Evaluation of C4d expression and staining patterns by immunohistochemistry in renal biopsy samples with focal segmental glomerulosclerosis and minimal change disease.

INTRODUCTION: C4d is an activation product of lectin pathway of complement. Glomerular deposition of C4d is associated with poor prognosis in different types of immune-related glomerulonephritis. The present study was conducted to investigate expression level of C4d and its staining pattern in renal biopsy of patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) by immunohistochemistry method. MATERIALS AND METHODS: In this retrospective cross-sectional study, renal biopsy specimens from 46 samples of MCD, 47 samples of FSGS, and 15 samples without glomerular disease as the controls, were subjected to immunohistochemistry staining with C4d. Demographic characteristics and information obtained from light and electron microscopy (EM) of patients were also extracted from their files. RESULTS: C4d positive staining was observed in 97.9 % of FSGS and 43.5 % of MCD samples, which showed a statistically significant difference (P < 0.001). The sensitivity and specificity of C4d expression for diagnosing FSGS were 97.9 % and 56.5 %, respectively. There was no significant correlation between C4d expression and any of the light and electron microscopy findings, including presence of foam cells, mesangial matrix expansion, interstitial fibrosis and tubular atrophy, and basement membrane changes in MCD patients. Also, no significant correlation was observed between C4d expression and clinical symptoms of proteinuria or prolonged high level of creatinine in patients with MCD. DISCUSSION AND CONCLUSION: The expression of C4d marker had a good sensitivity and negative predictive value in the diagnosis of FSGS.

Antibiotic Resistance Pattern in Intensive Care Units in a Large Referral Hospital in Iran.

Background & Objective: Antibiotic resistance, especially in the form of multidrug-resistant (MDR), is a big problem, especially in intensive care units (ICUs). This study aimed to evaluate antibiotic resistance and MDR patterns among patients hospitalized in the ICUs in one of the large referral centers in Iran. Methods: The present study was conducted at Imam Khomeini Hospital in Tehran (a great referral hospital), which admits critically ill patients requiring ICU services. To determine the rate of positive cultures for resistant strains, the patient's blood specimens were sent to the laboratory of the hospital for inoculation on proper culture media within 2 hours of extraction. Antimicrobial susceptibility tests were done using the Bauer-Kirby disk diffusion method. Results: A total of 1,755 samples were collected from the patients to assess microbial strains and antibiotic resistance. The most common microbial strains detected in the cultures extracted from peripheral blood samples were Klebsiella pneumonia (22.1%), Staphylococcus epidermidis (7.9%) and another coagulase-negative Staphylococcus (15.0%). The antibiogram test showed antibiotic resistance in 1,509 cases, leading to a resistance prevalence rate of 85.9%. The most common antimicrobial resistance observed was against cotrimoxazole (61.7%), ciprofloxacin (51.3%), imipenem (50.0%), and ampicillin (49.6%). The rate of MDR was found to be 96.3%. Conclusion: In Iran's ICUs, a significantly high level of antibiotic resistance may be seen especially the MDR pattern, which indicates the need to change the pattern of prescribing and managing these drugs in ICU centers.

Evaluation of HER2 Positivity Based on Clinicopathological Findings in HER2 Borderline Tumors in Iranian Patients with Breast Cancer.

Background & Objective: Human epidermal growth receptor-2 (HER2) gene amplification is an important predictive and prognostic factor in breast cancer treatment. However, the expression of HER2 determined by immunohistochemistry (IHC) is considered as borderline in some cases, and confirmation of the HER2 status by either fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) is necessary for correct treatment decision-making. Considering the high cost of FISH and CISH, we aimed to investigate whether clinicopathological findings of the tumor could predict the HER2 status. Methods: A retrospective study was performed using the data from 584 patients with breast cancer with HER2-borderline disease, confirmed by IHC. Final HER2 status, pathologic tumor size and type, nodal involvement, Ki67 index, presence of estrogen and progesterone receptors (ER, PR), lymphovascular invasion (LVI), and stage were retrieved from the clinical records. Results: One hundred twenty-one (20.7%) patients were HER2-positive according to the FISH or CISH results. Logistic regression analysis showed that the pathologic size was positively associated with HER2 positivity with an odds ratio (OR) of 1.02 (95% CI: 1.01-1.04). In addition, the adjusted OR illustrated a statistically significant association between HER2 positivity and PR negativity (OR= 2.22, 95% CI: 1.29-3.83). Conclusion: In HER2 borderline breast cancer, HER2 positivity significantly increases with tumor size and PR negativity. Further studies are recommended that may find an applicable model to predict the actual status of HER2 in borderline cases.

