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Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad spectrum antibiotic in use for more than 50 years. It has an important indication as first line agent in the prophylaxis of opportunistic infections, particularly Pneumocystis jirovecii pneumonia (PJP), in immunosuppressed patients. For those who have a history of allergy or severe intolerance to TMP-SMX, pentamidine, dapsone or atovaquone may be substituted; however there is evidence that TMP-SMX offers superior coverage for PJP, toxoplasmosis, and nocardiosis. Compared to pentamidine, it has the added benefit of cost-effectiveness and self-administration as opposed to required hospital attendance for administration. Many patients who report a history of allergy or adverse reaction to TMP-SMX (or “sulfur allergy”) will be found not to be allergic; and even those who are allergic may be able to be desensitized. The evaluation and, where appropriate, removal of TMP-SMX allergy label enables the use of TMP-SMX for prophylaxis against opportunistic infections. This is a cost-effective intervention to optimize antimicrobial prescribing and reduce the risk of opportunistic infections in immunosuppressed patients.

BackgroundStrategies to improve the selection of appropriate target journals may reduce delays in disseminating research results. Machine learning is increasingly used in content-based recommender algorithms to guide journal submissions for academic articles. ObjectiveWe sought to evaluate the performance of open-source artificial intelligence to predict the impact factor or Eigenfactor score tertile using academic article abstracts. MethodsPubMed-indexed articles published between 2016 and 2021 were identified with the Medical Subject Headings (MeSH) terms “ophthalmology,” “radiology,” and “neurology.” Journals, titles, abstracts, author lists, and MeSH terms were collected. Journal impact factor and Eigenfactor scores were sourced from the 2020 Clarivate Journal Citation Report. The journals included in the study were allocated percentile ranks based on impact factor and Eigenfactor scores, compared with other journals that released publications in the same year. All abstracts were preprocessed, which included the removal of the abstract structure, and combined with titles, authors, and MeSH terms as a single input. The input data underwent preprocessing with the inbuilt ktrain Bidirectional Encoder Representations from Transformers (BERT) preprocessing library before analysis with BERT. Before use for logistic regression and XGBoost models, the input data underwent punctuation removal, negation detection, stemming, and conversion into a term frequency-inverse document frequency array. Following this preprocessing, data were randomly split into training and testing data sets with a 3:1 train:test ratio. Models were developed to predict whether a given article would be published in a first, second, or third tertile journal (0-33rd centile, 34th-66th centile, or 67th-100th centile), as ranked either by impact factor or Eigenfactor score. BERT, XGBoost, and logistic regression models were developed on the training data set before evaluation on the hold-out test data set. The primary outcome was overall classification accuracy for the best-performing model in the prediction of accepting journal impact factor tertile. ResultsThere were 10,813 articles from 382 unique journals. The median impact factor and Eigenfactor score were 2.117 (IQR 1.102-2.622) and 0.00247 (IQR 0.00105-0.03), respectively. The BERT model achieved the highest impact factor tertile classification accuracy of 75.0%, followed by an accuracy of 71.6% for XGBoost and 65.4% for logistic regression. Similarly, BERT achieved the highest Eigenfactor score tertile classification accuracy of 73.6%, followed by an accuracy of 71.8% for XGBoost and 65.3% for logistic regression. ConclusionsOpen-source artificial intelligence can predict the impact factor and Eigenfactor score of accepting peer-reviewed journals. Further studies are required to examine the effect on publication success and the time-to-publication of such recommender systems.

Soft tissue sarcomas are pleiotropic tumors of mesenchymal cell origin. These tumors are rare in humans but common in veterinary practice, where they comprise up to 15% of canine skin and subcutaneous cancers. Because they present similar morphologies, primary sites, and growth characteristics, they are treated similarly, generally by surgical resection followed by radiation therapy. Previous studies have examined a variety of genetic changes as potential drivers of tumorigenesis and progression in soft tissue sarcomas as well as their use as markers for soft tissue sarcoma subtypes. However, few studies employing next generation sequencing approaches have been published. Here, we have examined gene expression patterns in canine soft tissue sarcomas using RNA-seq analysis of samples obtained from archived formalin-fixed and paraffin-embedded tumors. We provide a computational framework for using resulting data to categorize tumors, perform cross species comparisons and identify genetic changes associated with tumorigenesis. Functional overrepresentation analysis of differentially expressed genes further implicate both common and tumor-type specific transcription factors as potential mediators of tumorigenesis and aggression. Implications for tumor-type specific therapies are discussed. Our results illustrate the potential utility of this approach for the discovery of new therapeutic approaches to the management of canine soft tissue sarcomas and support the view that both common and tumor-type specific mechanisms drive the development of these tumors.

