and some organs weights were calculated towards the conclusion of the investigation. Also, liver enzymes, lipids profile, serum glucose, kidney function, brain enzymes, oxidative activity and immunoglobulin were determined. Results showed that tested sprouts had high protein, fiber, vital minerals, total phenols and total flavonoid components. In addition, there were significant positive effects on the biochemical parameters that were tested, such as lipids profile, serum glucose, liver function, kidney functions, oxidative activity, brain enzyme and immunity responses, particularly at the 10% level, of tested sprouts and pea sprouts had high effect on tested parameters more than broccoli sprouts. In conclusion, pea and broccoli sprouts could potentially be used as protective agents against the toxic effect of acrylamide and the obtained results suggested that tested sprouts can be used as ideal candidates of natural antioxidant agents. [ABSTRACT FROM AUTHOR]

Background Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. Methods To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. Results Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P <.001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. Conclusions Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration.  Clinical Trials.gov; identifier: NCT05624840. [ABSTRACT FROM AUTHOR]

Introduction: The human immunodeficiency virus (HIV)/AIDS in India came into public view in 1986 with the detection of the first case of HIV in Chennai, Tamil Nadu, and the first AIDS case in Mumbai, Maharashtra in 1987. In acute phase response, iron distribution occurs in the liver and mononuclear phagocytic system. A high prevalence of elevated serum ferritin levels is reported in HIV infection and serum ferritin levels increase with the clinical worsening of infection and with decreasing CD4 lymphocyte counts. This study is designed to find the role of acute phase reactant serum ferritin in the progression of the disease of HIV which is complicated by opportunistic infections, by finding the correlation of serum ferritin with immunological stages of HIV. Materials and Methods: This cross‑sectional study was conducted on 75 patients admitted to various wards of the Department of Medicine or attending medicine outdoor or ART Centre, Maharana Bhupal Government Hospital, RNT Medical College Udaipur. Serum ferritin, total iron binding capacity, and total serum iron were analyzed in Cobas® analyzer. CD4 cells are measured using the flow cytometry technique. The results were tabulated and subjected to statistical analysis. Results and Conclusion: There was a negative correlation among serum ferritin and CD4 cells with r = −0.195 which was statistically significant (P < 0.05). As the CD4 cell count decreased incidence of serum ferritin increased. Elevation of serum ferritin levels is associated with a low count of the CD4+ in HIV‑diagnosed patients. In a patient diagnosed with HIV, elevated serum ferritin indicates underlying inflammatory pathology. Serum ferritin can be used as a guide to further evaluation of underlying disease in HIV patients. [ABSTRACT FROM AUTHOR]

Anti-human leukocyte antigen (HLA) donor-specific antibodies (DSAs) are associated with antibody-mediated rejection and chronic allograft nephropathy in kidney transplantation. The interpretation of immunological assays for DSAs can be challenging due to discordant results. In this report, we present two cases of kidney transplantation involving patients with anti-HLA-C DSAs. We discuss the interpretation of their immunological tests, including complement-dependent cytotoxicity (CDC) crossmatches, flow cytometry crossmatches, and donor-specific antigen using single-antigen bead (SAB) assays, which influenced therapeutic decisions. In the first case, the patient exhibited isolated B-cell-positive crossmatch and autoantibodies, prompting the consideration of polyclonal autoantibodies in the context of underlying hepatitis C infection. The SAB assay detected only one DSA against HLA-C 03:03:01 (mean fluorescence intensity - 27,127). After careful evaluation and confirmation of negative CDC crossmatch, transplantation proceeded, and the patient demonstrated good graft function. In the second case, the patient showed a positive T-cell crossmatch along with anti-Class I HLA DSAs against HLA C*07:01 and HLA C*07:02. Despite these findings, transplantation was performed based on the absence of complement-binding antibodies. The patient experienced good graft recovery with stable kidney function. The presence of HLA-C DSAs poses challenges in transplantation decision-making. Despite conflicting studies, the pathological nature of these antibodies has been demonstrated. Careful interpretation of immunological tests and consideration of the overall clinical context are essential in making therapeutic decisions. Further research is needed to understand the clinical significance of HLA-C DSAs and their impact on graft outcomes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to analyze a group of patients with severe and refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) managed with rituximab and to report on treatment outcomes. Patients and methods: A total of 78 patients (41 females, 37 males; mean age: 50.1±13.4 years; range, 18 to 76 years) with AAV on rituximab treatment were included in the single-center, retrospective study conducted between 2009 and 2018. The diagnosis was established based on the 1990 classification criteria of the American College of Rheumatology and the definitions of vasculitis of Chapel Hill Consensus Conference. Laboratory and immunological tests were conducted. Disease activity was determined through the Birmingham Vasculitis Activity Score. Results: Rituximab was preferred over cyclophosphamide in 37 patients and used as a second-line therapy after cyclophosphamide in 41 cases. Rituximab treatment showed favorable outcomes with regard to serum creatinine levels, proteinuria, and hematuria, as well as in cases of isolated lung involvement. Nearly half of patients with pulmonary renal syndrome also improved, with 22.2% achieving remission. ANCAs were positive in 85.9% of patients at the onset of rituximab treatment and became negative in 82% of the positive cases. Adverse events were rare and included infusion reactions (one case of reactivation of a herpes zoster infection and one case of allergic reaction). Conclusion: Rituximab is an efficient and safe therapeutic option in patients with AAV who are difficult to treat, have insufficient response, or have not tolerated other treatments. [ABSTRACT FROM AUTHOR]

