Common Comorbidities in Patients with Remitting Seronegative and Symmetrical Synovitis with Pitting Edema (RS3PE).

OBJECTIVES: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is considered a rare inflammatory rheumatologic disorder that is seen primarily in older adult men. Patients present with arthralgias of large joints accompanied by painful pitting edema of the hands and feet. Few studies have reported the prevalence of metabolic syndromes, including diabetes mellitus and hyperlipidemia in these patients. METHODS: This case series reviewed 25 patients who were diagnosed as having RS3PE in a private outpatient clinic. RESULTS: Nearly half of the patients (48%) had diabetes mellitus, predominantly type 2, and more than half of the patients (60%) had hyperlipidemia. CONCLUSIONS: We believe that future case studies on RS3PE should include an assessment of various comorbidities that can be seen in patients with this autoinflammatory disorder. The increased availability of musculoskeletal ultrasound provides a potential area of study to differentiate this disorder from other inflammatory arthritis and improve reaching the correct diagnosis.

Autologous neutralizing antibodies increase with early antiretroviral therapy and shape HIV rebound after treatment interruption.

Early initiation of antiretroviral therapy (ART) alters viral rebound kinetics after analytic treatment interruption (ATI) and may play a role in promoting HIV-1 remission. Autologous neutralizing antibodies (aNAbs) represent a key adaptive immune response in people living with HIV-1. We aimed to investigate the role of aNAbs in shaping post-ATI HIV-1 rebound variants. We performed single-genome amplification of HIV-1 env from pre-ART and post-ATI plasma samples of 12 individuals who initiated ART early after infection. aNAb activity was quantified using pseudoviruses derived from the most common plasma variant, and the serum dilution that inhibited 50% of viral infections was determined. aNAb responses matured while participants were on suppressive ART, because on-ART plasma and purified immunoglobulin G (IgG) demonstrated improved neutralizing activity against pre-ART HIV-1 strains when compared with pre-ART plasma or purified IgG. Post-ATI aNAb responses exerted selective pressure on the rebounding viruses, because the post-ATI HIV-1 strains were more resistant to post-ATI plasma neutralization compared with the pre-ART virus. Several pre-ATI features distinguished post-treatment controllers from noncontrollers, including an infecting HIV-1 sequence that was more similar to consensus HIV-1 subtype B, more restricted proviral diversity, and a stronger aNAb response. Post-treatment control was also associated with the evolution of distinct N-glycosylation profiles in the HIV-1 envelope. In summary, aNAb responses appeared to mature after early initiation of ART and applied selective pressure on rebounding viruses. The combination of aNAb activity with select HIV-1 sequence and reservoir features identified individuals with a greater chance of post-treatment control.

Genome-wide association analysis of COVID-19 mortality risk in SARS-CoV-2 genomes identifies mutation in the SARS-CoV-2 spike protein that colocalizes with P.1 of the Brazilian strain.

