Middle East respiratory syndrome coronavirus (MERS-CoV) infections sharply increased in the Arabian Peninsula during spring 2014. In Abu Dhabi, United Arab Emirates, these infections occurred ...primarily among healthcare workers and patients. To identify and describe epidemiologic and clinical characteristics of persons with healthcare-associated infection, we reviewed laboratory-confirmed MERS-CoV cases reported to the Health Authority of Abu Dhabi during January 1, 2013-May 9, 2014. Of 65 case-patients identified with MERS-CoV infection, 27 (42%) had healthcare-associated cases. Epidemiologic and genetic sequencing findings suggest that 3 healthcare clusters of MERS-CoV infection occurred, including 1 that resulted in 20 infected persons in 1 hospital. MERS-CoV in healthcare settings spread predominantly before MERS-CoV infection was diagnosed, underscoring the importance of increasing awareness and infection control measures at first points of entry to healthcare facilities.
Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis ...and management of HAE provides up‐to‐date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on‐demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast‐feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.
Background Molecular genetics techniques are an essential diagnostic tool for primary immunodeficiency diseases (PIDs). The use of next-generation sequencing (NGS) provides a comprehensive way of ...concurrently screening a large number of PID genes. However, its validity and cost-effectiveness require verification. Objectives We sought to identify and overcome complications associated with the use of NGS in a comprehensive gene panel incorporating 162 PID genes. We aimed to ascertain the specificity, sensitivity, and clinical sensitivity of the gene panel and its utility as a diagnostic tool for PIDs. Methods A total of 162 PID genes were screened in 261 patients by using the Ion Torrent Proton NGS sequencing platform. Of the 261 patients, 122 had at least 1 known causal mutation at the onset of the study and were used to assess the specificity and sensitivity of the assay. The remaining samples were from unsolved cases that were biased toward more phenotypically and genotypically complicated cases. Results The assay was able to detect the mutation in 117 (96%) of 122 positive control subjects with known causal mutations. For the unsolved cases, our assay resulted in a molecular genetic diagnosis for 35 of 139 patients. Interestingly, most of these cases represented atypical clinical presentations of known PIDs. Conclusions The targeted NGS PID gene panel is a sensitive and cost-effective diagnostic tool that can be used as a first-line molecular assay in patients with PIDs. The assay is an alternative choice to the complex and costly candidate gene approach, particularly for patients with atypical presentation of known PID genes.
•suPAR has been suggested as having good prognostic utility for severe complications of COVID-19.•COVID-19 patients with increased suPAR are at high risk of developing complications.•Increasing suPAR ...by 1 ng/mL leads to 58% rise in the risk of getting complications.
To examine the association between plasma levels of the soluble urokinase plasminogen activator receptor (suPAR) and the incidence of severe complications of COVID-19.
403 RT-PCR-confirmed COVID-19 patients were recruited and prospectively followed-up at a major hospital in the United Arab Emirates. The primary endpoint was time from admission until the development of a composite outcome, including acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, or death from any cause. Patients discharged alive were considered as competing events to the primary outcome. Competing risk regression was used to quantify the association between suPAR and the incidence of the primary outcome.
6.2% of patients experienced ARDS or ICU admission, but none died. Taking into account competing risk, the incidence of the primary outcome was 11.5% (95% confidence interval CI, 6.7–16.3) in patients with suPAR levels >3.91 ng/mL compared to 2.9% (95% CI, 0.4–5.5) in those with suPAR ≤3.91 ng/mL. Also, an increase by 1 ng/mL in baseline suPAR resulted in a 58% rise in the hazard of developing the primary outcome (hazard ratio 1.6, 95% CI, 1.2–2.1, p = 0.003).
suPAR has an excellent prognostic utility in predicting severe complications in hospitalised COVID-19 patients.
Combined immunodeficiencies are a heterogeneous collection of primary immune disorders that exhibit defects in T cell development or function, along with impaired B cell activity even in light of ...normal B cell maturation. CARMIL2 (RLTPR) is a protein involved in cytoskeletal organization and cell migration, which also plays a role in CD28 co-signaling of T cells. Mutations in this protein have recently been reported to cause a novel primary immunodeficiency disorder with variable phenotypic presentations. Here, we describe seven patients from three unrelated, consanguineous multiplex families that presented with dermatitis, esophagitis, and recurrent skin and chest infections with evidence of combined immunodeficiency. Through the use of whole exome sequencing and autozygome-guided analysis, we uncovered two mutations not previously reported (p.R50T and p.L846S
) in CARMIL2. Real-time PCR analysis revealed that the biallelic frameshift mutation is under negative selection, likely due to nonsense-mediated RNA decay and leading to loss of detectable protein upon immunoblotting. Protein loss was also observed for the missense mutation, and 3D modeling suggested a disturbance in structural stability due to an increase in the electrostatic energy for the affected amino acid and surrounding residues. Immunophenotyping revealed that patient T
counts were significantly depressed, and that CD4
T cells were heavily skewed towards the naïve status. CD3/CD28 signaling impairment was evidenced by reduced proliferative response to stimulation. This work broadens the allelic heterogeneity associated with CARMIL2 and highlights a deleterious missense alteration located outside the leucine-rich repeat of the protein, where all other missense mutations have been reported to date.
