Is endoscopic third ventriculostomy a viable treatment option for normal pressure hydrocephalus? A systematic review.

Background: Endoscopic third ventriculostomy (ETV) is considered an alternative treatment for hydrocephalus and has become a standard of care for obstructive hydrocephalus. Recent studies have also explored its role in normal pressure hydrocephalus (NPH). We conducted a systematic review aiming to assess the outcomes of this minimally invasive endoscopic technique as a viable treatment option for NPH. Methods: A systematic literature search was performed using PubMed and Scopus databases, using iterations of search terms "Endoscopic third ventriculostomy," "Idiopathic normal pressure hydrocephalus," and "Normal pressure hydrocephalus." To be eligible for inclusion in the review, articles had to report the usage of ETV as a primary treatment modality for NPH, report its outcomes, and be published in the English language. Results: Out of the 13 studies selected for qualitative synthesis, nine supported the use of ETV for NPH as an effective treatment option with improvement in the preoperative symptoms. Two studies favored shunt over ETV, stating that quality of life is better with VP shunt insertion. One study reported that ETV has higher perioperative mortality rates that outweigh its benefits. One study reported it to be an ineffective surgical option. Conclusion: The current review of evidence does not support the use of ETV for the treatment of NPH, except perhaps in a small subset of patients. These patients have a shorter duration of symptoms and a better preoperative neurological status. The lumbar infusion test and ventricular infusion test are modalities useful for selecting these candidates.

Surface-Enhanced Raman Scattering (SERS) in Combination with PCA and PLS-DA for the Evaluation of Antibacterial Activity of 1-Isopentyl-3-pentyl-1H-imidazole-3-ium Bromide against Bacillus subtilis.

In the current study, surface-enhanced Raman scattering (SERS) was performed to evaluate the antibacterial activity of lab-synthesized drug (1-isopentyl-3-pentyl-1H-imidazole-3-ium bromide salt) and commercial drug tinidazole againstBacillus subtilis. The changes in SERS spectral features were studied for unexposed bacillus and exposed one with various dosages of drug synthesized in the lab (1-isopentyl-3-pentyl-1H-imidazole-3-ium bromide salt), and SERS bands were assigned associated with the drug-induced biochemical alterations in bacteria. Multivariate data analysis tools including principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) have been utilized to analyze the antibacterial activity of the imidazole derivative (lab drug). PCA was employed in differentiating all the SERS spectral data sets associated with the various doses of the lab-synthesized drug. There is clear discrimination among the spectral data sets of a bacterial strain treated with different concentrations of the drug, which are analyzed by PLS-DA with 86% area under the curve in receiver operating curve (ROC), 99% sensitivity, 100% accuracy, and 98% specificity. Various dominant spectral features are observed with a gradual increase in the different concentrations of the applied drug including 715, 850, 1002, 1132, 1237, 1396, 1416, and 1453 cm-1, which indicate the possible biochemical changes caused in bacteria during the antibacterial activity of the lab-synthesized drug. Overall, the findings show that imidazole and imidazolium compounds generated from tinidazole with various alkyl lengths in the amide substitution can be effective antibacterial agents with low cytotoxicity in humans, and these results indicate the efficiency of SERS in pharmaceuticals and biomedical applications.

Punicalagin, a pomegranate polyphenol sensitizes the activity of antibiotics against three MDR pathogens of the Enterobacteriaceae.

