Prevalence of DFU among diabetic patients and its management

: To study the prevalence of DFU among diabetic patients and the management of DFU among diabetic patients.: Prospective observational study. : The study was conducted in inpatients with diabetes of all departments and inpatients with diabetic foot ulcer (DFU) of surgical department of age 20 to 80 of both genders with sample size 150 were included from September 2019 to march 2020. The prevalence of DFU among diabetic patients was 16%. Among them more diabetic cases were seen in age group of 50-59 and DFU in 40-49 and More diabetic cases are observed in male compared to female. DFU observed equally and the most common causative organism for DFU was staphylococcus aureus followed by proteus species, klebsiella and pseudomonas aeruginosa and more cases of DFU were noticed in diabetic patients with duration of 6-10 years. As the main cause of DFU is infection the primary treatment is anti microbial therapy and the most prescribed class of antibiotics is cephalosporins followed by nitroimidazoles, penicillins, oxazolidinones, lincosamides etc. surgical procedures like debridement, amputation and sometimes both were done in 9,14,1 patients respectively. : Our study revealed the information regarding the prevalence of DFU among diabetic patients is due to lack of knowledge and uncontrolled diabetes may develop poor circulation which leads to wound that may heal slowly which leads to DFU.

Schwannoma Gene Therapy via Adeno-Associated Viral Vector Delivery of Apoptosis-Associated Speck-like Protein Containing CARD (ASC): Preclinical Efficacy and Safety

Schwannomas are tumors derived from Schwann-lineage cells, cells that protect and support myelinated nerves in the peripheral nervous system. They are typically slow-growing, encapsulated and benign. These tumors develop along peripheral, spinal and cranial nerves causing pain, sensory-motor dysfunction and death. Primary treatment for schwannoma is operative resection which can be associated with significant morbidity. Pharmacotherapy is largely restricted to bevacizumab, which has minimal or no efficacy for many patients and can be associated with treatment-limiting adverse effects. Given the suffering and morbidity associated with schwannoma and the paucity of therapeutic options, there is an urgent need for safe and effective therapies for schwannomas. We previously demonstrated that adeno-associated virus serotype 1 (AAV1) vector mediated delivery of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) under the control of the P0 promoter, produced a prolonged reduction in tumor volume and tumor-associated pain in human xenograft and mouse syngeneic schwannoma models. Here, we present data essential for the translation of our AAV1-P0-ASC schwannoma gene therapy to clinical trials. We determine the minimum effective dose of AAV1-P0-hASC required to induce an anti-tumor effect in the xenograft human-schwannoma model. We also show that the presence of preexisting AAV1 immunity does not alter the antitumor efficacy of AAV-P0-mASC in a syngeneic mouse schwannoma model. Furthermore, the maximum deliverable intratumoral dose of AAV1-P0-ASC was not associated with neuronal toxicity in immunocompetent mice. Taken together, these safety and efficacy data support the translation of the AAV1-P0-ASC schwannoma gene therapy strategy to clinical trials.

Endothelial Cell Distribution After Flow Exposure With Two Stent Struts Placed in Different Angles

Stent implantation has been a primary treatment for stenosis and other intravascular diseases. However, the struts expansion procedure might cause endothelium lesion and the structure of the struts could disturb the blood flow environment near the wall of the blood vessel. These changes could damage the vascular innermost endothelial cell (EC) layer and pose risks of restenosis and post-deployment thrombosis. This research aims to investigate the effect of flow alterations on EC distribution in the presence of gap between two struts within the parallel flow chamber. To study how the gap presence impacts EC migration and the endothelialization effect on the surface of the struts, two struts were placed with specific orientations and positions on the EC layer in the flow chamber. After a 24-h exposure under wall shear stress (WSS), we observed the EC distribution conditons especially in the gap area. We also conducted computational fluid dynamics (CFD) simulations to calculate the WSS distribution. High EC-concentration areas on the bottom plate corresponded to the high WSS by the presence of gap between the two struts. To find the relation between the WSS and EC distributions on the fluorescence images, WSS condition by CFD simulation could be helpful for the EC distribution. The endothelialization rate, represented by EC density, on the downstream sides of both struts was higher than that on the upstream sides. These observations were made in the flow recirculation at the gap area between two struts. On two side surfaces between the gaps, meaning the downstream at the first and the upstream at the second struts, EC density differences on the downstream surfaces of the first strut were higher than on the upstream surfaces of the second strut. Finally, EC density varied along the struts when the struts were placed at tilted angles. These results indicate that, by the presence of gap between the struts, ECs distribution could be predicted in both perpendicular and tiled positions. And tiled placement affect ECs distribution on the strut side surfaces.

