Prognostic Biomarkers for Acute Graft-versus-Host Disease Risk after Cyclophosphamide–Fludarabine Nonmyeloablative Allotransplantation

AbstractFive candidate plasma biomarkers (suppression of tumorogenesis 2 [ST2], regenerating islet-derived-3α [REG3α], elafin, tumor necrosis factor receptor 1 [TNFR1], and soluble IL-2 receptor-alpha [sIL2Rα]) were measured at specific time points after cyclophosphamide/fludarabine-based nonmyeloablative allotransplantation (NMAT) in patients who did or did not develop acute graft-versus-host disease (aGVHD). Plasma samples from 34 patients were analyzed at days +7, +14, +21, and +30. At a median follow-up of 358 days, 17 patients had experienced aGVHD with a median time to onset at day +36. Risk of aGVHD was associated with elevated plasma ST2 concentrations at day +7 (c-statistic = .72, P = .03), day +14 (c-statistic = .74, P = .02), and day +21 (c-statistic = .75, P = .02); elevated plasma REG3α concentrations at day +14 (c-statistic = .73, P = .03), day +21 (c-statistic = .76, P = .01), and day +30 (c-statistic = .73, P = .03); and elevated elafin at day +14 (c-statistic = .71, P = .04). Plasma concentrations of TNFR1 and sIL2Rα were not associated with aGVHD risk at any of the time points studied. This study identified ST2, REG3α, and elafin as prognostic biomarkers to evaluate risk of aGVHD after cyclophosphamide/fludarabine-based NMAT. These results need to be confirmed in an independent validation cohort

Sonic Hedgehog Gene Delivery to the Rodent Heart Promotes Angiogenesis via iNOS/Netrin-1/PKC Pathway

We hypothesized that genetic modification of mesenchymal stem cells (MSCs) with Sonic Hedgehog (Shh) transgene, a morphogen during embryonic development and embryonic and adult stem cell growth, improved their survival and angiogenic potential in the ischemic heart via iNOS/netrin/PKC pathway.MSCs from young Fisher-344 rat bone marrow were purified and transfected with pCMV Shh plasmid ((Shh)MSCs). Immunofluorescence, RT-PCR and Western blotting showed higher expression of Shh in (Shh)MSCs which also led to increased expression of angiogenic and pro-survival growth factors in (Shh)MSCs. Significantly improved migration and tube formation was seen in (Shh)MSCs as compared to empty vector transfected MSCs ((Emp)MSCs). Significant upregulation of netrin-1 and iNOS was observed in (Shh)MSCs in PI3K independent but PKC dependent manner. For in vivo studies, acute myocardial infarction model was developed in Fisher-344 rats. The animals were grouped to receive 70 microl basal DMEM without cells (group-1) or containing 1x10(6) (Emp)MSCs (group-2) and (Shh)MSCs (group-3). Group-4 received recombinant netrin-1 protein injection into the infarcted heart. FISH and sry-quantification revealed improved survival of (Shh)MSCs post engraftment. Histological studies combined with fluorescent microspheres showed increased density of functionally competent blood vessels in group-3 and group-4. Echocardiography showed significantly preserved heart function indices post engraftment with (Shh)MSCs in group-3 animals.Reprogramming of stem cells with Shh maximizes their survival and angiogenic potential in the heart via iNOS/netrin-1/PKC signaling

Ocular metastasis of colorectal cancer: An uncommon presentation of a common malignancy

AbstractApproximately 20% of patients with colorectal cancer have metastatic disease at time of diagnosis, and another 25–35% develop metastases during the course of their disease. Liver, peritoneum, and lungs are the most common sites of metastases. We report the case of a 60-year-old female who presented with ocular metastasis 4years after her initial curative-intent treatment for T3N1M0 rectal adenocarcinoma. After local eye radiation therapy, she received palliative systemic chemotherapy and enjoyed a good quality of life for 32months before succumbing to progressive disease. Ocular metastasis of colorectal cancer is rare. When present, it usually occurs in the setting of diffuse hematogenous spread. In addition to local therapy, systemic chemotherapy should also be considered

Dry eye disease and high disease activity score (DAS-28) in rheumatoid arthritis: an underrated combination

Objective: To determine the association of dryness of eyes with rheumatoid arthritis severity. Method: The cross-sectional, observational study was conducted at the Jinnah Medical College Hospital, Karachi, from December 2020 to May 2021, and comprised adult patients of either gender with rheumatoid arthritis who were diagnosed on the basis of clinical and serological investigations. Data was collected using a structured pre-tested questionnaire. Ocular Surface Disease Index questionnaires with Tear Film Breakup Time were used to assess the severity of dry eyes. Disease Activity Score-28 with erythrocyte sedimentation rate was used to assess the severity of rheumatoid arthritis. Association between the two was explored. Data was analysed using SPSS 22. Results: Of the 61 patients, 52(85.2%) were females and 9(14.8%) were males. The overall mean age was 41.7±12.8 years, with 4(6.6%) aged 60years. Further, 46(75.4%) subjects had sero-positive rheumatoid arthritis, 25(41%) had high severity, 30(49.2%) had severe Occular Surface Density Index score and 36(59%) had decreased Tear Film Breakup Time. Logistic Regression analysis showed there were 5.45 times higher odds of having severe disease among the people with Occular Surface Density Index score >33 (p=0.003). In patients with positive Tear Film Breakup Time, there were 6.25 higher odds of having increased disease activity score (p=0.001). Conclusion: Disease activity scores of rheumatoid arthritis were found to have strong association with dryness of eyes, high Ocular Surface Disease Index score and increased erythrocyte sedimentation rate. Key Words: Rheumatoid arthritis, Tear film breakup time, Disease activity score-28, Dry eye, Ocular surface disease index

