Shift in SARS-CoV-2 variants of concern from Delta to Omicron was associated with reduced hospitalizations, increased risk of breakthrough infections but lesser disease severity.

BACKGROUND: COVID-19 epidemiology changed with the emergence of SARS-CoV-2 variants of concern (VOC). Pakistan administered mostly inactivated vaccines. We investigated the association between VOC and breakthrough infections in a mixed-vaccination-status population of Karachi. METHODS: We investigated SARS-CoV-2 VOC tested in 392 respiratory specimens collected between May and December 2021. Data for age, sex, hospital admission, vaccinations, together with CT values of the diagnostic PCR test were analyzed. RESULTS: The median age of COVID-19 cases tested was 40 (27-57) years and 43.4% were female. Delta variants were most common (56.4%) followed by Alpha (15.9%), Omicron (12.2%), Beta/Gamma (11.3%), and others (4.3%). Eighteen percent of cases were hospitalized whereby, predominant VOC were Beta/Gamma (40.8%), Alpha (35.2%) and Delta (22.5%). Overall, 55.4% of individuals were fully vaccinated, 7.4% were partially vaccinated and 37.2% were unvaccinated. Most (74.6%) inpatients were unvaccinated. Vaccines comprised inactivated (85.34%), single-shot vector (8.62%), two-shot vector (3.02%) and mRNA (3.02%) types. Omicron variants showed lower viral loads as compared to Alpha, Beta/Gamma, and Delta (p = 0.017). The risk of infection with Delta and Omicron variants was higher, 8 weeks after vaccination. The majority of those with breakthrough infections after receiving inactivated vaccines acquired COVID-19 within 4 months of vaccination. CONCLUSION: Our data highlights the shifting of VOC from Delta to Omicron during 2021 and that COVID-19 vaccinations reduced both hospitalizations and viral transmission. It informs on the increased risk of breakthrough infection within 8 weeks of vaccination, indicating the need for booster vaccinations.

A Retrospective Two-Year Review of the Outcomes of Surgical Rib Fixation Following Chest Wall Injury by the Multidisciplinary Chest Wall Injury Group in a Major Trauma Centre and the Change in Outcomes as the Service Has Developed.

Aims All English major trauma centres (MTCs) offer rib fixation, which the National Institute for Health and Care Excellence (NICE) guidance indicates in patients with multiple rib fractures or a flail segment; however, the data does not identify the appropriate patients. Our aims were to establish improvements in outcomes following rib fixation at our trust and then determine if the rib fixation service has improved. Methods We performed a matched cohort study whereby 32 patients who underwent rib fixation were independently matched with conservatively managed patients. We then performed a retrospective re-audit to compare outcomes with the matched cohort study. The outcomes analysed were mortality, critical care length of stay (LOS) and total hospital LOS. Results Our initial study revealed a 33.4% reduction in mortality in patients over 55 years. There was also a reduction in average total hospital LOS by 4.5 days in patients under 55 years when comparing rib fixation to conservative management. The results also revealed an average of 4.1 days from admission to operation, 12.7 days of critical care LOS and 29.1 days of total hospital LOS. The re-audit showed improvements in all outcomes. Time from admission to fixation was reduced to 2.1 days, critical care LOS was reduced to 7.5 days and total hospital LOS was reduced to 20.7 days. Conclusions Reduced mortality and LOS reinforce evidence that rib fixation improves outcomes. The re-audit shows that patients are identified for fixation sooner, which is important as the evidence has not identified optimal time for fixation. LOS further decreased in our re-audit, which indicates that earlier fixation results in patients avoiding the sequelae of rib fractures.

Sequential viral introductions and spread of BA.1 across Pakistan provinces during the Omicron wave.

