Construction, Features and Regulatory Aspects of Organ-Chip for Drug Delivery Applications: Advances and Prospective.

Organ-on-chip is an innovative technique that emerged from tissue engineering and microfluidic technologies. Organ-on-chip devices (OoCs) are anticipated to provide efficient resolutions to dealing with challenges in pharmaceutical advancement and individualized illness therapies. Organ-on-chip is an advanced method that can replicate human organs' physiological conditions and functions on a small chip. It possesses the capacity to greatly transform the drug development process by enabling the simulation of diseases and the testing of drugs. Effective integration of this advanced technical platform with common pharmaceutical and medical contexts is still a challenge. Microfluidic technology, a micro-level technique, has become a potent tool for biomedical engineering research. As a result, it has revolutionized disciplines including physiological material interpreting, compound detection, cell-based assay, tissue engineering, biological diagnostics, and pharmaceutical identification. This article aims to offer an overview of newly developed organ-on-a-chip systems. It includes single-organ platforms, emphasizing the most researched organs, including the heart, liver, blood arteries, and lungs. Subsequently, it provides a concise overview of tumour-on-a-chip systems and emphasizes their use in the evaluation of anti-cancer medications.

The Study of the Feasibility of Ultrasound-guided Catheterization of the Right Brachiocephalic Vein in Adult Patients: A Prospective Observational Study.

Background: The brachiocephalic vein (BCV) is a feasible option for central venous access in the pediatric population and is rapidly developing as an alternative site for insertion of the central line in young children with faster insertion times, fewer attempts, and lower rates of complications. However, studies demonstrating the feasibility of BCV catheterization in adult patients are insufficient. The current study sought to assess the safety and effectiveness of ultrasound-guided supraclavicular right BCV cannulations in adults. Methods: A linear array Ultrasound (US) probe was used to obtain a longitudinal picture of the BCV beginning at the junction of the internal jugular vein and the subclavian vein in the supraclavicular region. Under US supervision, the needle was guided into the BCV using the in-plane approach. A prospective study was performed on 80 adult patients scheduled for elective and emergency operative procedures under general anesthesia requiring a central venous catheter (CVC). Success rates and complications that occurred during catheter insertion were analyzed. Results: CVC placement was successful in all adults. The procedure was successful at the first attempt in 74 cases (92.5%) and after 2 attempts in six patients (7.5%). The time to guide wire insertion was 31.26 s (19-58 s), and catheter insertion took 88.44 s (63-145 s). The mean length of catheter insertion was 10.46 cm. No complications were noted. Conclusion: Ultrasound-guided supraclavicular BCV catheterization offers a new and safe method for central venous line catheterization in adults. However, larger trials and meta-analyses are needed to confirm these findings and evaluate the safety of this technique.

Carbon Nanotubes for Targeted Therapy: Safety, Efficacy, Feasibility and Regulatory Aspects.

It is crucial that novel and efficient drug delivery techniques be created in order to improve the pharmacological profiles of a wide variety of classes of medicinal compounds. Carbon nanotubes (CNTs) have recently come to the forefront as an innovative and very effective technique for transporting and translocating medicinal compounds. CNTs were suggested and aggressively researched as multifunctional novel transporters designed for targeted pharmaceutical distribution and used in diagnosis. CNTs can act as vectors for direct administration of pharmaceuticals, particularly chemotherapeutic medications. Multi-walled CNTs make up the great majority of CNT transporters, and these CNTs were used in techniques to target cancerous cells. It is possible to employ Carbon nanotubes (CNTs) to transport bioactive peptides, proteins, nucleic acids, and medicines by functionalizing them with these substances. Due to their low toxicity and absence of immunogenicity, carbon nanotubes are not immunogenic. Ammonium-functionalized carbon nanotubes are also attractive vectors for gene-encoding nucleic acids. CNTs that have been coupled with antigenic peptides have the potential to be developed into a novel and efficient approach for the use of synthetic vaccines. CNTs bring up an enormous number of new avenues for future medicine development depending on targets within cells, which have until now been difficult to access. This review focuses on the numerous applications of various CNT types used as medicine transport systems and on the utilization of CNTs for therapeutical purposes.