Background There are nonestablished protocols in use for first-line allergy screening based on IgE testing. These protocols attempt to address an unmet need for sustainability of clinical laboratories, at a time when demand is increasing.  Objective To present a novel protocol for first-line allergy screening and to evaluate the implementation benefits for patients, the health care system, and payers. Methods We carried out an observational retrospective study analyzing 4359 interventions on primary care testing requests. Interventions included overriding redundant serum IgE (sIgE) testing for allergen mixes, extracts included in mixes, low-prevalence extracts, and milk and egg molecular components without previous positive results when exposed to extracts. We also added prevalent allergen testing. Results The strategy saved 683 tests from being performed unnecessarily. Test volume decline was primarily driven by the cancelation of 2186 egg and milk components tests; 561 tests were added for mixes, together with 942 allergen extracts tests. Discussion The results of this study show how the allergy laboratory plays a key role in actively managing demand for sIgE testing, leading to optimized diagnosis. [ABSTRACT FROM AUTHOR]

Controlled human infection model trials for hepatitis C virus represent an important opportunity to identify correlates of protective immunity against a well-characterized inoculum of hepatitis C virus and how such responses are modified by vaccination. In this article, we discuss the approach to immunological monitoring during such trials, including a set of recommendations for optimal sampling schedule and preferred immunological assays to examine the different arms of the immune response. We recommend that this approach be adapted to different trial designs. Finally, we discuss how these studies can provide surrogate predictors of the success of candidate vaccines. [ABSTRACT FROM AUTHOR]

Background Vaccination may control the coronavirus disease 2019 (COVID-19) pandemic, including in nursing homes where many high-risk people live. We conducted extensive outbreak investigations. Methods We studied an outbreak at a nursing home in Switzerland, where the uptake of messenger RNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 82% among residents as of 21 January 2021. After diagnosis of COVID-19 in a vaccinated symptomatic healthcare worker (HCW) on 22 February, we performed outbreak investigations in house A (47 residents; 37 HCWs), using SARS-CoV-2–specific polymerase chain reaction testing of nasopharyngeal swab samples. We performed whole-genome sequencing of SARS-CoV-2 and serological analyses. Results We identified 17 individuals with positive polymerase chain reaction results, 10 residents (5 vaccinated) and 7 HCWs (3 vaccinated). The median age (interquartile range) was 86 (70–90) years among residents and 49 (29–59) years among HCWs. Of the 5 vaccinated residents, 3 had mild disease and 2 had no symptoms, whereas all 5 unvaccinated residents had mild to severe disease, and 2 died. Vaccine effectiveness for the prevention of infection among residents was 73.0% (95% confidence interval, 24.7%–90.1%). The 12 available genomes were all alpha variants. Neutralizing titers were significantly higher in vaccinated individuals on reexposure (>1 week after diagnosis) than in vaccinated, unexposed HCWs (P  = .01). Transmission networks indicated 4 likely or possible transmissions from vaccinated to other individuals and 12 transmission events from unvaccinated individuals. Conclusions COVID-19 outbreaks can occur in nursing homes, including transmission from vaccinated persons to others. Outbreaks might occur silently, underlining the need for continued testing and basic infection control measures in these high-risk settings. [ABSTRACT FROM AUTHOR]

