PET/CT in the Evaluation of CAR-T Cell Immunotherapy in Hematological Malignancies.

Chimeric antigen receptor (CAR)-T cell-based immunotherapy has emerged as a path-breaking strategy for certain hematological malignancies. Assessment of the response to CAR-T therapy using quantitative imaging techniques such as positron emission tomography/computed tomography (PET/CT) has been broadly investigated. However, the definitive role of PET/CT in CAR-T therapy remains to be established. [18F]FDG PET/CT has demonstrated high sensitivity and specificity for differentiating patients with a partial and complete response after CAR-T therapy in lymphoma. The early therapeutic response and immune-related adverse effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome can also be detected on [18F]FDG PET images. In otherwise asymptomatic lymphoma patients with partial response following CAR-T therapy, the only positive findings could be abnormal PET/CT results. In multiple myeloma, a negative [18F]FDG PET/CT after receiving B-cell maturation antigen-directed CAR-T therapy has been associated with a favorable prognosis. In leukemia, [18F]FDG PET/CT can detect extramedullary metastases and treatment responses after therapy. Hence, PET/CT is a valuable imaging tool for patients undergoing CAR-T therapy for pretreatment evaluation, monitoring treatment response, assessing safety, and guiding therapeutic strategies. Developing guidelines with standardized cutoff values for various PET parameters and tumor cell-specific tracers may improve the efficacy and safety of CAR-T therapy.

Imaging features of soft-tissue infections.

Skin and soft tissues are among the most common sites of infections. Infections can involve the superficial epidermis to deep muscles and bones. Most infections spread through contiguous structures, although hematogenous spread can occur in the setting of an immunocompromised state and with atypical infections. While clinical diagnosis of infections is possible, it often lacks specificity, necessitating the use of imaging for confirmation. Cross-sectional imaging with US, CT, and MRI is frequently performed not just for diagnosis, but to delineate the extent of infection and to aid in management. Nonetheless, the imaging features have considerable overlap, and as such, it is essential to integrate imaging features with clinical features for managing soft tissue infections. Radiologists must be aware of the imaging features of different infections and their mimics, as well as the pros and cons of each imaging technique to properly use them for appropriate clinical situations. In this review, we summarize the most recent evidence-based features of key soft tissue infections.

Colorimetric detection of hydrogen peroxide and cholesterol using Fe3O4-brominated graphene nanocomposite.

Fe3O4-brominated graphene (Fe3O4-GBR) nanocomposites were synthesized via an in situ method using the precursors FeSO4.7H2O and GBR in different (1:1, 1:2, 2:1, 1:5, 1:10, 1:20, and 5:1) weight ratios at pH 11.5. The Fe3O4-GBR (1:5) nanocomposite in combination with H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB) showed swift and superior intrinsic peroxidase mimetic enzyme activity compared with the other Fe3O4-GBR composites, GBR and Fe3O4, as observed by colorimetry. It was characterized using high-resolution scanning electron microscopy (HRSEM), energy dispersive X-ray spectroscopy (EDX), Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA). Its catalytic activity was optimized by varying different parameters, and the optimum conditions for peroxidase mimetic activity were observed using 100 µL Fe3O4-GBR (1 mg/mL), 50 µL TMB (1 mg/mL), and 200 µL H2O2(1 mM) in 400 µL of acetate buffer of pH 2.3 at 30 °C temperature. Kinetic analysis has revealed the Michaelis-Menten kinetic behavior of peroxidase activity with Michaelis-Menten constants (Km) and maximum initial velocities (Vmax) of 0.082 mM and 14.1 nMs-1 respectively, for H2O2 and 0.086 mM and 5.1 nMs-1, respectively for TMB. The limit of detection and linear range were found to be 49.6 µM and 100-880 µM, respectively, for H2O2 and 41.9 µM and 47.6-952.3 µM, respectively, for cholesterol. On this basis, a simple, swift, sensitive, selective, and reproducible colorimetric assay to detect cholesterol levels in blood serum samples using Fe3O4-GBR nanocomposite has been developed. Thus, Fe3O4-GBR composite as compared to Fe3O4 and GBR has shown better peroxidase mimicking activity for biosensing.

Highly selective fluorescence 'turn off' sensing of picric acid and efficient cell labelling by water-soluble luminescent anthracene-bridged poly(N-vinyl pyrrolidone).

