Unleashing the potential of gene signatures as prognostic and predictive tools: A step closer to personalized medicine in hepatocellular carcinoma (HCC).

Hepatocellular carcinoma (HCC) is one of the growing malignancies globally, affecting a myriad of people and causing numerous cancer-related deaths. Despite therapeutic improvements in treatment strategies over the past decades, HCC still remains one of the leading causes of person-years of life lost. Numerous studies have been conducted to assess the characteristics of HCC with the aim of predicting its prognosis and responsiveness to treatment. However, the identified biomarkers have shown limited sensitivity, and the translation of these findings into clinical practice has faced challenges. The development of sequencing techniques has facilitated the exploration of a wide range of genes, leading to the emergence of gene signatures. Although several studies assessed differentially expressed genes in normal and HCC tissues to find the unique gene signature with prognostic value, to date, no study has reviewed the task, and to the best of our knowledge, this review represents the first comprehensive analysis of relevant studies in HCC. Most gene signatures focused on immune-related genes, while others investigated genes related to metabolism, autophagy, and apoptosis. Even though no identical gene signatures were found, NDRG1, SPP1, BIRC5, and NR0B1 were the most extensively studied genes with prognostic value. Finally, despite challenges such as the lack of consistent patterns in gene signatures, we believe that comprehensive analysis of pertinent gene signatures will bring us a step closer to personalized medicine in HCC, where treatment strategies can be tailored to individual patients based on their unique molecular profiles.

The impact of the COVID-19 pandemic on pediatric bloodstream infections and alteration in antimicrobial resistance phenotypes in Gram-positive bacteria, 2020-2022.

BACKGROUND: Alteration in the etiology of pediatric bloodstream infections (BSIs) and antimicrobial resistance (AMR) is not well known during the Coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the impact of the COVID-19 pandemic on pediatric BSIs and alteration in antimicrobial resistance phenotypes in Gram-positive bacteria. METHODS: The frequency of BSIs among children under 18 years old was retrospectively recorded in a tertiary children's hospital in Tehran, Iran from February 2020 to December 2022. The status of COVID-19 infection using reverse transcription polymerase chain reaction, bacteremia/fungemia according to BACTEC 9120 Culture System results, characterization of bacteria using biochemical tests, and antimicrobial susceptibility patterns for Gram-positive bacterial isolates using disk diffusion method were determined. Statistical analysis was done to measure the correlation of COVID-19 infection with BSIs and AMR. RESULTS: Out of 13,345 COVID-19 tests and 4,194 BACTEC blood culture requests, bacteremia/fungemia were confirmed in 10.37% (435/4,194) of the patients who requested both tests simultaneously. The COVID-19 infection was confirmed in 25.3% (110/435) of the patients with bacteremia/fungemia. The infection with characterized Gram-positive bacteria (GPB) and fungi was detected in 32.3% (140/433) and 8.31% (36/433) of the cases, respectively. Coagulase-negative Staphylococcus (CNS, 72, 16.62%), S. aureus (36, 8.3%), and Enterococcus spp. (22, 5%) were among the common isolates. Candida spp. and non-Candida yeasts were detected in 6.7% and 13.4% of the cases, respectively. A positive correlation was shown between the CNS bacteremia and COVID-19 infection (p-value = 0.019). Antibiotic susceptibility testing results showed the highest frequency of resistance to azithromycin among CNS, azithromycin and tetracycline among S. aureus and tetracycline among Enterococcus spp. Methicillin-resistance phenotype in the S. aureus (MRSA) and coagulase-negative Staphylococcus spp. (MR-CNS) was detected in 40% and 61.5% of the strains, respectively and the Enterococci were resistant to vancomycin in 33.3% of the isolates. CONCLUSION: A decline in the trend of BSIs by GPB and an increase in AMR was shown in children during the COVID-19 pandemic. Increasing antibiotic resistance is a concern; however, chloramphenicol, linezolid, and vancomycin remain active against common causes of GPB-BSIs.