Background: The immune system is well known to exert tumor immunosurveillance effects, and that immune cells circulating in the peripheral blood affect tumor prognosis. The study investigated the effect of estimated dose of radiation on circulating immune cells (EDRIC) and tumor control for esophageal cancer patients treated with concurrent chemo-radiotherapy. Materials and Methods: A total of 146 esophageal cancer patients treated with radiotherapy between January 2016 and June 2020 were retrospectively identified. We determined EDRIC, known prognostic factors, and the association of these factors with progression-free survival (PFS) and overall survival (OS). Results: The median follow-up was 17.9 months (2.7–60.4 months). The 3-year OS was 39.2%. Severe post-treatment lymphopenia was observed in 84.2% of patients. A negative correlation between EDRIC and absolute lymphocyte count was found (r = −0.679; p < 0.001). Patients with EDRIC ≥10.3 Gy were more likely to demonstrate grade 4 lymphopenia (55.2% vs. 4.5%; p < 0.001). Patients with grade 4 lymphopenia had a worse OS and PFS. On multivariate analysis, EDRIC was independently associated with OS (hazard ratio [HR], 1.142; p = 0.016) and PFS (HR, 1.121; p = 0.019). Conclusions: EDRIC can predict lymphocyte reduction and poor prognosis for esophageal cancer patients treated with radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Methicillin-susceptible Staphylococcus aureus (MSSA) occurs more frequently in the neonatal intensive care unit (NICU) than methicillin-resistant S. aureus (MRSA) and can result in comparable morbidity and mortality in the neonatal population. MSSA infection may present as pustulosis or cellulitis and evolve into bacteremia, pneumonia, endocarditis, brain abscesses, and osteomyelitis. There is a paucity of literature regarding the treatment and long-term outcomes in the premature infant. Clinical Findings: A 32-week twin developed MSSA sepsis with presentation of pain, decreased movement of upper extremities, and global hypotonia. Blood cultures remained positive despite antibiotic coverage. Primary Diagnosis: The infant was admitted to the level IV NICU with the diagnosis of MSSA bacteremia, with concern for dissemination and osteomyelitis. Interventions: Diagnostic studies included laboratory testing for sepsis evaluation, radiologic studies to evaluate for dissemination, immunologic testing to rule out complement deficiency, and hematology testing to rule out hypercoagulable conditions. Outcomes: Diagnostic testing showed extensive cellulitis, osteomyelitis, multiple liver abscesses, and epidural abscesses suggestive of spinal epidural abscess (SEA). Abscess debridement and irrigation on the left distal femur, left elbow, and right tibia were performed. The infant completed 8 weeks of IV antibiotic therapy. Immunologic and hematology testing was within normal limits. Practice Recommendations: Prompt recognition and follow-up for clinical signs of sepsis are vital when caring for premature infants. Inclusion of pediatric subspecialist recommendations to assure all diagnostic studies and treatments are completed can significantly impact the patient's outcome. Long-term follow-up is needed for premature infants with the diagnosis of SEA. [ABSTRACT FROM AUTHOR]

In recent years screening of type 1 diabetes (T1D) in both at risk children and general population has been widely discussed with the aim of increasing awareness of the importance to early detect (and possibly treat) at-risk children in early stages of the chronic autoimmune progression to T1D. In fact, it is well known that first-degree relatives have the highest risk of T1D, but up to 90% of children who develop T1D do not have a family history and belong to the general population. The reasons for screening children well before the clinical onset of T1D include prevention of DKA (still up to 60% children are diagnosed with DKA) and related morbidities and mortality, reducing the need for hospitalisation, time to provide emotional support and education to ensure a smooth transition to insulin treatment, and opportunities for new treatments to prevent or delay progression. There are pros and cons of screening of T1D in children, but recent evidences suggest that it is now time to consider possible a screening for T1D in children. Recently, the European Society for Paediatric Endocrinology (ESPE) has endorsed a Position Statement, discussing the pros and cons of screening for T1D in the general population; ESPE supports national Societies for Paediatric Endocrinology to spread information on this important issue in various countries throughout Europe; the Italian Society for Paediatric Endocrinology and Diabetes (SIEDP-ISPED) and the Italian Society of Paediatrics (SIP) endorse this document with the specific aim of increasing awareness on screening for paediatric T1D in the general population. [ABSTRACT FROM AUTHOR]

Introduction: In locally advanced gastric cancer (GC), FLOT represents the standard perioperative regimen and combination with immunotherapy is under investigation. However, the role of immune tumor microenvironment (TME) is poorly recognized in this setting. We aimed to study TME characteristics and dynamics during FLOT. Methods: Paired biopsy (PRE) and surgical (POST) samples of 25 patients treated with FLOT were prospectively analyzed. After collection of clinic-pathological data, NanoString analyses were performed. The primary objective of the study was to assess the changes induced by chemotherapy in POST compared to PRE samples. Results: The unsupervised hierarchical method analysis clearly distinguished PRE and POST samples, even though some cases showed high immune gene expression at baseline. When POST samples were compared with PRE, a differential expression in hyper-expressed gene sets related to cytotoxicity, T-cell functions, complement system, tumor necrosis factor superfamily, cell cycle, and regulation was recognized. Downstaging of the primary tumor (T-regression, measured by pathologic compared to clinical T stage) was the covariate most frequently associated with these changes. Using the immune cell profiling, cases with T-regression reported a significant increase of T, CD8+ T and B cells and a decrease in mast cells, while nonresponders demonstrated an increase of T, B, cytotoxic, and mast cells. Conclusion: Our analysis shows that FLOT significantly influences immune TME of GC. While relevant modifications preferentially occur in tumors showing primary tumor regression, response to treatment seems to be associated with a specific immune profile. [ABSTRACT FROM AUTHOR]