BACKGROUND: COVID-19 waves caused by specific SARS-CoV-2 variants have occurred globally at different times. We focused on Omicron variants to understand the genomic diversity and phylogenetic relatedness of SARS-CoV-2 strains in various regions of Pakistan. METHODS: We studied 276,525 COVID-19 cases and 1,031 genomes sequenced from December 2021 to August 2022. Sequences were analyzed and visualized using phylogenetic trees. RESULTS: The highest case numbers and deaths were recorded in Sindh and Punjab, the most populous provinces in Pakistan. Omicron variants comprised 93% of all genomes, with BA.2 (32.6%) and BA.5 (38.4%) predominating. The first Omicron wave was associated with the sequential identification of BA.1 in Sindh, then Islamabad Capital Territory, Punjab, Khyber Pakhtunkhwa (KP), Azad Jammu Kashmir (AJK), Gilgit-Baltistan (GB) and Balochistan. Phylogenetic analysis revealed Sindh to be the source of BA.1 and BA.2 introductions into Punjab and Balochistan during early 2022. BA.4 was first introduced in AJK and BA.5 in Punjab. Most recent common ancestor (MRCA) analysis revealed relatedness between the earliest BA.1 genome from Sindh with Balochistan, AJK, Punjab and ICT, and that of first BA.1 from Punjab with strains from KPK and GB. CONCLUSIONS: Phylogenetic analysis provides insights into the introduction and transmission dynamics of the Omicron variant in Pakistan, identifying Sindh as a hotspot for viral dissemination. Such data linked with public health efforts can help limit surges of new infections.

Imaging Biomarkers to Predict Outcomes in Patients With Large B-Cell Lymphoma With a Day 28 Partial Response by 18F-FDG PET/CT Imaging Following CAR-T Therapy.

BACKGROUND: CD19 directed CAR-T therapy for Large B-cell lymphoma (LBCL) has shown great therapeutic response in patients with relapsed/refractory disease with response rates of 60-80%. However, in patients with a partial response (PR) on initial day 28 post CAR-T therapy imaging, clinical uncertainty remains as half of these patients will ultimately have relapsed disease.   PATIENTS: In 24 patients receiving CD19 directed CAR-T therapy for relapsed/refractory LBCL achieving a PR on day 28, we utilize imaging biomarkers by 18F-FDG PET/CT imaging at pre CAR-T therapy baseline and day 28 to determine factors that may predict best overall response (B-OR), progression free survival (PFS), and overall survival (OS).   METHODS: Out of 75 patients receiving CAR-T therapy at a single institution, we retrospectively identified and reviewed 25 (33%) as achieving a PR on day 28. PR was defined using the 2014 Lugano classification system. All patients received standard of care CD19 directed CAR-T therapy with axicabtagene ciloleucel. Two independent nuclear medicine physicians measured baseline (pre-CAR-T therapy) and day 28 PET/CT SUVmax, SUVmean and TMV (cm3) of each lesion (node, organ or marrow uptake, if any) using ROVER software. All statistical tests were two-sided and conducted at the 0.05 level of significance. R version 1.3.1099 (R-studio) was used for statistical modeling.   CONCLUSION: We demonstrate that a higher day 28 SUVmax was significantly higher in those with a B-OR of PR and in our modeling, a lower day 28 SUVmax may predict favorable PFS and OS. Additionally, lower TMV, both at baseline and day 28, may also be predictive of longer PFS and OS, while lower TLG at baseline, but not day 28 is significantly associated with a B-OR of CR. While further study is warranted, these imaging biomarkers may allow for early identification of those with a day 28 PR at highest risk for relapse leading to early intervention to improve long term outcomes.

Tracking SARS-CoV-2 variants through pandemic waves using RT-PCR testing in low-resource settings.

COVID-19 resulted in extensive morbidity and mortality worldwide. SARS-CoV-2 evolved rapidly, with increasing transmission due to Variants of Concern (VOC). Identifying VOC became important but genome submissions from low-middle income countries (LMIC) remained low leading to gaps in genomic epidemiology. We demonstrate the use of a specific mutation RT-PCR based approach to identify VOC in SARS-CoV-2 positive samples through the pandemic in Pakistan. We selected 2150 SARS-CoV-2 PCR positive respiratory specimens tested between April 2021 and February 2022, at the Aga Khan University Hospital Clinical Laboratories, Karachi, Pakistan. Commercially available RT-PCR assays were used as required for mutations in Spike protein (N501Y, A570D, E484K, K417N, L452R, P681R and deletion69_70) to identify Alpha, Beta, Gamma, Delta, and Omicron variants respectively. Three pandemic waves associated with Alpha, Delta and Omicron occurred during the study period. Of the samples screened, VOC were identified in 81.7% of cases comprising mainly; Delta (37.2%), Alpha (29.8%) and Omicron (17.1%) variants. During 2021, Alpha variants were predominant in April and May; Beta and Gamma variants emerged in May and peaked in June; the Delta variant peaked in July and remained predominant until November. Omicron (BA.1) emerged in December 2021 and remained predominant until February 2022. The CT values of Alpha, Beta, Gamma and Delta were all significantly higher than that of Omicron variants (p<0.0001). We observed VOC through the pandemic waves using spike mutation specific RT-PCR assays. We show the spike mutation specific RT-PCR assay is a rapid, low-cost and adaptable for the identification of VOC as an adjunct approach to NGS to effectively inform the public health response. Further, by associating the VOC with CT values of its diagnostic PCR we gain information regarding the viral load of samples and therefore the level of transmission and disease severity in the population.