BACKGROUND: Multidrug resistance (MDR) in the family Enterobacteriaceae is a perniciously increasing threat to global health security. The discovery of new antimicrobials having the reversing drug resistance potential may contribute to augment and revive the antibiotic arsenal in hand. This study aimed to explore the anti-Enterobacteriaceae capability of bioactive polyphenols from Punica granatum (P. granatum) and their co-action with antibiotics against clinical isolates of Enterobacteriaceae predominantly prevalent in South Asian countries. METHODS: The Kandhari P. granatum (Pakistani origin) extracts were tested for anti-Enterobacteriaceae activity by agar well diffusion assay against MDR Salmonella enterica serovar Typhi, serovar Typhimurium and Escherichia coli. Predominant compounds of active extract were determined by mass spectrometry and screened for bioactivity by agar well diffusion and minimum inhibitory concentration (MIC) assay. The active punicalagin was further evaluated at sub-inhibitory concentrations (SICs) for coactivity with nine conventional antimicrobials using a disc diffusion assay followed by time-kill experiments that proceeded with SICs of punicalagin and antimicrobials. RESULTS: Among all P. granatum crude extracts, pomegranate peel methanol extract showed the largest inhibition zones of 25, 22 and 19 mm, and the MICs as 3.9, 7.8 and 7.8 mg/mL for S. typhi, S. typhimurium and E. coli, respectively. Punicalagin and ellagic acid were determined as predominant compounds by mass spectrometry. In plate assay, punicalagin (10 mg/mL) was active with hazy inhibition zones of 17, 14, and 13 mm against S. typhi, S. typhimurium and E. coli, respectively. However, in broth dilution assay punicalagin showed no MIC up to 10 mg/mL. The SICs 30 µg, 100 µg, and 500 µg of punicalagin combined with antimicrobials i.e., aminoglycoside, ß-lactam, and fluoroquinolone act in synergy against MDR strains with % increase in inhibition zone values varying from 3.4 ± 2.7% to 73.8 ± 8.4%. In time-kill curves, a significant decrease in cell density was observed with the SICs of antimicrobials/punicalagin (0.03-60 µg/mL/30, 100, 500 µg/mL of punicalagin) combinations. CONCLUSIONS: The P. granatum peel methanol extract exhibited antimicrobial activity against MDR Enterobacteriaceae pathogens. Punicalagin, the bacteriostatic flavonoid act as a concentration-dependent sensitizing agent for antimicrobials against Enterobacteriaceae. Our findings for the therapeutic punicalagin-antimicrobial combination prompt further evaluation of punicalagin as a potent activator for drugs, which otherwise remain less or inactive against MDR strains.

Inhibition of NS2B-NS3 protease from all four serotypes of dengue virus by punicalagin, punicalin and ellagic acid identified from Punica granatum.

Despite a major threat to the public health in tropical and subtropical regions, dengue virus (DENV) infections are untreatable. Therefore, efforts are needed to investigate cost-effective therapeutic agents that could cure DENV infections in future. The NS2B-NS3 protease encoded by the genome of DENV is considered a critical target for the development of anti-dengue drugs. The objective of the current study was to find out a specific inhibitor of the NS2B-NS3 proteases from all four serotypes of DENV. To begin with, nine plant extracts with a medicinal history were evaluated for their role in inhibiting the NS2B-NS3 proteases by Fluorescence Resonance Energy Transfer (FRET) assay. Among the tested extracts, Punica granatum was found to be the most effective one. The metabolic profiling of this extract revealed the presence of several active compounds, including ellagic acid, punicalin and punicalagin, which are well-established antiviral agents. Further evaluation of IC50 values of these three antiviral molecules revealed punicalagin as the most potent anti-NS2B-NS3 protease drug with IC50 of 0.91 ± 0.10, 0.75 ± 0.05, 0.42 ± 0.03, 1.80 ± 0.16 µM against proteases from serotypes 1, 2, 3 and 4, respectively. The docking studies demonstrated that these compounds interacted at the active site of the enzyme, mainly with His and Ser residues. Molecular dynamics simulations analysis also showed the structural stability of the NS2B-NS3 proteases in the presence of punicalagin. In summary, this study concludes that the punicalagin can act as an effective inhibitor against NS2B-NS3 proteases from all four serotypes of DENV.Communicated by Ramaswamy H. Sarma.

Spinal Schwannomas; Classification, Management And Outcomes.

Schwannomas are benign tumours of the peripheral nerve sheath. When they occur in spine, they are most commonly found in intradural-extramedullary location. Surgery is the mainstay of treatment. Radiation has a limited role in the management of residual or recurrent lesions not suitable for surgery. Here we discuss the existing literature on the outcomes of spinal schwannoma after surgery.

Identification of additional mechanistically important residues in the multidrug transporter styMdtM of Salmonella Typhi.