Fascioliasis is an important zoonotic disease prevalent in domestic animals and it leads to socioeconomic impact in rural farming communities of the developing world. The gold standard diagnosis of ruminant fascioliasis involves coprological detection of Fasciola spp. eggs or recovery of flukes in infected livers. Coprological analysis is unreliable in the patent period of chronic infection, and even then, its sensitivity is relatively low. Robust diagnostic tools that can promptly and accurately detect an active infection are crucial to avoid complications and further losses in ruminant livestock productivity, as well as to preserve the livelihood of communities at risk. Immunodiagnosis determined by antibody and antigen detection in the sera and faeces of infected ruminants provides a valuable alternative to the parasitological diagnostic approach. This review discusses current developments in immunological techniques by enzyme-linked immunosorbent assay (ELISA) in the detection of ruminant fascioliasis and summarises the performance of various ELISAs in studies conducted to date. Indirect ELISAs demonstrated effective immunodiagnostic performance with high sensitivities and specificities. Cathepsin L ELISA is the most favourable antigen in serodiagnosis, among other recombinant and native proteins evaluated. Sandwich ELISA provides excellent sensitivity and specificity, which correlates well with the fluke burden. Utilising monoclonal antibodies in sandwich ELISA reduces the detection time and performance variations that commonly occur in polyclonal antibody ELISA. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between maternal asthma (MA) and obstetric complications, while considering subdivided total serum immunoglobulin E (IgE) levels. Methods: Data of the participants enrolled in the Japan Environment and Children's Study between 2011 and 2014 were analyzed. In total, 77,131 women with singleton live births at and after 22 weeks of gestation were included. MA was defined based on a self-administered questionnaire. Women with MA were stratified based on the quartile of total serum IgE levels during pregnancy as follows: low IgE levels (< 52.40 IU/mL), moderate IgE levels (52.40–331.00 IU/mL), and high IgE levels (> 331.00 IU/mL). The adjusted odds ratios (aORs) for preterm births (PTB), small for gestational age (SGA) infants, gestational diabetes mellitus, and hypertensive disorders of pregnancy (HDP) were calculated using multivariable logistic regression, while considering women without MA as reference and maternal socioeconomic factors as confounders. Results: The aORs for SGA infants and HDP in women with MA and high total serum IgE levels were 1.26 (95% confidence interval [CI], 1.05–1.50) and 1.33 (95% CI, 1.06–1.66), respectively. The aOR for SGA infants among women with MA and moderate total serum IgE levels was 0.85 (95% CI, 0.73–0.99). The aOR for PTB among women with MA and low total serum IgE levels was 1.26 (95% CI, 1.04–1.52). Conclusions for Practice: MA with subdivided total serum IgE levels was associated with obstetric complications. Total serum IgE level may be a potential prognostic marker to predict obstetric complications in pregnancies with MA. Significance: What is Already Known on this Subject? Maternal asthma (MA) is associated with several obstetric complications, including preterm births (PTB), small for gestational age (SGA) infants, and hypertensive disorders of pregnancy (HDP). Few studies with data from nationwide cohorts have elucidated the association between MA and obstetric complications comprehensively while accounting for the subdivided objective biomarkers of MA. What this Study Adds? MA with subdivided total serum IgE levels was associated with various obstetric complications. Total serum IgE level may be a potential prognostic marker for pregnant women with MA to predict the potential risk of PTB, SGA infants, and HDP. [ABSTRACT FROM AUTHOR]

Little is published on cytomegalovirus (CMV) serological screening at the first antenatal visit or the contemporary CMV seroprevalence rates among the Australian pregnant population. We performed a retrospective analysis of public hospital births in a major tertiary centre (n = 840) over a two month period. We found that 13.6% (95% confidence interval (CI) 11.4–16.1%) of women had been screened for CMV at their first antenatal visit with their general practitioner. Of these, 43.0% (95% CI 34.3–52.1%) were CMV seronegative and therefore susceptible to primary infection. Seronegative women were also more likely to have been born in an economically developed country, to live in a socio‐economically advantaged postcode and to be nulliparous. The information from this study may help guide future studies of congenital CMV risk reduction strategies. [ABSTRACT FROM AUTHOR]

Purpose: Immunological phenomena are a minor criteria in the modified Duke Criteria for endocarditis. Given the changes in epidemiology and diagnostics, the added value of determining these phenomena in today's patients with suspected endocarditis is unknown. Methods: In a retrospective cohort study of all patients with suspected endocarditis admitted to our hospital and discussed in our endocarditis team, we determined the proportion of patients classified as definite endocarditis because of either positive IgM rheumatoid factor (IgM RF), haematuria, or Roth's spots on ophthalmology consultation. We also determined diagnostic accuracy of each of these immunological phenomena separately and combined. Results: Of 285 patients included, 138 (48%) had definite endocarditis and at least one immunological test was performed in 222 patients (78%). Elevated IgM RF was found in 22 of 126 patients tested (17%), haematuria in 78 of 196 tested (40%) and Roth's spots in six of 120 tested (5%). Eighteen of 138 patients with definite IE (13%) were classified as such because of a positive IgM RF, haematuria or Roth's spots. Haematuria had the highest sensitivity: 50.5% (95% CI 40.4–60.6) and Roth's spots the highest specificity: 98.3% (95% CI 90.8–99.9). The diagnostic accuracy results were robust in a sensitivity analysis aimed at avoiding incorporation bias. Conclusion: Among patients with a clinical suspicion of endocarditis, recommended systematic testing for immunological phenomena helped classify more patients as definite IE and is useful to confirm the diagnosis of endocarditis. [ABSTRACT FROM AUTHOR]

The article focuses on the false positive results of the Hb Bart's immunochromatographic strip test (AT-ICT) for alpha thalassaemia in individuals with delta-beta thalassaemia trait, as confirmed by genetic analysis of the alpha globin gene cluster. Topics include the clinical significance of alpha thalassaemia mutations, the introduction and advantages of the AT-ICT, and the identification of cases with discordant results, highlighting the need for genetic analysis in such instances.