Circulating tumor DNA adds specificity to PET after axicabtagene ciloleucel in large B-cell lymphoma.

We examined the meaning of metabolically active lesions on 1-month restaging nuclear imaging of patients with relapsed/refractory large B-cell lymphoma receiving axicabtagene ciloleucel (axi-cel) by assessing the relationship between total metabolic tumor volume (MTV) on positron emission tomography (PET) scans and circulating tumor DNA (ctDNA) in the plasma. In this prospective multicenter sample collection study, MTV was retrospectively calculated via commercial software at baseline, 1, and 3 months after chimeric antigen receptor (CAR) T-cell therapy; ctDNA was available before and after axi-cel administration. Spearman correlation coefficient (rs) was used to study the relationship between the variables, and a mathematical model was constructed to describe tumor dynamics 1 month after CAR T-cell therapy. The median time between baseline scan and axi-cel infusion was 33 days (range, 1-137 days) for all 57 patients. For 41 of the patients with imaging within 33 days of axi-cel or imaging before that time but no bridging therapy, the correlation at baseline became stronger (rs, 0.61; P < .0001) compared with all patients (rs, 0.38; P = .004). Excluding patients in complete remission with no measurable residual disease, ctDNA and MTV at 1 month did not correlate (rs, 0.28; P = .11) but correlated at 3 months (rs, 0.79; P = .0007). Modeling of tumor dynamics, which incorporated ctDNA and inflammation as part of MTV, recapitulated the outcomes of patients with positive radiologic 1-month scans. Our results suggested that nonprogressing hypermetabolic lesions on 1-month PET represent ongoing treatment responses, and their composition may be elucidated by concurrently examining the ctDNA.

Do Platelet-Rich Plasma Injections for Knee Osteoarthritis Work?

BACKGROUND: Recent evidence suggests a benefit in platelet-rich plasma injections (PRP) for the knee in the management of mild to moderate osteoarthritis (OA). There is a reported reduction in pain, stiffness, and improved function. However, there is very little level-one literature available that supports this practice and conclusively proves a benefit gained throughout the course. Three main randomized control trials (RCTs) conducted in North America are often referenced and cited to prove their efficacy. This study aimed to look at the outcomes of patients having undergone this treatment to determine if there was any benefit. AIMS: This study aimed to determine if PRP injections administered in patients with knee OA over a six to eight-week time period demonstrated any benefit. METHODS: The Western Ontario and McMaster Universities arthritis index (WOMAC) tool was used before each of the three PRP injections over the six to eight-week period, and six weeks after the final injection in 31 patients. Each injection was given spaced two to three weeks apart. The outcomes observed were pain, stiffness, and physical function, and the total WOMAC score was calculated. RESULTS: The third injection showed a reduction in total WOMAC score, pain, stiffness, and physical function by 16.36%, 16.37%, 5.12%, and 18.03%, respectively. However, all scores returned close to baseline at the sixth-week follow-up post treatment. CONCLUSION: Results showed a trend of reduction in the WOMAC score. However, they are overall indicative of a placebo effect from the injections. Further studies are needed to explore whether the grade of OA and patients' weight have a significant impact on the results.

Outcomes of Busulfan, Fludarabine, and 400 cGy Total Body Irradiation Compared With Busulfan and Fludarabine Reduced-Intensity Conditioning Regimens for Allogeneic Stem Cell Transplantation in Adult Patients With Hematologic Diseases: A Single-Center Experience.