SARS-CoV-2 mortality has been extensively studied in relation to host susceptibility. How sequence variations in the SARS-CoV-2 genome affect pathogenicity is poorly understood. Starting in October 2020, using the methodology of genome-wide association studies (GWAS), we looked at the association between whole-genome sequencing (WGS) data of the virus and COVID-19 mortality as a potential method of early identification of highly pathogenic strains to target for containment. Although continuously updating our analysis, in December 2020, we analyzed 7548 single-stranded SARS-CoV-2 genomes of COVID-19 patients in the GISAID database and associated variants with mortality using a logistic regression. In total, evaluating 29,891 sequenced loci of the viral genome for association with patient/host mortality, two loci, at 12,053 and 25,088 bp, achieved genome-wide significance (p values of 4.09e-09 and 4.41e-23, respectively), though only 25,088 bp remained significant in follow-up analyses. Our association findings were exclusively driven by the samples that were submitted from Brazil (p value of 4.90e-13 for 25,088 bp). The mutation frequency of 25,088 bp in the Brazilian samples on GISAID has rapidly increased from about 0.4 in October/December 2020 to 0.77 in March 2021. Although GWAS methodology is suitable for samples in which mutation frequencies varies between geographical regions, it cannot account for mutation frequencies that change rapidly overtime, rendering a GWAS follow-up analysis of the GISAID samples that have been submitted after December 2020 as invalid. The locus at 25,088 bp is located in the P.1 strain, which later (April 2021) became one of the distinguishing loci (precisely, substitution V1176F) of the Brazilian strain as defined by the Centers for Disease Control. Specifically, the mutations at 25,088 bp occur in the S2 subunit of the SARS-CoV-2 spike protein, which plays a key role in viral entry of target host cells. Since the mutations alter amino acid coding sequences, they potentially imposing structural changes that could enhance viral infectivity and symptom severity. Our analysis suggests that GWAS methodology can provide suitable analysis tools for the real-time detection of new more transmissible and pathogenic viral strains in databases such as GISAID, though new approaches are needed to accommodate rapidly changing mutation frequencies over time, in the presence of simultaneously changing case/control ratios. Improvements of the associated metadata/patient information in terms of quality and availability will also be important to fully utilize the potential of GWAS methodology in this field.

SARS-CoV-2 detection in different respiratory sites: A systematic review and meta-analysis.

BACKGROUND: The accurate detection of SARS-CoV-2 through respiratory sampling is critical for the prevention of further transmission and the timely initiation of treatment for COVID-19. There is a diverse range of SARS-CoV-2 detection rates in reported studies, with uncertainty as to the optimal sampling strategy for COVID-19 diagnosis and monitoring. METHODS: We performed a systematic review and meta-analysis of studies comparing respiratory sampling strategies for the detection of SARS-CoV-2 RNA. The inclusion criteria were studies that assessed at least two respiratory sampling sites (oropharyngeal swab, nasopharyngeal swab, and sputum) in participants with COVID-19. The percentage positive tests were compared between sampling modalities by constructing a Z-test assuming independence and using the standard errors obtained from the random effects meta-analysis. FINDINGS: From 1039 total studies, we identified 11 studies that met our inclusion criteria, with SARS-CoV-2 testing results from a total of 3442 respiratory tract specimens. Compared to nasopharyngeal swab sampling, sputum testing resulted in significantly higher rates of SARS-CoV-2 RNA detection while oropharyngeal swab testing had lower rates of viral RNA detection. Earlier sampling after symptom onset was associated with improved detection rates, but the differences in SARS-CoV-2 RNA detection by sampling method was consistent regardless of the duration of symptoms. INTERPRETATION: The results support sputum sampling as a valuable method of COVID-19 diagnosis and monitoring, and highlight the importance of early testing after symptom onset to increase the rates of COVID-19 diagnosis. FUNDING: This study was funded in part by the NIH grants U01AI106701 and by the Harvard University for AIDS Research (NIAID 5P30AI060354).

SARS-CoV-2 Detection in Different Respiratory Sites: A Systematic Review and Meta-Analysis.

BACKGROUND: The accurate detection of SARS-CoV-2 through respiratory sampling is critical for the prevention of further transmission and the timely initiation of treatment for COVID-19. There is a diverse range of SARS-CoV-2 detection rates in reported studies, with uncertainty as to the optimal sampling strategy for COVID-19 diagnosis and monitoring. METHODS: We performed a systematic review and meta-analysis of studies comparing respiratory sampling strategies for the detection of SARS-CoV-2 RNA. The inclusion criteria were studies that assessed at least two respiratory sampling sites (oropharyngeal swab, nasopharyngeal swab, and sputum) in participants with COVID-19. The percentage positive tests were compared between sampling modalities by constructing a Z-test assuming independence and using the standard errors obtained from the random effects meta-analysis. FINDINGS: From 1039 total studies, we identified 11 studies that met our inclusion criteria, with SARS-CoV-2 testing results from a total of 3442 respiratory tract specimens. Compared to nasopharyngeal swab sampling, sputum testing resulted in significantly higher rates of SARS-CoV-2 RNA detection while oropharyngeal swab testing had lower rates of viral RNA detection. Earlier sampling after symptom onset was associated with improved detection rates, but the differences in SARS-CoV-2 RNA detection by sampling method was consistent regardless of the duration of symptoms. INTERPRETATION: The results support sputum sampling as a primary method of COVID-19 diagnosis and monitoring, and highlight the importance of early testing after symptom onset to increase the rates of COVID-19 diagnosis.