Evaluation of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early diagnostic marker of acute kidney injury (AKI) in critically ill trauma patients.

Background and Aims: Acute kidney injury (AKI) is a frequent complication of severe trauma associated with high mortality. The aim of this study was to evaluate the diagnostic ability of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of AKI assessed by RIFLE criteria as reference in trauma patients in intensive care unit (ICU). Material and Methods: This was a prospective observational study. Four hundred and eighteen patients admitted in the trauma ICU with age ≥18 years without known renal diseases were followed-up (serum creatinine, urine output, and estimated glomerular filtration rate) for 5 consecutive days. As per RIFLE criteria, 70 patients were broadly classified as AKI and rest of the patients (n = 348) as non-AKI. Plasma and urine samples of AKI (n = 70) and non-AKI (n = 70) patients were further assessed for 3 consecutive days following admission. Results: Mean plasma NGAL (pNGAL) was significantly elevated in AKI patients as compared with non-AKI patients; on admission: 204.08 versus 93.74 ng/mL (P = 0.01); at 24 h: 216.73 versus 94.63 ng/mL (P = 0.01); and 48 h: 212.77 versus 86.32 ng/mL (P = 0.01). Mean urine NGAL (uNGAL) at 48 h was also significantly elevated: 15.45 ng/mL in AKI patients as compared with 13.48 ng/mL in non-AKI patients (P = 0.01). Plasma and urine NGAL levels were significantly associated with increased mortality. Conclusion: pNGAL had good predictive value on admission (area under the receiver operative characteristic [AUROC] 0.84), at 24 h (AUROC 0.88) and 48 h (AUROC 0.87), while uNGAL had moderate performance at 24 h (AUROC 0.61) and 48 h (AUROC 0.71). pNGAL can be used as an early and potent diagnostic and predictive marker of AKI and mortality in critically ill trauma patients.

Early total care to early appropriate care - What every anesthesiologist must know!

Orthopedic trauma is one of the commonest injuries necessitating surgical intervention in a trauma patient. The management protocols in such severely injured orthopedic patients have evolved from conservative treatment to 'early total care' (ETC) to 'damage control orthopedics' (DCO) and recently to 'early appropriate care' (EAC)/'safe definitive surgery' (SDS). 'DCO' involves emergent, basic minimum life- or limb-saving surgery with continued resuscitation and definitive fixation of fractures being done later, once the patient has been resuscitated and stabilized. An insight into the immunological processes at a molecular level evoked in a poly-traumatized patient led to the evolution of the 'two-hit theory;' 'first hit' being the injury itself while the 'second hit' caused by the surgical trauma. As the 'two-hit theory' gained popularity, it led to a delay of definitive surgery for 2-5 days following trauma, since a higher complication rate was observed following definitive surgery within the first 5 days of the injury. This is a review article on the historical perspectives of DCO, immunological mechanisms involved, and various injuries requiring damage control approach or EAC/ETC and their anesthetic management.

Comprehensive Management of the Patient With Traumatic Cardiac Injury.

Cardiac injuries are rare but potentially life-threatening, with a significant proportion of victims dying before arrival at the hospital. The in-hospital mortality among patients who arrive in-hospital alive also remains significantly high, despite major advancements in trauma care including the continuous updating of the Advanced Trauma Life Support (ATLS) program. Stab and gunshot wounds due to assault or self-inflicted injuries are the common causes of penetrating cardiac injuries, while motor vehicular accidents and fall from height are attributable causes of blunt cardiac injury. Rapid transport of victim to trauma care facility, prompt recognition of cardiac trauma by clinical evaluation and focused assessment with sonography for trauma (FAST) examination, quick decision-making to perform emergency department thoracotomy, and/or shifting the patient expeditiously to the operating room for operative intervention with ongoing resuscitation are the key components for a successful outcome in cardiac injury victims with cardiac tamponade or exsanguinating hemorrhage. Blunt cardiac injury with arrhythmias, myocardial dysfunction, or cardiac failure may need continuous cardiac monitoring or anesthetic care for operative procedure of other associated injuries. This mandates a multidisciplinary approach working in concert with agreed local protocols and shared goals. An anesthesiologist has a pivotal role to play as a team leader or member in the trauma pathway of severely injured patients. They are not only involved in in-hospital care as a perioperative physician but also participate in the organizational aspects of prehospital trauma systems and training of prehospital care providers/paramedics. There is sparse literature available on the anesthetic management of cardiac injury (penetrating as well as blunt) patients. This narrative review discusses the comprehensive management of cardiac injury patients, focusing on the anesthetic concerns and is guided by our experience in managing cardiac injury cases at Jai Prakash Narayan Apex Trauma Center (JPNATC), All India Institute of Medical Sciences, New Delhi. JPNATC is the only level 1 trauma center in north India, providing services to a population of approximately 30 million with around 9000 operations being performed annually.