BACKGROUND: Reduced intensity conditioning (RIC) regimens decrease the risk for nonrelapse mortality (NRM) in adult patients undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies but increase the risk for relapse. The aim of this study was to compare the outcomes of fludarabine-total body irradiation (TBI) with fludarabine among patients with hematologic diseases. PATIENTS AND METHODS: This retrospective study of 137 patients with different hematologic malignancies compared the outcomes of 63 patients who received a conventional RIC regimen with 2 days of IV busulfan (3.2 mg/kg/d × 2 days) and fludarabine with 74 patients who received the same regimen plus 400 cGy of fludarabine and busulfan (FB)-TBI divided in 2 doses over 1 day (200 cGy BID). Median follow-up was 4.62 years. RESULTS: The donors were either HLA-matched siblings (36%) or HLA-matched unrelated donors (64%). The FB-TBI showed trends toward improvement in progression-free survival (PFS) and overall survival (OS) over FB (5-year PFS rates 50% vs 34%, P = .06, and 5-year OS rate 53% vs 39%, P = .13). Acute graft-vs-host disease (aGVHD), relapse, and NRM were similar between the 2 groups. The 5-year cumulative incidence of chronic GVHD (cGVHD) was lower in the FB-TBI group compared with the FB group (29% vs 52%, P = .003). Multivariable analysis revealed that grade III-IV aGVHD was the only independent risk factor for worse OS (P = .001) in both groups. A high disease risk index was possibly associated with inferior OS (P = .07) in both groups. CONCLUSIONS: The FB-TBI is a safe and effective intensified RIC regimen for adult patients with hematologic malignancies. It predicted a lower risk for cGVHD and showed possibly improved PFS and OS compared with FB.

Refractory chylothorax in a patient with Waldenström Macroglobulinemia: A case report.

A refractory chylothorax secondary to Waldenström Macroglobulinemia (WM) has rarely been reported in literature, but often responds to chemotherapy and conservative measures. Few reports have been published reporting the use of surgical intervention when standard medical therapies fail. We present a 76-year-old male who developed a large right sided chylothorax with a soft tissue mass encasing the descending thoracic aorta. Pleural fluid flow cytometry and biopsy of the mass demonstrated findings diagnostic of WM. Despite chemoimmunotherapy and conservative measures, he required frequent, high-volume, therapeutic thoracentesis for relief of dyspnea. Thoracic duct embolization (TDE) was performed which resolved the patient's chylothorax, however he subsequently developed lower volume serosanguinous pleural effusions. Patient continued requiring therapeutic thoracentesis bimonthly and ultimately proceeded with pleurectomy of the right lung to achieve resolution of symptoms. To our knowledge, this is the first reported case where pleurectomy has successfully treated refractory pleural effusions in a patient with WM.

Evolutionary history and introduction of SARS-CoV-2 Alpha VOC/B.1.1.7 in Pakistan through international travelers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge, and their identification is important for the public health response to coronavirus disease 2019 (COVID-19). Genomic sequencing provides robust information but may not always be accessible, and therefore, mutation-based polymerase chain reaction (PCR) approaches can be used for rapid identification of known variants. International travelers arriving in Karachi between December 2020 and February 2021 were tested for SARS-CoV-2 by PCR. A subset of positive samples was tested for S-gene target failure (SGTF) on TaqPathTM COVID-19 (Thermo Fisher Scientific) and for mutations using the GSD NovaType SARS-CoV-2 (Eurofins Technologies) assays. Sequencing was conducted on the MinION platform (Oxford Nanopore Technologies). Bayesian phylogeographic inference was performed integrating the patients' travel history information. Of the thirty-five COVID-19 cases screened, thirteen had isolates with SGTF. The travelers transmitted infection to sixty-eight contact cases. The B.1.1.7 lineage was confirmed through sequencing and PCR. The phylogenetic analysis of sequence data available for six cases included four B.1.1.7 strains and one B.1.36 and B.1.1.212 lineage isolate. Phylogeographic modeling estimated at least three independent B.1.1.7 introductions into Karachi, Pakistan, originating from the UK. B.1.1.212 and B.1.36 were inferred to be introduced either from the UK or the travelers' layover location. We report the introduction of SARS-CoV-2 B.1.1.7 and other lineages in Pakistan by international travelers arriving via different flight routes. This highlights SARS-CoV-2 transmission through travel, importance of testing, and quarantine post-travel to prevent transmission of new strains, as well as recording detailed patients' metadata. Such results help inform policies on restricting travel from destinations where new highly transmissible variants have emerged.

Characteristics Associated with the Dual Behavior of Mask Wearing and Vaccine Acceptance: A Pooled Cross-Sectional Study among Adults in Saskatchewan.