Learning From the Exceptions: HIV Remission in Post-treatment Controllers.

Among the top priorities of the HIV field is the search for therapeutic interventions that can lead to sustained antiretroviral therapy (ART)-free HIV remission. Although the majority of HIV-infected persons will experience rapid viral rebound after ART interruption, there are rare individuals, termed post-treatment controllers (PTCs), who demonstrate sustained virologic suppression for months or years after treatment cessation. These individuals are considered an ideal example of durable HIV control, with direct implications for HIV cure research. However, understanding of the mechanisms behind the capacity of PTCs to control HIV remains incomplete. This is in part due to the scarcity of PTCs identified through any one research center or clinical trial, and in part because of the limited scope of studies that have been performed in these remarkable individuals. In this review, we summarize the results of both clinical and basic research studies of PTCs to date, explore key differences between PTCs and HIV spontaneous controllers, examine potential mechanisms of post-treatment control, and discuss unanswered questions and future research directions in this field.

Epidemiology of Severe Cutaneous Adverse Drug Reaction and Its HLA Association among Pediatrics.

Severe cutaneous adverse drug reaction (SCAR) is considered to be a multifactorial drug side effect. This study was designed to investigate the epidemiology and human leukocyte antigen (HLA)-A and -B gene polymorphisms in pediatric patients with SCAR admitted in tertiary referral center, southwestern of Iran from 2013 to 2017. Demographic data, past allergy and autoimmune history, clinical presentations, drugs confirmed to be the cause of SCAR as well as its therapy were reviewed for each patient. HLA-A and -B allele frequencies were determined in 40 of the patients using polymerase chain reaction based on sequence specific primers (PCR-SSP) and compared with 40 healthy individuals as control group. Sixty-one patients with mean age of 6 years old and boy to girl ratio was 1.2/1 in this study. The most common type of SCAR in our patients was Steven Johnson Syndrome (SJS)/Toxic Epidermal Necrosis (TEN) mainly caused by beta-lactam antibiotics. Carbamazepine was the second cause of drug-induced SCAR. Moreover, HLA-A*02:01 and A*51:01 were related to the increased risk of SCAR while A*11:01 seemed to be protective against SCAR. HLA-A*02:01, HLA-A*24:02, and HLA-B*51:01 showed associations to the increased risk of SJS. Based on our results, beta-lactam antibiotics and antiepileptic drugs are the most common causes of severe adverse drug reaction in southwestern Iranian pediatric patients. Moreover, some HLA-A alleles can influence risk of SCAR.

Gauzoma in A Scleroderma Patient Following Open Heart Surgery: A Case Report.

INTRODUCTION: Gauzoma is an iatrogenic complication which occurs rarely due to surgical team negligence. Depending on the sterility of the retained tissue, it can lead to life threatening surgical complications or may remain asymptomatic for many years and be detected incidentally in imaging studies. It may be mistaken as tumors or aneurysms. Thus, high clinical suspicion is needed to diagnose them in patients with past history of operation. Reporting Case: A 35 years old woman, a known case of scleroderma underwent open-heart surgery 20 years before being diagnosed as scleroderma, presented by dyspnea especially on activity. The High Resolution CT (HRCT) for evaluating the interestial lung disease was done which detected a 7 cm (in greatest diameter) inflammatory mass in posterior aspect of left hemi thorax with a radiopaque thread in its center. True cut biopsy was done and sent for pathology, which revealed fragments of foreign body materials probably gauze pad fibers with cell debris and blood. CONCLUSION: Here, we highlighted the details in clinical history, CT findings, and pathology report of gauzoma in thorax of a scleroderma patient following previous open-heart surgery. It can be guidance for clinician to consider this diagnosis in patients with past history of operation.