This work presents an opto-electrical method that measures the viral nucleocapsid protein and anti-N antibody interactions to differentiate between SARS-CoV-2 negative and positive nasal swab ...samples. Upon light exposure of the patient nasal swab sample mixed with the anti-N antibody, charge transfer (CT) transitions within the altered protein folds are initiated between the charged amino acids side chain moieties and the peptide backbone that play the role of donor and acceptor groups. A Figure of Merit (FOM) was introduced to correlate the relative variations of the samples with and without antibody at two different voltages. Empirically, SARS-CoV-2 in patient nasal swab samples was detected within two minutes, if an extracted FOM threshold of >1 was achieved; otherwise, the sample wasconsidered negative.
Background: Primary immune deficiency (PID) patients may develop acute or chronic pain. Pain has not been studied in this population until now.
Objectives: This study systematically assessed the pain ...of various durations in PID patients using validated pain questionnaires.
Subjects and Methods: A Short-Form McGill Pain Questionnaire (SF-MPQ), already validated in the Arabic language, was used to ascertain the characteristics and severity of pain. Additionally, an Arabic version of the Neuropathic Pain Questionnaire-Short Form (NPQ-SF) was employed to evaluate neuropathic pain in the same group of patients.
Results: Forty-six patients participated in the study. The mean age of the patients was 25 years. The most commonly diagnosed PID was a common variable immune deficiency (32.6%), followed by severe combined immune deficiency (19.57%). Based on the SF-MPQ, the pain was experienced by 30.4 % of the subjects who participated in the study; 57% of whom were on regular pain medications. The most common site reported for pain was the abdomen (35.7%). The mean duration of pain was 36.1 days ± 34.6 days. The most common comorbidities in these patients were bronchiectasis, followed by immune thrombocytopenic purpura, and scoliosis. None of the PID patients had significant neuropathic pain based on NFQ-SF.
Conclusion: To the best of our knowledge, this is the first study to assess the prevalence as well as the severity and duration of pain in PID patients. There were significantly more subjects who had continuous pain. Treatment of pain in PID patients will have a significant effect on improving their quality of life.
We compared the antibiotic susceptibility, clonal lineages and resistance genes of singleton Acinetobacter baumannii strains to those of isolates representing repeatedly encountered molecular types ...in five Abu Dhabi hospitals. One hundred and ten clinically relevant, non-repeat strains were typed by blaOXA-51-like allele sequencing and by PFGE, and selected isolates also by MLST. Resistance was assessed by MIC determinations and by disc diffusion. Genotyping was carried out by PCR, targeting 28 genes. The 80 epidemic strains belonged to worldwide lineages 1, 2 and 7, representing 11 pulsotypes and 9 genotypes, while the 30 sporadic isolates exhibited a high level of genetic variability and, with the exception of a small subgroup, were not associated with any recognized epidemic lineages. All epidemic subtypes carried the ISAba1-linked blaOXA-23 gene, and harboured the int, the blaPER and the armA genes significantly more frequently than their sporadic counterparts. They were all multi-drug resistant, including non-susceptibility to carbepenems, and were often extensively drug resistant, a phenomenon rarely seen among sporadic strains. Epidemic strains represented 78.8 % of intensive care unit isolates, causing more respiratory infections, while sporadic strains were more frequently isolated from wound and soft tissue infections. The study showed that among strains collected at the same time and from the same region, the very heterogeneous, sensitive sporadic strains, with the exception of a few non-susceptible singleton isolates, clearly differed from the highly resistant epidemic ones, which belonged to multiple pulsotypes and genotypes clustered into three worldwide clonal lineages carrying blaOXA-64, blaOXA-66 and blaOXA-69, respectively.
Mammary carcinoma arising in ectopic breast tissue is an uncommon occurrence. Most reported cases have involved ductal carcinoma, but other types, such as medullary, papillary, and lobular ...carcinomas, have been described. For pathologists, the diagnosis of mammary carcinoma arising in ectopic breast tissue can be difficult, especially in the axilla, where carcinoma of adnexal origin must be excluded. We describe a 46-year-old woman who developed invasive (juvenile) secretory carcinoma in ectopic right axillary breast tissue and micrometastatic carcinoma in an ipsilateral axillary lymph node. The carcinoma arose in a right axillary mass that had been present for 8 years, from which she had secreted fluid during prior breast-feeding. To our knowledge, this is the first report of secretory carcinoma arising in axillary breast tissue to be documented in the current literature.
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Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may ...occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment.
We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE).
The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022).
The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms.
The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.
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