Assessment of early and post COVID-19 vaccination antibody response in healthcare workers: a multicentre cross-sectional study on inactivated, mRNA and vector-based vaccines.

In this multicentre study, we compared the status of antibody production in healthcare personnel (HCP) before and after vaccination using different brands of COVID-19 vaccines between March 2021 and September 2021. Out of a total of 962 HCP enrolled in our study, the antibody against the S1 domain of SARS-CoV-2 was detected in 48.3%, 95.5% and 96.2% of them before, after the first and the second doses of the vaccines, respectively. Our results showed post-vaccination infection in 3.7% and 5.9% of the individuals after the first and second doses of vaccines, respectively. The infection was significantly lower in HCP who presented higher antibody titres before the vaccination. Although types of vaccines did not show a significant difference in the infection rate, a lower infection rate was recorded for AstraZeneca after the second vaccination course. This rate was equal among individuals receiving a second dose of Sinopharm and Sputnik. Vaccine-related side effects were more frequent among AstraZeneca recipients after the first dose and among Sputnik recipients after the second dose. In conclusion, our results showed diversity among different brands of COVID-19 vaccines; however, it seems that two doses of the vaccines could induce an antibody response in most of HCP. The induced immunity could persist for 3-5 months after the second vaccination course.

Intestinal colonization of vancomycin-resistant Enterococcus in children admitted to Mofid children's hospital intensive care unit at admission and at discharge.

BACKGROUND: This study aimed to investigate the frequency of intestinal colonization by vancomycin-resistant Enterococcus (VRE) carrying vanA and vanB genes in patients at ICU admission and at discharge from ICU in Mofid children's Hospital, Tehran, Iran. METHOD: Sampling was performed using rectal swabs and vancomycin susceptibility testing for Enterococcus spp. was carried out using a minimum inhibitory concentration (MIC) assay on Muller Hinton Agar (MHA) medium using an E-test kit. The molecular detection of VRE isolates was performed by the PCR method using the vanA and vanB resistance genes. RESULTS: A total of 234 and 186 non-duplicate rectal swab samples were collected from patients at ICU admission and at discharge from ICU, respectively. Enterococcus spp. was detected in 34.6% (n = 81/234) of rectal swab samples collected from patients at ICU admission, of which 44.4% (n = 36/81) were VRE isolates. In contrast, the prevalence of Enterococcus spp. and VRE isolates among patients at discharge from ICU was 17.7% (n = 33/186) and 57.6% (n = 19/33), respectively. Out of 19 VRE isolated from patients at ICU admission, 4 (21%) and 1 (5.3%) contained vanA and vanB genes, respectively. In contrast, out of 36 VRE isolated from patients at discharge from ICU, 11 (30.5%) were positive for the vanA gene. CONCLUSION: Results revealed that the prevalence of Enterococcus spp. among patients at ICU admission was high. However, VRE was frequently isolated from patients who were hospitalized for several days in ICUs. The implementation of proper infection control strategies and the use of suitable protocols to guide the appropriate prescribing of antibiotics are necessary.

JAGN1 mutation with distinct clinical features; two case reports and literature review.

Jagunal homolog 1 (JAGN1) has been recognized as an essential protein in neutrophil function. The mutated JAGN1 is responsible for immunodeficiency related to innate and humoral defense mechanisms. This deficiency impairs neutrophil development and function, leading to recurrent infections and facial dysmorphism as phenotypic consequences of severe congenital neutropenia (SCN). We report two siblings having the reported JAGN1 mutation with different clinical manifestations. Recurrent abscess formation unresponsive to antibiotic therapy, a history of delayed umbilical separation, frequent bacterial or fungal infection, dysmorphic face, failure to thrive, and other coexisting organ abnormalities should prompt physicians to syndromic immunodeficiencies involving neutrophils. Genetic investigations to elucidate the responsible mutation is critical as clinical management varies. Once the diagnosis is confirmed, a multi-disciplinary team should perform further workups to investigate other coexisting malformations and neurodevelopmental evaluation.