Severe Allergic Bronchopulmonary Mycosis and Long-Term Follow-Up.

Allergic bronchopulmonary aspergillosis (ABPA) is the most common immunologic reaction following fungal allergen exposure in asthmatic patients. A less frequent syndrome in response to other fungal species like candida is allergic bronchopulmonary mycosis (ABPM). This reaction is mostly associated with asthma exacerbation, changes in Immunoglobulin E levels, and nonspecific findings in high resolution computed tomography (HRCT). This study presents a 9-year-old girl, a known case of childhood asthma, resolved 4 years ago as a novel case of ABPM due to Candida albicans manifested by severe emphysema, bronchiectasis, and pneumothorax which consequently required long-term treatment to get relieved.

The effect of baked milk on accelerating unheated cow's milk tolerance: A control randomized clinical trial.

BACKGROUND: Assessing the effect of adding baked milk products to the diet of patients with cow's milk allergy on accelerating the formation of tolerance. METHOD: A randomized clinical trial was carried out with 84 patients (6 months-3 years old) diagnosed with allergy to cow's milk who tolerated baked milk in form of muffin in oral food challenge (OFC). The subjects were divided randomly into case and control groups matched for age and sex. Patients in the case group were asked to consume baked milk in the form of muffin for 6 months and then to consume baked cheese in the form of pizza for another 6 months. The control group were instructed to strictly avoid any milk products for 1 year. Skin prick test (SPT) and serum-specific immunoglobulin E (sIgE) levels (ImmunoCAP) of milk, casein, and beta-lactoglobulin were measured before and after the study. In addition, those in the case group who had satisfactorily tolerated baked products during the study as well as all the subjects in the control group underwent an OFC to evaluate unheated milk tolerance at the end of the study. RESULTS: It was shown that by the end of the 1-year study period, 88.1% (37/42) of the patients in the case group and 66.7% (28/42) of those in control group had developed tolerance to unheated milk (P-value: 0.018). The results of milk-specific SPT and sIgE levels showed a significant decrease in the case group. Initial sIgE levels could not predict unheated milk tolerance in case and control groups. CONCLUSION: Introducing baked milk products into the diet of patients with milk allergy can accelerate the tolerance of unheated milk in these patients. sIgE levels of milk, casein, and beta-lactoglobulin did not predict the tolerance of unheated milk.

Salicylate Food Intolerance and Aspirin Hypersensitivity in Nasal Polyposis.

BACKGROUND: A clear association between allergy and nasal polyposis (NP) is not determined and the role of food intolerance in patients with NP is not investigated by oral food challenge (OFC). OBJECTIVE: To investigate the relation of salicylate food intolerance and atopy in patients with NP according to recurrence and aspirin sensitivity. METHODS: A cross sectional multicenter study was done in two tertiary centers for allergy in Iran. Adult patients with NP were selected for the study that had been referred to allergy clinics. The oral aspirin challenge (OAC) test was performed to identify aspirin exacerbated respiratory disease (AERD) and the OFC test was used to investigate food intolerance. Atopic evaluation was performed by skin-prick tests, nasal smear and blood eosinophil count as well as serum total IgE. RESULTS: One hundred and nineteen Iranian patients (female to male ratio 1.05) with NP were enrolled (mean age, 38 ± 11 years). Recurrence of nasal polyposis was 64.7%. OAC was performed in all cases; 43.79% cases had aspirin hypersensitivity. In addition, OFC tests determined that 69.9% of patients had salicylate food allergy. Salicylate food intolerance was significantly higher in NP cases with AERD than in aspirin tolerant patients (p<0.05). Yet, positive skin prick test was not associated with NP recurrence and AERD. CONCLUSION: Atopy and NSAID exacerbated respiratory disease; therefore, they can both be considered as predictors of NP recurrence. Our study also showed that salicylate food intolerance was associated with AERD in nasal polyposis.