Multidrug efflux is a well-established mechanism of drug resistance in bacterial pathogens like Salmonella Typhi. styMdtM (locus name; STY4874) is a multidrug efflux transporter of the major facilitator superfamily expressed in S. Typhi. Functional assays identified several residues important for its transport activity. Here, we used an AlphaFold model to identify additional residues for analysis by mutagenesis. Mutation of peripheral residue Cys185 had no effect on the structure or function of the transporter. However, substitution of channel-lining residues Tyr29 and Tyr231 completely abolished transport function. Finally, mutation of Gln294, which faces peripheral helices of the transporter, resulted in the loss of transport of some substrates. Crystallization studies yielded diffraction data for the wild-type protein at 4.5 Å resolution and allowed the unit cell parameters to be established as a = b = 64.3 Å, c = 245.4 Å, α = ß = γ = 90°, in space group P4. Our studies represent a further stepping stone towards a mechanistic understanding of the clinically important multidrug transporter styMdtM.Communicated by Ramaswamy H. Sarma.

Synthesis, Characterization, and Evaluation of Antifungal Activity of 1-Butyl-3-hexyl-1H-imidazol-2(3H)-selenone by Surface-Enhanced Raman Spectroscopy.

In the present research work, a selenium N-heterocyclic carbene (Se-NHC) complex/adduct was synthesized and characterized by using different analytical methods including FT-IR, 1HNMR, and 13CNMR. The antifungal activity of the Se-NHC complex against Aspergillus flavus (A. flavus) fungus was investigated with disc diffusion assay. Moreover, the biochemical changes occurring in this fungus due to exposure of different concentrations of the in-house synthesized compound are characterized by surface-enhanced Raman spectroscopy (SERS) and are illustrated in the form of SERS spectral peaks. SERS analysis yields valuable information about the probable mechanisms responsible for the antifungal effects of the Se-NHC complex. As demonstrated by the SERS spectra, this Se-NHC complex caused denaturation and conformational changes in the proteins as well as decomposition of the fungal cell membrane. The SERS spectra were analyzed using two chemometric tools such as principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). The fungal samples' SERS spectra were differentiated using PCA, while various groups of spectra were discriminated with ultrahigh sensitivity (98%), high specificity (99.7%), accuracy (100%), and area under the receiver operating characteristic curve (87%) using PLS-DA.

Agonistic antibacterial potential of Loigolactobacillus coryniformis BCH-4 metabolites against selected human pathogenic bacteria: An in vitro and in silico approach.

Lactic acid bacteria are known to produce numerous antibacterial metabolites that are active against various pathogenic microbes. In this study, bioactive metabolites from the cell free supernatant of Loigolactobacillus coryniformis BCH-4 were obtained by liquid-liquid extraction, using ethyl acetate, followed by fractionation, using silica gel column chromatography. The collected F23 fraction effectively inhibited the growth of pathogenic bacteria (Escherichia coli, Bacillus cereus, and Staphylococcus aureus) by observing the minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC). The evaluated values of MIC were 15.6 ± 0.34, 3.9 ± 0.59, and 31.2 ± 0.67 µg/mL and MBC were 15.6 ± 0.98, 7.8 ± 0.45, and 62.5 ± 0.23 µg/mL respectively, against the above-mentioned pathogenic bacteria. The concentration of F23 fraction was varying from 1000 to 1.9 µg/mL. Furthermore, the fraction also exhibited sustainable biofilm inhibition. Using the Electrospray Ionization Mass Spectrometry (ESI-MS/MS), the metabolites present in the bioactive fraction (F23), were identified as phthalic acid, myristic acid, mangiferin, 16-hydroxylpalmatic acid, apigenin, and oleandomycin. By using in silico approach, docking analysis showed good interaction of identified metabolites and receptor proteins of pathogenic bacteria. The present study suggested Loigolactobacillus coryniformis BCH-4, as a promising source of natural bioactive metabolites which may receive great benefit as potential sources of drugs in the pharmacological sector.

Spinal meningiomas: Management and outcomes.

Spinal meningiomas are relatively rare, benign, intradural, extramedullary tumours, that are typically slow-growing and well-defined. Surgery is always the first line for treating spinal meningiomas. Here, we have discussed the existing literature on spinal meningiomas and the role of surgery in determining the outcomes.