Abstract Background Traumatic, non-iatrogenic esophageal injuries, despite their rarity, are associated with significant morbidity and mortality. The optimal management of these esophageal perforations remains largely debated. To date, only a few small case series are available with contrasting results. The purpose of this study was to examine a large contemporary experience with traumatic esophageal injury management and to analyze risk factors associated with mortality. Methods This National Trauma Data Bank (NTDB) database study included patients with non-iatrogenic esophageal injuries. Variables abstracted were demographics, comorbidities, mechanism of injury, Abbreviated Injury Scale (AIS), esophageal Organ Injury Scale (OIS), Injury Severity Score (ISS), level of injury, vital signs, and treatment. Multivariate analysis was used to identify independent predictors for mortality and overall complications. Results A total of 944 patients with non-iatrogenic esophageal injury were included in the final analysis. The cervical segment of the esophagus was injured in 331 (35%) patients. The unadjusted 24-h mortality (8.2 vs. 14%, p = 0.008), 30-day mortality (4.2 vs. 9.3%, p = 0.005), and overall mortality (7.9 vs. 13.5%, p = 0.009) were significantly lower in the group of patients with a cervical injury. The overall complication rate was also lower in the cervical group (19.8 vs. 27.1%, p = 0.024). Multilogistic regression analysis identified age >50, thoracic injury, high-grade esophageal injury (OIS IV–V), hypotension on admission, and GCS

Objective: The purpose of this study was to investigate the effect of prophylactic anticoagulation on the incidence of venous thromboembolic events (VTE) in patients suffering from isolated severe traumatic brain injury (TBI). Materials and Methods: Retrospective matched case-control study in adult patients sustaining isolated severe TBI (head AIS ≥3, with extracranial AIS ≤2) receiving VTE prophylaxis while in the surgical intensive care unit from 1/2007 through 12/2009. Patients subjected to VTE prophylaxis were matched 1:1 by age, gender, glasgow coma scale (GCS) score at admission, presence of hypotension on admission, injury severity score, and head abbreviated injury scale (AIS) score, with patients who did not receive chemical VTE prophylaxis. The primary outcome measure was VTE. Secondary outcomes were SICU and hospital length of stay (HLOS), adverse effects of anticoagulation, and mortality. Results: After propensity matching, 37 matched pairs were analysed. Cases and controls had similar demographics, injury characteristics, rate of craniotomies/craniectomies, SICU LOS, and HLOS. The median time of commencement of VTE prophylaxis was 10 days. The incidence of VTE was increased 3.5-fold in the controls compared to the cases (95% CI 1.0-12.1, P=0.002). The mortality was higher in patients who did not receive anticoagulation (19% vs. 5%, P=0.001). No adverse outcomes were detected in the anticoagulated patients. Conclusion: Prophylactic anticoagulation decreases the overall risk for clinically significant VTE in patients with severe isolated TBI. Prospective validation of the timing and safety of chemical VTE prophylaxis in these instances is warranted.

Multiple assays have been developed for the characterization of the functional activation of SARS-CoV-2 specific T-cells. This study was conducted to assess the post-vaccination and post-infection T cell response, as detected by the QuantiFERON-SARS-CoV-2 assay using the combination of three SARS-CoV-2 specific antigens (Ag1, Ag2 and Ag3). An amount of 75 participants with different infection and vaccination backgrounds were recruited for the evaluation of humoral and cellular immune responses. An elevated IFN-γ response in at least one Ag tube was observed in 69.2% of convalescent subjects and 63.9% of vaccinated ones. Interestingly, in a healthy unvaccinated case and three convalescents with negative IgG-RBD, we detected a positive QuantiFERON test after stimulation with Ag3. The majority of the T cell responders reacted simultaneously to the three SARS-CoV-2 specific antigens, and Ag3 demonstrated the highest rate of reactivity. At univariable analysis, the only factor that was associated with an absence of a cellular response was time from blood collection, being less than 30 days (OR:3.5, CI95% [1.15–10.50], p = 0.028). Overall, the inclusion of Ag3 improved the performance of the QuantiFERON-SARS-CoV-2 and showed a particular interest among subjects who fail to achieve a measurable antibody response after infection or vaccination.

