Safety and Efficacy of Genicular Artery Embolization for the Treatment of Knee Pain Secondary to Osteoarthritis-Initial Indian Experience.

Background Osteoarthritis (OA) is the commonest form of arthritis with pain and disability as hallmark symptoms. Despite various nonpharmacologic, pharmacologic, and surgical approaches, pain control may be hard to achieve. Over the last few years, few studies have been conducted on managing knee OA using novel endovascular genicular artery embolization (GAE) with varied outcomes. No such study has been reported in India yet to the best of our knowledge. Purpose The main aim of this article was to evaluate the efficacy and safety of transcatheter GAE in relieving knee pain in patients with mild-to-moderate OA. Materials and Methods Ten patients with radiographic knee OA and moderate-to-severe pain refractory to conservative therapy were enrolled in a prospective observational study. GAE was performed with 100 to 300-µm spherical particles. Patients were assessed with magnetic resonance imaging at the baseline. Visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess pain and disability respectively at the baseline, 1 month, and 3 months. Clinical success was asserted by the downstaging of VAS and WOMAC scores. Adverse events were recorded at all-time points. Descriptive and inferential statistics have been performed using SPSS. A p -Value less than 0.05 was considered statistically significant. Results Embolization of at least 1 genicular artery was achieved in all the patients (100%). Clinical success was demonstrated in 08 (80%) of the patients. Median VAS reduced from 07 at baseline to 3.5 at 3-month follow-up ( p < 0.001). Median WOMAC score improved from 53 to 23.50 at 3-month follow-up ( p < 0.001). Minor complications were seen in two patients in the form of puncture site hematoma and mild petechial spots over the knee. Conclusion Our pilot study demonstrates GAE as a safe and efficacious procedure to treat knee pain secondary to OA. Further randomized comparative studies with a larger sample size are needed to determine the true treatment effect versus the placebo effect.

Anaesthesia Challenges in a Neonate Having Supracardiac Total Anomalous Pulmonary Venous Return With Incidental Stridor for Non-operating Room Anaesthesia (NORA): Feed and Wrap Technique as a Rescue.

This case represents anaesthetic challenges while managing a neonate having a congenital cardiac anomaly with incidental stridor for the non-operating room anaesthesia (NORA). Anaesthesia management of neonates is demanding even for experienced anaesthetists in terms of vascular access, airway management, relatively poor respiratory reservoir and transitional cardiac physiology. Neonate having cyanotic congenital heart disease with abnormal cardiac physiology demands further attention. In children with congenital heart disease, difficult intubation remains a possibility as they are more often associated with airway anomalies. NORA has its own set of anaesthesia challenges related to a lack of adequate anaesthesia equipment and monitoring devices, a limited and unfamiliar workspace, lack of trained support staff along with more medically complex patients. Recently there has been concern regarding the safety of anaesthetic agents in children < 3 years. So, techniques are being developed to promote immobilisation without using anaesthesia in short procedures. One such technique is the "feed and wrap" technique where feeding and swaddling induce natural sleep in infants. Here, we have used the "feed and wrap technique" in a 24-day-old neonate having supracardiac total anomalous pulmonary venous return with incidental stridor posted for contrast-enhanced computed tomography angiography.

Melatonin and andrographolide synergize to inhibit the colospheroid phenotype by targeting Wnt/beta-catenin signaling.

ß-catenin signaling, and angiogenesis are associated with colospheroid (CSC), development. CSCs, spheroids derived from colon cancer cells, are responsible for metastasis, drug resistance, and disease recurrence. Whether dysregulating ß-catenin and inhibiting angiogenesis reduce CSC growth is unknown. In this study, the molecular mechanism of CSC growth inhibition was evaluated using a novel combination of melatonin (MLT) and andrographolide (AGP). These drugs have anticarcinogenic, antioxidant, and antimetastatic properties. CSCs were obtained from two metastatic colon cancer cell lines (HT29 and HCT-15). The viability and stemness were monitored (FDA propidium iodide staining and immunoblot for CD44, CD133, Nanog, Sox2, and Oct4). The drug combination synergistically diminished stemness via increased reactive oxygen species (ROS) levels, reduced mitochondrial membrane potential and ATP level. MLT + AGP induced cell death by inhibiting ß-catenin expression and its downregulatory signals, Cyclin D1, c-Myc. MLT + AGP treated cells exhibited translocation of phospho-ß-catenin to the nucleus and dephosphorylated-ß-catenin. Downregulation of ß-catenin activation and its transcription factors (TCF4 and LEF1) and GTP binding/G-protein related activity were found in the dual therapy. Angiogenic inhibition is consistent with downregulation of VEGF messenger RNA transcripts (VEGF189), phosphorylated VEGF receptor protein expression, matrigel invasion, and capillary tube inhibition. In vivo, the intravenous injection of MLT + AGP slowed HT29 metastatic colon cancer. Histopathology indicated significant reduction in microvascular density and tumor index. Immunohistochemistry for caspase 7, and ß-catenin found increased apoptosis and downregulation of ß-catenin signals. The mechanism(s) of decreased colospheroids growth were the inhibition of the Wnt/ß-catenin pathway. Our results provide a rationale for using MLT in combination with AGP for the inhibition of CRCs.

