bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Lipid & Hematological Profiles in Assessing Single & Multiple Soil-Transmitted Helminth Infections among Direct Fecal Smear Positive Patients in a Tertiary Provincial Hospital in Sorsogon, Philippines
Authors: San Pedro R S , Nicolas R F , Ramos A M , Robles T D , Rosales D S , Sagabaen R C , Santos G T , Sison R G , Nieto X A 
Published: November 2022

Abstract

Introduction/Objective
Soil-transmitted helminth (STH) infections have been recognized to be a global phenomenon and are still prevalent in tropical countries, particularly those with low human development index such as the Philippines. Previous literature have reported changes in the hematologic and serum lipid parameters of individuals with STH infections, however, there has yet to be a study in the Philippines regarding the association of said parameters to STH infections. This correlation could be valuable in evaluation, diagnosis, and treatment of STH infected patients.

Methods/Case Report
The study assessed single and multiple helminth infections caused by STH, particularly A. lumbricoides, T. trichiura, and hookworm direct fecal smear (DFS) positive patients and its correlation to hematologic and serum lipid parameters. The researchers followed a retrospective and systematic approach wherein data readily available from DFS positive patients aged 5-19 years old with complete serum lipid profile (total cholesterol, HDL, LDL, and triglycerides) and complete blood count (RBC count, hemoglobin, hematocrit, MCV, MCH, MCHC, WBC count, neutrophil count, lymphocyte count, monocyte count, eosinophil count, and platelet count) from the tertiary provincial hospital were utilized. Mean and standard deviation were used for the age and hematologic parameters. One-way analysis of variance (ANOVA) with Tukey’s HSD was used for post hoc analysis while Fisher exact test was used to compare the percentages among the groups of patients. Statistical tests were performed using RStudio, at 5% level of significance.

Results (if a Case Study enter NA)
Patients with multiple STH infection have greater risk of lymphopenia than patients with single helminth infection (p=0.053). Moreover, eosinophilia is more observed in patients infected with T. trichiura, hookworm, or with multiple STH infections compared to patients infected with A. lumbricoides alone (p=0.023).

Conclusion
This study demonstrated significant differences among DFS positive patients with single and multiple STH infections in both serum and hematological profiles.
In-vitro Activity of Ceftazidime-Avibactam Against Carbapenem-Resistant K. pneumoniae in a Tertiary-Care Center in Al-Ahsa, KSA
Authors: Jaber F , Aljawad H 
Published: November 2022

Abstract

Introduction/Objective
Carbapenem-resistant Enterobacteriaceae (CRE) represents an urgent global threat. Klebsiella pneumoniae is a common cause of various clinical infections showing increased rates of resistance. Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is often multi-drug resistant and sometimes becomes pan-drug resistant causing serious infections with substantial morbidity, mortality and cost. Ceftazidime-avibactam (CZA) is considered to be a good alternative to standard CRE therapy. In our region, CRE is mostly due to OXA-type carbapenemases which are inhibited by CZA, however, metallo-beta-lactamases (MBLs) are being increasingly reported and against which CZA is inactive. The aim of this study is to determine the activity of CZA against CRE-KP isolated in our hospital.

Methods/Case Report
Single-center, prospective study on consecutive non-duplicate CRE-KP isolates recovered from various clinical specimens in 2020 and 2021. BD Phoenix® system was used for initial Identification and susceptibility testing. E-test was done to confirm susceptibility and determine the minimum inhibitory concentration (MIC) for CZA. The standards of the Clinical and Laboratory Standards Institute were followed.

Results (if a Case Study enter NA)
95 CRE-KP isolates were collected. CRE-KP was mostly isolated from: Respiratory samples: 36% (n=34), bedsores: 28% (n=27), urine: 23% (n=22) and 11% (10 isolates) were retrieved from blood cultures. 65% of patients were admitted to the intensive care unit (ICU), 13% were in long-term care wards and 13% were admitted for management of infected bedsores. 88 isolates were susceptible to CZA (93%) with MIC50= 1.5 μg/mL and MIC90= 4.0 μg/mL. 26 isolates (27%) were sensitive only to CZA. Susceptibility to tigecycline was 54%, amikacin 18% and gentamicin 17%. Other antimicrocbials including ceftolozane-tazobactam were basically ineffective.