BackgroundInborn errors of immunity (IEI) predispose patients to various infectious and non-infectious complications. Thanks to the development and expanding use of flow cytometry and increased awareness, the diagnostic rate of IEI has markedly increased in Algeria the last decade.AimThis study aimed to describe a large cohort of Algerian patients with probable IEI and to determine their clinical characteristics and outcomes.MethodsWe collected and analyzed retrospectively the demographic data, clinical manifestations, immunologic, genetic data, and outcome of Algerian IEI patients - diagnosed in the department of medical immunology of Beni Messous university hospital center, Algiers, from 2008 to 2021.ResultsEight hundred and seven patients with IEI (482 males and 325 females) were enrolled, 9.7% of whom were adults. Consanguinity was reported in 50.3% of the cases and a positive family history in 32.34%. The medium age at disease onset was 8 months and at diagnosis was 36 months. The median delay in diagnosis was 16 months. Combined immunodeficiencies were the most frequent (33.8%), followed by antibody deficiencies (24.5%) and well-defined syndromes with immunodeficiency (24%). Among 287 patients tested for genetic disorders, 129 patients carried pathogenic mutations; 102 having biallelic variants mostly in a homozygous state (autosomal recessive disorders). The highest mortality rate was observed in patients with combined immunodeficiency (70.1%), especially in patients with severe combined immunodeficiency (SCID), Omenn syndrome, or Major Histocompatibility Complex (MHC) class II deficiency.ConclusionThe spectrum of IEI in Algeria is similar to that seen in most countries of the Middle East and North Africa (MENA) region, notably regarding the frequency of autosomal recessive and/or combined immunodeficiencies.

Background: Cross-reactivity between shrimp and house dust mite (HDM) proteins has been widely documented. However, a significant geographical variability in sensitization patterns and cross-reactive allergens has been reported which may impact the diagnosis and management of shrimp allergy among HDM-shrimp co-sensitized patients. This study aimed to investigate the prevalence of shrimp and tropomyosin sensitization among HDM-allergic patients in order to understand the local epidemiology to inform the development of targeted diagnostic and therapeutic tools. Methods: Four hundred forty-six (446) HDM-allergic patients and 126 atopic controls were screened for shrimp-specific IgE using the IMMULITE 2000 XPI® System. HDM-shrimp sensitized subjected were also tested for IgE tropomyosin (nPen m 1) and thoroughly interviewed about their shellfish consumption habits. Tropomyosin sensitized patients were subjected to further analysis including measurement of IgE specific to squid and crab. Results: The prevalence of shrimp sensitization in the HDM-allergic population was 20.4% vs 0% in the control group. Of them 63.7% were clinically allergic to shrimp, while 9 cases had no history of allergic reaction to this food and 24 patients reported not having consumed shrimp before. Besides, 72.5% of the HDM-shrimp sensitized subjects had tropomyosin-specific IgE with a positivity rate of 82.8% among shrimp-allergic patients. Among tropomyosin reactors, 95.5% were sensitized to crab and 89.5% to squid, none of them had previously ingested neither crab nor squid. Nevertheless, one-third of HDM-shrimp sensitized patients who never consumed shrimp before did not react to tropomyosin. Conclusions: Shrimp allergy seems to be strictly dependent on HDM sensitization, at least in this geographical area. Therefore, HDM allergic patients should be systematically screened for shrimp sensitization and asked about the consumption of shellfish. Tropomyosin is a major and clinically relevant shrimp allergen that accounts for shellfish-HDM cross-reactivity. However, other components could be involved.

Aphasia is language impairment due to acquired brain damage. It affects people’s ability to communicate effectively in everyday life. Little is known about the influence of environmental factors on everyday communication for people with aphasia (PWA). It is generally assumed that for PWA speaking to a familiar person (i.e. with shared experiences and knowledge) is easier than speaking to a stranger (Howard, Swinburn, and Porter). This assumption is in line with existing psycholinguistic theories of common ground (Clark, 1996), but there is little empirical data to support this assumption. The current study investigated whether PWA benefit from conversation partner (CP) familiarity during goal-directed communication, and how this effect compared to a group of neurologically healthy controls (NHC). Sixteen PWA with mild to severe aphasia, sixteen matched NHC, plus self-selected familiar CPs participated. Pairs were videotaped while completing a collaborative communication task. Pairs faced identical Playmobile rooms: the view of the other’s room was blocked. Listeners attempted to replicate the 5-item set-up in the instructor’s room. Roles were swapped for each trial. For the unfamiliar condition, participants were paired with another participant’s CP (PWA were matched with another PWA’s CP based on their aphasia profile). The outcomes were canonical measures of communicative efficiency (i.e. accuracy, time to complete, etc.). Results showed different effects in response to the unfamiliar partner for PWA compared to NHC: In the instructor role, PWA showed faster trial times with the unfamiliar partner, but similar accuracy scores in both conditions. NHC, on the other hand, showed similar trial times across CPs, but higher accuracy scores with the unfamiliar partner. In the listener role, PWA showed a pattern more similar to NHC: equal trial times across conditions, and an improvement in accuracy scores with the unfamiliar partner. Results show that conversation partner familiarity significantly affected communication for PWA dyads on a familiar task, but not for NHC. This research highlights the importance of identifying factors that influence communication for PWA and understanding how this effect varies across aphasia profiles. This knowledge will ultimately inform our assessment and intervention of real-world communication.

