Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29 ± 13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P < .001]), rituximab use (HR = 21.2, P = .05), and diabetic ketoacidosis (HR = 3.58, P = .009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR = 8.81, P < .001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments, and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

Delayed Diagnosis of Chronic Necrotizing Granulomatous Skin Lesions due to TAP2 Deficiency.

Major histocompatibility complex class I (MHC-I) deficiency, also known as bare lymphocyte syndrome type 1 (BLS-1), is a rare autosomal recessively inherited immunodeficiency disorder with remarkable clinical and biological heterogeneity. Transporter associated with antigen processing (TAP) is a member of the ATP-binding cassette superfamily of transporters and consists of two subunits, TAP1 or TAP2. Any defect resulting from a mutation or deletion of these two subunits may adversely affect the peptide translocation in the endoplasmic reticulum, which is an important process for properly assembling MHC-I molecules. To date, only 12 TAP2-deficient patients were reported in the literature. Herein, we described two Iranian cases with 2 and 3 decades of delayed diagnosis of chronic necrotizing granulomatous skin lesions due to TAP2 deficiency without pulmonary involvement. Segregation analysis in family members identified 3 additional homozygous asymptomatic carriers. In both asymptomatic and symptomatic carriers, HLA-I expression was only 4-15% of the one observed in healthy controls. We performed the first deep immunophenotyping in TAP2-deficient patients. While total CD8 T cell counts were normal as previously reported, the patients showed strongly impaired naïve CD8 T cell counts. Mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cell counts were increased.

Clinicopathological profile of peritoneal tuberculosis and a new scoring model for predicting mortality: an international ID-IRI study.

Existing literature about peritoneal tuberculosis (TBP) is relatively insufficient. The majority of reports are from a single center and do not assess predictive factors for mortality. In this international study, we investigated the clinicopathological characteristics of a large series of patients with TBP and determined the key features associated with mortality. TBP patients detected between 2010 and 2022 in 38 medical centers in 13 countries were included in this retrospective cohort. Participating physicians filled out an online questionnaire to report study data. In this study, 208 patients with TBP were included. Mean age of TBP cases was 41.4 ± 17.5 years. One hundred six patients (50.9%) were females. Nineteen patients (9.1%) had HIV infection, 45 (21.6%) had diabetes mellitus, 30 (14.4%) had chronic renal failure, 12 (5.7%) had cirrhosis, 7 (3.3%) had malignancy, and 21 (10.1%) had a history of immunosuppressive medication use. A total of 34 (16.3%) patients died and death was attributable to TBP in all cases. A pioneer mortality predicting model was established and HIV positivity, cirrhosis, abdominal pain, weakness, nausea and vomiting, ascites, isolation of Mycobacterium tuberculosis in peritoneal biopsy samples, TB relapse, advanced age, high serum creatinine and ALT levels, and decreased duration of isoniazid use were significantly related with mortality (p < 0.05). This is the first international study on TBP and is the largest case series to date. We suggest that using the mortality predicting model will allow early identification of high-risk patients likely to die of TBP.

Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Evaluation of the epidemiologic, clinical, radiologic, and treatment methods of patients with subacute and chronic meningitis.

BACKGROUND: Meningitis is known as a meningeal inflammation accompanied by pleocytosis in the cerebrospinal fluid (CSF), and can be classified into acute, subacute, and chronic meningitis based on symptoms duration of ≤ 5 days, ≥ 5 days and ≥ 4 weeks, respectively. Subacute and chronic meningitis are caused mainly by indolent infectious agents and noninfectious causes such as autoimmune, and neoplastic. In this study, we investigated the characteristics, diagnosis, and treatment of subacute and chronic meningitis. METHODS: We extracted the medical records of patients with chronic and subacute meningitis who were referred to three tertiary centers from Jun 2011 to Jun 2021. Initially, 2050 cases of meningitis were screened, and then 79 patients were included in the study. RESULTS: Headache (87.3%), nausea and vomiting (74.7%), fever (56.4%), and visual impairments (55.7%) were the most prevalent symptoms. The most common signs were nuchal rigidity (45.3%), altered mental status (26.9%), and papillary edema (37.5%). Brain computed tomography (CT) was normal in 68.6% of the patients while 22.9% of the cases had hydrocephalus. Brain magnetic resonance imaging (MRI) was normal in 60.0% of the patients. The most common abnormal MRI findings were leptomeningeal enhancement (16.0%) and hydrocephalus (16.0%). We had a 44.3% definite diagnosis with bacterial (n:25, 31.6%) and neoplastic (n:8, 10.1%) being the most prevalent etiologies. Mycobacterium tuberculosis (60%) and Brucella spp. (12%) were the most prevalent bacterial pathogens. CONCLUSIONS: The most common etiologies include infectious, neoplastic, and immunologic. Due to insidious presentation and uncommon etiologies, establishing a proper diagnosis, and providing timely targeted treatment for patients with subacute and chronic meningitis remains a challenge for clinicians.