Conclusion
Ceftazidime-avibactam shows excellent in-vitro activity against CR-KP isolates tested in this study. Further clinical studies on treatment efficacy and emergence of resistance are needed. Moreover, with the recent increase in reported MBLs-mediated resistance in our region, infection control measures, resistance-surveillance programs, and molecular testing may prove essential in the fight against carbapenem-resistant Enterobacteriaceae.
Biofilm Formation on Intrauterine Devices in Diabetic and Nondiabetic Patients with Vulvovaginal Candidiasis
Authors: Abdelmonem M , Eldaly R , Wasim H , Elhusseny A , Abdelmageed M , Saleh Abdelfattah M 
Published: November 2022

Abstract

Introduction/Objective
Women with diabetes mellitus (DM) are more susceptible to vulvovaginal candidiasis (VVC) than non-diabetics. This could be due to higher glucose levels predisposing VVC by damaging basic host defense mechanisms and stimulating Candida adhesion to vaginal cells.

Objectives
Investigating the prevalence of Candida albicans and biofilm formation in diabetic and nondiabetic IUD users.

Methods/Case Report
A total of 325 vaginal swabs and IUDs were enrolled in this study from the Delta region in Egypt. Females with a median age of 17 to 45 years were divided into two groups; diabetic (29.8%) and nondiabetic (70.1%). They were all vaginitis having one of these symptoms; irritation on the surface of the genital tract, uterine cervix ulcer, vaginal bleeding, and acute vaginal exudates. C. albicans were isolated and identified using cultural characters. Biofilm formation by Candida on removed IUDs and swabs was examined by XTT-reduction assay, scanning electron microscope (SEM), and transmission electron microscope (TEM). Antifungal susceptibility to fluconazole and amphotericin B (AMB) to isolated strains and in vitro experimental biofilm formation was performed.

Results (if a Case Study enter NA)
In diabetic cases, the highest percentage (91.1%) of isolated C.albicans was found among patients with irritation on the surface of the genital tract, whereas the lowest one (83.3%) was in the symptoms of acute vaginal exudates. In nondiabetic cases, the highest percentage of isolated C.albicans (51.7%) was found among patients with symptoms of acute vaginal exudates. In contrast, the lowest one (32.5%) was in the symptoms of irritation on the surface of the genital tract. XTT method illustrated the biofilm formation; SEM revealed a heterogeneous thick biofilm. Biofilm MIC to strains with AMB &gt;1μg\ml was considered resistant, while those for which AMB concentration were ≤1μg\ml were deemed sensitive. Strains with Fluconazol 64 μg\ml were considered resistant, while those for which Fluconazol concentration was ≤8 μg\ml were deemed sensitive.

Conclusion
There was a significant direct relationship between diabetic cases and C.albicans prevalence in the current study. Furthermore, the ability to form biofilm was found to be the same in diabetic and nondiabetic patients.
Optimizing Detection of MEC-Mediated Methicillin Resistance in Coagulase Negative Staphylococcus Species
Authors: Givi J P , LaSala R , Miller B , Rybakov I 
Published: November 2022

Abstract

Introduction/Objective
Parenteral therapy for invasive staphylococcal infections often comprises lipo/glycopeptides for methicillin resistant (MR) organisms, with extended spectrum penicillins reserved for those confirmed as methicillin susceptible (MS). While phenotypic antimicrobial susceptibility testing (AST) using cefoxitin has high accuracy for differentiating MR/MS for S. aureus, the same, simple approach does not reliably distinguish resistance among all coagulase negative Staphylococcus species (CoNS). As such, clinicians may work under an assumption that MS CoNS cannot be reliably predicted by laboratories, leading to lipo/glycopeptide therapeutic use for invasive infections caused by both MR and MS isolates. To better inform laboratory practice, this study aimed to establish the accuracy of multiple phenotypic and genotypic tests for differentiation of MR/MS among commonly recovered CoNS species producing invasive infections.

Methods/Case Report
A convenience sample of 155 unique invasive CoNS isolates with historic Vitek 2 and/or disc diffusion (DD) AST results (~50% MR) were retrieved from frozen storage and tested by: (1) cefoxitin and oxacillin DD, (2) a lateral flow immunoassay for PBP2a without beta-lactam induction, and (3) a lab-developed PCR for mecA. A commercial real-time PCR for mecA/C was also employed for a subset of isolates.

Results (if a Case Study enter NA)
A total of 144 isolates belonging to 11 taxa were evaluated by all tests after accounting for missing, non-viable, and incorrectly cataloged isolates. Using PCR mecA/C detection as the reference standard, categorical agreement for MR/MS status was 95.5% (127/133) for original Vitek GP75 results, 98.6% (142/144) for DD interpreted using updated, species-specific CLSI guidelines, and 100% (144/144) for the lateral flow PBP2a assay. Six MR isolates from five different taxa that were repeatedly mecA-negative by lab-developed PCR confirmed as mecA/C-positive by a commercial assay.