The intestinal carrier status of Enterococcus spp. in children: clonal diversity and alterations in resistance phenotypes before and after admission to a pediatric intensive care unit.

BACKGROUND: This study aimed to investigate the intestinal carrier status of Enterococcus spp. among children in a pediatric intensive care unit (PICU) and reveal the role of hospitalization in the alteration of resistance phenotypes and clonal diversity of the isolates during admission and discharge periods. METHODS: Two separate stool samples were collected from hospitalized patients in the pediatric intensive care unit at admission and discharge times. The culture was done, and Enterococcus species were tested for antimicrobial susceptibility and carriage of vanA-D gene subtypes. Random Amplified Polymorphic DNA (RAPD)-PCR was used for a phylogenetic study to check the homology of pairs of isolates. RESULTS: The results showed carriage of Enterococci at admission, discharge, and at both time points in 31%, 28.7%, and 40.1% of the cases, respectively. High frequencies of the fecal Enterococcus isolates with vancomycin-resistance (VR, 32.6% and 41.9%), high-level of gentamicin-resistance (HLGR, 25.6% and 27.9%), and multi-drug resistance phenotypes (MDR, 48.8% and 65.1%) were detected at admission and discharge times, respectively. Resistance to vancomycin, ampicillin, and rifampicin was higher among E. faecium, but resistance to ciprofloxacin was higher in E. faecalis isolates. The increased length of hospital stay was correlated with the carriage of resistant strains to vancomycin, ampicillin, and ciprofloxacin. While the homology of the isolates was low among different patients during hospitalization, identical (9%) and similar (21%) RAPD-PCR patterns were detected between pairs of isolates from each patient. CONCLUSIONS: The high rate of intestinal carriage of VR, HLGR-, and MDR-Enterococci at admission and during hospitalization in the PICU, and the impact of increased length of hospital stay on the fecal carriage of the resistant strains show the importance of antibiotic stewardship programs to control their transmission and spread in children.

Tracing the Negative Results of Multiplex Real-Time PCR Assay for Diagnosis of Bacterial Pediatrics Meningitis.

The death because of meningitis remains high in some parts of the world. It is important to know the specific cause of meningitis because the treatment differs depending on the cause. This study aimed to trace the false-negative results of multiplex RT-PCR to detect Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis serogroup by two different molecular methods. In this study, the CSF of the suspicious pediatric for acute bacterial meningitis among children aged 1 month to 14 years who are admitted to the hospitals in four cities of a certain region of Iran was collected. S. pneumoniae, H. influenzae, and N. meningitidis in CSF samples were detected by single-tube multiplex RT-PCR and specific RT-PCR with a probe on the same specimens. In this cross-sectional study, 506 CSF samples were collected during one year. The multiplex RT-PCR can detect 3.3% and 2.2% of S. pneumoniae and H. influenzae, respectively. N. meningitidis was not detected. The CSF analysis was abnormal in 53% of 506 patients. On the other hand, 11.5%, 4.8%, and 4.1% of S. pneumoniae, H. influenzae, and N. meningitidis were identified, respectively, by specific RT-PCR assay, exactly on the same specimens. Various types of PCR can be used for pathogen identification. As we change the type of PCR in our study, we could approximately increase 15% our positive results and also consequently decrease our false-negative responses.

Co-infection with dual Streptococcus pneumoniae serotypes as a cause of pediatric bacterial meningitis in Iran: a multi-center cross-sectional study.