X-linked severe combined immunodeficiency (X-SCID) is caused by mutations of IL2RG, the gene encoding the interleukin common gamma chain (IL-2Rγ or γc) of cytokine receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Hypomorphic mutations of IL2RG may cause combined immunodeficiencies with atypical clinical and immunological presentations. Here, we report a clinical, immunological, and functional characterization of a missense mutation in exon 1 (c.115G>A; p. Asp39Asn) of IL2RG in a 7-year-old boy. The patient suffered from recurrent sinopulmonary infections and refractory eczema. His total lymphocyte counts have remained normal despite skewed T cell subsets, with a pronounced serum IgE elevation. Surface expression of IL-2Rγ was reduced on his lymphocytes. Signal transducer and activator of transcription (STAT) phosphorylation in response to IL-2, IL-4, and IL-7 showed a partially preserved receptor function. T-cell proliferation in response to mitogens and anti-CD3/anti-CD28 monoclonal antibodies was significantly reduced. Further analysis revealed a decreased percentage of CD4+ T cells capable of secreting IFN-γ, but not IL-4 or IL-17. Studies on the functional consequences of IL-2Rγ variants are important to get more insight into the pathogenesis of atypical phenotypes which may lay the ground for novel therapeutic strategies.

Abstract Extraintestinal pathogenic and intestinal pathogenic (diarrheagenic) Escherichia coli differ phylogenetically and by virulence profiles. Classic theory teaches simple linear descent in this species, where non‐pathogens acquire virulence traits and emerge as pathogens. However, diarrheagenic Shiga toxin‐producing E. coli (STEC) O2:H6 not only possess and express virulence factors associated with diarrheagenic and uropathogenic E. coli but also cause diarrhea and urinary tract infections. These organisms are phylogenetically positioned between members of an intestinal pathogenic group (STEC) and extraintestinal pathogenic E. coli. STEC O2:H6 is, therefore, a ‘heteropathogen,’ and the first such hybrid virulent E. coli identified. The phylogeny of these E. coli and the repertoire of virulence traits they possess compel consideration of an alternate view of pathogen emergence, whereby one pathogroup of E. coli undergoes phased metamorphosis into another. By understanding the evolutionary mechanisms of bacterial pathogens, rational strategies for counteracting their detrimental effects on humans can be developed.

Nous nous sommes intéressée à trois journaux intimes publiés à cette période cruciale des débuts de la mobilisation communautaire autour du VIH. Nous avons choisi trois ouvrages parus à la même époque qu’un texte marquant l’émergence de la littérature du sida, celui d’Hervé Guibert, A l’ami qui ne m’a pas sauvé la vie.

Intraosseous (IO) needle placement is an alternative for patients with difficult venous access. The purpose of this retrospective study was to examine indications and outcomes associated with IO use at a Level 1 trauma center (January 2008-May 2015). Data points included demographics, time to insertion, intravenous (IV) access points, indications, infusions, hospital and intensive care unit length of stay, and mortality. Of 68 patients with IO insertion analyzed (63.2% blunt trauma, 29.4% penetrating trauma, and 7.4% medical), 56 per cent were hypotensive on arrival and 38.2 per cent asystolic. The most common indications for IO infusion were difficult IV access (69%) and rapid sequence intubation (20.6%). The median time to IO access was three minutes. IV access was gained after IO in 72.1 per cent of patients. Through IO access, 30.9 per cent patients received crystalloid, 29.4 per cent received Advanced Care Life Support (ACLS) medications, 25 per cent rapid sequence intubation medications, 20.6 per cent blood products, and 2.9 per cent seizure medications. Overall, 80.9 per cent were intubated in the Emergency Department (ED), 26.5 per cent had ED thoracotomy, and 20.6 per cent had a laparotomy. Median crystalloid infused through IO was 180 cc in pediatric patients and 1 L in adults, respectively. Extravasation, the most common complication, was experienced by 7.4 per cent of patients. Inhospital mortality was 72.9 per cent. IO access should be considered when there is a need for rapid intervention requiring vascular access. [ABSTRACT FROM AUTHOR]