Conclusion
Although all methods evaluated distinguish MR/MS CoNS with sufficient accuracy, definitive determination is best achieved using off-label/lab-developed PCR for mec or lateral flow immunoassay for PBP2a.
To Be or Not to Be Resistant: CLSI Versus EUCAST Guidelines for Staphylococcus lugdunensis
Authors: Benitez Barzaga M , Yee R 
Published: November 2022

Abstract

Introduction/Objective
Staphylococcus lugdunensis is a coagulase-negative Staphyloccocus, but infections can be as severe as S. aureus. Performing antimicrobial susceptibility testing (AST) is paramount to appropriate treatment. Recently, the College of American Pathologists is requiring clinical labs to implement updated guidelines. We evaluated how the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines would impact our hospital’s resistance rates for S. lugdunensis.

Methods/Case Report
Cultures with S. lugdunensis isolated between 04/2018 to 02/2022 were included. Minimal inhibitory concentrations (MICs) (Vitek2 and Microscan Walkaway) reported (clindamycin, doxycycline, daptomycin, linezolid, and vancomycin) were interpreted using CLSI (M100Ed32) and EUCAST (v12.0) guidelines. The range of MICs (95% Confidence Interval) was calculated.

Results (if a Case Study enter NA)
A total of 125 isolates from 120 patients from specimen types including wound (49%), tissue (42%), blood (6%), and body fluid (3%) were identified. Five patients had multiple cultures of S. lugdunensis, four from two wound/tissue sites and one with blood and biopsy positive. For clindamycin (0.7-1.3 ug/mL), EUCAST guidelines determined two more isolates (from blood and wound, MIC=0.5 ug/mL) as resistant. Most drastically, the rate of resistance for doxycycline (0.6-1.0 ug/mL) was 11% higher per EUCAST guidelines (susceptible: 89% EUCAST vs 100% CLSI). The difference was seen in isolates &gt; 2 ug/mL, all isolated from wound and tissue. Regardless of the guidelines used, 100% of the isolates were susceptible to daptomycin (0.4-0.5 ug/mL), linezolid (1.2-1.4 ug/mL), and vancomycin (0.6-0.7 ug/mL); 23% were resistant to oxacillin (1.7-2.0 ug/mL).

Conclusion
EUCAST guidelines would have reported more resistant doxycycline and clindamycin isolates at our institution. To ensure that clinical teams are utilizing AST results to provide appropriate care, a team effort consisting of the microbiology lab, infectious diseases physicians, and antibiotic stewardship committee is needed to determine which guidelines should be followed.
Thermal Shock Viral RNA Release in COVID-19 Testing
Authors: Ledesma C J , Cavazos M , Chase L 
Published: November 2022

Abstract

Introduction/Objective
The public health emergency of the COVID-19 pandemic emphasized the crucial role of medical laboratory professionals and scientists in molecular diagnostics laboratories to ensure success in infection control strategies. The demand for laboratory testing using nucleic acid amplification tests to detect SARS-CoV-2 RNA imposed strains in laboratory supplies. Here, we explored an alternative cost-effective solution that will simplify the pre-PCR steps by using a simple heating method to release viral RNA.

Methods/Case Report
Samples tested using the reference automated extraction method were used:100 samples identified as positive for SARS-CoV-2 RNA and 500 samples tested negative for SARS-CoV-2 RNA were used for the study and sorted with equal distribution according to Ct values of (a) &lt;20, (b) 20–30, and (c) &gt;30.100 ul from swab preserved in Universal Transport Medium was treated with 30 μg of proteinase K, and another set was tested without proteinase K pre-treatment. All samples with or without proteinase K were diluted to minimize PCR inhibitors. The thermal shock protocol was set at (98°C, 5 minutes; 4°C, 2 minutes) and screened for purity. Performance and method verification studies were performed. Internal extraction, positive template, and no template controls were markers used for testing quality. The experimental study was performed by qualified testing personnel and all under the same experimental conditions.

Results (if a Case Study enter NA)
The Ct values from the thermal shock RNA release were compared to the automated extraction method and statistically analyzed.The criteria for acceptability for validation of this new RNA extraction proceeding were set to 100% concordance compared to the commercial kit using an automated extraction. PCR efficiency was at 98% and a slope of -3.3. Within run precision of 2% and limits of detection from 200 to 20,000 copies/uL The method 100% (50/50) concordance on samples previously identified as negative by automated methods and identified 86% (86/100) with a mean difference of 3 Ct.