Synergistic potential of dual andrographolide and melatonin targeting of metastatic colon cancer cells: Using the Chou-Talalay combination index method.

Colorectal cancer (CRC) mortality has diminished for decades due to new and improved treatment profiles. However, CRC still ranks as the third most diagnosed cancer in the US. Therefore, a new therapeutic approach is needed to overcome colospheroids inhibition and drug resistance. It is well documented that andrographolide (AGP) and melatonin (MLT) have anti-carcinogenic properties. Our goal was to evaluate their synergistic effects on metastatic colon cancer cells (mCRC) and colospheroids. HT-29 and HCT-15 mCRC cells were simultaneously treated with serial dilutions of AGP and MLT for 24, 48 and 72 h. Cell viability was monitored using the MTT assay. The Chou-Talalay method for drug combination is based on the median effect equation, providing a theoretical basis for the combination index and the isobologram equation. This allows quantitative determination of drug interactions using the CompuSyn software, where CI < 1, = 1, and >1 indicates synergistic, additive, and antagonistic effects respectively. Our results demonstrate that AGP and MLT in combination show synergism with CI values of 0.35293 and 0.34152 for HT-29 and HCT-15 respectively and a fractional inhibition of Fa = 0.50-0.90, as shown by the Fa-CI plot and isobologram. The synergism value was validated in colospheroids (HT-29-s and HCT-15-s) based on morphology, viability, and colony formation and in 5-FU drug resistant cell (HT-29R and HCT-116R) viability. The mechanism(s) of decreased cell viability are due to the induction of ER stress proteins and angiogenic inhibition. Our results provide rationale for using AGP in combination with MLT on mCRC.

Radiotracer investigation on the measurement of residence time distribution in an ethyl acetate reactor system with a large recycle ratio.

A radiotracer investigation was carried out on the measurement of residence time distribution (RTD) of process fluid in an industrial-scale ethyl acetate reactor system, which consists of two independent reactors with recirculation and connected in series with each other. Bromine-82 as ammonium bromide was used as the radiotracer for the RTD experiments at different operating conditions. The individual reactors and the overall reactor system were modelled using physically representative phenomenological models comprising of continuously stirred tank reactors (CSTRs). The results showed that the recirculation rate considerably affected the flow mixing behaviour and mean residence time of the process fluid in the reactor system. The results also showed that there was bypassing of the fluid in the first reactor that ranged from 12% to 22% and 40% dead volume at different operating conditions, whereas the second reactor behaved closely as an ideal CSTR. The results of the investigation can be used to optimise the process parameters and design new improved reactor systems for the production of ethyl acetate.

Minimally invasive transforaminal lumbar interbody fusion: Results of 23 consecutive cases.

BACKGROUND: The use of minimally invasive surgical (MIS) techniques represents the most recent modification of methods used to achieve lumbar interbody fusion. The advantages of minimally invasive spinal instrumentation techniques are less soft tissue injury, reduced blood loss, less postoperative pain and shorter hospital stay while achieving clinical outcomes comparable with equivalent open procedure. The aim was to study the clinicoradiological outcome of minimally invasive transforaminal lumbar interbody fusion. MATERIALS AND METHODS: This prospective study was conducted on 23 patients, 17 females and 6 males, who underwent MIS-transforaminal lumbar interbody fusion (TLIF) followed up for a mean 15 months. The subjects were evaluated for clinical and radiological outcome who were manifested by back pain alone (n = 4) or back pain with leg pain (n = 19) associated with a primary diagnosis of degenerative spondylolisthesis, massive disc herniation, lumbar stenosis, recurrent disc herniation or degenerative disc disease. Paraspinal approach was used in all patients. The clinical outcome was assessed using the revised Oswestry disability index and Macnab criteria. RESULTS: The mean age of subjects was 55.45 years. L4-L5 level was operated in 14 subjects, L5-S1 in 7 subjects; L3-L4 and double level was fixed in 1 patient each. L4-L5 degenerative listhesis was the most common indication (n = 12). Average operative time was 3 h. Fourteen patients had excellent results, a good result in 5 subjects, 2 subjects had fair results and 2 had poor results. Three patients had persistent back pain, 4 patients had residual numbness or radiculopathy. All patients had a radiological union except for 1 patient. CONCLUSION: The study demonstrates a good clinicoradiological outcome of minimally invasive TLIF. It is also superior in terms of postoperative back pain, blood loss, hospital stay, recovery time as well as medication use.

Finger clubbing in a patient of myelofibrosis with renal cell carcinoma.

Finger clubbing has many well known causes. We present a rare association of finger clubbing in patient with myelofibrosis and non metastatic renal cell carcinoma, with no evidence of these well known.