BACKGROUND: Meningitis is considered a life-threatening infection with high mortality all over the world. Hemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S. pneumoniae) are regarded as the two most common infectious agents causing bacterial meningitis. This study aimed to identify H. influenzae and S. pneumoniae serotypes in blood and cerebrospinal fluid (CSF) of pediatric patients with meningitis, using polymerase chain reaction (PCR). METHODS: This multi-center cross-sectional study included 284 children with suspected meningitis referred to 4 target hospitals. Overall, 412 samples (128 blood and 284 CSF samples) were obtained from the patients from November 14, 2016 to November 15, 2017. The extracted DNA was examined using multiplex real time PCR to screen for S. pneumoniae and H. influenzae. S. pneumoniae serotyping was also done by multiplex PCR. RESULTS: Out of 284 CSF specimens, 22 were positive for ply S. pneumoniae. Of 20 DNA samples meeting the Quality Control (QC) standards for serotyping, 7 (35%), 6 (30%), 2 (10%), 2 (10%), 2 (10%), 1 (5%), 1 (5%), 1 (5%), 1 (5%) and 1 (5%) were positive for serotypes 3, 11A, 6A, 14, 7C, 23F, 23B, 19A, and 19F and 5, respectively. Overall, nine samples were positive for two serotypes, of whom 3 and 11A were the most common from Tehran province. Of note, one of these CSF samples showed a new co-infection with serotypes 7C and 14. Also, 6 samples (30%) were positive for H. influenzae detected by bexA primer. None of the blood samples were positive for S. pneumoniae or H. influenzae. CONCLUSION: Co-infection with S. pneumoniae serotypes can occur in bacterial meningitis and it might be missed if all serotypes are not evaluated in CSF specimens.

Re-positive PCR of SARS-CoV-2 in health care persons during COVID-19 pandemic.

Reinfection rate with SARS-CoV-2 and degree of protection by the induced antibody after the first episode of the infection is not well known, so it makes a big dilemma for health care personnel (HCP) who work in the front line of combating SARS-CoV-2. In this study, we investigated the frequency of SARS-CoV-2 redetection among HCP after the initial onset of the infection in a children's hospital during one year. Out of 131 seropositive HCP, 13.7% of them were symptomatic and PCR positive during 74-360 days after first sampling. Analysis of demographic data of seropositive HCP showed a correlation between a higher number of family members, higher body mass index, and the existence of underlying diseases with SARS-CoV-2 redetection. In conclusion, reinfection is one of the important problems in the SARS-CoV-2 pandemic. Research on this topic can help us to find answers to questions for estimating the duration of human protection with produced immunity after the infection or vaccination.

Evidence-Based Prediction of COVID-19 Severity in Hospitalized Children.

Objective: In this study, by using clinical and paraclinical characteristics, we have aimed to predict the severity of the disease in hospitalized COVID-19 children. Method: This cross-sectional study was conducted on medical records about epidemiologic data, underlying diseases, symptoms, and laboratory tests from March to October, 2020, on 238 hospitalized confirmed COVID-19 paediatric cases in several children's hospitals of Tehran, Ahwaz, Isfahan, and Bandar Abbas. Results: From 238 patients, 140 (59%) were male and most of them were in the age group of 1 to 5 years (34.6%). Among all hospitalized patients, 38% had an underlying disease and in total, 5% of cases were expired. Conclusion: Determining patient severity is essential for appropriate clinical decision making; our results showed that in hospitalized pediatric patients, by using several variables such as SGOT, CRP, ALC, LDH, WBC, O2sat, and ferritin, we can use clinical and paraclinical characteristics for predicting the severity of COVID-19.

COVID-19 Mortality in Children: A Referral Center Experience from Iran (Mofid Children's Hospital, Tehran, Iran).