Conclusion
Our findings suggest that the thermal shock treatment of nasopharyngeal swabs in viral transport media can successfully extract viral nucleic acid for nucleic acid amplification and is a reasonable alternative for chemical extraction methods when molecular diagnostic laboratories persistently encounter supply chain issues.
Analysis of microRNAs by the Stem-Loop Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction Using A Double Quencher Probe
Authors: Kikuchi A , Naruse A , Takagi K 
Published: November 2022

Abstract

Introduction/Objective
We created a universal probe that can be used with mature micro RNAs (miRNAs) using a double quencher incorporating the ZEN quencher into the hydrolysis probe required for miRNA analysis by the real- time quantitative polymerase chain reaction (RT-qPCR) using a stem-loop primer. The main purpose of this approach was to improve sensitivity and convenience.

Methods/Case Report
We conducted studies on miR-21, miR-30a and miR-200c. To assess the relationship between the sequence interval and reactivity between the miRNA-specific sequence on the stem-loop primer and detection probe, various sequence patterns were examined using miRNA from K562 cells. The sensitivity and reactivity of the designed primers and probes were examined using each synthetic miRNA and transurethral resection of bladder tumor (TURBT) samples. The synthetic RNA was serially diluted in 10% increments. Twenty-seven TURBT cases were examined. The prepared samples were extracted with the FastGene RNA Basic Kit and FastGene miRNA Enhancer. After extraction, cDNA was prepared using FastGene Scriptase II. We performed quantitative analysis by the RT-qPCR using a ZEN double quencher probe. The samples were analyzed with the Taq Man miRNA assay.

Results (if a Case Study enter NA)
The probe and miRNA-specific sequences of the stem-loop primer showed better reactivity when the design contained less space within the sequences. Serial dilution of the samples using synthetic miRNA showed that linearity depended on the addition amount, and occurred at a concentration of log 7 or more. In the TURBT samples, the Δ of the mean Cp value, and the correlation coefficients of miR-21, miR-30a, and miR-200c, were 3.13 and 0.966; 1.10 and 0.991; and 0.39 and 0.997, respectively, compared with the TaqMan miRNA assay.

Conclusion
This demonstrates that our method has the same or higher sensitivity than the TaqMan miRNA assay. Overall, these findings suggest that the analysis of miRNA with a stem-loop primer using the double quencher probe is useful.
Homologous Recombination Deficiency and Tumor Mutational Burden as Clinical Biomarkers for Melanoma
Authors: Yip J , Lum C , Halford Z , Pon J , Woron A 
Published: November 2022

Abstract

Introduction/Objective
Homologous recombination deficiency (HRD) cancers have high levels of genetic instability, potentially being targets for platinum agents or poly-ADP ribose polymerase inhibitors. Tumor mutational burden (TMB), which is used to guide immunotherapy, is thought to be associated with HRD. This study aimed to evaluate the frequency of HRD and its correlation with other genomic parameters in melanoma.

Methods/Case Report
A total of 14 cases with the diagnosis of melanoma were found in the genomic database between March 1, 2021 to July 30, 2021. One case had an EWSR1-ATF1 translocation and was excluded. Copy number variations and absence of heterozygosity detection were analyzed by the NxClinical software (BioDiscovery, El Segundo, CA). HRD was scored by three DNA-based measures of genomic instability (loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale transitions (LST)). HRD-LOH is the number of LOH regions &gt; 15 Mb and do not cross the centromere. HRD-TAI is the number of regions &gt; 10 Mb with allelic imbalance that extend to one of the subtelomeres and do not cross the centromere. HRD-LST is the number of break points between regions &gt; 10 Mb. A high HRD score and LOH percentage were defined as ≥ 42 and ≥ 16%, respectively.

Results (if a Case Study enter NA)
Of the 13 cases, 10 had a high TMB and 3 had a low TMB. A high HRD score was found in 3 cases; high LOH percentage was found in 4 cases. PDL-1 was expressed in 8 of the 11 cases tested. A high HRD score correlated with high LOH percentage by Pearson’s chi-squared test (p &lt; 0.01). No significant association was found between TMB and HRD score or LOH percentage. Common alterations among cases with high TMB included mutations in NRAS (3/13; 23.1%), CDKN2A (2/13; 15.4%), BRAF (2/13; 15.4%), BRCA2 (2/13; 15.4%), RAF1 (2/13; 15.4%), RET (1/13; 7.7%), IDH1 (1/13; 7.7%), PALB2 (1/13; 7.7%), BRCA1 (1/13; 7.7%), ERBB2 (1/13; 7.7%), NF1 (1/13; 7.7%), MLH1 (1/13; 7.7%), ATM (1/13; 7.7%) and MET (1/13; 7.7%). One case had amplifications in CCND1, FGF 3/4/19 and MET. Among cases with low TMB, alterations included MYC amplification (1/3; 33.3%) and BRAF mutations (2/3; 66.6%).

