Advances in Vibrio-related infection management: an integrated technology approach for aquaculture and human health.

Vibrio species pose significant threats worldwide, causing mortalities in aquaculture and infections in humans. Global warming and the emergence of worldwide strains of Vibrio diseases are increasing day by day. Control of Vibrio species requires effective monitoring, diagnosis, and treatment strategies at the global scale. Despite current efforts based on chemical, biological, and mechanical means, Vibrio control management faces limitations due to complicated implementation processes. This review explores the intricacies and challenges of Vibrio-related diseases, including accurate and cost-effective diagnosis and effective control. The global burden due to emerging Vibrio species further complicates management strategies. We propose an innovative integrated technology model that harnesses cutting-edge technologies to address these obstacles. The proposed model incorporates advanced tools, such as biosensing technologies, the Internet of Things (IoT), remote sensing devices, cloud computing, and machine learning. This model offers invaluable insights and supports better decision-making by integrating real-time ecological data and biological phenotype signatures. A major advantage of our approach lies in leveraging cloud-based analytics programs, efficiently extracting meaningful information from vast and complex datasets. Collaborating with data and clinical professionals ensures logical and customized solutions tailored to each unique situation. Aquaculture biotechnology that prioritizes sustainability may have a large impact on human health and the seafood industry. Our review underscores the importance of adopting this model, revolutionizing the prognosis and management of Vibrio-related infections, even under complex circumstances. Furthermore, this model has promising implications for aquaculture and public health, addressing the United Nations Sustainable Development Goals and their development agenda.

Structural dynamics and mechanistic action guided engineering of lipolytic enzymes.

Lipases have been established as important biocatalysts in several industrial applications, owing to their diverse substrate specificity. The availability of data on three-dimensional crystal structures for various lipases offers an opportunity for modulating their structural and functional aspects to design and engineer better versions of lipases. With the aim of investigating the structural components governing the extremophilic behavior of lipases, structural analysis of microbial lipases was performed using advanced bioinformatics and molecular dynamics simulation approaches. In sequences and functionally distinct alkaliphilic and thermophilic lipases were investigated for their functional properties to understand the distinguishing features of their structures. The alkaliphilic lipase from Bacillus subtilis (LipA) showed conformational changes in the loop region Ala132-Met137, subsequently, the active site residue His156 shows two conformations, toward the active site nucleophilic residues Ser77 and away from the Ser77. Interestingly, the active site of LipA is more solvent-exposed and can be correlated with the adoption of an open conformation which might extend and expose the active site region to solvents during the catalysis process. Furthermore, the MD simulation of thermophilic lipase from marine Streptomyces (MAS1) revealed the role of N- and C-terminal regions with disulfide bridges and identified a metal ion binding site that facilitates the enzyme stability. The novel thermo-alkaliphilic lipase can be designed to integrate the stability features of MAS1 into the alkaliphilic LipA. These structural-level intrinsic characteristics can be used for lipase engineering to amend the lipase activity and stability as per the requirements of the industrial processes.

Recurrent mutations in Refractory/Relapsed Diffuse Large B cell Lymphoma by targeted gene sequencing.

Introduction-Whole genome sequencing of diffuse large B-cell lymphoma [DLBCL] has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and methods- A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and nine eight cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results- A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion-The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.

Antifungal activity of sustainable histone deacetylase inhibitors against planktonic cells and biofilms of Candida spp. and Cryptococcusneoformans.