Investigation of pharmacokinetic and clinical outcomes of various meropenem regimens in patients with ventilator-associated pneumonia and augmented renal clearance.

INTRODUCTION: Augmented renal clearance (ARC) defined as creatinine clearance (Clcr) above 130 mL/min/1.73m2 may lead to suboptimal antibacterial treatment. The aim of this study was to determine a strategy for meropenem administration to achieve both pharmacodynamic-pharmacokinetic (PK-PD) target (50%fT > MIC) and better clinical outcomes in patients with VAP and ARC. MATERIALS AND METHODS: In this randomized clinical trial, patients with VAP and high risk for ARC were recruited. An 8-h urine collection was performed on the 1st, 3rd, and 5th days of study to measure Clcr. Included patients were divided into three groups: (1) 1 g meropenem, 3-h infusion, (2) 2 g meropenem, 3-h infusion, (3) 1 g meropenem, 6-h infusion. On the 2nd, 3rd, and 5th days of treatment, peak and trough blood samples were collected to undergo HPLC assay. MICs were assessed using microdilution method. Patients were also clinically monitored for 14 days. RESULTS: Forty-five patients were included. Group 3 showed significanty higher rate of patients achieving fT > MIC > 50% (100% for group 3 versus 40% for group 2 and 13% for group 1; p = 0.0001). Mean fT > MIC% was significantly higher in group 3 (78.77 ± 5.87 for group 3 versus 49.6 ± 7.38 for group 2 and 43.2 ± 7.98 for group 1; p = 0.0001). Statistical analysis showed no significant differences among groups regarding clinical improvement. CONCLUSION: According to the findings of this trial, prolonged meropenem infusion is an appropriate strategy compared to dose elevation among ARC patients.

Benefit of Hemoadsorption Therapy in Patients Suffering Sepsis-Associated Acute Kidney Injury: A Case Series.

INTRODUCTION: Sepsis is defined as life-threatening organ dysfunction in result of the host's dysregulated response to infection and septic shock. Sepsis-associated kidney injury is usually defined as concurrent presence of acute kidney injury (AKI) and sepsis without other significant causative factors. METHOD: The current retrospective study was conducted to elucidate beneficial and side effects of CytoSorb®. A total of 17 patients were primarily treated with continuous renal replacement therapy in combination with CytoSorb. The demand for norepinephrine, mean arterial pressure, lactate, and procalcitonin (PCT) levels, as well as ICU length of stay, was measured. RESULT: The blood lactate levels decreased by 32.30% when comparing mean levels before and after treatment. All patients who survived (n = 14) had reduction in vasopressor demand to 68.96% of their initial dose before the start of treatment. Hospital survival was greater in patients who initially had higher vasopressor demand compared to their nonsurviving counterparts, but in whom vasopressor dosages were reduced significantly during their treatments. Mortality as predicted by APACHE II score in the overall patient population was 79.9%, whereas, the observed ICU mortality was 31%. The baseline PCT levels on patients received 1, 2, and 3 CytoSorbs were 27.08 ± 5.81 ng/mL, 13.28 ± 2.62 ng/mL, and 21.03 ± 6.56 ng/mL, respectively. Observed PCT levels at 24 h after the last treatment on patients received 1, 2, and 3 CytoSorb were 31.55 ± 15.70 ng/mL, 5.61 ± 1.77 ng/mL, and 8.11 ± 3.62 ng/mL, respectively. CONCLUSION: In conclusion, it seems that applying the CytoSorb in combination with CRRT in ICU septic patients with AKI, is related to a significant decrease in mortality, if the integrity and continuity of the treatment be kept, as much as possible. This study presented an effectively positive outcome with cytokine adsorber treatment as an adjuvant along with standard treatment in a high-risk mortality case of septic shock with organ failure.