While the dual behavior of consistent mask wearing and vaccine acceptance represents an effective method of protecting oneself and others from COVID-19, research has yet to directly examine its predictors. A total of 3347 responses from a pooled cross-sectional survey of adults living in Saskatchewan, Canada, were analyzed using a multinomial logistic regression model. The outcome variable was the combined behavior of mask-wearing and vaccine intention in four combinations, while covariates consisted of socio-demographic factors, risk of exposure to coronavirus, mitigating behaviors, and perceptions of COVID-19. Those who were 65 years and older, financially secure, consistently practiced social distancing and had no or very few contacts with people outside their households, were concerned about spreading the virus, and perceived they would be seriously sick if infected were likely to engage in both mask wearing and vaccine acceptance, rather than one or the other, with adjusted odds ratios ranging from 2.24 to 27.54. Further, within mask wearers, these factors were associated in a graded manner with vaccine intent. By describing the characteristics of those who engage in both mask wearing and vaccine acceptance, these results offer a specific set of characteristics for public health authorities to target and, therefore, contribute to the rapidly evolving body of knowledge on protective factors for COVID-19.

Low utility of the H-Score and HLH-2004 criteria to identify patients with secondary hemophagocytic lymphohistiocytosis after CAR-T cell therapy for relapsed/refractory diffuse large B-Cell lymphoma.

Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation disorder. Use of chimeric antigen receptor T-cell therapy (CAR-T) is associated with cytokine release syndrome (CRS), Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) and secondary HLH. However, application of HLH scoring systems (H-score, HLH-2004 criteria) are not validated in this setting. We analyzed the utility of applying the H-score and the HLH-2004 criteria to identify patients with possible HLH post-CAR-T for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Only two of four patients with post CAR-T HLH met five or more of the diagnostic criteria for HLH by HLH 2004 criteria. In contrast all four post CAR-T HLH patients had a high H-score (>169); however, an additional ten patients that did not have HLH also had a high H-score. Thus, in this patient population, both scoring systems were demonstrated to have low prognostic significance in differentiating between high grade CRS and HLH.

Sequencing of SARS-CoV-2 in local transmission cases through Oxford Nanopore MinION platform from Karachi Pakistan.

INTRODUCTION: The first case of severe acute respiratory syndrome 2 (SARS-CoV-2) was imported to Pakistan in February 2020, since then 8,260 deaths have been witnessed. The virus has been constantly mutating and local transmission cases from different countries vary due to host dependent viral adaptation. Many distinct clusters of variant SARS-CoV-2 have been defined globally. In this study, the epidemiology of SARS-CoV-2 was studied and locally transmitted SARS-CoV-2 isolates from Karachi were sequenced to compared and identify any possible variants. METHODOLOGY: The real time PCR was performed on nasopharyngeal specimen to confirm SARS-CoV-2 with Orf 1ab and E gene as targets. The virus isolates were sequenced through oxford nanopore technology MinION platform. Isolates from the first and second wave of COVID-19 outbreak in Karachi were compared. RESULTS: The overall positivity rate for PCR was 26.24% with the highest number of positive cases in June. Approximately, 37.45% PCR positive subjects aged between 19-40 years. All the isolates belonged to GH clade and shared missense mutation D614G in spike protein linked to increased transmission rate worldwide. Another spike protein mutation A222V coexisted with D614G in the virus from the second wave of COVID-19. CONCLUSIONS: Based on the present findings it is suggested that the locally transmitted virus from Karachi varies from those reported from other parts of Pakistan. Slight variability was also observed between viruses from the first and second wave. Variability in any potential vaccine target may result in failed trials, therefore information on any local viral variants is always useful for effective vaccine design and/or selection.

The impact of bridging therapy prior to CD19-directed chimeric antigen receptor T-cell therapy in patients with large B-cell lymphoma.