Evaluation of Etiology, Clinical Manifestations, Diagnosis, Follow-up, Histopathology and Prognosis Factors in Papillary Thyroid Microcarcinoma: A Systematic Review and Meta-analysis.

Background & Objective: The most frequent type of cancer found in the endocrine system is thyroid carcinoma. Among well-differentiated thyroid malignancies, the most commonly occurring type is identified as papillary thyroid carcinoma (PTC), which makes up 70-90% of the cases. A subtype of PTC is papillary thyroid microcarcinoma (PTMC), which includes tumors smaller than 10 mm in diameter. Due to the advancements in diagnostic techniques, the incidence of this type of cancer is on the rise. In this study, we aimed to analyze the factors worsening the PTMC prognosis. Methods: In the first step, we searched various databases for the factors affecting this tumor. The relevant articles were collected and different outcomes of this tumor and its associated factors which were studied in more than one article, were classified. Finally, we conducted a meta-analysis of these outcomes and their related factors. Results: In the meta-analysis, a significantly association was found between the following factors: recurrence with gender (P<0.001) lymph node metastasis (LNM) (P= 0.003), and extrathyroidal invasion (P<0.001); lymph node metastasis with extrathyroidal invasion (P<0.001), and multifocality (P<0.001); central lymph node metastasis (CLNM) with gender (P=0.001), tumor size (P<0.001), extracapsular invasion (P<0.001), lateral cervical lymph node metastasis (P<0.001), and extrathyroidal invasion (P<0.001); lymph node metastasis resulted in poor outcomes (P<0.001); and finally tumor size with BRAFV600E mutation (P<0.001). Conclusion: In conclusion, it is essential to note that greater awareness and understanding of this tumor characteristics and special and separate attention to PTMC can significantly improve the society overall health.

Maximum Surgical Blood Ordering Schedule in Common Pediatric Cardiac Surgeries in a Tertiary Center.

Background & Objective: Unnecessary pre-operative ordering of red blood cells (RBCs) in elective surgeries increases costs and waste of blood inventory. Maximum surgical blood order schedule (MSBOS) is a helpful strategy in the estimation of blood units needed for surgery and the prevention of overconsumption. In this study, an MSBOS for pediatric cardiac surgeries is designed. Methods: In this cross-sectional study, we included all pediatric patients who underwent elective cardiac surgery in Children's Medical Center in Tehran, Iran, from March 21, 2019, to September 22, 2019. Data consisted of the type of surgery and the number of blood units transfused and units cross-matched, based on which cross-match to transfusion ratio (CTR), the transfusion index (TI), and transfusion probability (T%) were calculated. Results: Overall 205 pediatric patients were included in the study. Four hundred and ten RBCs units were cross-matched, and 262 were transfused. The overall results of the CTR, T%, and TI for all the eight types of cardiac surgery were 1.56 (410/262), 76% (157/205), and 1.28 (262/205), respectively. The raw MSBOS for cardiac surgeries included ventricular septal defect, tetralogy of fallot, dextro-transposition of the great arteries, atrial septal defect, aortic coarctation, patent ductus arteriosus, pulmonary stenosis, and pacemaker insertion, which were 1.58, 1.03, 1.54, 1.66, 0.77, 0, 1.25, and 0 unit, respectively, and the figures were rounded up. Conclusion: Accurate MSBOS protocols reduce cross-match workload in laboratories, lead to the appropriate use of blood stocks with less wastage, save human and economic resources, and eventually, promote patient safety.

Desmopressin enhances random-pattern skin flap survival in rats: Possible role of vasopressin Type-1a and 2 receptors.

