Retinoblastoma: A review of the molecular basis of tumor development and its clinical correlation in shaping future targeted treatment strategies.

Retinoblastoma is a retinal cancer that affects children and is the most prevalent intraocular tumor worldwide. Despite tremendous breakthroughs in our understanding of the fundamental mechanisms that regulate progression of retinoblastoma, the development of targeted therapeutics for retinoblastoma has lagged. Our review highlights the current developments in the genetic, epigenetic, transcriptomic, and proteomic landscapes of retinoblastoma. We also discuss their clinical relevance and potential implications for future therapeutic development, with the aim to create a frontline multimodal therapy for retinoblastoma.

Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.

Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe2+) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml-1), carotenoid accumulation (1.96-2.08 µg ml-1), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm-1) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.

Rapid Response Preparedness for Management of Post-Covid Invasive Rhino-Orbito-Cerebral Fungal Infections: Experience from a Tertiary Care Government Institute in India.

Sudden surge of Post Covid-19 Rhino-orbito-mucormycosis cases has left entire ENT fraternity in the center of a war room. We present a quick administrative preparedness for this situation in a tertiary care Government Institute in India. This model may serve as a reference for other centers.

Infection and utilization rates of bone allografts in a hospital-based musculoskeletal tissue bank in north India.

BACKGROUND: The bone bank unit of interest in this article was established in January 2018, in a tertiary care teaching institute of north India. Aim of this article is to describe the sources of allografts obtained, discard rates of allografts and infection rates in the recipients after use. MATERIAL AND METHODS: All the relevant details of donors and recipients were maintained, and donors were screened for standard inclusion and exclusion criteria before obtaining the grafts. Aerobic culture was performed before storage and just prior to use. Samples with incomplete documentation, incomplete donor screening or positive cultures were discarded. Data on surgical site infection in recipients was collected from hospital records retrospectively. Initially ELISA based serological tests were used for screening. Donor has to undergo these tests again after 6 months to account for the window period of proliferation of viruses. Nucleic acid amplification tests (NAAT) for these viral agents were introduced in the hospital in May 2018. RESULTS: Allografts from a total of 196 donors were obtained in the bone bank over 2 years. Major source of bone was femoral heads harvested during total hip arthroplasty or hemi-arthroplasty. 44(22.4%) grafts had to be discarded. 95 allografts were used in 88 patients during this time. Most common indication for use was surgery for bone tumors (40%), followed by complex primary or revision arthroplasty (30.5%). Three (3.4%) recipients developed deep infection postoperatively. CONCLUSION: Frozen allograft bone from hospital based bone banks is a reliable source of allografts. When meticulous precautions for sterility are followed, risk of infection is low. Monitoring of such bone banks should fall within a framework of the local legislature. Incomplete documentation is the major reason for wastage of the samples obtained. NAAT may be useful in screening of donors, as it reduces the wastage and the holding time of the allografts.

Ollier's Disease - Rare Presentation of the Rare Disease.

Introduction: Enchondromas are benign lesion of cartilaginous origin seen in early childhood. Multiple enchondromatosis is also known as Ollier's disease which involves the appendicular skeleton with multiple site involvement. We present a rare case of appendicular as well as axial skeleton involvement in a case of Ollier's disease. Case Report: A 13-year-old male with multiple enchondromas including all the appendicular skeleton along with ribs and cervical spine. Patient was evaluated with X-rays and non-contrast computerized tomography and is on conservative treatment and on regular monthly follow-up with no neurological deficit and no respiratory complications till now. Further evaluation for deformity correction if required, will be considered after skeletal maturity. Conclusion: Ollier's disease is a rare presentation with multiple enchondromas in the appendicular skeleton. Current case is further rare presentation of the Ollier's disease with involvement of cervical spine and ribs as well.

Hyperleukocytosis increases risk of fatal hyperkalemia with new ibrutinib/venetoclax regimen for refractory mantle cell lymphoma.