Prospective Assessment of the Prevalence of Enter Hyperoxalosis in Kidney Transplant Candidates.

Enteric hyperoxalosis (EH) is an emerging cause of kidney transplantation (KT) dysfunction. We sought to determine the prevalence of EH and factors that affect plasma oxalate (POx) among at-risk KT candidates. Methods: We prospectively measured POx among KT candidates evaluated at our center from 2017 to 2020 with risk factors for EH namely bariatric surgery, inflammatory bowel disease, or cystic fibrosis. EH was defined by a POx ≥10 µmol/L. Period-prevalence of EH was calculated. We compared mean POx across 5 factors: underlying condition, chronic kidney disease (CKD) stage, dialysis modality, phosphate binder type, and body mass index. Results: Of 40 KT candidates screened, 23 had EH for a 4-y period prevalence of 58%. Mean POx was 21.6 ± 23.5 µmol/L ranging from 0 to 109.6 µmol/L. 40% of screened had POx >20 µmol/L. Sleeve gastrectomy was the most common underlying condition associated with EH. Mean POx did not differ by underlying condition (P = 0.27), CKD stage (P = 0.17), dialysis modality (P = 0.68), phosphate binder (P = 0.58), and body mass index (P = 0.56). Conclusions: Bariatric surgery and inflammatory bowel disease were associated with a high prevalence of EH among KT candidates. Contrary to prior studies, sleeve gastrectomy was also associated with hyperoxalosis in advanced CKD. POx concentrations observed in EH reached levels associated with tissue and potentially allograft deposition. Concentrations can be as high as that seen in primary hyperoxaluria. More studies are needed to assess if POx is indeed a modifiable factor affecting allograft function in patients with EH.

Subclinical hyperthyroidism presenting with hypokalemic periodic paralysis in the emergency department.

Subclinical hyperthyroidism (SH) is a condition in which blood levels of Thyroxine (T4) and Triiodothyronine (T3) are normal in the presence of low levels of thyroid-stimulating hormone (TSH). Patients with SH have either no symptoms or mild nonspecific symptoms. Hypokalemic periodic paralysis (HPP) is one of the rare presentations of overt hyperthyroidism; however, only a few cases are reported to date to occur with SH. This case report presents a case of a young Asian male who was admitted to the emergency department (ED) with paralysis of the lower extremities that progressed to the upper extremities and neck muscles in 2 days. Clinically, he was euthyroid; however, his thyroid profile revealed normal levels of T3 and T4 with undetectable TSH levels. This case report aims to add to the limited literature on SH that presents with HPP in the ED.

The Antibacterial and Larvicidal Potential of Bis-(2-Ethylhexyl) Phthalate from Lactiplantibacillus plantarum.

Lactic acid bacteria produce a variety of antibacterial and larvicidal metabolites, which could be used to cure diseases caused by pathogenic bacteria and to efficiently overcome issues regarding insecticide resistance. In the current study, the antibacterial and larvicidal potential of Bis-(2-ethylhexyl) phthalate isolated from Lactiplantibacillus plantarum BCH-1 has been evaluated. Bioactive compounds were extracted by ethyl acetate and were fractionated by gradient column chromatography from crude extract. Based on FT-IR analysis followed by GC-MS and ESI-MS/MS, the active compound was identified to be Bis-(2-ethylhexyl) phthalate. Antibacterial potential was evaluated by disk diffusion against E. coli (12.33 ± 0.56 mm inhibition zone) and S. aureus (5.66 ± 1.00 mm inhibition zone). Larvicidal potency was performed against Culex quinquefasciatus Say larvae, where Bis-(2-ethylhexyl) phthalate showed 100% mortality at 250 ppm after 72 h with LC50 of 67.03 ppm. Furthermore, after 72 h the acetylcholinesterase inhibition was observed as 29.00, 40.33, 53.00, 64.00, and 75.33 (%) at 50, 100, 150, 200, and 250 ppm, respectively. In comet assay, mean comet tail length (14.18 ± 0.28 µm), tail DNA percent damage (18.23 ± 0.06%), tail movement (14.68 ± 0.56 µm), comet length (20.62 ± 0.64 µm), head length (23.75 ± 0.27 µm), and head DNA percentage (39.19 ± 0.92%) were observed at 250 ppm as compared to the control. The current study for the first time describes the promising antibacterial and larvicidal potential of Bis-(2-ethylhexyl) phthalate from Lactiplantibacillus plantarum that would have potential pharmaceutical applications.