The limited therapeutic options for fungal infections and the increased incidence of fungal strains resistant to antifungal drugs, especially Candida spp., require the development of new antifungal drugs and strategies. Histone deacetylase inhibitors (HDACi), like vorinostat, have been studied in cancer treatment and have antifungal effects, acting alone or synergistically with classical antifungals. Here we investigated the antifungal activity of two novel sustainable HDACi (LDT compounds) based on vorinostat structure. Molecular docking simulation studies reveal that LDT compounds can bind to Class-I HDACs of Candida albicans, C. tropicalis, and Cryptococcus neoformans, which showed similar binding mode to vorinostat. LDT compounds showed moderate activity when tested alone against fungi but act synergistically with antifungal azoles against Candida spp. They reduced biofilm formation by more than 50% in C. albicans (4 µg/mL), with the main action in fungal filamentation. Cytotoxicity of the LDT compounds against RAW264.7 cells was evaluated and LDT536 demonstrated cytotoxicity only at the concentration of 200 µmol/L, while LDT537 showed IC50 values of 29.12 µmol/L. Our data indicated that these sustainable and inexpensive HDACi have potential antifungal and antibiofilm activities, with better results than vorinostat, although further studies are necessary to better understand the mechanism against fungal cells.

Fungal infections are neglected diseases that affect more than a billion people worldwide. Some histone deacetylase inhibitors can act against fungal cells. Our data reveal that HDACi LDT536 and LDT537 have potential antibiofilm and antifungal activities.

Association of CT Findings With Perineural Invasion in Gallbladder Cancer: Preliminary Assessment.

Perineural invasion (PNI) indicates a worse prognosis for patients with gallbladder cancer (GBC). This preliminary retrospective study included 19 patients with GBC who under-went contrast-enhanced CT in the 4 weeks before undergoing surgical resection. GBC showed PNI on pathologic assessment in eight of 19 patients. On CT, wall thickening morphology had sensitivity of 75.0% and specificity of 81.8% for PNI; soft-tissue stranding around the celiac plexus had sensitivity of 62.5% and specificity of 100.0% for PNI.

Structural Distortion of ß-Cyclodextrin Plays a Key Role in the pH-dependent Host-Guest Chemistry with Doxorubicin, Evident by the Electrochemical and Molecular Dynamics Approach.

ß-Cyclodextrin (ß-CD) is the potential drug carrier to deliver antitumor drugs like doxorubicin (DOX). However, the mechanism for the inclusion complex formation is still unclear and needs to be explored. This study investigated the effect of pH on the inclusion of DOX into thiolated ß-CD (ß-CD-SH) by electrochemical and molecular dynamics (MD) simulation. The electrochemical study shows a clear difference at different pH values. The redox peak due to the DOX is strongly influenced by pH. At neutral pH, the peak intensity decreases with time, while slight variation is observed at acidic and basic pH, depicting the association of DOX to the ß-CD-SH cavity at neutral pH. Also, due to the association, the charge transfer resistance variation increased with time at neutral pH and decreased at basic and acidic pH. The electrochemical study was further supported by MD simulation, suggesting that the cyclodextrin (CD) ring gets slightly elongated due to the flipping of glucose units, specifically at neutral pH leading to a strong association. Also, another significant result observed that the DOX forms an inclusion complex with ß-CD-SH in quinol conformation, not in quinone. Briefly, the study provides the necessary molecular binding information for designing an effective ß-CD-based targeted drug delivery system.

Pharmacoinformatic approach to identify potential phytochemicals against SARS-CoV-2 spike receptor-binding domain in native and variants of concern.

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) pathogenesis is initiated by the binding of SARS-CoV-2 spike (S) protein with the angiotensin-converting enzyme 2 receptor (ACE2R) on the host cell surface. The receptor-binding domain (RBD) of the S protein mediates the binding and is more prone to mutations resulting in the generation of different variants. Recently, molecules with the potential to inhibit the interaction of S protein with ACE2R have been of interest due to their therapeutic value. In this context, the present work was performed to identify potential RBD binders from the Indian medicinal plant's phytochemical database through virtual screening, molecular docking, and molecular dynamic simulation. Briefly, 1578 compounds filtered from 9596 phytochemicals were chosen for screening against the RBD of the native SARS-CoV-2 S protein. Based on the binding energy, the top 30 compounds were selected and re-docked individually against the native and five variants of concern (VOCs: alpha, beta, gamma, delta, and omicron) of SARS-CoV-2. Four phytochemicals, namely withanolide F, serotobenine, orobanchol, and gibberellin A51, were found to be potential RBD binders in native and all SARS-CoV-2 VOCs. Among the four, withanolide F exhibited lower binding energy (- 10.84 to - 8.56 kcal/mol) and better ligand efficiency (- 0.3 to - 0.25) against all forms of RBD and hence was subjected to a 100 ns MD simulation which confirmed its stringent binding to the RBDs in native and VOCs. The study prioritizes withanolide F as a prospective COVID-19 (Coronavirus disease) therapeutic agent based on the observations. It warrants deeper investigations into the four promising leads for understanding their precise therapeutic value.