In the relapsed/refractory setting for treatment of large B-cell lymphoma (LBCL), chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective treatment modality. Patients often have aggressive disease that requires prompt treatment in the form of bridging therapy (BT) for disease stabilisation while CAR-T cells are manufactured. Patients (n = 75) undergoing CAR-T therapy infusion for LBCL at our institution were identified. A total of 52 (69·3%) received BT and 23 (30·7%) received no BT (NBT). BT modalities included systemic BT (SBT) in 28 patients, radiation BT (RBT) in 14, and high-dose steroid BT (HDS) in 10. There was no difference in incidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome between BT and NBT (P = 0·18 and P = 0·53 respectively). Prolonged cytopenias at Day 180 were more common in BT than NBT (50% vs. 13·3%, P = 0·04). The SBT and RBT subgroups had more cytopenias at Day 180 compared to the HDS and NBT subgroups (58·3% and 57·1% vs. 20% and 13·3% respectively, P = 0·04). Disease response at last follow-up, progression-free survival and overall survival were similar between BT, NBT, and BT subgroups. In summary, BT can be safely considered in patients undergoing CAR-T therapy. However, those undergoing BT with SBT or RBT are at higher risk of prolonged cytopenias after CAR-T therapy.

Monitoring of Circulating Tumor DNA Improves Early Relapse Detection After Axicabtagene Ciloleucel Infusion in Large B-Cell Lymphoma: Results of a Prospective Multi-Institutional Trial.

PURPOSE: Although the majority of patients with relapsed or refractory large B-cell lymphoma respond to axicabtagene ciloleucel (axi-cel), only a minority of patients have durable remissions. This prospective multicenter study explored the prognostic value of circulating tumor DNA (ctDNA) before and after standard-of-care axi-cel for predicting patient outcomes. METHODS: Lymphoma-specific variable, diversity, and joining gene segments (VDJ) clonotype ctDNA sequences were frequently monitored via next-generation sequencing from the time of starting lymphodepleting chemotherapy until progression or 1 year after axi-cel infusion. We assessed the prognostic value of ctDNA to predict outcomes and axi-cel-related toxicity. RESULTS: A tumor clonotype was successfully detected in 69 of 72 (96%) enrolled patients. Higher pretreatment ctDNA concentrations were associated with progression after axi-cel infusion and developing cytokine release syndrome and/or immune effector cell-associated neurotoxicity syndrome. Twenty-three of 33 (70%) durably responding patients versus 4 of 31 (13%) progressing patients demonstrated nondetectable ctDNA 1 week after axi-cel infusion (P < .0001). At day 28, patients with detectable ctDNA compared with those with undetectable ctDNA had a median progression-free survival and OS of 3 months versus not reached (P < .0001) and 19 months versus not reached (P = .0080), respectively. In patients with a radiographic partial response or stable disease on day 28, 1 of 10 patients with concurrently undetectable ctDNA relapsed; by contrast, 15 of 17 patients with concurrently detectable ctDNA relapsed (P = .0001). ctDNA was detected at or before radiographic relapse in 29 of 30 (94%) patients. All durably responding patients had undetectable ctDNA at or before 3 months after axi-cel infusion. CONCLUSION: Noninvasive ctDNA assessments can risk stratify and predict outcomes of patients undergoing axi-cel for the treatment of large B-cell lymphoma. These results provide a rationale for designing ctDNA-based risk-adaptive chimeric antigen receptor T-cell clinical trials.

Assessment of antibacterial and antifungal potential of Curcuma longa and synthesized nanoparticles: A comparative study.

Curcumin nanoparticles were most recently considered in medical research because of their antibacterial properties. The main objective of the study was to develop the green synthesis and antibacterial activity of curcumin nanoparticles using Curcuma longa. The processing of curcumin nanoparticles was carried out after the collection, identification, and extraction of curcumin. The effect of a sample on the synthesis of nanoparticles, such as curcumin aqueous concentrations (5, 10, and 20 mg/ml) and curcumin nanoparticles (5, 10, and 20 mg/ml), and the antibacterial effect of these nanoparticles on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and the fungal strain Aspergillus niger. For examining antibacterial and anti-fungal activity disc diffusion method was performed, followed by the zone of inhibition. According to X-ray diffraction and scanning electron microscope analysis, nanoparticles have spherical shapes and size of 42.64 nm. Results showed that a high dose of 20 mg/ml curcumin nanoparticles have more antibacterial activity than curcumin extracts in E. coli as it showed the largest diameter of zone of inhibition as compared to other doses. Other bacterial and fungal strains also showed significant results but E. coli was most prominent. The biosynthesis of curcumin nanoparticles using an aqueous extract of C. longa is a clean, inexpensive, and safe method that has not been used any toxic substance and consequently does not have side effects. Since several pathogenic species have acquired antibiotic resistance, the combination of curcumin with various nanoparticles would be beneficial in the cure of pathogenic diseases.

Immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy for lymphoma: predictive biomarkers and clinical outcomes.

BACKGROUND: CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has emerged as effective for relapsed/refractory large B-cell lymphoma (R/R LBCL). The neurologic toxicity seen with CAR-T, referred to as immune effector cell-associated neurotoxicity syndrome (ICANS), is poorly understood. To better elucidate the clinical characteristics, treatment outcomes, and correlative biomarkers of ICANS, we review here a single-center analysis of ICANS after CAR T-cell therapy in R/R LBCL. METHODS: Patients (n = 45) with R/R LBCL treated with axicabtagene ciloleucel (axi-cel) were identified. Data regarding treatment course, clinical outcomes, and correlative studies were collected. Patients were monitored and graded for ICANS via CARTOX-10 scoring and Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria, respectively. RESULTS: Twenty-five (56%) patients developed ICANS, 18 (72%) of whom had severe (CTCAE grades 3-4) ICANS. Median time to development of ICANS was 5 days (range, 3-11). Elevated pre-infusion (day 0 [D0]) fibrinogen (517 vs 403 mg/dL, upper limit of normal [ULN] 438 mg/dL, P = 0.01) and D0 lactate dehydrogenase (618 vs 506 units/L, ULN 618 units/L, P = 0.04) were associated with ICANS. A larger drop in fibrinogen was associated with ICANS (393 vs 200, P < 0.01). Development of ICANS of any grade had no effect on complete remission (CR), progression-free survival (PFS), or overall survival (OS). Duration and total dose of steroid treatment administered for ICANS did not influence CR, PFS, or OS. CONCLUSIONS: ICANS after CAR-T with axi-cel for R/R LBCL was seen in about half of patients, the majority of which were high grade. Contrary to previous reports, neither development of ICANS nor its treatment were associated with inferior CR, PFS, or OS. The novel finding of high D0 fibrinogen level can identify patients at higher risk for ICANS.

Construct validity and reproducibility of the Prescription Opioid Misuse And Abuse Questionnaire (POMAQ).

OBJECTIVE: The Prescription Opioid Misuse and Abuse Questionnaire was developed to identify prescription opioid abuse and misuse among patients with chronic pain, however, evidence of construct validity and reproducibility is needed. METHODS: Chronic pain patients were recruited from five Department of Defense Military Health System clinics across the United States. Construct validity was examined using subjective clinician-reported and patient-reported measures as well as objective information (e.g. hair/urine drug screens and electronic medical records). Test-retest reliability was assessed across 2 timepoints among a subgroup of patients with stable chronic pain. RESULTS: Of 3,263 screened patients, 938 (28.7%) met eligibility and were enrolled; 809 (86.2%) completed the Prescription Opioid Misuse and Abuse Questionnaire. Construct validity was supported by comparison to other validated questionnaires and hair and urine screens which yielded high agreements with patient reports on the Prescription Opioid Misuse and Abuse Questionnaire. Electronic medical record data supported patients' Prescription Opioid Misuse and Abuse Questionnaire responses regarding physician and emergency room visits and opioid refills. The Prescription Opioid Misuse and Abuse Questionnaire had excellent test-retest reliability; the percentage agreement between the two Prescription Opioid Misuse and Abuse Questionnaire administrations was high (>90%) for most questions. DISCUSSION: Results suggest that the Prescription Opioid Misuse and Abuse Questionnaire is a valid and reproducible tool that can be used to assess the presence of prescription opioid misuse and abuse among patients with chronic pain.

Updates in Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Lymphoma and Leukemia from the Annual Meeting of American Society of Hematology 2019.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the field of hematologic malignancies and are potentially curative in patients with previously limited options. This review highlights key abstracts focusing on clinical studies in CAR-T therapy in leukemia and lymphoma presented at the 61 st annual meeting of the American Society of Hematology (December 2019, Orlando, FL). Selected studies discuss data on novel CAR-T constructs aimed at enhancing efficacy and durability of responses, improving toxicity mitigation strategies, challenging clinical scenarios in routine clinical practice for standard of care CAR-T therapy (role of bridging therapy, CNS involvement, and quality of life studies), and new technologies aiming to decrease production time to minimize delay in definitive therapy, all within the rapidly-evolving cellular immunotherapy landscape.