BACKGROUND: Many drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of anti-diuretic hormone (ADH) and a selective agonist for vasopressin type-2 receptors (V2 receptors). Desmopressin has been shown to improve endothelial function, induce vasodilation, and reduce inflammation. We aimed to evaluate its efficacy in enhancing flap survival and assess the role of vasopressin receptors in this process. MATERIALS AND METHODS: We randomly assigned six male Wistar rats to each study group. Different doses of desmopressin were injected intraperitoneally to find the most effective amount (8 µg/rat). SR-49059, a selective V1a receptor antagonist, was given at 2µg/rat before providing the most effective dose of desmopressin (8µg/rat). Histopathological assessments, quantitative measurements of interleukin-1ß (IL-1ß), Tumor necrosis factor-alpha (TNF-α), and Nuclear Factor-κB (NF-κB), optical imaging, and measurement of the expression levels of V2 receptor in the rat skin tissue were performed. RESULTS: Desmopressin (8µg/rat) significantly reduced the mean percentage of necrotic area compared to the control group (19.35% vs 73.57%). Histopathological evaluations revealed a notable reduction in tissue inflammation, edema, and degeneration following administration of desmopressin (8). The expression of the V2 receptor was increased following desmopressin administration. It also led to a reduction in IL-1ß, TNF-α, and NF-κB levels. The protective effect of desmopressin on flap survival was reversed upon giving SR-49059. The optical imaging revealed enhanced blood flow in the desmopressin group compared to the control group. CONCLUSIONS: Desmopressin could be repurposed to improve flap survival. V1a and V2 receptors probably mediate this effect.

Effects of nebulized hypertonic saline on inflammatory mediators in patients with severe COVID-19 pneumonia: A double-blinded randomized controlled trial.

INTRODUCTION: An exaggerated immune response is considered the most important aspect of COVID-19 pathogenesis. Hypertonic saline (HS) has shown promise in combating inflammation in several respiratory diseases. We investigated the effects of nebulized HS on clinical symptoms and inflammatory status in patients with severe novel coronavirus infection (COVID-19) pneumonia. MATERIALS AND METHODS: We randomly assigned 60 adults admitted to the intensive care unit (ICU) due to severe COVID-19 pneumonia to the experimental (received nebulized 5% saline) and control (received nebulized distilled water) groups. All interventions were applied 4 times daily for 5 days. The levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and other clinical factors from venous blood were evaluated before and after intervention application. Mortality rate, intubation rate, and durations of ICU and hospital stay were also compared between groups. RESULTS: The levels of TNF-α (MD: -21.35 [-32.29, -10.40], P = 0.000) and IL-6 (-9.94 [-18.86, -1.02], P = 0.003) were lower in the experimental group compared to the control group after applying the interventions. The levels of white blood cell count, PO2, and serum sodium were also statistically significant differences between groups. However, we did not observe significant differences in terms of hospitalization durations and mortality rates. CONCLUSION: Nebulization of HS in patients with severe COVID-19 pneumonia appears to be effective in reducing inflammation, but does not appear to affect intubation rates, mortality, hospitalization, or length of stay in ICU.

Evaluation of Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus aureus respiratory tract superinfections among patients with COVID-19 at a tertiary-care hospital in Tehran, Iran.

BACKGROUND: The emergence of healthcare-associated infections (HAIs) or superinfections in COVID-19 patients has resulted in poor prognosis and increased mortality. METHODS: In a cross-sectional study, 101 respiratory samples were collected from ICU-admitted COVID-19 patients. The HAI rate, demographics, and antibiotic resistance were assessed. RESULTS: The HAI rate was 83.16% (76.62% bacterial and 6.54% fungal). The prevalence of 3 major HAI-causing organisms included Klebsiella pneumoniae (41.5%), Acinetobacter baumannii (20.8%), and Staphylococcus aureus (4.9%). Mortality and intubation ventilation proportions of 90% (p = 0.027) and 92.2% (p = 0.02) were significant among patients with superinfection, respectively. Multiple logistic regression analysis showed SpO2 pressure (odds ratio 0.842; 95% CI 0.750-0.945; p = 0.004) as a predictive factor in the association between antibiotic usage and mortality. More than 50% of patients received carbapenems. The resistance rates to at least one antibiotic of third-generation cephalosporins, aminoglycosides, quinolones/fluoroquinolones, tetracyclines, and ß-lactam inhibitors were 95.2%, 95.2%, 90%, 57.1%, and 100% among A. baumannii isolates and 71.4%, 55%, 69%, 61.9%, and 59.5% among K. pneumoniae isolates, respectively. A proportion of 60% was recorded for methicillin-resistant S. aureus isolates. CONCLUSION: As a result, antibiotic treatment should be administered following the microbial resistance profile. Contact isolation and infection control measures should be implemented as needed.

COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis: Clinical Features, Antifungal Susceptibility, Management and Outcome in a Tertiary Hospital in Iran.

BACKGROUND: Despite the unprecedented surge in the incidence of mucormycosis in the COVID-19 era, the antifungal susceptibility patterns (ASPs) of COVID-19 associated mucormycosis (CAM) isolates have not been investigated so far and it is unclear if the high mortality rate associated with CAM is driven by decreased susceptibility of Mucorales to antifungal drugs. OBJECTIVES: To describe the clinical, mycological, outcome and in vitro ASPs of CAM cases and their etiologies from Iran. PATIENTS/METHODS: A prospective study from January 2020 to January 2022 at a referral tertiary hospital in Tehran, Iran was conducted for screening mucormycosis through histopathology and mycological methods. The identity of Mucorales isolates was revealed with ITS-panfungal PCR& sequencing and MALDI-TOF. The AS for amphotericin B, itraconazole, isavuconazole and posaconazole was cleared according to the EUCAST antifungal susceptibility testing protocol. RESULT: A total of 150 individuals were diagnosed with CAM. Males constituted 60.7% of the population. The mean age was 54.9 years. Diabetes was the leading risk factor (74.7%). The median interval between diagnosis of COVID-19 and CAM was 31 days. The recovery rate of culture was as low as 41.3% with Rhizopus arrhizus being identified as the dominant (60; 96.7%) agent. Amphotericin B (MIC50 = 0.5 µg/ml) demonstrated the highest potency against Mucorales. CONCLUSION: Majority of the cases had either diabetes, history of corticosteroid therapy or simultaneously both conditions. Accordingly, close monitoring of blood glucose should be considered. The indications for corticosteroids therapy are recommended to be optimized. Also, an anti Mucorales prophylaxis may be necessitated to be administrated in high risk individuals. Although amphotericin B was the most active agent, a higher rate of resistance to this antifungal was noted here in comparison with earlier studies on mucormycetes from non-CAM cases.

Analysis of Prevalence and Trends in the Biopsy-Proven Native Kidney Diseases in Iranian Population: A 12-year Survey from a Referral Center.

Background & Objective: The prevalence of glomerular diseases, as the leading cause of chronic kidney disease, is increasing. Renal biopsy is still the gold standard for diagnosis of the most kidney disorders. Data on prevalence of the biopsy-proven kidney diseases in Iran is limited and none of the previously reported studies used electron microscopic (EM) evaluation for the diagnosis. This study was conducted to analyze the prevalence of biopsy-proven kidney diseases in a referral center in Iran. Methods: The reports of kidney biopsy samples from 2006 to 2018 referred to a pathology center, affiliated with Tehran University of Medical Sciences were reviewed. The prevalence of different disorders was assessed based on the clinical presentation in 3 age categories, including childhood, adulthood, and elderly. Results: Among 3455 samples, 2975 were analyzed after excluding transplant-related specimens, suboptimal specimens, and those with uncertain diagnoses. Nephrotic syndrome (NS) (39%) was the most common cause of biopsy followed by subnephrotic proteinuria (18%), hematuria in association with proteinuria (15%), renal failure (9%), isolated hematuria (6%), lupus (4%) and the other non-specific manifestations such as hypertetion or malaise (each one less than 2%). The most common diagnoses included membranous nephropathy (MGN) (17.9%), focal segmental glomerulosclerosis (FSGS) (15.9%), lupus nephritis (LN) (13.7%), minimal histopathological findings (unsampled FSGS versus Minimal Change Disease, 12.1%), Immunoglobulin-A (IgA) nephropathy (6.5%) and Alport syndrome (6.1%). MGN was the most frequent disease before 2013, but FSGS became more frequent after that. Conclusion: NS and proteinuria were the most indications for kidney biopsy. Although MGN was the most common disease, the prevalence of FSGS has been increasing in recent years and making it the most common disease after 2013. LN and IgA nephropathy are the most common causes of secondary and primary GN presenting with proteinuria and hematuria, respectively.

Occurrence of Acinetobacter baumannii genomic resistance islands (AbGRIs) in Acinetobacter baumannii strains belonging to global clone 2 obtained from COVID-19 patients.