A Century of Laffer-Ascher Syndrome.

Laffer-Ascher syndrome is characterized by double lips, blepharochalasis, and nongoiter thyroid enlargement. The syndrome was first described in 1923 and several case reports have been published thereafter. We illustrate the syndrome through a case of a 46-year-old woman who presented with both upper and lower double lips and blepharochalasis, and review the literature published. Thyroid involvement is the most inconsistent feature of the syndrome complex described in reported cases.

Safety and Diagnostic Yield of 68Ga Prostate-specific Membrane Antigen PET/CT-guided Robotic-assisted Transgluteal Prostatic Biopsy.

Background Transrectal US-guided biopsy with or without MRI fusion is performed for diagnosing prostate cancer (PCa) but has limitations. Gallium 68 (68Ga) prostate-specific membrane antigen (PSMA) PET/CT-guided targeted biopsy has the potential to improve diagnostic yield of PCa. Purpose To evaluate the safety and diagnostic yield of 68Ga PSMA PET/CT-guided, robotic-arm assisted transgluteal prostatic biopsy. Materials and Methods In this single-center nonrandomized prospective trial, participants with a clinical suspicion of PCa (serum prostate-specific antigen level > 4 ng/mL) were recruited from January 2019 to September 2020. After whole-body 68Ga PSMA PET/CT, participants with PSMA-avid intraprostatic lesions underwent PET-guided transgluteal biopsy by using an automated robotic arm. To assess safety and diagnostic yield, procedure-related complications and histopathologic results were documented. Pain during the procedure was scored by a visual analog scale. Descriptive statistics were applied; qualitative variables were reported in percentages. Results Seventy-eight participants (mean age, 66 years ± 7 [standard deviation]; 36 participants [46%] with prior negative results at transrectal US-guided biopsy) were enrolled. Fifty-six (72%) participants had PSMA-avid lesions (prior negative results at transrectal US-guided biopsy in 22 of 56 [39%]) and underwent targeted biopsy. PCa was confirmed in 54 of 56 (96%) participants, and clinically significant PCa (Gleason score ≥ 7) was confirmed in 24 of 54 (44%). Two participants had nonrepresentative samples that required rebiopsy. All participants experienced pain during the procedure, mild (median visual analog scale score, 1; interquartile range, 1-2) in 36 of 56 (64%) and moderate (median visual analog scale score, 5; interquartile range, 5-6) in 20 of 56 (36%). Postprocedure complications were noted in five of 56 (9%) participants and were minor (hematuria, four participants; hematospermia, one participant; and gluteal pain, two participants). No participant developed a postprocedural infection. Conclusion Transgluteal prostate-specific membrane antigen (PSMA) PET/CT-guided, robotic-targeted prostatic biopsy is safe with a high diagnostic yield of prostate cancer for PSMA-avid lesions. Clinical trial registration no. NCT05022576 © RSNA, 2022.

Dissociation between the critical role of ClpB of Francisella tularensis for the heat shock response and the DnaK interaction and its important role for efficient type VI secretion and bacterial virulence.