Successful airway management of traumatic complete tracheal transection.

A man in his 20s sustained complete tracheal transection after being injured by a sandbag pile falling on his neck. An oral endotracheal tube (ETT) was inserted by rapid sequence induction in view of respiratory distress. CT revealed that the ETT did not traverse the distal tracheal segment; however, there were rebreathing bag movements, and normal capnograph and oxygen saturation, which were misleading clinical findings. We describe the successful airway management in this challenging case.

Impact of the COVID-19 Pandemic on the Health Workforce in Canada.

Healthcare workers are the foundation that keep our healthcare systems running. The recent COVID-19 pandemic has placed unprecedented demands on Canada's health workforce. The Canadian Institute for Health Information has compiled data and information to help inform how the pandemic has impacted healthcare workers and the care Canadians received. This article deliberates on the many challenges of the pandemic, such as safety and access to personal protective equipment, faced by healthcare workers along with its impact on health workers and the health care system. The article also shares how the system responded to protect the health workforce and boost capacity by expanding provider roles and adapting new ways of delivering services, including quickly adapting to virtual care.

Internal iliac artery transposition for vascular reconstruction in a patient with life-threatening iatrogenic common iliac artery injury.

Major vascular injury during surgery is life threatening and can be a nightmare for any surgeon.We share our experience of a 42-year-old woman where right common iliac artery and both common iliac veins were accidentally injured during lumbar discectomy leading to haemorrhagic shock. Patient was resuscitated and explored. A 4 cm segment of right common iliac artery was found lacerated along with perforations of both iliac veins. Proximal segment of internal iliac artery was mobilised quickly and vascular continuity was restored by end-to-end anastomosis of this segment to the proximal segment of common iliac artery after excising the damaged segment. Iliac veins were repaired primarily. Patient made an uneventful recovery. We share this technique as it was found expeditious and effective and may benefit surgeons working in this field.

An Analysis of Presentation, Pattern and Outcome of Chest Trauma Patients at an Urban Level 1 Trauma Center.

Chest trauma is an important public health problem accounting for a substantial proportion of all trauma admissions and deaths. It directly account for 20-25 % of deaths due to trauma. Therefore, this study was conducted to analyze the presentation, patterns, and outcome of chest trauma in a level-1 urban trauma center. It was a prospective observational study of all patients presented with chest trauma to an urban level 1-trauma center over a period of 3 years. Demographic profile, mechanism of injury, injury severity scores (ISS), associated injuries, hospital stay, etc. were recorded. Morbidity and mortality rates were analyzed and compared with the published literature. Chest injuries comprised 30.9 % of all trauma admissions and the mechanism was blunt in majority (83.5 %) of the cases. Vehicular crashes (59.7 %) followed by assault were the most common modes of injury. Rib fracture was the most common chest injury seen in 724 of the 1258 patients while abdominal visceral injuries were the commonest associated injuries in polytrauma cases. Majority of the patients were managed non-operatively. Inter costal tube drainage (ICD) was the main stay of treatment in 75 % of the cases, whereas, thoracotomy was required only in 5.56 % of the patients. Overall mortality was 11 % and it was found to be significantly higher following blunt chest trauma. We observed that associated extra thoracic injuries resulted in higher mortality as compared to isolated chest injuries. Thoracic injuries can be readily diagnosed in the emergency department by meticulous and repeated clinical evaluation and majority require simple surgical procedures to prevent immediate mortality and long-term morbidity.