A novel, water-soluble, luminescent anthracene-bridged AA-type bi-arm poly(N-vinylpyrrolidone) (ATC-PNVP) was synthesized using a click reaction between alkyne-terminated PNVP and 9,10-bis(azidomethyl)anthracene. The resultant anthracene-bridged PNVP (ATC-PNVP) was characterized using 1H NMR, FTIR, UV-Vis, and fluorescence spectroscopic methods and GPC analysis. ATC-PNVP showed effective fluorescence properties in an aqueous medium. It showed highly selective "turn off" sensing behaviour towards picric acid, a common nitro-aromatic explosive, with a wide linear range of detection of 0.01-0.3 mM and LOD value of 0.006 mM in water. ATC-PNVP-based paper sensors also showed very effective detection of picric acid in the concentration range 0.001-1.0 mM. Its binding with bovine serum albumin (BSA) was studied using steady-state, synchronous and 3D fluorescence spectroscopy and this study showed effective quenching of the intrinsic fluorescence of BSA and occurrence of a FRET-type interaction. Furthermore, this luminescent ATC-PNVP was efficiently used as a fluorescence microscopy labelling agent in NIH-3T3 and HeLa cells, and showed greater uptake and hence better fluorescent labelling in the cytosols of the tested cells than free 9,10-bis(azidomethyl) anthracene. The cell viability study also showed a very good biocompatible and non-toxic nature of ATC-PNVP at lower working concentrations towards each of the types of cells tested.

Brominated Graphene as Mimetic Peroxidase for Sulfide Ion Recognition.

Brominated graphene (GBR) with ∼3% bromine content has shown novel peroxidase mimetic activity toward 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. Optimum activity has been observed at pH 4.48 and after a minimum ∼30 min of equilibration time. Among the different analytes studied using the sensor combining TMB, H2O2, and GBR in phosphate buffer of pH 4.48, the S2- ion has effectively shown a short duration of sensing (∼2 min) within the detection range of 0.04-1 mM. A calibration curve for S2- ion estimation has been constructed with the experimental linearity in 0.04-0.4 mM range and having the limit of detection (LOD) value of 25.3 µM. A standard addition experiment has validated the method. A paper strip sensor has been fabricated for successful detection of S2- ion.

Role of PET/CT in diagnosing and monitoring disease activity in rheumatoid arthritis: a review.

Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.

[18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO).

Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.

Cancer burden in Nepal, 1990-2017: An analysis of the Global Burden of Disease study.

INTRODUCTION: Cancer is the second leading cause of death and a major public health problem in the world. This study reports the trend and burden of cancer from 1990 to 2017 along with its risk factors in Nepal. METHODS: This study used the database of the Institute of Health Metrics and Evaluation's Global Burden of Diseases on cancer from Nepal to describe the most recent data available (2017) and trends by age, gender, and year from 1990 to 2017. The data are described as incidence, prevalence, disability-adjusted life years (DALY), and percentage change. RESULTS: In 2017, the age-standardized cancer incidence and mortality rates were 101.8/100,000 and 86.6/100,000 respectively in Nepal. Cancer contributed to 10% of total deaths and 5.6% of total DALYs in Nepal. The most common cancers were the breast, lung, cervical, stomach and oral cavity cancers. The number of new cancer cases and deaths in Nepal have increased from 1990 to 2017 by 92% and 95% respectively. On the other hand, age-standardized incidence and mortality rates decreased by 5% and 7% respectively. The leading risk factors of cancer were tobacco use, dietary factors, unsafe sex, air pollution, drug use, and physical inactivity. CONCLUSIONS: This study highlighted the burden of cancer in Nepal, contributing to a significant number of new cancer cases, deaths and DALY. A comprehensive approach including prevention, early diagnosis and treatment, and rehabilitation should be urgently taken to reduce the burden of cancer.

An Unusual Case of Tetanus Masquerading as an Acute Abdomen: A Case Report.