Francisella tularensis, a highly infectious, intracellular bacterium possesses an atypical type VI secretion system (T6SS), which is essential for its virulence. The chaperone ClpB, a member of the Hsp100/Clp family, is involved in Francisella T6SS disassembly and type VI secretion (T6S) is impaired in its absence. We asked if the role of ClpB for T6S was related to its prototypical role for the disaggregation activity. The latter is dependent on its interaction with the DnaK/Hsp70 chaperone system. Key residues of the ClpB-DnaK interaction were identified by molecular dynamic simulation and verified by targeted mutagenesis. Using such targeted mutants, it was found that the F. novicida ClpB-DnaK interaction was dispensable for T6S, intracellular replication, and virulence in a mouse model, although essential for handling of heat shock. Moreover, by mutagenesis of key amino acids of the Walker A, Walker B, and Arginine finger motifs of each of the two Nucleotide-Binding Domains, their critical roles for heat shock, T6S, intracellular replication, and virulence were identified. In contrast, the N-terminus was dispensable for heat shock, but required for T6S, intracellular replication, and virulence. Complementation of the ΔclpB mutant with a chimeric F. novicida ClpB expressing the N-terminal of Escherichia coli, led to reconstitution of the wild-type phenotype. Collectively, the data demonstrate that the ClpB-DnaK interaction does not contribute to T6S, whereas the N-terminal and NBD domains displayed critical roles for T6S and virulence.

Enantioseparation of linezolid and tedizolid using validated high-performance liquid chromatographic method.

This paper reports the separation of two chiral antibacterial agents namely, linezolid and tedizolid using a validated high-performance liquid chromatographic method. In the current work, glycopeptide-based chiral column, CHIROBIOTIC® V2 (5-µm particle size, L × I.D. 25 cm × 4.6 mm) was employed with a mobile phase containing methanol and 0.15% aq. trifluoracetic acid (75:25%, v/v) in isocratic elution approach at flow rate of 1 ml min-1 . The separation condition was customized (in terms of resolution values and retention times) was carried out by changing the content of the mobile phase, column temperature, flow rate, and so on. Results showed that the chromatographic separation was achieved within 15 min and average resolution values were 4.6 and 4.8 for tedizolid and linezolid, respectively. The detection limit values were 14.85 and 14.16 ng ml-1 , respectively, for tedizolid enantiomers. Further, validation of separation parameters was performed by considering the international conference on harmonization guidelines, and ultimately, the mechanism of chiral recognition was also established.

Retrospective single-center experience with OEPA/COPDAC and PET-CT based strategy for pediatric Hodgkin lymphoma in a LMIC setting.

ABVD regimen for Hodgkin lymphoma (HL) is frequently used in children and young adults in low-middle income countries (LMIC). The feasibility and safety data for 'non-ABVD' protocols from LMIC is limited. The retrospective study was conducted in a single center in India. The Euronet PHL-C1 based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following two OEPA cycles. Radiotherapy was administered for inadequate PET response. During the 10-year period, 143 patients with HL were treated. The mean age was 7.8 ± 2.5 years. Bulky disease was observed in 82 (59%). Treatment abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET response was observed in 41/119 (34.4%), of which 56.1% received radiotherapy. Twelve (29.3%) patients who were supposed to receive radiotherapy received 2-cycles of COPDAC instead. Sixty-nine episodes of febrile neutropenia were observed in 54 patients. Treatment-related mortality (TRM) was observed in 7 (5.3%). The majority of episodes of febrile neutropenia (61%) and TRM (86%) occurred in the first cycle of OEPA. The 4-year event-free survival (EFS) and overall survival (OS) were 86.2 ± 3.4% and 93.5 ± 2.2%, respectively. Nine (6.3%) patients relapsed. Bulky disease lacked association with inadequate PET response (p = .800) or relapse (p = 1.000). OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently in the first cycle of OEPA. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.

Improved Binding Affinity of Omicron's Spike Protein for the Human Angiotensin-Converting Enzyme 2 Receptor Is the Key behind Its Increased Virulence.