AIM: The Acinetobacter baumannii genomic resistance islands (AbGRIs), which were characterized in the genome of the global clone 2 (GC2) A. baumannii contain resistance genes. Here, we aimed to determine the occurrence of AbGRIs in GC2 A. baumannii obtained from COVID-19 patients in a referral hospital in Tehran, Iran. METHODS: A total of 19 carbapenem-resistant A. baumannii (CRAB) isolates belonging to GC2 and sequence type 2 (ST2), including 17 from COVID-19 patients and two from the devices used in the ICU that the COVID-19 patients were admitted, were examined in this study. Antibiotic susceptibility testing was performed by the disk diffusion method. PCR and PCR mapping, followed by sequencing, were performed to characterize the structure of AbGRI resistance islands in the isolates tested. RESULTS: The AbGRI3 was the most frequent resistance island (RI) detected, present in all the 19 isolates, followed by AbGRI1 (15 isolates; 78.9%) and AbGRI2 (three isolates; 15.8%). Notably, AbGRIs were identified in one of the A. baumannii strains, which was isolated from a medical device used in the ICU where COVID-19 patients were admitted. Furthermore, new structures of AbGRI1 and AbGRI3 resistance islands were found in this study, which was the first report of these structures. CONCLUSIONS: The present study provided evidence for the circulation of the GC2 A. baumannii strains harboring AbGRI resistance islands in a referral hospital in Tehran, Iran. It was found that resistance to several classes of antibiotics in the isolates collected from COVID-19 patients is associated with the resistance genes located within AbGRIs.

Percentage of Th1 and Th17 cells and serum level of IL-17 and IFN-γ cytokines in COVID-19-associated mucormycosis.

The considerable number of the 2019 coronavirus disease (COVID-19) patients who developed mucormycosis infections in West and Central Asia urged a need to investigate the underlying causes of this fatal complication. It was hypothesized that an immunocompromised state secondary to the excessive administration of anti-inflammatory drugs was responsible for the outburst of mucormycosis in COVID-19 patients. Therefore, we aimed to study the implication of two major subsets of adaptive immunity T helper (Th)-1 and Th17 cells in disease development. Thirty patients with COVID-19-associated mucormycosis, 38 with COVID-19 without any sign or symptom of mucormycosis, and 26 healthy individuals were included. The percentage of Th1 and Th17 cells in peripheral blood, as well as the serum levels of interleukin (IL)-17 and interferon-gamma (IFN-γ), were evaluated using flow cytometry and ELISA techniques, respectively. Th17 cell percentage in patients with COVID-19-associated mucormycosis was significantly lower than in COVID-19 patients (P-value: <0.001) and healthy subjects (P-value: 0.01). In addition, the serum level of IL-17 in COVID-19 patients was significantly higher than that of healthy individuals (P-value: 0.01). However, neither the frequency of Th1 cells nor the serum level of IFN-γ was different between the study groups. Given the critical role of Th17 cells in the defense against mucosal fungal infections, these findings suggest that low numbers of Th17 and insufficient levels of IL-17 might be a predisposing factor for the development of mucormycosis during or after COVID-19 infection.

Considering the critical role of Th17 cells in defense against mucosal fungal infections, the low numbers of Th17 and insufficient amounts of IL-17 might be a predisposing factor to develop mucormycosis during or after COVID-19 infection.

Implementation of an In-House Platform for Rapid Screening of SARS-CoV-2 Genome Variations.

BACKGROUND: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings. METHODS: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021. RESULTS: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants. CONCLUSION: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic.

The Evaluation of Hematological Parameters and Their Correlation with Disease Prognosis in COVID-19 Disease in Iran.