Objectives Autoantibodies to ENA are frequently ordered during the workup of suspected autoimmune connective tissue diseases. There are no current guidelines for repeat test ordering. The objective of this study was to assess the utility of repeat ENA testing after an initial negative result. Methods A retrospective study was conducted in a single, multicentre tertiary health network in Melbourne, Australia. Results of all ENA tests were extracted from the hospital laboratory information system. For patients who had a change in ENA result from negative to positive, clinical information was obtained from the hospital records regarding new diagnosis of an ANA-associated rheumatic disease (AARD). Results A total of 23 438 ENA tests were performed in 19 603 patients from 29 July 2013 to 28 September 2020. In total, 20 918 (89.2%) were negative with 215 (0.9%) being equivocal. Of the 2305 positive tests, the most common ENA auto-antibody specificity detected was anti-Ro52 (1185, 51.4%). A total of 2636 of 19 603 patients (13.4%) had more than one ENA test performed during the study period. Of these, most (2523, 95.7%) had stable ENA results with no change compared with the first test. Only 53 patients (2.2%) had an ENA result that changed from negative to positive. Excluding patients with pre-existing rheumatic conditions and those under 18, there were five new AARDs found in the remaining 34 patients. Conclusion Repeat ENA test results rarely change or result in a new diagnosis of an AARD, with repeated testing only warranted if there is a change in clinical manifestations. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 is a serious threat to human life, and early diagnosis and screening can help control the COVID-19 pandemic. The high sensitivity of reverse transcriptase–polymerase chain reaction (RT-PCR) assay is the gold standard for the diagnosis of COVID-19, but there are still some false-negative results. Rapid antigen detection (RAD) is recommended by the World Health Organization (WHO) as a screening method for COVID-19. This review analyzed the characteristics of RDT and found that although the overall sensitivity of RAD was not as high as that of RT-PCR, but RAD was more sensitive in COVID-19 patients within 5 days of the onset of symptoms and in COVID-19 patients with Ct ≤ 25. Therefore, RAD can be used as an adjunct to RT-PCR for screening patients with early COVID-19. Finally, this review provides a combined diagnostic protocol for RAD and nucleic acid testing with the aim of providing a feasible approach for COVID-19 screening. [ABSTRACT FROM AUTHOR]

Evaluating the magnitude of overdiagnosis associated with stool-based service screening for colorectal cancer (CRC) beyond a randomized controlled trial is often intractable and understudied. We aim to estimate the proportion of overdiagnosis in population-based service screening programs for CRC with the fecal immunochemical test (FIT). The natural process of overdiagnosis-embedded disease was first built up to learn transition parameters that quantify the pathway of non-progressive and progressive screen-detected cases calibrated with sensitivity, while also taking competing mortality into account. The Markov algorithms were then developed for estimating these transition parameters based on Taiwan FIT service CRC screening data on 5,417,699 residents aged 50–69 years from 2004 to 2014. Following the digital twin design with the parallel universe structure for emulating the randomized controlled trial, the screened twin, mirroring the control group without screening, was virtually recreated by the application of the above-mentioned trained parameters to predict CRC cases containing overdiagnosis. The ratio of the predicted CRCs derived from the screened twin to the observed CRCs of the control group minus 1 was imputed to measure the extent of overdiagnosis. The extent of overdiagnosis for invasive CRCs resulting from FIT screening is 4.16% (95% CI: 2.61–5.78%). The corresponding figure is increased to 9.90% (95% CI: 8.41–11.42%) for including high grade dysplasia (HGD) and further inflated to 15.83% (95% CI: 15.23–16.46%) when the removal adenoma is considered. The modest proportion of overdiagnosis modelled by the digital twin method, dispensing with the randomized controlled trial design, suggests the harm done to population-based FIT service screening is negligible. [ABSTRACT FROM AUTHOR]

Checkpoint markers and immune checkpoint inhibitors have been increasingly identified and developed as potential immunotherapeutic targets in various human cancers. Despite valuable efforts to discover novel immune checkpoints and their ligands, the precise roles of their therapeutic functions, as well as the broad identification of their counterpart receptors, remain to be addressed. In this context, it has been suggested that various putative checkpoint receptors can be induced upon activation. In the tumor microenvironment, T cells, as crucial immune response against malignant diseases as well as other immune central effector cells, such as natural killer cells, are regulated via co-stimulatory or co-inhibitory signals from immune or tumor cells. Studies have shown that exposure of T cells to tumor antigens upregulates the expression of inhibitory checkpoint receptors, leading to T-cell dysfunction or exhaustion. Although targeting immune checkpoint regulators has shown relative clinical efficacy in some tumor types, most trials in the field of cancer immunotherapies have revealed unsatisfactory results due to de novo or adaptive resistance in cancer patients. To overcome these obstacles, combinational therapies with newly discovered inhibitory molecules or combined blockage of several checkpoints provide a rationale for further research. Moreover, precise identification of their receptors counterparts at crucial checkpoints is likely to promise effective therapies. In this review, we examine the prospects for the application of newly emerging checkpoints, such as T-cell immunoglobulin and mucin domain 3, lymphocyte activation gene-3, T-cell immunoreceptor with Ig and ITIM domains (TIGIT), V-domain Ig suppressor of T-cell activation (VISTA), new B7 family proteins, and B- and T-cell lymphocyte attenuator, in association with immunotherapy of malignancies. In addition, their clinical and biological significance is discussed, including their expression in various human cancers, along with their roles in T-cell-mediated immune responses. [ABSTRACT FROM AUTHOR]

