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Given that radium-223 is a radiopharmaceutical that induces DNA damage, and olaparib is a PARP inhibitor that interferes with DNA repair mechanisms, we hypothesized their synergy in metastatic castration-resistant prostate cancer (mCRPC). We sought to demonstrate the safety and efficacy of olaparib + radium-223. We conducted a multicenter phase I 3+3 dose escalation study of olaparib with fixed dose radium-223 in patients with mCRPC with bone metastases. The primary objective was to establish the RP2D of olaparib, with secondary objectives of safety, PSA response, alkaline phosphatase response, radiographic progression-free survival (rPFS), overall survival, and efficacy by homologous recombination repair (HRR) gene status. Twelve patients were enrolled; all patients received a prior androgen receptor signaling inhibitor (ARSI; 100%) and 3 patients (25%) prior docetaxel. Dose-limiting toxicities (DLT) included cytopenias, fatigue, and nausea. No DLTs were seen in the observation period however delayed toxicities guided the RP2D. The RP2D of olaparib was 200 mg orally twice daily with radium-223. The most common treatment-related adverse events were fatigue (92%) and anemia (58%). The rPFS at 6 months was 58% (95% confidence interval, 27%-80%). Nine patients were evaluable for HRR gene status; 1 had a BRCA2 alteration (rPFS 11.8 months) and 1 had a CDK12 alteration (rPFS 3.1 months). Olaparib can be safely combined with radium-223 at the RP2D 200 mg orally twice daily with fixed dose radium-223. Early clinical benefit was observed and will be investigated in a phase II study.

Background: Ultrasound has become the standard of care for the insertion of central venous catheters (CVCs) in the intensive care unit. With the introduction of ultrasonography in CVC insertion, there has been an improvement in the success rate and a dramatic decrease in the rate of complications. Aims and Objectives: The aim of this study was to compare the safety and ease of insertion of ultrasonically guided cannulation of the internal jugular vein (IJV) with that of the supraclavicular subclavian vein (SCV) in adult patients undergoing various surgical procedures. Materials and Methods: All the patients in whom central venous cannulation was planned were assigned to two groups. Group I underwent ultrasound-guided IJV while as Group II underwent cannulation ultrasound-guided SCV cannulation. A comparison was made between the two groups, of the success rates, durations of procedure, number of attempts at needle redirections, difficulties if any during insertion of guidewires, and the complications encountered. Results: The IJV group had a higher proportion of first-attempt success (93.2% versus 62.7%). The IJV group had a lesser incidence (3.2%) of complications such as guidewire progression and needle redirections compared with SCV (15.2%). The frequency of adverse events did not differ between the two study groups with an incidence in 3.2% in IJV group and 9.6% in the subclavian group. Higher first-attempt success rates and fewer procedural complications were seen with ultrasound-guided IJV. Conclusion: IJV central venous catheterization is an easier and less invasive and less risky procedure for patients.

Abstract Background A ventriculoperitoneal (VP) shunt is a cerebral shunt that diverts excess cerebrospinal fluid (CSF).Obstruction in the normal outflow or decreased absorption of the fluid is the usual cause. Hydrocephalus is treated by cerebral shunts.In paediatric patients, untreated hydrocephalus can be lethal and leads to many adverse effects including increase irritabilities, chronic headaches, learning difficulties, visual disturbances, and, in more advanced cases, severe mental retardation. Malfunction of the shunt with excess CSF accumulated can increase the intracranial pressure resulting in cerebral oedema and ultimately herniation. Objective To study and evaluate the mechanical causes of shunt failure and their surgical remedies and reduce the preventable morbidity, cost and mortality associated with shunt failure. Methods We conducted a prospective observational study including 70 patients who developed pure mechanical shunt failure for the first time from 2017 to 2020 in the Department of Neurosurgery Sher-i-kashmir Institute of Medical Sciences. Patients with previous shunt surgeries which include VP shunting and shunt revision or failure and shunt infections were excluded. Identity of all the patients has been kept anonymus. Written informed consent was obtained from all patients or their guardians in case of minors. Shunt malfunction was in the form of catheter misplacement, kinking, displacement from the ventricle or peritoneal cavity, disconnection, migration,inadvertent suturing of the catheter, air in shunt bulb. Results We found kinking at the proximal end in 25 (35%) patients as the most common cause of shunt failure. It was mostly as a result of inadequate and less spacious tunnelling made for the reservoir. Inadvertant suturing of shunt while closing abdomen in 7 (10%), shunt disconnection in 6 (8.5%), air in shunt bulb in 2 (2.8%), wrong placement at ventricular end in 10 (14.2%), shunt migration into the brain parenchyma in 5 (7.1%), shunt migration through the anal canal in 1(1.4%), pseudomeningocele around catheter valve in 3 (4.2%), placement of lower end into the preperitoneal space in 4 (5.7%) patients. Conclusions Shunt surgery is seemingly a straightforward operation for neurosurgeons. But considering the incidence of shunt failure and its associated morbidity and mortality, it should always be done with trepidation and extreme caution. Exclusive mechanical shunt malfunction is a major concern and leads to great deal of morbidity in the shunt operations. However, there are trivial remedies and technical nuances which needs to be followed during surgery to avoid these complications.