Association between serum inflammatory parameters and the disease severity in COVID-19 patients.

OBJECTIVE: Most patients infected with the novel coronavirus (SARS-CoV-2), as the causative agent of COVID-19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID-19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity. METHODS: In this prospective cross-sectional study, 50 patients with COVID-19 and 20 patients without COVID-19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non-severe and severe. Differences in the serum levels of C-reactive protein (CRP), IL-6, and TNF-α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed. RESULTS: Out of the 50 patients with COVID-19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID-19 patients in terms of gender and age. Blood tests of COVID-19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL-6, TNF-α, and CRP between the severe and non-severe groups, which were higher in the severe group. Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL-6 (r = 0.74), LYM with NEU (r = -0.97), and ESR with TNF-α (r = 0.7). CONCLUSION: The findings of this study, as the first study in Iran, suggest that the levels of IL-6, TNF-α, ESR, and CRP could be used to predict the severity of COVID-19 disease.

Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19.

As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study.

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. RESULTS: We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up. CONCLUSION: Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.

Detection of Enterovirus, Herpes Simplex, Varicella Zoster, Epstein-Barr and Cytomegalovirus in cerebrospinal fluid in meningitis patients in Iran.

BACKGROUND: Despite medical advances, central nervous system (CNS) diseases put a pressure on the health care system. A number of risk factors, especially infectious agents can accelerate the progression of meningitis. As viruses probably account for most cases of meningitis, the diagnosis of them can reduce antibiotic prescriptions. Among various types of infectious diseases, the relationship between two important virus families, including Picornaviridae and Herpesviridae, and meningitis has attracted attraction. METHODS: In this study, one hundred and two samples were collected from patients who experienced symptoms, such as the loss of consciousness, seizures, muscle weakness, fever, headache, rash, and severe dementia, between November 2018 and September 2019. After RNA and DNA extraction, the prevalence of Enterovirus (EV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), and Varicella zoster virus (VZV) was evaluated using PCR, multiplex PCR, and nested PCR. RESULTS: Results indicated that there were two VZV DNA-positive specimens, while six and five samples were infected with HSV-1 and EBV, respectively. CONCLUSION: We reported that the prevalence of EBV, HSV-1, and VZV in patients, suffering from meningitis cannot be ignored; however, further investigation is needed.

Community-acquired methicillin-resistant Staphylococcus aureus carriage rate and antimicrobial susceptibility in a tertiary center, Iran.

BACKGROUND: This study was aimed to determine frequency and antimicrobial susceptibility of Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) among colonized patients in outpatient status. MATERIALS AND METHODS: A total of 2000 nasal nares specimens were collected and inoculated on mannitol salt agar. MRSAs were identified based on mannitol positivity and coagulase test followed by cefoxitin disc diffusion test. Antimicrobial susceptibility of MRSA isolates was performed by E-test method for vancomycin and doxycycline as well as disc diffusion method for sulfamethoxazole-trimethoprim (SMX-TMP), erythromycin, linezolid, and clindamycin. D-test was performed for detection of inducible resistance to clindamycin. RESULTS: Overall, nasal carrier rate of S. aureus and CA-MRSA was estimated 22% and 1.25%, respectively. Out of the 440 S. aureus isolates, 25 isolates were MRSA. All were susceptible to vancomycin and linezolid, and susceptibility rates to SMX-TMP, erythromycin, levofloxacin, doxycycline, and clindamycin were 68%, 44%, 48%, 40% and 44%, respectively; furthermore, 28.5% of resistant isolates to erythromycin had inducible resistance to clindamycin. CONCLUSION: It seems susceptibility to clindamycin and SMX-TMP, recommended agents for empirical treatment of suspected CA-MRSA, are not promising. Vancomycin and linezolid are effective and reliable antibiotics for the treatment of S. aureus infections.

Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both.