Intraperitoneal lignocaine (lidocaine) versus bupivacaine after laparoscopic cholecystectomy: Results of a randomized controlled trial

Abstract Background Intraperitoneal local anesthetics have been shown to improve postoperative pain after laparoscopic cholecystectomy (LC). However, the choice of local anesthetic agent is debatable. We compared the analgesic efficacy of intraperitoneal lignocaine (lidocaine) versus bupivacaine after elective LC. Methods We conducted a double-blind, randomized, controlled trial. We randomized consecutive patients undergoing LC into two groups. Group L received 10 mL 2% lignocaine (lidocaine), whereas Group B received 10 mL 0.5% bupivacaine, each diluted in 10 mL normal saline. All patients underwent standard perioperative anesthesia and analgesia protocol. We assessed patients at 0, 4, 8, 12, and 24 h postoperatively for pain using the visual analogue scale and verbal rating scale, and the need for additional analgesic medications. Results We analyzed a total of 206 patients: 106 in Group L and 100 in Group B. Demographic details were similar between groups (P \u3e 0.05). Abdominal pain decreased significantly with time in both groups, with a similar mean response profile (P \u3c 0.001). There was no statistically significant difference between groups with regard to abdominal or shoulder pain by both visual analogue scale and verbal rating scale at all five time intervals (P \u3e 0.05). There was also no significant difference in the side effect profile of both drugs (P \u3e 0.05). A lower proportion of patients in Group B required additional narcotic analgesia (87%) compared with Group L (94%). This difference was marginally significant (P = 0.057). Conclusions Bupivacaine and lignocaine (lidocaine) are both safe and equally effective at decreasing postoperative pain after LC

Antibacterial, antioxidant, and anticancer potential of green fabricated silver nanoparticles made from Viburnum grandiflorum leaf extract

Abstract Background Recently, researchers are focusing on creating new tools to combat the antibiotic resistant bacteria and malignancy issues, which pose significant threats to humanity. Biosynthesized silver nanoparticles (AgNPs) are thought to be a potential solution to these issues. The biosynthesis method, known for its environmentally friendly and cost-effective characteristics, can produce small-sized AgNPs with antimicrobial and anticancer properties. In this study, AgNPs were bio-fabricated from the distilled water and methanolic extracts of Viburnum grandiflorum leaves. Physio-chemical characterization of the bio-fabricated AgNPs was conducted using UV-visible spectroscopy, scanning electron microscopy, energy dispersive X-ray, and X-ray diffraction analysis. Results AgNPs produced from the methanol extract were smaller in size (12.28 nm) compared to those from the aqueous extract (17.77 nm). The bioengineered AgNPs exhibited a circular shape with a crystalline nature. These biosynthesized AgNPs demonstrated excellent bactericidal activity against both gram-negative (Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. Highest antibacterial activity was observed with the methanol extract against P. aeruginosa (14.66 ± 0.74 mm). AgNPs from the methanol extract also displayed the highest antioxidant activity, with an IC50 value of 188.00 ± 2.67 μg/mL against 2,2-diphenyl-1-picrylhydrazyl (DPPH). Furthermore, AgNPs exhibited notable cytotoxic activity against Rhabdomyosarcoma cell line (RD cell) of human muscle cancer cell. The IC50 values calculated from the MTT assay were 26.28 ± 1.58 and 21.49 ± 1.44 μg/mL for AgNPs synthesized from aqueous and methanol extracts, respectively. Conclusion The methanol extract of V. grandiflorum leaves demonstrates significant potential for synthesizing AgNPs with effective antibacterial, antioxidant, and anticancer actions, making them applicable in various biomedical applications

Immune-mediated diseases and immunodeficiencies associated with thymic epithelial neoplasms

INTRODUCTION: This retrospective study aimed to characterize the clinical hematological and immunological features of patients with thymic epithelial neoplasms. METHODS: From a cohort of 512 patients with thymic epithelial neoplasms, 79 patients diagnosed with autoimmune/immunodeficiency conditions or signs and/or symptoms suggesting an autoimmune or immunodeficiency state were evaluated by standard immunological and hematological testing. RESULTS: Elevated percentages of CD2+, CD3+, and CD8+ lymphocytes were observed in 44 (57.1%), 33 (41.8%), and 32 (40.5%) patients. Low CD4+ and CD19+ percentages were observed in 25 (31.6%) and 36 (46.2%), respectively; CD4+:CD8+ ratios were inverted in 18 (22.8%). IgG, IgA, and IgM levels were low in 12 (15.8%), 9 (11.7%) and 15 (19.7%) patients, respectively. Patients with immunodeficiency condition(s) were more likely to have high CD8+ percentages (p = 0.040), low CD19+ percentages (p = 0.025), and/or inverted CD4+/CD8+ ratios (p = 0.034). Patients with autoimmune condition(s) were more likely to have a high/normal CD4+ percentage (p = 0.038). High CD2+ percentages were associated with lower mean IgG and IgA levels (p = 0.030 and p = 0.017, respectively). High CD3+ and CD8+ percentages were associated with lower mean IgA levels (p = 0.046 and p = 0.013, respectively). Low CD19+ percentages were associated with lower mean IgG and IgA levels (p = 0.004 and p < 0.001, respectively). CONCLUSION: Signs/symptoms and history of autoimmune and immunodeficiency conditions among patients with thymic epithelial neoplasms are associated with high frequencies of abnormalities in immunoglobulin levels and lymphocyte immunophenotypes, suggesting a role for their assessment