Conclusion
In our study, HRD score is not associated with TMB status. There is a strong correlation between HRD score and LOH percentage, suggesting that LOH is a major component in the genomic scarring seen in HRD. HRD may be an independent biomarker of immunogenicity to guide immunotherapy.
Enhancing Coordination Around Cancer Biomarker and Hereditary Genetic Testing Among Members of the Multidisciplinary Care Team
Authors: Kim J , Boehmer L , Plotkin E , Allen T , Gutman P , Shiller M , Brown S , Pan V 
Published: November 2022

Abstract

Introduction/Objective
Advances in precision medicine necessitate a closer integration across pathologists, genetic counselors, and other members of the multidisciplinary cancer care team (MDT). Recognizing that physical distancing and fragmented communication may hinder care delivery, the Association of Community Cancer Centers (ACCC) ran a multi-year initiative to explore ways to improve MDT care coordination.

Methods/Case Report
ACCC held a multistakeholder leadership summit to identify and discuss critical issues regarding biomarker and hereditary genetic testing and the ways in which pathology and genetic counseling professionals interface with the cancer MDT. Through a consensus-driven process, participants identified key opportunities for achieving optimal integration. ACCC also conducted a national survey to explore barriers around biomarker and hereditary genetic testing. Building off these insights, ACCC conducted virtual workshops at three community cancer programs to improve processes around biomarker testing and targeted treatment planning.

Results (if a Case Study enter NA)
The pathology leadership summit identified the following priorities: 1) streamline and standardize the biomarker test ordering process; 2) improve tissue handling to optimize timely biomarker testing; 3) strengthen communication between pathologists and genetic counselors; 4) empower pathologists with leadership opportunities. In the ACCC survey (n=659), 57% indicated that some or most of their pathologists were generalists. 21% only held one general tumor board. 6% indicated that pathologists often do not attend tumor boards or cancer committee meetings. 64% indicated that pathologists can directly access some or all medical oncology patient records. 67% sent some or most biopsy samples out for biomarker testing. In the ACCC workshops, cancer programs in KS, NC, and NV identified ways to improve the timeliness of genetic counseling referrals and coordinate biomarker testing. Following the workshops, 64% indicated they planned to make moderate or significant changes in their processes.

Conclusion
Improving collaboration across pathologists, genetic counselors, and the rest of the cancer MDT may lead to more timely and comprehensive biomarker and hereditary genetic testing. These findings may help cancer programs refine processes of care.
Clinico-pathological and Molecular Features of Pancreatic Acinar Cell Carcinoma: Association with BRCA2 Mutation
Authors: Goyal G , Reusner J V , Haye K K , Tondon R 
Published: November 2022

Abstract

Introduction/Objective
Pancreatic acinar cell carcinoma (ACC) is a rare neoplasm of exocrine epithelial origin and accounts to &lt;1% of primary neoplasms of pancreas.

Methods/Case Report
The cases diagnosed as ACC were retrieved from Pathology data base between January 2010 to July 2021. A retrospective review of clinical, pathological, molecular findings along with follow up was performed.

Results (if a Case Study enter NA)
Eight patients with resection specimens were identified over a period of 11 years. Median age of diagnosis was 74.5 yrs with M: F ratio of 3:1 and size range of 1.8 to 10.9 cm. The tumor was located in body/tail (5) and head of pancreas (3). Immunohistochemical stains for BCL10 and trypsin were utilized in 4 cases. One patient had lymph node metastasis and two patients had liver metastasis at the time of presentation. One patient presented with lipase hypersecretion syndrome. Four cases (50%) had pT3 stage. Follow-up period was available in 7 patients and ranged from 1-3 yrs, of which 3 died within 2 yrs of surgery while 4 patients were disease free. Three patients (35%) were found to have germline (1) and somatic BRCA2 mutations (2). These patients received platinum- based chemotherapy and were free from recurrence upon follow-up of 3 yrs.

Conclusion
Pancreatic ACC is a rare entity. In our study, 35% (3/8) cases were associated with somatic/germline BRCA2 mutations. Our results suggest that patients with ACC should undergo genetic testing for BRCA 1/2 mutations. This would not only enable treatment of these patients with specific targeted therapies, but also aid in screening of their families.