The new variant of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), Omicron, has been quickly spreading in many countries worldwide. Compared to the original virus, Omicron is characterized by several mutations in its genomic region, including the spike protein's receptor-binding domain (RBD). We have computationally investigated the interaction between the RBD of both the wild type and Omicron variant of SARS-CoV-2 with the human angiotensin-converting enzyme 2 (hACE2) receptor using molecular dynamics and molecular mechanics-generalized Born surface area (MM-GBSA)-based binding free energy calculations. The mode of the interaction between Omicron's RBD with the hACE2 receptor is similar to the original SARS-CoV-2 RBD except for a few key differences. The binding free energy difference shows that the spike protein of Omicron has an increased affinity for the hACE2 receptor. The mutated residues in the RBD showed strong interactions with a few amino acid residues of hACE2. More specifically, strong electrostatic interactions (salt bridges) and hydrogen bonding were observed between R493 and R498 residues of the Omicron RBD with D30/E35 and D38 residues of the hACE2, respectively. Other mutated amino acids in the Omicron RBD, e.g., S496 and H505, also exhibited hydrogen bonding with the hACE2 receptor. A pi-stacking interaction was also observed between tyrosine residues (RBD-Tyr501: hACE2-Tyr41) in the complex, which contributes majorly to the binding free energies and suggests that this is one of the key interactions stabilizing the formation of the complex. The resulting structural insights into the RBD:hACE2 complex, the binding mode information within it, and residue-wise contributions to the free energy provide insight into the increased transmissibility of Omicron and pave the way to design and optimize novel antiviral agents.

Larvicidal potential and residual activity effect of kinnow peel oil against Aedes aegypti L.

BACKGROUND & OBJECTIVES: Transmission of dengue virus by Aedes aegypti mosquito is one of the major global health concerns. The present study was aimed to explore the larvicidal potential of oil extracted from kinnow peel waste to be used as an efficient, economic and safe agent against Ae. aegypti. METHODS: Kinnow peel oil was extracted and its five concentrations at 40, 50, 60, 70 and 80 ppm were tested against 4th instar larvae of Ae. aegypti. Larval mortality (%) and LC50 and LC90 values of toxicity were determined followed by evaluation of the residual activity effect of its leftover effective concentration on larval mortality, development and emergence. Effect of storage (2, 4 and 6 months) on larvicidal potential of kinnow peel oil was also determined. RESULTS: Out of the tested concentrations, 70 ppm of kinnow peel oil was found to be the effective concentration against 4th instar larvae of Ae. aegypti. LC50 and LC90 toxicity values were 47.26 and 61.56 ppm, respectively. No residual activity effect in terms of larval mortality was found, however a significant delay in development (L4 to adult) was observed after placing new larvae in the leftover effective oil concentration. No effect of storage on larvicidal potential of 2, 4 and 6 months old kinnow peel oil in comparison to freshly extracted oil was observed. INTERPRETATION & CONCLUSION: Kinnow peel oil proved to have a good potential as a biolarvicide against Ae. aegypti and could be used as an effective and eco-friendly mosquito control agent in the future.

Seroprevalence and immunological characterization of Trypanosoma evansi infection in livestock of four agro-climatic zones of Himachal Pradesh, India.

Trypanosoma evansi, a hemoflagellate protozoan parasite, causes wasting disease called surra in wide range of animals. Although the organism has been reported from various parts of India, data generated from organized epidemiological study is still in infancy in majority states of India. In the present study, livestock of Himachal Pradesh, India, was targeted for epidemiological investigation of T. evansi infections. A total of 440 equines and 444 cattle serum samples were collected from four agro-climatic zones. Furthermore, serum samples of 280 buffaloes from three different agro-climatic zones of Himachal Pradesh were also collected and evaluated for the presence of T. evansi infection by indirect ELISA. Data generated showed higher prevalence in buffalo (23.57%) followed by cattle (22.52%) and equines (1.82%). Disease was found to be more prevalent (P < 0.01) in cattle of lower altitude as compared to those of higher altitudes. No significant variation was seen in prevalence of disease on the basis of age and sex of the animals. Serum biochemical analysis revealed increased levels of BUN in T. evansi-infected equines. Levels of liver function enzymes such as ALT/GGT and AST were found to be significantly elevated (P < 0.01) in seropositive animals whereas glucose levels were significantly lower in surra-seropositive animals as compared to seronegative animals. Immunoblot analysis of whole cell lysate (WCL) antigen of T. evansi using surra-seropositive samples of equines showed immunodominant bands in the range of 100-25 kDa. Bovine-seropositive samples recognized polypeptide bands in the range of 85-32 kDa, including protein clusters of 52-55 and 48-46 kDa. Polypeptide cluster of 62-66 kDa was found common in seropositive samples of bovines and equines from all agro-climatic zones. T. evansi was found to be highly prevalent in livestock of Himachal Pradesh, and thus, there is dire need for designing of proper control strategies against surra.