Background: Rheumatic heart disease (RHD) and dental caries (DC) disproportionately affect children and young adults in sub-Saharan countries, with major impact on schoolchildren's health and education. DC in children with RHD constitutes an important risk for fatal complications. Our study aimed at assessing the feasibility of simultaneous RHD and DC screening in school environment. Methods: March 20–24, 2022, we performed an observational descriptive study of schoolchildren in a public school in Maputo City, Mozambique. RHD screening involved two stages: first, a physical examination (including cardiac auscultation and direct observation of the oral cavity), and second, an abbreviated echocardiography performed by a cardiologist. Rapid testing for group A Streptococcus (GAS) was done to every eighth child in the classroom and for those with signs suggesting recent infection, in accordance with the study protocol developed for screening. A multidisciplinary team collected the data. Data were analyzed using descriptive statistics. Findings: A total of 954 students (median age 9; range 6–15) were screened. One hundred and twenty-five participants were eligible for a rapid antigen test, of which 6 (4.8%) tested positive. On clinical evaluation 52 children (5.3%) presented a heart murmur. Echocardiography on 362 children showed borderline RHD in 35 children and definite RHD in 2 (0.6%); 1 child had a ventricular septal defect. Dental cavities were present in 444 (48.4%), despite 904 out of 917 students reporting brushing of their teeth once to three times daily (98.6%). Conclusion: School-based integrated oral and cardiovascular screenings and use of rapid tests for GAS carriage provide crucial information to create customized preventive strategies for rheumatic fever (RF) and RHD in low- and middle-income countries (LMICs), in addition to detecting children at very high risk of bacterial endocarditis. The sustainability of such interventions and acceptability by health providers needs to be assessed. [ABSTRACT FROM AUTHOR]

We studied the cellular immune response in a patient infected since 10 months (along with other 51 people) during a trichinellosis outbreak caused by Trichinella spp. A 46 years old female resulted serologically positive for trichinellosis. We isolated peripheral blood mononuclear cells (PBMCs) and incubated them with excretory/secretory antigens (ESA) of Trichinella spiralis (T1) or Trichinella pseudospiralis (T4) to produce antigen specific T cell lines and clones, analysed for the phenotype (T helper or cytotoxic cells), for their T4 or T1 antigens specificity and for their cytokine profile (IFNγ, IL-17A, IL-4) by flow cytometry, thymidine incorporation assay and ELISpot. The test performed using ESA from T1 or T4 has identified the species responsible for infection as T. pseudospiralis since the proliferative responses (evaluated by CFSE, Carboxyfluorescein succinimidyl ester, FACS analysis) was higher for T4 (72,8%) than T1 (23.6 %) antigen. The cell lines produced significant levels of IFNγ, IL-4 and IL-17A after stimulation. From the T cell line obtained in response to T1 ESA, as regards CD4 + cells, 12 % Th2, 22.8 % Th1, 6.6 % Th17, 6 % Th0, 2.2 % Th1/Th17 and 0.7 % Th2/Th17, were obtained. From the T1-specific TCL we generated 15 clones. From the TCL specific for T4 ESA, as regards CD4+, 15.2 % Th2, 27.1 % Th1, 3 % Th17, 10.3 %Th0, 1.9 % Th1/Th17 and 1 % Th2/ Th17 were obtained. From such TCL 4 clones were isolated, 1Th2, 1 Th1, 1 Th17, 1 Th1/Th17 and no Th0 nor Th2/Th17. By cellular immunology techniques the species responsible of the infection resulted T. pseudospiralis , confirming the results previously obtained by serology. For the first time it was revealed in a human chronic infection the presence of Th17 cells. [ABSTRACT FROM AUTHOR]