BACKGROUND: Invasive infections of the central nervous system (CNS) or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningoencephalitis, colitis, or both caused by Candida species remain unexplained. OBJECTIVE: We studied 5 previously healthy children and adults with unexplained invasive disease of the CNS, digestive tract, or both caused by Candida species. The patients were aged 39, 7, 17, 37, and 26 years at the time of infection and were unrelated, but each was born to consanguineous parents of Turkish (2 patients), Iranian, Moroccan, or Pakistani origin. Meningoencephalitis was reported in 3 patients, meningoencephalitis associated with colitis was reported in a fourth patient, and the fifth patient had colitis only. METHODS: Inherited caspase recruitment domain family, member 9 (CARD9) deficiency was recently reported in otherwise healthy patients with other forms of severe disease caused by Candida, Trichophyton, Phialophora, and Exophiala species, including meningoencephalitis but not colitis caused by Candida and Exophiala species. Therefore we sequenced CARD9 in the 5 patients. RESULTS: All patients were found to be homozygous for rare and deleterious mutant CARD9 alleles: R70W and Q289* for the 3 patients with Candida albicans-induced meningoencephalitis, R35Q for the patient with meningoencephalitis and colitis caused by Candida glabrata, and Q295* for the patient with Candida albicans-induced colitis. Regardless of their levels of mutant CARD9 protein, the patients' monocyte-derived dendritic cells responded poorly to CARD9-dependent fungal agonists (curdlan, heat-killed C albicans, Saccharomyces cerevisiae, and Exophiala dermatitidis). CONCLUSION: Invasive infections of the CNS or digestive tract caused by Candida species in previously healthy children and even adults might be caused by inherited CARD9 deficiency.

An 11-month-old boy with tuberculous meningitis presenting as progressive limb weakness, fever, developmental retardation, and loss of consciousness: a case report.

BACKGROUND: Tuberculous meningitis (TBM) accounts for about 1% of all tuberculosis cases and about 5% of extrapulmonary tuberculosis cases. However, it poses major importance because approximately half of those affected die or become severely disabled. Herein, the successful treatment of an 11-month-old boy with progressive limb weakness, fever, developmental retardation, and loss of consciousness due to tuberculosis, was reported. CASE PRESENTATION: An 11-month-old (Iranian Turk) boy was referred to Loghman Hakim hospital for progressive limb weakness and loss of previously attained developmental milestones for the past 2 months. He also had persistent fever and loss of consciousness for about 14 to 21 days. Before being referred to our center, the patient had been diagnosed with hydrocephalus at another center due to possible acute bacterial meningitis based on a CT scan and MRI imaging. On physical examination, anterior fontanel bulging and neck stiffness were observed on the admission. His body temperature and heart rate were 38.1 C and 86 beats per minute (bpm), respectively. He had left 6 cranial nerve palsy and spastic quadriparesis with a power of grade 3/5. Other systemic examinations were normal. Endoscopic third ventriculostomy (ETV) (and leptomeningeal biopsy) revealed diffuse thickening of the floor and lateral walls of the 3rd ventricle and also a cobblestone appearance in the form of multiple white patchy lesions was detected on the floor of the 3rd ventricle. CSF analysis and polymerase chain reaction confirmed the TB meningitis. During hospitalization, a temporary EVD (external ventricular drain) was initially inserted. Eventually, defervescence was denoted 5-6 days after initiation of anti-TB medications, and a permanent ventriculoperitoneal shunt was inserted due to hydrocephalus. Gradually his truncal and limb tone and motor function improved, as did his emotional responses to his parents and ability to eat. The patient can walk without help in the 15th month following the operation and resolved hydrocephalus demonstrated on follow-up imaging. CONCLUSION: Over half of treated TB meningitis patients die or suffer severe neurological sequelae, mainly due to late diagnosis. Hence, early diagnosis and prompt initiation of TB treatment offer the best chance of a good neurological outcome.

The Frequency of AmpC Overproduction, OprD Downregulation and OprM Efflux Pump Expression in Pseudomonas aeruginosa: A Comprehensive Meta-Analysis.

BACKGROUND: Pseudomonas aeruginosa is a major opportunistic pathogen responsible for a wide range of infections. The emergence of antibiotic resistance in this pathogen poses a significant public health challenge. This study aims to conduct a comprehensive meta-analysis of studies conducted in Iran to determine the frequency of key antibiotic resistance mechanisms in Pseudomonas aeruginosa and their association with multidrug-resistant and extensively drug-resistant strains or pandrug-resistant strains. METHODS: Systematic database searches encompassing literature up to June 2023 were undertaken. The selected studies centered on OprD downregulation, efflux pump (mexAB-OprM, mexXY-OprM) expression, and AmpC overproduction. Extracted data were synthesized in a meta-analysis for pooled frequency determination of each resistance mechanism. RESULTS: In total, 24 studies were included. OprD downregulation exhibited a pooled frequency of 61%. Efflux pump component frequency ranged from 48% to 77.5%. AmpC overproduction was identified in 29.1% of isolates. Polymyxin B and colistin demonstrated lower antibiotic resistance rates, with pooled frequency of 1% and 1.6%, respectively. Conversely, resistance to other antibiotics ranged widely, with pooled frequency spanning 38.4% to 98.2%. CONCLUSION: This study underscores the concerning frequency of diverse antibiotic resistance mechanisms in Pseudomonas aeruginosa strains from Iran. Concurrent OprD downregulation, mexAB, mexXY, OprM expression, and AmpC overproduction highlight the urgent need for stringent infection control and prudent antibiotic usage to curb the dissemination of these resistant strains. PROSPERO: CRD42022379311.