Surgical Resection is Preferred in Selected Solitary Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Backgrounds: Sorafenib is the standard care for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT), though it offers limited survival. This study was designed to compare clinical outcomes between liver resection (surgery) and trans-arterial chemoembolization plus radiotherapy (TACE-RT) as the initial treatment modality for resectable treatment-naïve solitary HCC combined with subsegmental (Vp1), segmental (Vp2), and lobar (Vp3) PVTT. Methods: From the institutional HCC registry, we identified 116 patients diagnosed with resectable treatment-naïve HCC with Vp1-Vp3 PVTT based on radiologic images who received surgery (n=44) or TACE-RT (n=72) as a primary treatment between 2010 and 2015. A propensity score matching (PSM) model was created. Results: The TACE-RT group had a higher tumor burden (tumor size, extent, and markers) than the surgery group. Cumulative patient survival curve in the surgery group was significantly higher than in the TACE-RT group before and after PSM. Liver function was relatively well-preserved in the surgery group compared with the TACE-RT group. TACE-RT group, male, increased alkaline phosphatase, and increased platelet count were predisposing factors for patient death in resectable treatment-naïve solitary HCC with PVTT. Conclusions: The present study suggests that surgery should be considered as an initial treatment in resectable treatment-naïve solitary HCC with Vp1-Vp3 PVTT.

Immunotherapy toxicity: identification and management

The widespread adoption of immunotherapy has revolutionized the treatment of various cancer types, including metastatic triple-negative breast cancer (TNBC), which has long been associated with poor prognostic outcomes. In particular, immune checkpoint inhibitors (ICIs) that target and inhibit programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have shown promising results in the treatment of patients with metastatic TNBC. However, while manipulating the immune system to induce antitumor response, ICIs can also lead to a unique set of immune-related adverse events (IRAEs), which differ from standard chemotherapy toxicities due to their immune-based origin. These toxicities require highly specific management, including guidance from multidisciplinary specialists. The primary treatment strategy against IRAEs is systemic corticosteroid use, but additional treatment approaches may also involve supportive care, additional immunosuppression, and concurrent treatment delay or discontinuation. Given the rising prevalence of ICI therapy, it is essential to educate clinicians on the presentation and management of these potentially life-threatening events so that they are identified early and treated appropriately. Using data from recent clinical trials, this review will focus on known IRAEs, particularly those seen in patients with breast cancer, and will summarize their prevalence, severity, and outcomes. We will discuss optimal strategies for early recognition and management, as well as approaches toward cautious retreatment following resolution of IRAEs.

68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Recurrent Prostate Cancer: Diagnostic Performance and Association with Clinical and Histopathological Data

The aim of the present study is to investigate and compare the performances of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in identifying recurrent prostate cancer (PCa) after primary treatment and to explore the association of dual-tracer PET findings with clinical and histopathological characteristics. Thirty-five patients with biochemical relapse (BCR) of PCa underwent 68Ga PSMA PET/MRI for restaging purpose, with 31/35 also undergoing 68Ga-DOTA-RM2 PET/MRI scan within 16 days (mean: 3 days, range: 2–16 days). Qualitative and quantitative image analysis has been performed by comparing 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings both on a patient and lesion basis. Clinical and instrumental follow-up was used to validate PET findings. Fisher’s exact test and Mann-Whitney U test were used to investigate the association between dual-tracer PET findings, clinical and histopathological data. p-value significance was defined below the 0.05 level. Patients’ mean age was 70 years (range: 49–84) and mean PSA at time of PET/MR scans was 1.88 ng/mL (range: 0.21–14.4). A higher detection rate was observed for 68Ga-PSMA PET/MRI, with more lesions being detected compared to 68Ga-DOTA-RM2 PET/MRI (26/35 patients, 95 lesions vs. 15/31 patients, 41 lesions; p = 0.016 and 0.002). 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings were discordant in 11/31 patients; among these, 10 were 68Ga-PSMA positive (9/10 confirmed as true positive and 1/10 as false positive by follow-up examination). Patients with higher levels of PSA and shorter PSA doubling time (DT) presented more lesions on 68Ga-PSMA PET/MRI (p = 0.006 and 0.044), while no association was found between PET findings and Gleason score. 68Ga-PSMA has a higher detection rate than 68Ga-DOTA-RM2 in detecting PCa recurrence. The number of 68Ga-PSMA PET positive lesions is associated with higher levels of PSA and shorter PSA DT, thus representing potential prognostic factors.