In vitro anti-trypanosomal effect of ivermectin on Trypanosoma evansi by targeting multiple metabolic pathways.

High cytotoxicity and increasing resistance reports of existing chemotherapeutic agents against T. evansi have raised the demand for novel, potent, and high therapeutic index molecules for the treatment of surra in animals. In this regard, repurposing approach of drug discovery has provided an opportunity to explore the therapeutic potential of existing drugs against new organism. With this objective, the macrocyclic lactone representative, ivermectin, has been investigated for the efficacy against T. evansi in the axenic culture medium. To elucidate the potential target of ivermectin in T. evansi, mRNA expression profile of 13 important drug target genes has been studied at 12, 24, and 48 h interval. In the in vitro growth inhibition assay, ivermectin inhibited T. evansi growth and multiplication significantly (p < 0.001) with IC50 values of 13.82 µM, indicating potent trypanocidal activity. Cytotoxicity assays on equine peripheral blood mononuclear cells (PBMCs) and Vero cell line showed that ivermectin affected the viability of cells with a half-maximal cytotoxic concentration (CC50) at 17.48 and 22.05 µM, respectively. Data generated showed there was significant down-regulation of hexokinase (p < 0.001), ESAG8 (p < 0.001), aurora kinase (p < 0.001), casein kinase 1 (p < 0.001), topoisomerase II (p < 0.001), calcium ATPase 1 (p < 0.001), ribonucleotide reductase I (p < 0.05), and ornithine decarboxylase (p < 0.01). The mRNA expression of oligopeptidase B remains refractory to the exposure of the ivermectin. The arginine kinase 1 and ribonucleotide reductase II showed up-regulation on treatment with ivermectin. The ivermectin was found to affect glycolytic pathways, ATP-dependent calcium ATPase, cellular kinases, and other pathway involved in proliferation and maintenance of internal homeostasis of T. evansi. These data imply that intervention with alternate strategies like nano-formulation, nano-carriers, and nano-delivery or identification of ivermectin homologs with low cytotoxicity and high bioavailability can be explored in the future as an alternate treatment for surra in animals.

Diagnostic values of 68Ga-labelled DOTANOC PET/CT imaging in pediatric patients presenting with paraneoplastic opsoclonus myoclonus ataxia syndrome.