Background: Since 2019, Coronavirus has been a highly contagious disease. The COVID-19 outbreak was declared a pandemic by the World Health Organization in March 2020. Variable laboratory findings are reported in COVID-19 patients, among which elevated levels of D-dimer, lactate dehydrogenase, as well as lymphopenia, have been reported to be associated with increased severity of disease symptoms requiring ventilator support, intensive care unit admission, and mortality. Materials and Methods: In the current study, inclusion criteria were: patient age above 18 years and hospitalization in the Imam Khomeini hospital with COVID-19 disease confirmed with nasopharyngeal swab polymerase chain reaction tests. Levels of white blood cells, neutrophils, lymphocytes, hemoglobin, platelets, D-dimer, C-reactive protein, LDH, and ferritin were measured and their correlation with the final patients' outcome was evaluated. Results: A total of 208 patients were included in the present study. Higher neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte, LDH, platelet to lymphocyte ratio, ferritin, and D-dimer were significantly related to O2 dependency. Neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte and LDH were significantly related to higher rates of mortality. Higher Hb and lymphocyte count were significantly related to higher rates of survival. Conclusion: Hematological parameters including neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte, LDH, platelet to lymphocyte ratio, ferritin, D-dimer, Hb, and lymphocyte count were significantly related to the prognosis of patients with COVID-19 disease. This could help decide which COVID-19 patients have priority for hospitalization and intensive medical care, particularly when the pandemic disease causes limitations in healthcare service.

Dissemination of the Acinetobacter baumannii isolates belonging to global clone 2 containing AbGRI resistance islands in a referral hospital.

Acinetobacter baumannii strains belonging to global clone 2 (GC2) contain resistance islands (AbGRIs), which are composed of genes conferring resistance to older and newer antibiotics. Here, to locate these genes in AbGRIs, the GC2 strains from Tehran, Iran were examined. Among the 170 A. baumannii, 90 isolates were identified as GC2. Of the genes that confer resistance to older antibiotics, tetA(B), tetR(B) (tetracyclines), strA, and strB (aminoglycosides) were located in AbGRI1 of 65 GC2 isolates (72.2%). Of the other aminoglycosides, the aphA1b was located in AbGRI2-12b (63.6%), AbGRI2-12a (21.2%), or AbGRI2-1 (15.1%). The aacC1 and aadA1 genes were co-located within AbGRI2-1 (5.5%). The armA was located in AbGRI3-4 (77.7%) and AbGRI3ABI221 (22.2%). Of sulfonamides, the sul1 was located within AbGRI2-1 (5.5%). Of beta-lactams, the blaTEM was located in AbGRI2-12b (42%), AbGRI2-12a (14%), AbGRI2-1 (10%), or AbGRI2ABI257 (34%). The oxa23 gene conferring resistance to newer antibiotics (carbapenems) was located in AbaR4 (81.1%); of them, the AbaR4 was located within AbGRI1 in 45.2% of the isolates. This study showed that the GC2 isolates, which contained at least one AbGRI, disseminate in the hospital. Hence, it is likely that the AbGRIs play a significant role in conferring resistance to older and newer antibiotics in GC2 isolates from Iran. IMPORTANCE The majority of Acinetobacter baumannii isolates that are resistant to multiple antibiotics belong to one of the two major global clones, namely global clone 1 (GC1) and global clone 2 (GC2). The resistance islands, which contain variable assortments of transposons, integrons, and specific resistance genes, have been characterized in the genome of these GCs. In GC2 A. baumannii, the chromosomally located A. baumannii genomic resistance islands (AbGRIs) carry the genes conferring resistance to older and newer antibiotics. In this context, we tested whether GC2 isolates collected from a referral hospital carry the AbGRIs containing these genes. This study provided evidence for the circulation of the GC2 A. baumannii strains harboring AbGRI resistance islands between different wards of a referral hospital.

Corrigendum to "Pneumocystis pneumonia in COVID-19 patients: A comprehensive review" [Heliyon 9(2) (February 2023) e13618].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13618.].

Mobile genetic elements carrying aminoglycoside resistance genes in Acinetobacter baumannii isolates belonging to global clone 2.

Aminoglycosides are used to treat infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) strains. However, resistance to aminoglycosides has increased remarkably in the last few years. Here, we aimed to determine the mobile genetic elements (MGEs) associated with resistance to aminoglycosides in the global clone 2 (GC2) A. baumannii. Among the 315 A. baumannii isolates, 97 isolates were identified as GC2, and 52 of GC2 isolates (53.6%) were resistant to all the aminoglycosides tested. The AbGRI3s carrying armA were detected in 88 GC2 isolates (90.7%), and of them, 17 isolates (19.3%) carried a new variant of AbGRI3 (AbGRI3ABI221). aphA6 was located in TnaphA6 of 30 isolates out of 55 aphA6-harboring isolates, and 20 isolates were found to harbor TnaphA6 on a RepAci6 plasmid. Tn6020 carrying aphA1b was detected in 51 isolates (52.5%), which was located within AbGRI2 resistance islands. The pRAY* carrying the aadB gene was detected in 43 isolates (44.3%), and no isolate was found to contain a class 1 integron harboring this gene. The GC2 A. baumannii isolates contained at least one MGE carrying the aminoglycoside resistance gene, located mostly either in the chromosome within AbGRIs or on the plasmids. Thus, it is likely that these MGEs play a role in the dissemination of aminoglycoside resistance genes in GC2 isolates from Iran.