Background: The novel coronavirus disease 2019 (COVID-19) started in Wuhan, China, in December 2019. It spread widely around the world and was described as a pandemic by the World Health Organization (WHO). The knowledge regarding the mortality rate and risk factors of COVID-19 among the pediatric population is lacking. In this regard, we aimed to report the clinical and laboratory characteristics of deceased pediatric patients with SARS-CoV-2 infection. Method: This cross-sectional study was conducted in Mofid Children's Hospital, Tehran, Iran, from February 2020 to April 2021. Recorded documents of 59 pediatric patients (under 18 years old) assumed to have COVID-19 who had died in the COVID-19 ward and COVID-19 intensive care unit (ICU) were retrospectively evaluated. All statistical analyses were performed using SPSS software (v. 26.0, Chicago, IL). A P value of less than 0.05 was considered statistically significant. Results: From 711 COVID-19 definite and suspected patients, 59 children died. Of these deceased pediatric patients, 34 were boys (57.62%) and 25 were girls (42.37%), with a total mean age of 5.6 years. The median length of stay in the hospital was 10 days (range 1-215). 91.52% had underlying comorbidities of which neurological diseases accounted for the largest share. 54 patients were admitted to the ICU and 83.05% of them had intubation during their hospitalization. In addition, the most common reasons for death in our study were related to respiratory and multiorgan failure. Conclusion: According to our knowledge, we are the first team to report such a thorough study in the field of COVID-19 pediatric mortality in Iran. Mortality was observed in all age groups of children, especially in those with previous comorbidities, specifically neurological disease. Abnormally elevated tests of ESR, CRP, LDH, AST, and ALT as well as the presence of proteinuria and hematuria were found in more than 50% of patients in our investigations, and ICU admission between both definite and suspected groups had significant differences, so monitoring and considering these factors may help to control and reduce the progression of the disease to death.

Evaluation of methicillin-resistant Staphylococcus virulence genes and antibiotics susceptibility in Iranian population.

Background: Methicillin resistance Staphylococcus aureus (MRSA) is one most important pathogens for human health. The ability of this organism for producing different kinds of disease is related to its virulence gene. The frequency of hemolysin alpha (hla), hemolysin beta (hlb), and exfoliative toxin A (eta) virulence genes of MRSA was evaluated, and the association of these genes with antibiotics susceptibility was investigated. Materials and Methods: In a cross-sectional study, a total of 695 Staphylococcus clinical samples from seven different provinces of Iran were evaluated. MRSA was detected by cefoxitin disk. Virulence genes were detected by polymerase chain reaction. Susceptibility to clindamycin and ciprofloxacin was evaluated according to the Clinical and Laboratory Standards Institute guideline. Results: From a total of 695 samples, 170 (24.46%) were found to be MRSA. 142, 82, and 132 samples of MRSA were hla, hlb, and eta positive, respectively. hla gene was significantly found more frequently in patients at least 18 years (P = 0.02). 105 (68.6%) and 93 (59.6%) of MRSA samples were resistance to ciprofloxacin and clindamycin, respectively. hlb gene was significantly more resistant to clindamycin (P = 0.04) and ciprofloxacin (P = 0.01). Logistic regression analysis displayed hlb-positive MRSA strains were significantly associated with ciprofloxacin (odds ratio [OR]: 3.6, 95% confidence interval [CI] = 1.637-8.00) and clindamycin (OR: 1.93, 95% CI 1.00-3.68). Conclusion: MRSA strains from Staphylococcus aureus which isolated from hospitalized Iranian patients are significantly resistant to clindamycin and ciprofloxacin and it is may be because of hlb virulence gene. These samples consist of both community-acquired MRS) and health-care associated MRSA, so we could not use this finding as a guide for local antibiotics usage.

Hospital-based prospective study of pertussis in infants and close contacts in Tehran, Iran.