Role of Laparoscopy in Patients With Abdominal Trauma at Level-I Trauma Center.

INTRODUCTION: Abdominal trauma is one of the preventable causes of death in polytrauma patients. Decision and timing of laparotomy is a major challenge. Rate of nontherapeutic laparotomy is still high. Laparoscopy can avoid nontherapeutic laparotomy and also provide a reliable and accurate diagnosis of injury. MATERIALS AND METHODS: This ambispective observational study was conducted in the division of Trauma Surgery and Critical Care, JPN Apex Trauma Centre, All India Institute Medical Sciences, New Delhi. Retrospective analysis of prospectively maintained data of cases from January 1, 2008 through April 30, 2013 and prospective analysis of cases from May 1, 2013 through March 31, 2015 was done using appropriate measures. Hemodynamically stable or responders fulfilling inclusion criteria were included. Selected patients underwent the laparoscopic procedure and if required converted to laparotomy. RESULTS: Of the 3610 patients of abdominal trauma, laparotomy was done in 1666 (46.14%) patients and laparoscopy was done in 119 (3.29%) patients. Rate of reduction of nontherapeutic laparotomy in patients with abdominal trauma using diagnostic laparoscopy was 55.4%. However laparotomy could be avoided in 59.7%. Laparoscopy was 100% accurate in identifying injuries in our study. No injuries were missed in these patients. Fever and wound infection were significantly higher in laparotomy group. Chest infection and sepsis were also higher in laparotomy group but the difference was not statistically significant. Median length of hospital stay in laparoscopy group was 4 days (range: 1 to 28 d) and in laparotomy group was 9.5 days (range: 2 to 55 d) with P-value of 0.001. CONCLUSIONS: Laparoscopy has a role in management of hemodynamically stable patients with suspected abdominal injury to prevent nontherapeutic laparotomies, and thereby decreasing postoperative complications.

Vasopressors: Do they have any role in hemorrhagic shock?

The priority in the management of patients with traumatic hemorrhagic shock is to control the bleeding with simultaneous volume resuscitation to maintain adequate tissue perfusion. Fluid replacement remains the mainstay of initial resuscitation in hemorrhagic shock. Traditionally, vasopressors are contraindicated in the early management of hemorrhagic shock due to their deleterious consequences, although vasopressors may have a role in resuscitation when vasoplegic shock ensues and blood pressure cannot be maintained by fluids alone. Use of vasopressors is not recommended according to the Advanced Trauma Life SupportR management principles. The role of vasopressors remains controversial with no clear guidelines on the timing, type, and dose of these drugs in hemorrhagic shock. Among vasopressors, norepinephrine and vasopressin have been used in the majority of the trials, although not many studies compare the effect of these two on long-term survival in trauma patients. This article reviews the pathophysiology of hemorrhagic shock, adverse effects of fluid resuscitation, and the various experimental and clinical studies on the use of vasopressors in the early phase of resuscitation in hemorrhagic shock.

Neglected Thoraco Lumbar Traumatic Spine Injuries.

STUDY DESIGN: Retrospective study. PURPOSE: To outline the etiology, complications and management difficulties encountered in the management of neglected thoracolumbar spine injuries. OVERVIEW OF LITERATURE: The English literature describes overlooked diagnosis as the most common cause of neglected spine injuries. However, the reasons differ in developing or under-developed nations. Moreover, there is scarcity of literature about the neglected spinal injuries. METHODS: Patients presenting with thoracolumbar traumatic injuries who had not received any form of treatment for more than three weeks were included in the study. The demographic details, operative procedure performed and complications encountered, along with American Spinal Injury Association grade and spinal cord independence measure score recorded on the history sheets were noted. The data were analyzed. RESULTS: Forty patients were included in the study. Inadequate treatment at the first contact hospital (45%) followed by late presentation (38%) and missed injury (17%) were the major etiological factors for the neglected traumatic injuries in the thoracolumbar spine. The most common complications seen in the management of these cases were pressure sores (58%), back pain (57%), urinary tract infection (42%) and residual kyphotic deformity (42%). CONCLUSIONS: Management of neglected thoracolumbar injuries is challenging. The delay in presentation should not prevent spine surgeon in proceeding with operative intervention as good results can be expected.