Pneumocystis pneumonia in COVID-19 patients: A comprehensive review.

The admitted patients of intensive care units with coronavirus disease 2019 (COVID-19) meet the challenges of subsequent infections. Opportunistic fungal infections such as Pneumocystis pneumonia (PCP) are among the important factors in the context of COVID-19 patients affecting illness severity and mortality. We reviewed the literature on COVID-19 patients with PCP to identify features of this infection. Although studies confirmed at least the presence of one immunosuppressive condition in half of PCP patients, this disease can also occur in immunocompetent patients who developed the immunosuppressive condition during Covid-19 treatment. The major risk factors associated with COVID-19 patients with PCP can be considered low lymphocyte counts and corticosteroid therapy. Diagnostic and treatment options are complicated by the overlapping clinical and radiologic characteristics of PCP and COVID-19 pneumonia. Therefore, physicians should comprehensively evaluate high-risk patients for PCP prophylaxis.

Tracing knowledge evolution flows in scholarly restaurant research: a main path analysis.

Restaurant research has received significant attention globally. This article aims to examine the evolution and the knowledge structure of restaurant research over the past decades. We also investigate the restaurant research hotspots and knowledge diffusion paths based on 1489 articles extracted from the Web of Science database. Furthermore, we conduct a keyword co-occurrence network analysis and four different types of main path analyses to scrutinize the historical formation of the restaurant research. Results revealed that restaurant research mainly focused on five research themes: consumer behavior, consumer satisfaction, social media, green restaurants, and authenticity. While consumer behavior has been the mainstream topic, the focus of this line of research has recently shifted from traditional to luxury and ethnic restaurants. Furthermore, our analysis has detected several recent changes in response to the COVID-19 pandemic. By examining the knowledge structure of restaurant research, we reveal its knowledge diffusion paths and provide avenues for future research in this vast and interdisciplinary research field.

Immunophenotyping characteristics of COVID-19 patients: Peripheral blood CD8+ HLA-DR+ T cells as a biomarker for mortality outcome.

INTRODUCTION: The goal of this study was to identify biomarker(s) to assign risk of mortality in COVID-19 patients to improve intensive care unit (ICU) and coronary care unit  management. A total of 100 confirmed COVID-19 patients admitted at Imam Khomeini Hospital in Tehran, were compared to 70 control subjects. Peripheral blood leukocyte was studied using staining reagents included CD3, CD4, CD8, HLA-DR, CD19, CD16, and CD56. The immunophenotyping analysis was evaluated using the FACSCalibur instrument. To investigate the cell density of lung infiltrating T cells, postmortem slides of needle necropsies taken from the lung tissue of 3 critical patients were evaluated by immunohistochemistry staining. The number of lymphocyte subpopulations was significantly lower in COVID-19 patients than in the control group. Regarding the disease severity, the absolute count of T, NK, and HLA-DR+ T cells were significantly reduced in severe patients compared to the moderate ones. The critical patients had a significantly lower count of CD8-HLA-DR+ T cells than the moderate cases. Regarding the disease mortality, based on univariate analysis, the count of HLA-DR+ T, CD8- HLA-DR+ T, and CD8+ HLA-DR+ T cells was associated with mortality in COVID-19 patients. Receiver operating characteristic curve analysis showed the count of CD8+ HLA-DR+ T cells is the best candidate as a biomarker for mortality outcome. Furthermore, pulmonary infiltration of T cells in the lung tissue showed only slight infiltrations of CD3+ T cells, with an equal percentage of CD4+ and CD8+ T cell subpopulation in the lung tissue. These findings suggest that close monitoring of the value of CD8+ HLA-DR+ T cells in COVID-19 patients may be helpful to identify high-risk patients. However, further studies with larger sample size are needed.