OBJECTIVES: Opsoclonus myoclonus ataxia (OMA) syndrome, also known as "Kinsbourne syndrome" or "dancing eye syndrome," is a rare, paraneoplastic entity which may be associated with pediatric neuroblastic tumors and carry a grave prognosis. We aimed to evaluate the role of 68Ga DOTANOC PET/CT for detecting neuroblastic tumors in patients with OMA syndrome. METHODS: We retrospectively evaluated the 68Ga-DOTANOC PET/CT data of pediatric patients presenting with OMA syndrome from March 2012 to November 2018. A somatostatin receptor (SSTR)-expressing lesion with corresponding morphological change on CT image was considered PET-positive, while no abnormal SSTR expression or lesion was noticed in PET-negative patients. Histopathology and/or clinical/imaging follow-up (minimum one year) was considered a reference standard for comparing the PET/CT findings. The results of 68Ga-DOTANOC PET/CT were also compared with 131I MIBG whole-body scintigraphy, which was available in five patients. RESULTS: Of 38 patients (13 males, 25 females, aged 3-96 months), 18 (47.3%) had SSTR-expressing lesions (PET-positive), and histopathology revealed neuroblastic tumors in 17/18 lesions (neuroblastoma 14, ganglioneuroblastoma 2, and ganglioneuroma 1) and reactive hyperplasia in 1/18. The remaining 20/38 (52.6%) patients did not demonstrate SSTR-expressing lesions (PET-negative) and had an uneventful follow-up. The average SUVmax of the PET-positive lesions was 10.3 (range 2.8-34.5). The PET/CT results revealed 17 true-positive, one false-positive, 20 true-negative, and zero false-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 95.2%, 94.4%, 100%, and 97.3% respectively. CONCLUSIONS: 68Ga-DOTANOC PET/CT identified neuroblastic tumors with a high diagnostic accuracy in our cohort compared to histology and follow-up. KEY POINTS: • Opsoclonus myoclonus ataxia (OMA) syndrome or "dancing eye syndrome" is a rare paraneoplastic entity which may be associated with pediatric neuroblastic tumors with a grave prognosis. • 123I/131I MIBG imaging has a proven role for functional imaging in neuroblastoma or patients with OMA, but the role of 68Ga-DOTANOC PET/CT is not yet studied. • 68Ga-labelled DOTANOC PET/CT (SSTR) imaging, in our cohort, was able to positively identify neuroblastic tumors with high diagnostic accuracy when compared with histology.

Differentiating benign and malignant pancreatic masses: Ga-68 PSMA PET/CT as a new diagnostic avenue.

OBJECTIVE: Differentiation of malignant and benign pancreatic lesions on anatomical imaging is difficult in some cases with overlapping features. Prostate-specific membrane antigen (PSMA) is overexpressed during angioneogenesis in many tumors. We aimed to evaluate the PSMA expression in pancreatic lesions to differentiate these lesions and explore the performance of Ga-68 PSMA-PET/CT vis-a-vis F-18 FDG-PET/CT. METHODS: Patients with pancreatic lesions on conventional imaging were prospectively recruited. All the patients underwent a whole-body F-18 FDG-PET/CT and a regional abdominal Ga-68 PSMA-PET/CT. Focal tracer uptake (FDG or PSMA) on PET images was considered positive. Histopathology and/or cytopathology were considered the reference standard. RESULTS: A total of forty patients (27 males, mean age 55.3 ± 9.8, range 37-71 years) were enrolled. Of these, 19 were diagnosed as malignant on histopathology/cytology. Patients with benign lesions showed no worsening of symptoms for at least 6 months on follow-up. FDG-PET/CT revealed 17 true-positive (TP), 9 false-positive (FP), 12 true-negative (TN), and 2 false-negative (FN) findings, whereas PSMA-PET/CT had 18 TP, 2 FP, 19 TN, and 1 FN finding. The sensitivity, specificity, PPV, NPV, and accuracy for FDG-PET/CT were 89.5%, 57.1%, 65.4%, 85.7%, and 72.5%, respectively, while for PSMA-PET/CT were 94.7%, 90.5%, 90%, 95%, and 92.5%, respectively. ROC curve analysis showed that the SUVmax value of 4.8 on PSMA-PET/CT could predict the malignant potential of a lesion with a specificity of 90.5% and a sensitivity of 84.2%. CONCLUSIONS: Ga-68 PSMA-PET/CT imaging helped in establishing a non-invasive pre-operative diagnosis of primary pancreatic malignancy with a higher degree of specificity and accuracy compared with FDG-PET/CT. KEY POINTS: • Conventional imaging such as CT and MRI are unable to reliably differentiate localized malignant pancreatic lesion from benign lesions mimicking malignancy such as mass-forming pancreatitis. • FDG PET/CT helps in detecting malignant foci in view of their increased glucose metabolism. However, it may be falsely positive in inflammatory lesions which may occasionally hinder its ability to differentiate between benign and malignant lesions. • Apart from prostatic malignancy, PSMA is overexpressed in neovasculature of many non-prostatic malignancies. The present study highlights that Ga68 PSMA PET/CT performed better in diagnosing malignancy non-invasively than FDG-PET/CT with a higher PPV (90.5% vs. 65.4%) and accuracy (92.5% vs. 72.5%).