BACKGROUND: Pertussis remain a global health concern, especially in infants too young to initiate their vaccination. Effective vaccination and high coverage limit the circulation of the pathogen, yet duration of protection is limited and boosters are recommended during a lifetime. In Iran, boosters are given at 18 months and 6 years old using whole pertussis vaccines for which efficacy is not known, and pertussis surveillance is scant with only sporadic biological diagnosis. Burden of pertussis is not well understood and local data are needed. METHODS: Hospital-based prospective study implementing molecular laboratory testing in infants aged ≤6 months and presenting ≥5 days of cough associated to one pertussis-like symptom in Tehran. Household and non-household contact cases of positive infants were evaluated by comprehensive pertussis diagnosis (molecular testing and serology) regardless of clinical signs. Clinical evaluation and source of infection were described. RESULTS: A total of 247 infants and 130 contact cases were enrolled. Pertussis diagnosis result was obtained for 199 infants and 104 contact cases. Infant population was mostly < 3 months old (79.9%; 157/199) and unvaccinated (62.3%; 124/199), 20.1% (40/199) of them were confirmed having B. pertussis infection. Greater cough duration and lymphocyte counts were the only symptoms associated to positivity. Half of the contact cases (51.0%; 53/104) had a B. pertussis infection, median age was 31 years old. A proportion of 28.3% (15/53) positive contacts did not report any symptom. However, 67.9% (36/53) and 3.8% (2/53) of them reported cough at inclusion or during the study, including 20.8% (11/53) who started coughing ≥7 days before infant cough onset. Overall, only five samples were successfully cultured. CONCLUSION: These data evidenced the significant prevalence of pertussis infection among paucy or poorly symptomatic contacts of infants with pertussis infection. Widespread usage of molecular testing should be implemented to identify B. pertussis infections.

Diagnosis of latent tuberculosis infection among pediatric household contacts of Iranian tuberculosis cases using tuberculin skin test, IFN- γ release assay and IFN-γ-induced protein-10.

BACKGROUND: Although the World Health Organization has recommended the diagnosis and prophylactic treatment of latent tuberculous infection (LTBI) in child household contacts of tuberculosis (TB) cases, the national programs in high-burden TB regions rarely implement adequate screening of this high-risk group, mainly because of resource limitations. We aimed to evaluate the prevalence of LTBI among pediatric household contacts of TB cases in two high-burden provinces in Iran. METHODS: We conducted a cohort study in children who had been in household contact with a TB index. All subjects were assessed for active TB disease. For LTBI diagnosis, tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were performed at the time of the index TB case diagnosis, as well as, 3, 12, and 18 months, if the first results were negative. In addition, interferon-γ-induced protein-10(IP-10) concentrations were measured for all participants. RESULTS: A total of 230 children were enrolled, who had contact with an index TB case. Three contacts were diagnosed with active TB. According to the TST/QFT-Plus results, 104 (45.2%) children were identified with LTBI during our study. Significantly increased IP-10 levels were found in LTBI patients compared to healthy contacts. Accordingly, more than 50% of LTBI contacts and about 10% of healthy contacts were considered as IP-10-positive. CONCLUSION: This study alarmingly illustrates a high prevalence of LTBI among Iranian children exposed to TB cases. We, therefore, emphasize that the children living in close contact with an infectious TB case should be screened effectively and receive prophylactic therapy.

Iranian Pediatric COVID-19 Epidemiology and Clinical Characteristics.

BACKGROUND: Despite the worldwide spread of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), information about the epidemiological and clinical patterns of this infection is still largely unknown in children. In addition, the prevalence of this disease is still very high in some parts of the world, including Iran. Thus, this study aims to evaluate the epidemiological features, laboratory and imaging findings, and the type of treatments in children with novel coronavirus 2019 (COVID-19). METHOD: This study is conducted from March 2020-March 2021 by using the medical records of hospitalized confirmed COVID-19 children younger than 18 years in five cities of Iran: Tehran, Ahwaz, Isfahan, Bandar-Abbas, and Khorramabad. In addition to demographic and epidemiological data, we also studied clinical signs and treatments. RESULTS: In total 278 confirmed COVID-19 children, the average age was 5.3 years, and 59.4%were boys. A total of 37.8% had an underlying disease, in which the most common was a malignancy. The most common symptoms were fever and cough. In this group of pediatrics, some abnormal laboratory findings have been seen. GGO (Ground-Glass Opacity) had been diagnosed in 58.6% of children. 3.6% needed oxygen therapy with ventilators, and 83.09% had received antibiotic treatments with the majority of ceftriaxone. Also, 10% had got steroids. In this study, the mortality rate was 4.3%. CONCLUSION: In this study, most of the children who died had an underlying disease, so timely care and action is important in them. Most children admitted to our study received antibiotics and were prescribed antivirals and steroids for a smaller number. Also, a small number of children received oxygen therapy, most of whom were in the age group of 1 to 5 years.

Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare congenital condition characterized by a selective predisposition to infections caused by weakly virulent mycobacteria and other types of intra-macrophagic pathogens. The 16 genes associated with MSMD display a considerable level of allelic heterogeneity, accounting for 31 distinct disorders with variable clinical presentations and prognosis. Most of MSMD deficiencies are isolated, referred to as selective susceptibility to mycobacterial diseases. However, other deficiencies are syndromic MSMD, defined by the combination of the mycobacterial infection with another, equally common, infectious, specific phenotypes. Herein, we described a series of 32 Iranian MSMD cases identified with seven distinct types of molecular defects, all of which are involved in the interferon gamma (IFNγ) immunity, including interleukin IL-12 receptor-ß1 (IL-12Rß1) deficiency (fifteen cases), IL-12p40 deficiency (ten cases), and IL-23R deficiency (three cases), as well as IFNγ receptor 1 (IFNγR1) deficiency, IFNγ receptor 2 (IFNγR2) deficiency, interferon-stimulated gene 15 (ISG15) deficiency, and tyrosine kinase 2 (TYK2) deficiency each in one case. Since the first report of two MSMD patients in our center, we identified 30 other affected patients with similar clinical manifestations. As the number of reported Iranian cases with MSMD diagnosis has increased in recent years and according to the national vaccination protocol, all Iranian newborns receive BCG vaccination at birth, early diagnosis, and therapeutic intervention which are required for a better outcome and also prevention of similar birth defects. Therefore, we investigated the clinical and molecular features of these 32 patients. The current report also defined novel classes of pathological mutations, further expanding our knowledge of the MSMD molecular basis and associated clinical manifestations.

Resistant/susceptible classification of respiratory tract pathogenic bacteria based on volatile organic compounds profiling.

Resistance to antibiotics is an emerging and growing threat. To address this threat, attempts are being made by researchers to identify the Volatile Organic Compounds (VOCs) of bacteria. It is believed that unique combinations could be found among the VOCs produced by each microorganism. The current study aimed to identify and compare the VOCs of antibiotic-resistant and standard strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. A polymer of divinylbenzene /carboxen /polydimethylsiloxane was applied for absorption of volatile compounds in headspace bacterial samples in form of a solid phase micro-extraction fiber holder. Gas chromatography-mass spectrometry technique was used for identification of volatile compounds. The analysis of the VOCs indicated that some VOCs appeared only in standard strains while others were common only among resistant strains. Exclusive VOCs to a specific strain were also detected. This study demonstrated that resistant strains of bacteria produced VOCs that were different from those of the standard strains. In addition, VOCs released by bacteria after passing the logarithmic growth phase showed no significant differences. The identification of VOCs can be a precise way to differentiate bacterial species, also it can be said that the VOCs produced by different pathogenic microorganisms can be the suitable biomarkers for their detection.

Warning: spread of NDM-1 in two border towns of Iran.

NDM-1 producing gram-negative bacteria can be resistant to every beta-lactam antibiotic, including carbapenem which is one of the last-lines of antibiotic therapy against multi-drug resistant bacteria. This study aimed to detect the metallo-beta-lactamase in the isolated gram-negative bacteria of the Iranian clinical specimens collected from two major cities in Iran. In this cross sectional study 171 Acinetobacter baumannii, 120 Enterobacter spp. and 145 Klebsiella pneumoniae isolated from clinical specimens of two training hospitals in Tabriz and Mashhad were evaluated. Carbapenem resistant screening was performed according to CLSI guide line. The antibiotic susceptibility testing was prepared for carbapenem resistant strains. Then, the metallo-beta- lactamase genes detection was also carried out by PCR assay and confirmed by sequencing. Sixty-eight, 12 and 22 carbapenem resistant Acinetobacter baumannii, Klebsiella pneumoniae and Enterobacter spp. were respectively confirmed, respectively. blaVIM in 9% and blaNDM-1  in 4% of isolated A. baumannii were observed. blaNDM-1 was also detected in 18% and 25% of K. pneumoniae and Enterobacter spp. isolates, respectively. This is the first report of NDM-1 producer A. baumannii and Enterobacter pp. in Iran. NDM-1 producing gram-negative bacteria can be resistant to all beta-lactam antibiotics and cause complicated challenges in health care systems.