Abstract Background Epidural hematomas have been treated with urgent surgical evacuation to prevent catastrophic neurological sequelae and death. Brain Trauma Foundation recommends EDH volume greater than 30 cm3 and warrants surgical evacuation irrespective of GCS. However, due to increase in number of patients undergoing brain CTs following head injuries, more patients have been detected with EDH causing minimal symptoms. Aims and objectives To study factors influencing patients being treated conservatively for head injury with supratentorial epidural hematomas. Material and methods Our study is a retrospective analysis of supratentorial epidural hematoma treated conservatively from august 2018 to July 2020 at Sher-i-Kashmir institute of medical sciences, Srinagar, Jammu and Kashmir. Results A total of 19 patients with EDH were treated conservatively and fulfilled the inclusion criteria.(GCS of 13–15 with no neurological deficit, mild signs of elevated ICP, EDH thickness 13 on admission. 8 patients were hospitalised for a week, whilst 2 patients stayed in the hospital for 20 and 25 days, respectively, due to problems not related to EDH. One patient in whom conservative treatment had to be changed to surgical evacuation after 6 days of observation because of worsening headache, impaired alertness repeated imaging showed slight increase in EDH. Conclusions EDH can be managed conservatively in carefully selected patients of minor head injury with radiological surveillance and close neurological monitoring. Patients with GCS on admission more than 13, midline shift of less than 5 mm, location and volume of EDH less than 30 ml. Thus, leading to optimal utilisation of hospital resources. So, we conclude that even a dreaded entity like extradural haemorrhage can be managed conservatively in selected cases with strict clinical and radiological surveillance. We have called them ‘’Benign extradural haemorrhages’’.

Rapid industrialization has led to an increase in cadmium pollution, a dangerously toxic heavy metal. Cadmium (Cd) is released into the environment through industrial processes and can contaminate air, water, and soil. This pollution poses a significant risk to human health and has become a pressing concern in many industrialized areas. Due to its extended half-life, it leads to a range of health problems, including hepato-nephritic toxicity, brain damage, and degenerative bone disorders. Intoxication alters various intracellular parameters, leading to inflammation, tissue injury, and oxidative stress within cells, which disrupts normal cellular functions and can eventually result in cell death. It has also been linked to the development of bone diseases such as osteoporosis. These adverse effects highlight the urgent need to address cadmium pollution and find effective solutions to mitigate its impact on human health. This article highlights the Cd-induced risks and the role of Catharanthus roseus (C. roseus) extract as a source of alternative medicine in alleviating the symptoms. Numerous herbal remedies often contain certain bioactive substances, such as polyphenols and alkaloids, which have the power to mitigate these adverse effects by acting as antioxidants and lowering oxidative cell damage. Research conducted in the field of alternative medicine has revealed its enormous potential to meet demands that may be effectively used in safeguarding humans and their environment. The point of this review is to investigate whether C. roseus extract, known for its bioactive substances, is being investigated for its potential to mitigate the harmful effects of cadmium on health. Further investigation is needed to fully understand its effectiveness. Moreover, it is important to explore the potential environmental benefits of using C. roseus extract to reduce the negative effects of Cd. This review conducted in the field of alternative medicine has revealed its enormous potential to meet demands that could have significant implications for both human health and environmental sustainability.