Background: A recent phase 2 study reported success using combination of ibrutinib and venetoclax for relapsed/refractory mantle cell lymphoma (MCL). We report a case of MCL with hyperleukocytosis that developed fatal hyperkalemia after a single low initiation dose of venetoclax.Case report: A 72-year-old man with known MCL was admitted for hyperkalemia and anemia (Hgb = 6.6 g/dL, K+ =9.6 mmol/L). Repeated K+ measurements and clinical evaluation were consistent with pseudohyperkalemia. The patient's lymphocyte count had risen from 15.2 to 466.8 K/uL in the preceding 1.5 months despite 8 cycles of ibrutinib. Based on the results of a recent phase 2 study Venetoclax was added; after a single very low initiation dose of venetoclax the patient developed fatal hyperkalemia.Discussion: The proliferation of new therapies is making difficult to perform randomized clinical trials large enough to capture potential risks of new therapies in specific scenarios. Fatal hyperkalemia resulted from use of a recently recommended combination regimen for refractory/relapsed MCL in a phase 2 study, despite dose escalation and TLS prophylaxis suggesting increased risk of this regimen for patients with hyperleukocytosis.

Implantless patellar fixation in medial patellofemoral ligament reconstruction.

PURPOSE: The medial patellofemoral ligament (MPFL) acts as primary restraint to lateral patellar dislocation and its rupture has been reported in almost all cases of acute patellar dislocation. Various surgical techniques have been described for MPFL reconstruction, using many femoral and patellar fixation techniques and different grafts. This article details our technique for MPFL reconstruction using semitendinosus graft which avoids the use of implant at patellar end. METHODS: Twenty patients (8 males and 12 females) with complaints regarding acute and chronic lateral patellar instability were evaluated and treated by MPFL reconstruction procedure. The mean age of patients was 21 years (range 17-34 years). MPFL reconstruction was performed using semitendinosus graft passing through two parallel, obliquely directed tunnels created in patella. Fixation of graft was done with an interference screw only at the femoral end. Mean follow-up period after intervention was 26.4 months (range 23-30 months). Results were evaluated using Kujala score. RESULTS: All patients gained adequate patellar stability and full arc of motion. No incidence of patella fracture was noted. There were no postoperative complications related to the procedure. There was no recurrence of instability in patella at final follow-up. CONCLUSION: Passing the graft through the tunnels in patella without use of any implant has given excellent functional outcome and moreover has the advantages of less implant-related complications and cost-effectiveness.

Risk of injury associated with opioid use in older adults.

OBJECTIVES: To estimate the dose-related risk of injuries in older adults associated with the use of low-, medium-, and high-potency opioids. DESIGN: Historical population-based cohort study: 2001 to 2003. SETTING: Quebec, Canada's, universal healthcare system. PARTICIPANTS: Four hundred three thousand three hundred thirty-nine adults aged 65 and older. MEASUREMENTS: Population-based health databases were used to measure preexisting risk factors for injuries in 2001/02 and drug use and injuries during follow-up (2003). Type and dose of opioids were measured as time-dependent variables, as were other drugs that may increase the risk of injury from sedating side-effects or hypotension. The risk of injury per one adult dose increase in opioid dose was estimated using multivariate Cox proportional hazards models. RESULTS: During the follow-up year, 50.7% of the study population were prescribed drugs with sedating side effects, 15.3% were prescribed an opioid, 20.7% were concurrently using more than one sedating medication, and 3.7% were treated for an injury, fractures (55.1%) being the most common. After adjusting for concurrent drug use and baseline risk factors, low- (hazard ratio (HR)=1.36, 95% confidence interval (CI)=1.33-1.39) and intermediate-potency (HR=1.05, 95% CI=1.02-1.07) opioids were associated with the risk of injury. Use of codeine combinations was associated with the highest risk of injury, a 127% greater risk (HR=2.27, 95% CI=2.21-2.34) per one adult dose increase. (The mean World Health Organization standardized dose in the study population was 1.71 ± 0.85 adult doses.) CONCLUSION: Opioids increase the risk of injury in older adults, particularly codeine combinations.