Diagnostic Accuracy of 68Ga-PSMA PET/CT for Initial Detection in Patients With Suspected Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND. Early diagnosis is important in the overall management of prostate cancer (PCa). Gallium-68-labeled prostate-specific membrane antigen (PSMA) PET/CT has an established role in the detection of recurrent disease and staging of patients with intermediate- to high-risk PCa. However, only a small number of studies have evaluated its role in the initial diagnosis of PCa. OBJECTIVE. This systematic review was conducted to evaluate the diagnostic performance of 68Ga-PSMA PET/CT in the initial detection of PCa in patients with clinical or biochemical findings suspicious for PCa. EVIDENCE ACQUISITION. This systematic review followed PRISMA guidelines. Searches in PubMed, Scopus, and Embase were conducted using relevant keywords, and articles published through April 30, 2020, were included. Using histopathology results as the reference standard, the numbers of true- and false-positives and true- and false-negatives were extracted. Pooled estimates of diagnostic test accuracy-including sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and summary ROC (SROC) curve-were generated using bivariate random-effects meta-analysis. EVIDENCE SYNTHESIS. Seven studies comprising 389 patients were included in the systematic review and meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for the initial diagnosis of PCa using 68Ga-PSMA PET/CT were 0.97 (95% CI, 0.90-0.99), 0.66 (95% CI, 0.52-0.78), 2.86 (95% CI, 1.95-4.20), and 0.05 (95% CI, 0.01-0.15), respectively. The test had high accuracy; the area under the SROC curve was 0.91 (95% CI, 0.88-0.93). CONCLUSION. Gallium-68-labeled PSMA PET/CT had excellent sensitivity and negative likelihood ratio in the initial diagnosis of PCa in patients with clinical or biochemical findings suspicious for PCa. CLINICAL IMPACT. Gallium-68-labeled PSMA PET/CT had high diagnostic accuracy for the initial detection of PCa in patients with clinical or biochemical findings suspicious for PCa and has potential utility as a rule-out test for these patients.

FDG-PET-CT Enterography Helps Determine Clinical Significance of Suspected Ileocecal Thickening: A Prospective Study.

BACKGROUND: Ileocecal thickening (ICT) on imaging could result from diverse etiologies but may also be clinically insignificant. AIM: Evaluation of role of combined 2-deoxy-2-fluorine-18-fluoro-D-glucose(18F-FDG)-positron emission tomography and computed tomographic enterography (PET-CTE) for determination of clinical significance of suspected ICT. METHODS: This prospective study enrolled consecutive patients with suspected ICT on ultrasound. Patients were evaluated with PET-CTE and colonoscopy. The patients were divided into: Group A (clinically significant diagnosis) or Group B (clinically insignificant diagnosis) and compared for various clinical and radiological findings. The two groups were compared for maximum standardized uptake values of terminal ileum, ileo-cecal valve, cecum and overall. RESULTS: Of 34 patients included (23 males, mean age: 40.44 ± 15.40 years), 12 (35.3%) had intestinal tuberculosis, 11 (32.4%) Crohn's disease, 3 (8.8%) other infections, 1 (2.9%) malignancy, 4 (11.8%) non-specific terminal ileitis while 3 (8.8%) had normal colonoscopy and histology. The maximum standardized uptake value of the ileocecal area overall (SUVmax-ICT-overall) was significantly higher in Group A (7.16 ± 4.38) when compared to Group B (3.62 ± 9.50, P = 0.003). A cut-off of 4.50 for SUVmax-ICT-overall had a sensitivity of 70.37% and a specificity of 100% for prediction of clinically significant diagnosis. Using decision tree model, the SUVmax-ICT with a cut-off of 4.75 was considered appropriate for initial decision followed by the presence of mural thickening in the next node. CONCLUSION: PET-CTE can help in discrimination of clinically significant and insignificant diagnosis. It may help guide the need for colonoscopy in patients suspected to have ICT on CT.