Bioprotection of Zea mays L. from aflatoxigenic Aspergillus flavus by Loigolactobacillus coryniformis BCH-4.

Fungal infection causes deterioration, discoloration, and loss of nutritional values of food products. The use of lactic acid bacteria has diverse applications in agriculture to combat pathogens and to improve the nutritional values of cereal grains. The current research evaluated the potential of Loigolactobacillus coryniformis BCH-4 against aflatoxins producing toxigenic Aspergillus flavus strain. The cell free supernatant (CFS) of Loig. coryniformis was used for the protection of Zea mays L. treated with A. flavus. No fungal growth was observed even after seven days. The FT-IR spectrum of untreated (T1: without any treatment) and treated maize grains (T2: MRS broth + A. flavus; T3: CFS + A. flavus) showed variations in peak intensities of functional group regions of lipids, proteins, and carbohydrates. Total phenolics, flavonoid contents, and antioxidant activity of T3 were significantly improved in comparison with T1 and T2. Aflatoxins were not found in T3 while observed in T2 (AFB1 and AFB2 = 487 and 16 ng/g each). HPLC analysis of CFS showed the presence of chlorogenic acid, p-coumaric acid, 4-hydroxybenzoic acid, caffeic acid, sinapic acid, salicylic acid, and benzoic acid. The presence of these acids in the CFS of Loig. coryniformis cumulatively increased the antioxidant contents and activity of T3 treated maize grains. Besides, CFS of Loig. coryniformis was passed through various treatments (heat, neutral pH, proteolytic enzymes and catalase), to observe its stability. It suggested that the inhibitory potential of CFS against A. flavus was due to the presence of organic acids, proteinaceous compounds and hydrogen peroxide. Conclusively, Loig. coryniformis BCH-4 could be used as a good bioprotecting agent for Zea mays L. by improving its nutritional and antioxidant contents.

Cyclo(L-Leucyl-L-Prolyl) from Lactobacillus coryniformis BCH-4 inhibits the proliferation of Aspergillus flavus: an in vitro to in silico approach.

Fungal spoilage led to a considerable economic loss of foodstuff which ultimately affects public health due to mycotoxins production. Moreover, the consumption of commercial antifungal drugs creates side effects and develops antifungal resistance. To overcome these challenges, the current work was aimed to investigate novel antifungal cyclic dipeptide (CDP) from Lactobacillus coryniformis (Loigolactobacillus coryniformis) BCH-4. CDPs have flexible, cyclic, and stable conformation. The proline-based CDPs provide additional structural compatibility and bio-functional values. Keeping in view, high-performance liquid chromatography (HPLC) was performed to explore cyclo(L-Leu-L-Pro) from L. coryniformis BCH-4. The HPLC detected concentration (135 ± 7.07 mg/mL) exhibited in vitro antifungal activity of 5.66 ± 0.57 mm (inhibitory zone) against Aspergillus flavus. Based on these results, cyclo(L-Leu-L-Pro) was used as a bioprotectant for selected food samples (grapes, lemon, cashew nuts, and almonds). A significant impact of cyclo(L-Leu-L-Pro) was observed in contrast with MRS broth (control) and cell-free supernatant. In silico molecular docking analysis of this CDP was carried out against FAD glucose dehydrogenase, dihydrofolate reductase, and urate oxidase of A. flavus as target proteins. Among these proteins, FAD glucose dehydrogenase exerted strong interactions with cyclo(L-Leu-L-Pro) having S-score of - 8.21. The results evaluated that the detected CDP has strong interactions with selected proteins, causing excellent growth inhibition of A. flavus. Therefore, cyclo(L-Leu-L-Pro) could be used as a potent bioprotectant against food-borne pathogenic fungi.

Rituximab-associated hypogammaglobulinemia in ANCA-associated vasculitis: Incidence and time course.