INTRODUCTION: Tetanus is an acute onset neurological disease that is often lethal. It has a high disease burden in low and middle-income countries. Tetanus is caused by a toxin made by spores of the bacterium Clostridium tetani, which are found in soil, dust, and animal feces. The toxin impairs the motor neurons leading to muscle stiffness. However, with the development of a toxoid vaccine, the incidence has sharply declined and is now categorized as a vaccine-preventable disease. The treatment of tetanus is primarily supportive and focuses on managing the complications until the effects of toxins resolve. CASE REPORT: We report the case of a 67-year-old farmer who previously sustained a laceration injury approximately 45 days prior to presenting to the emergency department with abdominal pain and rigidity. After a comprehensive evaluation to rule out other items in the differential diagnoses, he was diagnosed with tetanus based on clinical symptoms and ultimately required mechanical ventilation. The patient was then managed in the intensive care unit and later made an uneventful recovery. CONCLUSION: This case illustrates an uncommon presentation of tetanus and the latency of the infectious process. Often when patients present with atypical symptoms, it poses a diagnostic dilemma to the clinicians. Thus, it is very important to carefully elicit a history of contaminated injury. This case also highlights the importance of prophylactic vaccine in low and middle-income countries, which can reduce disease-related mortality and morbidity.

Tuberous sclerosis complex-associated neuropsychiatric disorder (TAND) in a low-resource setting - From seizure to psychosis: A case report.

INTRODUCTION: Tuberous sclerosis complex (TSC) patients commonly present with neuropsychiatric symptoms - grouped as TSC-associated neuropsychiatric disorder (TAND) - incorporating Autism Spectrum Disorder (ASD) symptoms, intellectual and learning disabilities, psychiatric and behavioral problems. A structured symptomatic assessment known as the TAND-checklist can be useful in reviewing these symptoms systematically and comprehensively. CASE SUMMARY: A 21-year-old woman presented with delusions of reference, auditory hallucinations, irritability, restlessness, aggressive behavior, new-onset tremors and rigidity in both upper limbs, and refusal of food and medication intake for 1 week. She has a history of several seizure episodes since 3 years of age which was controlled on oral sodium valproate, carbamazepine, and clobazam. MRI revealed tubers in frontal and insular cortex.Ultrasound of the abdomen showed bilateral renal angiomyolipomas. She was diagnosed with TSC with psychotic symptoms. DISCUSSION: TSC2 mutations usually present early with epileptic spasms (ES), complex epilepsies, intellectual and cognitive deficits, cardiac rhabdomyomas, and sub-ependymal giant-cell astrocytomas (SEGAs) with high tuber-to-brain proportions (TBP). There is also a remarkable symptom overlap between autism spectrum disorder (ASD) and TSC with behavioral/psychiatric disorders. Social and behavioral problems seen in our patient may be a manifestation of either TSC, ASD, or both. Cost-effectiveness and pragmatism must be considered for TAND-patients in low-resource settings. While it may be theoretically valid to seek genetic testing, TBP-measurement, and mTOR-inhibitor therapy to address TAND-symptoms, they are impractical when compared to TAND-checklist during follow-up.

Efficacy and safety of solriamfetol for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea: a systematic review and meta-analysis of clinical trials.

INTRODUCTION: Excessive daytime sleepiness (EDS) is the inability to maintain wakefulness and alertness during the major waking episodes of the day, with sleep occurring unintentionally or at inappropriate times. Solriamfetol is a selective norepinephrine-dopamine reuptake inhibitor approved for EDS. This review was done to assess the efficacy and safety of solriamfetol in patients with EDS in narcolepsy or OSA. METHODS: A systematic search of the electronic database was conducted for relevant studies. Any randomized controlled trial with outcome measures on the efficacy or safety of solriamfetol in EDS were eligible for inclusion. The primary outcomes were mean difference in the maintenance of wakefulness test (MWT), Epworth sleepiness scale (ESS) score, and risk ratio of adverse events. The random-effects model was used to calculate pooled effect estimates. RESULTS: We identified 336 records from the database search. We analyzed eight articles reported from six clinical trials. We pooled outcome measures from five trials. The overall mean difference for MWT was 9.93 min (95% CI: 8.25-11.61), and the mean difference of ESS score was -4.44 (95% CI: -5.50 to -3.38), both in favor of solriamfetol over placebo. The overall risk ratio of adverse events with solriamfetol was 1.47 (95% CI: 1.28-1.69). The most common adverse events reported were headache, nausea, decreased appetite, anxiety, nasopharyngitis, and insomnia. CONCLUSIONS: Solriamfetol is efficacious and has a favorable safety profile in the treatment of EDS in patients with narcolepsy and OSA. Solriamfetol is well tolerated and may be recommended for the treatment of EDS in these patients.

Cell proliferation influenced by matrix compliance of gelatin grafted poly(d,l-Lactide) three dimensional scaffolds.