Normal density granulocytes (NDGs) can suppress T-cell responses in a similar way as myeloid-derived suppressor cells (MDSCs). In this study, we tested the hypothesis that NDGs from healthy donors preferentially inhibit T helper 1 (Th1) cells and investigated the myeloid-derived suppressive effect in different T-cell populations. We found that NDG-induced suppression of T-cell proliferation was contact dependent, mediated by integrin CD11b, and dependent on NDG-production of reactive oxygen species (ROS). The suppression was rapid and occurred within the first few hours of coculture. The suppression did not influence the CD8+/CD4+ ratio indicating an equal sensitivity in these populations. We further analyzed the CD4+ T helper subsets and found that NDGs induced a loss of Th1 surface marker, CD183, that was unrelated to ligand-binding to CD183. In addition, we analyzed the Th1, Th2, and Th17 cytokine production and found that all cytokine groups were suppressed when T-cells were incubated with NDGs. We therefore concluded that NDGs do not preferentially suppress Th1-cells. Instead, NDGs generally suppress Th cells and cytotoxic T-cells but specifically downregulate the Th1 marker CD183. [ABSTRACT FROM AUTHOR]

Objectives: In 2012, onetime hepatitis C virus (HCV) screening was recommended for all baby boomers (people born during 1945-1965) in the United States, but only 4.0%-12.9% of baby boomers have ever had a screening ordered by a health care provider. This study examined the HCV screening prevalence among adult patients in a large academic health care system and assessed factors associated with the completion of screening when ordered for baby boomers. Methods: We defined HCV screening completion as the completion of an HCV antibody test when it was ordered. We used electronic health records to examine HCV screening completion rates among adults (N = 106 630) from August 1, 2015, through July 31, 2020, by birth cohort. Among baby boomers whose health care provider ordered HCV screening, we examined frequency and percentages of HCV screening completion by sociodemographic and clinical characteristics. We conducted univariate and multivariable logistic regression analyses to assess factors associated with HCV screening completion among baby boomers. Results: During the study period, 73.0% of baby boomers completed HCV screening when it was ordered. HCV completion did not differ by sex or race and ethnicity among baby boomers. Baby boomers with Medicare supplemental health insurance compared with commercial health insurance (adjusted odds ratio [aOR] = 1.87) and those seeing only advanced practice professionals compared with specialty care physicians (aOR = 2.24) were more likely to complete HCV screening when it was ordered. Conclusions: Noncompletion of HCV screening is one of many barriers along the HCV treatment continuum. Our findings suggest a need for interventions targeting systems, health care providers, and patients to increase HCV screening rates in the United States. [ABSTRACT FROM AUTHOR]

Purpose: Zika (ZIKV) is a viral inflammatory disease affecting adults, children, and developing fetuses. It is endemic to tropical and sub-tropical countries, resulting in half the global population at risk of infection. Despite this, there are no approved therapies or vaccines against ZIKV disease. Non-invasive imaging biomarkers are potentially valuable tools for studying viral pathogenesis, prognosticating host response to disease, and evaluating in vivo efficacy of experimental therapeutic interventions. In this study, we evaluated [18F]fluorodeoxyglucose ([18F]FDG)-positron emission tomography (PET) as an imaging biomarker of ZIKV disease in a mouse model and correlated metabolic tracer tissue uptake with real-time biochemical, virological, and inflammatory features of tissue infection. Methods: [18F]FDG-PET/CT imaging was performed in an acute, lethal ZIKV mouse infection model, at increasing stages of disease severity. [18F]FDG-PET findings were corroborated with ex vivo wholemount-tissue autoradiography and tracer biodistribution studies. Tracer uptake was also correlated with in situ tissue disease status, including viral burden and inflammatory response. Immune profiling of the spleen by flow cytometry was performed to identify the immune cell subsets driving tissue pathology and enhancing tracer uptake in ZIKV disease. Results: Foci of increased [18F]FDG uptake were consistently detected in lymphoid tissues—particularly the spleen—of ZIKV-infected animals. Splenic uptake increased with disease severity, and corroborated findings in tissue pathology. Increased splenic uptake also correlated with increased viral replication and elevated expression of pro-inflammatory cytokines within these tissues. ZIKV-infected spleens were characterized by increased infiltration of myeloid cells, as well as increased proliferation of both myeloid and lymphoid cells. The increased cell proliferation correlated with increased tracer uptake in the spleen. Our findings support the use of [18F]FDG as an imaging biomarker to detect and track ZIKV disease in real time and highlight the dependency of affected tissue on the nature of the viral infection. Conclusion: [18F]FDG uptake in the spleen is a useful surrogate for interrogating in situ tissue viral burden and inflammation status in this ZIKV murine model. [ABSTRACT FROM AUTHOR]

It is critical to detect latent tuberculosis infection through screening and testing individuals at high risk of progression to active tuberculosis, including patients who are immunocompromised. NPs should be familiar with available testing for accurate diagnosis in order to expedite treatment. [ABSTRACT FROM AUTHOR]