OBJECTIVE: Rituximab (RTX) is approved for remission induction and maintenance of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Observational studies demonstrate decline in immunoglobulin (IgG) in AAV post-RTX. The time course for the onset of hypogammaglobulinemia (Hypo-IgG) post-RTX is unknown. This is a key determinant in deciding whether to continue RTX for reinduction or maintenance of remission for AAV. We evaluated the trends of Hypo-IgG among AAV patients post-RTX therapies. METHODS: An observational single-tertiary-center study of AAV patients treated with RTX for remission induction or maintenance (induction therapy, maintenance therapy, and combined induction and maintenance therapy) between 1998 and 2018. Poisson regression was used to compare the inciden- ces of Hypo-IgG: mild (450-700 mg dL-1), moderate (200-450 mg dL-1), and severe (􏰃200 mg dL-1). Ig levels were measured every 3-6 months after RTX use. RESULTS: Mean (SD) age at last visit was 59 (16) years, 93% were Caucasians, 64% were females, and 71 (63%) had granulomatosis with polyangiitis (GPA). Hypo-IgG occurred in 47 patients: one (2%) severe, 13 (28%) moderate, and 33 (70%) mild. Lower incidences of mild Hypo-IgG post-RTX were seen during induction compared to maintenance (IR 5.04 per 100 000 days vs 5.45 per 100 000 days, incidence rate ratio (IRR) 1.08, 95% CI 0.34, 3.19). Moderate Hypo-IgG occurred at 2.29 per 100 000 days during induc- tion and 1.82 per 100 000 days during maintenance (IRR 0.79, 95% CI 0.08, 4.84). CONCLUSION: Hypo-IgG is common among AAV treated with RTX, occurring in 42% of patients in this single-center cohort. The nadir IgG levels occur during remission induction, and the IgG levels remain relatively stable or increase over time in those receiving RTX for remission maintenance.

Metabolomics of Dietary Acid Load and Incident Chronic Kidney Disease.

OBJECTIVE: Blood biomarkers of dietary intake are more objective than self-reported dietary intake. Metabolites associated with dietary acid load were previously identified in 2 chronic kidney disease (CKD) populations. We aimed to extend these findings to a general population, replicating their association with dietary acid load, and investigating whether the individual biomarkers were prospectively associated with incident CKD. METHODS: Among 15,792 participants in the Atherosclerosis Risk in Communities cohort followed up from 1987 to 1989 (baseline) to 2019, we evaluated 3,844 black and white men and women with dietary and metabolomic data in cross-sectional and prospective analyses. We hypothesized that a higher dietary acid load (using equations for potential renal acid load and net endogenous acid production) was associated with lower serum levels of 12 previously identified metabolites: indolepropionylglycine, indolepropionate, N-methylproline, N-δ-acetylornithine, threonate, oxalate, chiro-inositol, methyl glucopyranoside, stachydrine, catechol sulfate, hippurate, and tartronate. In addition, we hypothesized that lower serum levels of these 12 metabolites were associated with higher risk of incident CKD. RESULTS: Eleven out of 12 metabolites were significantly inversely associated with dietary acid load, after adjusting for demographics, socioeconomic status, health behaviors, health status, and estimated glomerular filtration rate: indolepropionylglycine, indolepropionate, N-methylproline, threonate, oxalate, chiro-inositol, catechol sulfate, hippurate, methyl glucopyranoside (α + ß), stachydrine, and tartronate. N-methylproline was inversely associated with incident CKD (hazard ratio: 0.95, 95% confidence interval: 0.91, 0.99, P = .01). The metabolomic biomarkers of dietary acid load significantly improved prediction of elevated dietary acid load estimated using dietary data, beyond covariates (difference in C statistics: 0.021-0.077, P ≤ 1.08 × 10-3). CONCLUSION: Inverse associations between candidate biomarkers of dietary acid load were replicated in a general population. N-methylproline, representative of citrus fruit consumption, is a promising marker of dietary acid load and could represent an important pathway between dietary acid load and CKD.

Mutational Diversity in the Quinolone Resistance-Determining Regions of Type-II Topoisomerases of Salmonella Serovars.