Oxygen care and treatment of retinopathy of prematurity in ocular and neurological prognosis

This retrospective cohort study aimed to investigate the effects of neonatal oxygen care and retinopathy of prematurity (ROP) treatment on ROP-related ocular and neurological prognoses. We included premature infants treated for ROP at a tertiary referral center between January 2006 and December 2019. Demographic and clinical data were collected from electronic medical records. Odds ratios (ORs) of oxygen care- and ROP treatment-related factors were calculated for ocular and neurological comorbidities 3 years after ROP treatment, after adjusting for potential confounders. ROP requiring treatment was detected in 171 eyes (88 infants). Laser treatment for ROP (OR = 4.73, 95% confidence interval [CI] 1.64–13.63) and duration of invasive ventilation (OR = 1.02, 95% CI 1.00–1.03) were associated with an increase in ocular comorbidities, along with a history of neonatal seizure (OR = 28.29, 95% CI 5.80–137.95) and chorioamnionitis (OR = 32.13, 95% CI 5.47–188.74). No oxygen care- or ROP treatment-related factors showed significant odds for neurological comorbidities. Shorter duration of invasive oxygen supply during neonatal care (less than 49 days) and anti-vascular endothelial growth factor injection as the primary treatment for ROP are less likely to cause ocular comorbidities. No association was identified between ROP treatment modalities and the risk of neurological comorbidities.

Primary non-Hodgkin’s lymphoma of the orbit: treatment outcomes from India

Background: Primary non-Hodgkin’s lymphoma (NHL) of the orbit is rare. Orbital NHLs show good response to both radiotherapy (RT) and chemotherapy, and hence, the emphasis should be to ensure maximum cure rate with minimum morbidity. In this study, we present the clinical profile and treatment outcomes of patients with NHL who had initial presentation in the orbit. Materials and methods: In this retrospective analysis, case records of patients with a diagnosis of NHL of the orbit were analysed from January 2005 to January 2015. Patients were worked up and staged according to the Ann Arbor system. Patients with large tumours were initially given chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin and prednisolone) three weekly for 4–6 cycles. Patients with residual disease were given RT 20–30 Gy at 2 Gy per fraction. RT when given as a primary treatment consisted of 36–45 Gy at 1·8–2 Gy per fraction on either Cobalt 60 machine or linear accelerator. Results: A total of 52 patients with diagnosis of orbital NHL were included in this study. Median age at presentation was 57 years (range 13–71). Left, right and bilateral orbit was involved in 21 (40%), 28(54%) and 3(6%) patients, respectively. Low- and high-grade pathology was seen in 39(75%) and 13(25%) patients, respectively. On immunohistochemistry, 23(44%) tumors were CD 20 positive. After staging, 33 (63%) patients had stage I disease. Median tumour size was 4·0 × 3·2 × 1·5 cm (1·7 × 1·7 × 1·4 cm to 5·8 × 4·0 × 4·7 cm). Primary RT was given to 7(13%) patients. Upfront chemotherapy was given in 45(86·5%) patients, out of which 24 had stage I disease. RT consolidation was done in 26 (50%) patients for residual disease after chemotherapy. Median follow-up was 88 months (range 29–183 months). Relapse occurred in 6(9·6%) patients; 2 local; 2 local + distant and in 2 distant alone. These patients were successfully salvaged with systemic chemotherapy and local RT. One patient died due to neutropenia. Overall survival in this series was 96%. Conclusions: Excellent local control was achieved with initial chemotherapy followed by RT for primary orbital NHL with minimal toxicity. We recommend a dose of 36–40 Gy for definitive RT and 30 Gy for lymphoma following chemotherapy using 2 Gy/fraction for Indian patients who present with bulky tumours. RT should be incorporated in treatment of orbital NHL whenever possible as it is safe, effective and is associated with minimal complications.