Key content: Referral criteria to recurrent pregnancy loss (RPL) services vary, owing in part to a lack of consensus on the definition of RPL.Good quality evidence is limited, and controversies exist on recommendations for investigations and management of RPL.People with RPL will most likely achieve a live birth in their next pregnancy but should have an individualised approach that identifies and corrects any modifiable risk factors and offers appropriate psychological support. Learning objectives: To look at the variations in definition and aetiology of RPL and use current evidence available for recommendations towards investigations and management of RPL.To be familiar with evidence‐based guidelines published by the Royal College of Obstetricians and Gynaecologists, the American Society for Reproductive Medicine and the European Society of Human Reproduction, as well as recently published data, which will help to improve clinical outcome utilising the interventions with proven efficacy. Ethical issues: Differences in referral criteria and the controversies around RPL mean there can be considerable variation in how these patients are managed between services.The lack of good quality evidence can result in patients opting for management strategies with unproven efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer immunosurveillance exists as a mechanism of efficient eradication of tumor establishment and progression. On the flip side, chronic inflammation functions as an ultimate background that may favor cancer development and advancement. Severe infection by the recently emerged SARS-CoV-2 virus often causes a multifaceted inflammation with acute and chronic characteristics that may affect several organs. The current review discusses the hypothesis of a potential interplay between the mechanisms of cancer immunosurveillance and the COVID-19-sustained inflammation, as well as the putative consequences that this cross-talk may have in oncogenesis and tumor progression. The COVID-19 pandemic accounts for more than 500 million confirmed infections and over 6 million deaths worldwide in the last 2 years. SARS-CoV-2 causes a highly complex form of inflammation that affects the human organism both acutely and chronically. In the same line, cancer as an inflammation-induced and immune-editing disease appears to cross-react with immune system at different levels including early interactions during carcinogenesis and later cross-talks within the tumor microenvironment. With all that in mind, a reasonable question one might address is whether the SARS-CoV-2 infection and the derived "long lasting inflammatory status" that is frequently observed in patients, might affect the cancer immunosurveillance mechanisms and consequently their risk of developing cancer, as well as the tumor and immune cell behaviors within the inflamed microenvironment. On this context, this review intends to outline and discuss the existing knowledge on SARS-CoV-2-mediated immunomodulation under the prism of changes that might be able to interfere with cancer cell immunoescape and the overall tumor progression and response to conventional therapeutics. Our goal is to highlight a potential interplay between the COVID-19 immunopathology and cancer immune-microenvironment that may pave the way for thorough investigation in the future. [ABSTRACT FROM AUTHOR]

FcγRIIB is an inhibitory receptor expressed throughout B cell development. Diminished expression or function is associated with lupus in mice and humans, in particular through an effect on autoantibody production and plasma cell (PC) differentiation. Here, we analyzed the effect of B cell-intrinsic FcγRIIB expression on B cell activation and PC differentiation. Loss of FcγRIIB on B cells in Fcgr2b-conditional KO (Fcgr2b-cKO) mice led to a spontaneous increase in autoantibody titers. This increase was most striking for IgG3, suggestive of increased extrafollicular responses. Marginal zone (MZ) B cells had the highest expression of FcγRIIB in both mice and humans. This high expression of FcγRIIB was linked to increased MZ B cell activation, Erk phosphorylation, and calcium flux in the absence of FcγRIIB triggering. We observed a marked increase in IgG3+ PCs and B cells during extrafollicular PC responses in Fcgr2b-cKO mice. The increased IgG3 response following immunization of Fcgr2b-cKO mice was lost in MZ-deficient Notch2 Fcgr2b-double KO mice. Importantly, patients with systemic lupus erythematosus (SLE) had a decrease in FcγRIIB expression that was strongest in MZ B cells. Thus, we present a model in which high FcγRIIB expression in MZ B cells prevented their hyperactivation and ensuing autoimmunity. [ABSTRACT FROM AUTHOR]

Cancer is a main life-threatening disease worldwide. Due to the adverse effects of conventional chemotherapies and radiotherapies, immunotherapy has emerged as a potent strategy to treat cancer. In cancer immunotherapy, cancer immune surveillance plays a crucial role in the cancer process, which contains various effector cells from innate and adaptive immunity. This review summarized the functions of innate and adaptive immune cells in cancer immunosurveillance and their main reported targets. Moreover, the potential targets about the modulatory effects of cancer immunosurveillance were predicted using network-based target analysis, with total predicted pathways not only reporting previously reported pathways, but also putative signaling pathways pending for investigation. In addition, the potential use of herbal medicines and their phytochemicals in the modulation of cancer immunosurveillance were also discussed. Taken together, this review paper aims to provide scientific insight into further drug development, particularly herbs, phytochemicals, and TCM formulae, in the modulatory effects of cancer immunosurveillance. [ABSTRACT FROM AUTHOR]

Abstract: Conventionally, adoptive cell therapies have been developed and optimized using αβ T cells. However, the understudied and less abundant γδ T cells offer unique advantages to the immunotherapy field especially for therapies against solid tumors. Recently, γδ T-cell potential against a broad spectrum of malignant cells has been demonstrated in the preclinical setting. In the clinic, γδ T-cell-based immunotherapies have proven to be safe; however, their efficacy needs improvement. Considering the growing body of literature reflecting the increasing interest in γδ T cells, we sought to capture the current topics of discussion in the field, pertaining to their use in adoptive immunotherapy. We aimed to compile information about γδ T-cell enhancement in terms of expansion, phenotype, and inhibitory receptors, in addition to the latest advances in preclinical and clinical research using γδ T cells specifically against solid epithelial tumors. [ABSTRACT FROM AUTHOR]