Quinolone resistance in bacterial pathogens has primarily been associated with mutations in the quinolone resistance-determining regions (QRDRs) of bacterial type-II topoisomerases, which are DNA gyrase and topoisomerase IV. Depending on the position and type of the mutation (s) in the QRDRs, bacteria either become partially or completely resistant to quinolone. QRDR mutations have been identified and characterized in Salmonella enterica isolates from around the globe, particularly during the last decade, and efforts have been made to understand the propensity of different serovars to carry such mutations. Because there is currently no thorough analysis of the available literature on QRDR mutations in different Salmonella serovars, this review aims to provide a comprehensive picture of the mutational diversity in QRDRs of Salmonella serovars, summarizing the literature related to both typhoidal and non-typhoidal Salmonella serovars with a special emphasis on recent findings. This review will also discuss plasmid-mediated quinolone-resistance determinants with respect to their additive or synergistic contributions with QRDR mutations in imparting elevated quinolone resistance. Finally, the review will assess the contribution of membrane transporter-mediated quinolone efflux to quinolone resistance in strains carrying QRDR mutations. This information should be helpful to guide the routine surveillance of foodborne Salmonella serovars, especially with respect to their spread across countries, as well as to improve laboratory diagnosis of quinolone-resistant Salmonella strains.

Higher Prevalence of Concurrent Thrombocytopenia in Patients Receiving Continuous Renal Replacement Therapy in the Cardiac Intensive Care Unit.

INTRODUCTION: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). OBJECTIVE: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. METHODS: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. RESULTS: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32-3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. CONCLUSION: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.

Chronic Active Antibody-Mediated Rejection Following COVID-19 Infection in a Kidney Transplant Recipient: A Case Report.

Kidney transplant recipients who develop coronavirus disease 2019 (COVID-19) are at increased risk of life-threatening illness, which often requires reducing immunosuppression despite the potential risk of causing an allograft rejection. Herein, we describe the clinical presentation and course of a kidney transplant recipient who acquired COVID-19 and was hospitalized with severe symptoms and hypoxemia. Upon admission, the patient was found to have elevated de novo donor-specific antibodies (DSA) yielding a positive cytotoxicity crossmatch and concurrent elevated plasma donor-derived cell-free DNA (dd-cfDNA) level, indicating a possible ongoing rejection despite improvement in his serum creatinine. Because of persistent positive COVID-19 tests and stable serum creatinine, a kidney allograft biopsy was initially deferred and his dd-cfDNA and DSA were monitored closely postdischarge. Three months later, because of persistent elevated dd-cfDNA and positive DSA, a kidney allograft biopsy was performed, which showed chronic active antibody-mediated rejection. Accordingly, the patient was treated with intravenous immunoglobulin and his maintenance immunosuppressive regimen was increased.

Pharmacotherapeutic options for kidney disease in HIV positive patients.

INTRODUCTION: Since the developmentof combined antiretroviral therapy (cART), HIV-associated mortality and the incidence of HIV-associated end-stage kidney disease (ESKD) has decreased. However, in the United States, an increase in non-HIV-associated kidney diseases within the HIV-positive population is expected. AREAS COVERED: In this review, the authors highlight the risk factors for kidney disease within an HIV-positive population and provide the current recommendations for risk stratification and for the monitoring of its progression to chronic kidney disease (CKD), as well as, treatment. The article is based on literature searches using PubMed, Medline and SCOPUS. EXPERT OPINION: The authors recommend clinicians (1) be aware of early cART initiation to prevent and treat HIV-associated kidney diseases, (2) be aware of cART side effects and discriminate those that may become more nephrotoxic than others and require dose-adjustment in the setting of eGFR ≤ 30ml/min/1.73m2, (3) follow KDIGO guidelines regarding screening and monitoring for CKD with a multidisciplinary team of health professionals, (4) manage other co-infections and comorbidities, (5) consider changing cART if drug induced toxicity is established with apparent eGFR decline of ≥ 10ml/min/1.73m2 or rising creatinine (≥0.5mg/dl) during drug-drug interactions, and (6) strongly consider kidney transplant in appropriately selected individuals with end stage kidney failure.