Surface and mechanical properties of the biomaterials are determinants of cellular responses. In our previous study, star-shaped poly(d,l-Lactide)-b-gelatin (ss-pLG) was reported for possessing improved cellular adhesion and proliferation. Here, we extended our investigation to establish the cellular compatibility of gelatin-grafted PDLLA with respect to mechanical properties of biological tissues. In this view, linear PDLLA-b-gelatin (l-pLG) was synthesized and tissue-level compatibility of 1-pLG and ss-pLG against fibroblasts (L929), myoblasts (C2C12) and preosteoblasts (MG-63) was examined. The cell proliferation of C2C12 was significantly higher within l-pLG scaffolds, whereas L929 showed intensified growth within ss-pLG scaffolds. The difference in cell proliferation may be attributed to the varying mechanical properties of scaffolds; where the stiffness of l-pLG scaffolds was notably higher than ss-pLG scaffolds, most likely due to the variable levels of gelatin grafting on the backbone of PDLLA. Therefore, gelatin grafting can be used to modulate mechanical property of the scaffolds and this study reveals the significance of the matrix stiffness to produce the successful 3D scaffolds for tissue engineering applications.

Study of the Fluorescence Based Applications of Pyrene-Tagged Poly(N-vinyl-2-pyrrolidone).

In this study we have explored the fluorescence based applications of luminescent pyrene-tagged PNVP (PyPNVP) reported in our previous work (Int. J. Polym. Mater. Polym. Biomater. 2016, 65, 269-276). PyPNVP has successfully acted as "turn off" chemosensor for metal ions Cu2+, Hg2+, and Pb2+. It has also successfully acted as a fluorescent probe for critical micellar concentration (CMC) determination of amphiphilic block copolymer of poly(d,l-lactide) and poly(N-vinylpyrrolidone) (PDLLA42-b-PNVP120) (Mn = 19 400 g/mol and PD = 1.52). It has also successfully shown an interaction with both plasmid and calf thymus (CT) deoxyribonucleic acids (DNAs) as evidenced by its fluorescence quenching. A different magnitude and type of quenching has been observed for both the cases which may be useful in distinguishing different kinds of DNAs. In order to further understand the potential of PyPNVP in various biotechnological processes, its binding property with bovine serum albumin (BSA) has also been studied. The efficient quenching of intrinsic fluorescence of BSA by PyPNVP through binding and the occurrence of the fluorescence resonance energy transfer (FRET) type of interaction have been studied using steady state, synchronous, and 3D fluorescence spectroscopies. Moreover, a fluorescence microscopic cell imaging study has revealed the significant uptake of PyPNVP in the nucleus of HEPG2 and U87 cells compared to free Py. In addition, the cytotoxicity study showed the tolerance of PyPNVP in all the cell lines tested with no significant cytotoxicity at lower concentrations.

What is the burden of submicroscopic malaria in pregnancy in central India?

BACKGROUND: Conventional microscopy underestimates the burden of malarial infection when compared with molecular diagnosis using polymerase chain reaction (PCR)-based methods. Lower density parasitemias serve as a reservoir for infection. We evaluated the prevalence of submicroscopic infections in an area of unstable malarial transmission in India and determined whether these infections negatively impacted maternal or fetal outcomes. METHODS: This cross-sectional study (2007-2008) was undertaken in two districts of Chhattisgarh, recruiting women from both antenatal clinics (ANCs) and delivery units (DUs). For ANC/DU subjects, peripheral/placental blood, respectively, was obtained for conventional microscopy and collected onto filter paper for PCR analysis. RESULTS: There were 3425 pregnant women, including 2477 ANC subjects and 948 DU subjects who had both microscopic and PCR samples available. Polymerase chain reaction detected significantly more Plasmodium infections than traditional light microscopy both from peripheral (3·4 vs 1·2%; OR 2·9, 95% confidence intervals (CIs) 1·9-4·5) and placental (4·2 vs 1·7%; OR 2·5, 95% CIs 1·4-4·8) blood samples. Submicroscopic infections were not associated with anemia or severe maternal anemia among ANC or DU participants and were not associated with low birth weight (LBW) among DU participants. In contrast, microscopically detected infections were associated with severe anemia and LBW. CONCLUSIONS: In this area of unstable malarial transmission from India, submicroscopic infections did not identify a set of pregnant women at increased risk for anemia or LBW. Until PCR techniques become much less expensive and available as a point of care test for the field setting, its use will be limited for malarial detection.