One decade distinct features, morbidity and mortality of scleroderma: a cross-sectional study.

OBJECTIVES: Conducting an epidemiologic study on scleroderma patients referred to hospitals and tertiary centres of rheumatologic diseases in Shiraz, located in south of Iran. METHODS: A cross-sectional study was done on patients' records registered in scleroderma outpatient clinics as well as hospitals associated with Shiraz University of Medical Sciences. Gathering data in pre-formed data sheets, descriptive analysis plus qualitative comparisons by chi-square test were done using SPSS 15. RESULTS: In 533 medical records, female to male ratio was 7.3:1. The disease is mostly seen in 3rd and 4th decades of life. More patients had negative family histories (56.1%). 37.5% of the patients had diffuse form of the disease, 36.8% had limited one, and 17.3% had overlap syndrome, mostly, by lupus erythematosus (33%). Most common first presentation was Raynaud phenomenon (40.7%). Two most prevalent clinical manifestations were skin thickening (97.2%) and gastrointestinal involvement (68.9%). Clinical presentations were compared between three most common types of the disease plus various stages of life. Among recorded capillaroscopies, active form was the most prevalent one (38.3%). In documented serologic markers, the most common positive one was anti-nuclear antibody (ANA) (75.6%). Two most common etiologies of hospitalisation were digital ulcer (30.9%) and pulmonary fibrosis (5.7%). The most common cause of death (17) was pulmonary fibrosis (35.2%). CONCLUSION: This study is the first epidemiologic survey on Iranian scleroderma patients with significantly large sample size compared to previous studies worldwide. It can thus provide some guidance for further multi-provincial, multinational and interracial studies on scleroderma.

Protective Effects of Co-Enzyme Q10 on Thioacetamide-Induced Acute Liver Damage and Its Correlation With Behavioral, Biochemical, and Pathological Factors.

BACKGROUND: Acute liver damage may be followed by biochemical, behavioral, and pathological alterations, which can result in serious complications and even death. OBJECTIVES: In this experimental study we determined whether coenzyme Q10 (CoQ10), a common supplementary medicine known to have protective, antioxidative, and anti-inflammatory effects in cells, has any protective effect against thioacetamide (TAA)-induced liver damage and its related neurobehavioral alterations in rats. MATERIALS AND METHODS: In this experimental study forty-eight Wistar rats were divided randomly into four groups (n = 12): C1 was the control group; C2 received a single-dose of TAA (350mg/kg; intraperitoneally) without any other treatment; E1 received TAA + 5 mg/kg CoQ10 (intraperitoneally); and E2 received TAA + 10 mg/kg CoQ10. After sacrificing the rats, liver enzymes and plasma-ammonia (NH4) were measured and histopathological analyses of the livers were carried out. Elevated-plus-maze, open-field, and forced-swimming tests were also performed to investigate behavioral correlations. RESULTS: The serum levels of alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), and NH4 show significant increases (P < 0.05). The groups treated with CoQ10 were shown to have significantly lower clinical grade of encephalopathy (P = 0.001), higher locomotor activity (P = 0.000), and lower levels of depression (P = 0.000). Furthermore, it was also shown that CoQ10 treatment may lead to significant decreases in scores of centrilobular necrosis, apoptosis, inflammatory cell infiltration, vacuolization, and liver necrosis (P < 0.05). CONCLUSIONS: Overall, CoQ10 was determined to have positive effects on liver injury and its related behavioral and biochemical changes.