Profiles of primary brain abscesses and their impact on survival: An international ID-IRI study.

OBJECTIVES: This study of 331 primary brain abscess (PBA) patients aimed to understand infecting agents, predisposing factors, and outcomes, with a focus on factors affecting mortality. METHODS: Data were collected from 39 centers across 16 countries between January 2010 and December 2022, and clinical, radiological, and microbiological findings, along with their impact on mortality, were analyzed. RESULTS: The patients had a mean ± SD age of 46.8 ± 16.3 years, with a male predominance of 71.6%. Common symptoms included headache (77.9%), fever (54.4%), and focal neurological deficits (53.5%). Gram-positive cocci were the predominant pathogens, with Viridans group streptococci identified as the most frequently isolated organisms. All patients received antimicrobial therapy and 71.6% underwent interventional therapies. The 42-day and 180-day survival rates were 91.9% and 86.1%, respectively. Significant predictors of 42-day mortality included intravenous drug addiction (HR: 6.02, 95% CI: 1.38-26.26), malignancy (HR: 3.61, 95% CI: 1.23-10.58), confusion (HR: 2.65, 95% CI: 1.19-5.88), and unidentified bacteria (HR: 4.68, 95% CI: 1.76-12.43). Significant predictors of 180-day mortality included malignancy (HR: 2.70, 95% CI: 1.07-6.81), confusion (HR: 2.14, 95% CI: 1.11-4.15), temporal lobe involvement (HR: 2.10, 95% CI: 1.08-4.08), and unidentified bacteria (HR: 3.02, 95% CI: 1.49-6.15). CONCLUSION: The risk of death in PBA extends beyond the infection phase, with different factors influencing the 42-day and 180-day mortality rates. Intravenous drug addiction was associated with early mortality, while temporal lobe involvement was associated with late mortality.

The effect of donepezil hydrochloride on post-COVID memory impairment: A randomized controlled trial.

BACKGROUND: Post-Coronavirus Disease (COVID-19) condition, known as "post-COVID syndrome," is associated with a range of complications persisting even after recovery. Among these complications, cognitive dysfunction, including memory impairment, has been relatively common observed, impacting executive function and quality of life. To date, no approved treatment exists for this specific complication. Therefore, the present clinical trial aimed to investigate the impact of Donepezil Hydrochloride on post-COVID memory impairment. METHODS: A randomized, controlled trial (Approval ID: IRCT20210816052203N1) was conducted, enrolling 25 patients with post-COVID memory impairment. Participants with a history of hospitalization were randomly assigned to either the drug group (n = 10) or the control group (n = 15). Memory indices were assessed at baseline, one month, and three months later using the Wechsler Memory Scale-Revised test. SPSS software and appropriate statistical tests were employed for data analysis. RESULTS: The statistical analysis revealed no significant difference in WMS-R subtest and index scores between the drug and control groups at the 4-week and 12-week follow-up periods. However, within the drug group, there was a notable increase in the visual reproduction I and verbal paired associates II subtests during the specified time intervals. CONCLUSION: While donepezil 5 mg did not exhibit a significant overall increase in memory scales compared to the control group over time, our findings suggest that this medication may exert a positive effect on specific memory subtests. Further research and exploration are warranted to better understand the potential benefits of donepezil in managing post-COVID-related memory impairment. TRIAL REGISTRATION: The study was approved by the Research Ethics Committee of Aja University of Medical Sciences (Approval ID: IR.AJAUMS.REC.1400.125) and registered in the Iranian Registry of Clinical Trials (IRCT) (Approval ID: IRCT20210816052203N1).