Genotyping, antimicrobial resistance and virulence factor gene profiles of vancomycin resistance Enterococcus faecalis isolated from blood culture.

BACKGROUND: Enterococcus spp. is the common of intestinal micro flora in humans but nowadays this gram-positive bacterium causes the variety of nosocomial infections. Resistance to antibiotic and also, presence of different virulence genes in the enterococcus spp. can change it to problematic microorganisms in the health care centers. The aim of this study was determined the genotyping, antimicrobial resistance and virulence factor gene profiles of vancomycin resistance Enterococcus faecalis isolated from blood culture. METHODS: In this study, enterococcus isolated from BACTEC was collected and antibiotic susceptibility testing was done according to CLSI recommendation. Important virulence genes and vancomyci resistance genes were detected by PCR and molecular typing was performed by RAPD PCR assay. RESULTS: Nine enterococcus collected from 194 positive BACTEC and seven out of nine were vancomycin-resistant enterococcus (VRE). vanA gene observed in all VRE and none of strains carried vanB and vanC genes. efbaA and gelE virulence factors have been detected in all strains. ace, esp, and cyl virulence factors genes harbored in two, seven and eight isolates respectively. asaI was not detected in any strains. All seven VRE isolates were related to the one specific molecular type and two different molecular types observed in the two vancomycin susceptible enterococci according to molecular epidemiology results. CONCLUSION: More prevalence of the VRE in enterococcus isolated from BACTEC is so important and on the other hand high genetic relationship in the isolated VRE can be very considerable for nosocomial infection committee in the hospital.

Acellular pertussis vaccine efficacy: An updated systematic review and meta -analysis.

Background: Recent studies indicate an increased incidence of pertussis disease in recent years. The aim of this study was to evaluate the efficacy of the acellular vaccine for children (as a replacement of current whole cell vaccine in the Expanded Program on Immunization) and for high-risk adults in Iran through updating current best available evidence. Methods: We performed a systematic literature review in relevant databases we focused on previously published systematic reviews to select those that address our questions. The AMSTAR (assessing the methodological quality of systematic reviews) tool was used for screening available reviews. Then search in databases was done until Feb 2014 to update the evidence. We pooled results using meta-analysis methods by Stata statistical package. Results: Eleven systematic review articles were included in the initial evaluation. In the end, two systematic reviews on acellular vaccine booster doses and the acellular vaccine in children were selected as the baseline evidence. In the update phase, new clinical trials were screened, and the results were updated. Overall pooled estimate of relative efficacy of acellular to whole cell was 0.68 (95% CI, 0.55-0.81) for children immunization Pooled estimates for the efficacy of acellular versus placebo were 0.70 (95% CI, 0.60-0.80). Overall pooled estimate of efficacy of booster dose of acellular was 0.87(95% CI, 0.85-0.88) compared to placebo. In addition pooled estimate of acellular vaccine efficacy based on response to antigen was 0.78(95% CI, 0.64-0.93) in highrisk group. Conclusion: The results show higher performance and safety of the acellular vaccine in the prevention of pertussis in children versus the whole cell vaccine. Moreover, the efficacy of the acellular vaccine in high-risk adult groups is acceptable. This study provides evidence in favor of the introduction of an acellular vaccine to the national program of immunization. Studies on cost effectiveness and aspects of policy analysis are recommended.