Sonographic assessment of predictors of depth of the corner pocket for ultrasound-guided supraclavicular brachial plexus block.

BACKGROUND AND AIMS: There is wide variation in depth of brachial plexus in patient population at supraclavicular region. We plan to find the depth of the corner pocket and correlate it with age, weight, height and body mass index (BMI). MATERIAL AND METHODS: After approval from Ethics Committee, right-sided supraclavicular region of volunteers was scanned. Once an optimal image, which included subclavian artery, pleura, first rib and nerve bundles, was obtained, the corner pocket was kept in the middle of the screen and the image was frozen. Depth of the corner pocket from the skin was measured. Thereafter longest distance (LD) approximating needle trajectory was calculated. The Pearson correlation was used to calculate the relation between these two distances and various predictors such as weight, height, and BMI. RESULTS: Mean shortest distance that is, vertical distance from skin to corner pocket for all volunteers was found to be 1.7 ± 0.8 cm and the mean LD that is, distance traveled by needle entering 1 cm from the edge of foot process to the corner pocket in an in-plane approach was 3.7 ± 0.2 cm. We did not find any significant correlation between age, height versus measured distances. However, significant correlation (0.11) was found between weights, BMI versus two lengths. CONCLUSION: Prescanning of supraclavicular region for estimating depth of corner pocket should be done before choosing an appropriate size needle. Furthermore, the needle should not be advanced more than the predicted corner pocket depth.

Analgesic efficacy of three different dosages of intra-articular morphine in arthroscopic knee surgeries: Randomised double-blind trial.

BACKGROUND AND AIMS: Arthroscopic knee surgery is a common procedure and may cause enough pain to delay rehabilitation. Intra-articular (IA) morphine is a known modality for post-operative pain relief. However, the optimal dose of IA morphine has not been studied. The current study has been conducted to find out the optimal dosage of IA morphine when administered with 0.25% bupivacaine. METHODS: Sixty adult patients of either sex, aged between 18 and 60 years, undergoing diagnostic/therapeutic knee arthroscopic surgery were included in the study and randomised into three groups. All patients underwent surgery under subarachnoid block. After the surgical closure, 20 ml of 0.25% bupivacaine with 1 mg, 3 mg and 5 mg of morphine as additive was injected intra-articularly in Group A, B and C patients, respectively. Post-operative pain assessment was performed with visual analogue scale score in the 1(st), 2(nd), 6(th), 12(th) and 24(th) post-operative hour. The common complications were also recorded. RESULTS: There was statistically significant analgesia in Group B and C than Group A in the 1(st) and 2(nd) post-operative hour; while at the 24(th) post-operative hour, Group C had statistically significant analgesia than the other two groups. Time to first rescue analgesia was statistically significantly less and consumption of supplemental analgesia was significantly higher in Group A than the other two groups. CONCLUSION: IA dose of 3 mg and 5 mg morphine with 20 ml of 0.25% bupivacaine provided adequate analgesia. However, 3 mg morphine group patients had fewer side effects than 5 mg group patients although the difference was not statistically significant.

Comparison of three supraglottic airway devices for airway rescue in the prone position: A manikin-based study.

BACKGROUND: Accidental extubation during surgery in prone position can be life-threatening. Supraglottic airway devices (SAD) have been used successfully in such situations to rescue the airway. However, which SAD would be most appropriate in this setting has not been described in the literature. AIMS: The aim of our study was to determine the most appropriate SAD for securing airway in a prone position during accidental extubation. MATERIALS AND METHODS: In the study, Airway Trainer (Laerdal) manikin was used for studying insertion of three SADs; I-gel, Laryngeal Mask Airway ProSeal™ (PLMA) and LMA Classic™ (CLMA) in the prone position. Forty anesthesia resident doctors participated in this study. The time taken for insertion; ease of insertion and ventilation; bronchoscopic view; and insertion score were compared among the three groups. RESULTS: The time taken for I-gel insertion was significantly lesser (12.89 ± 3.94 seconds) as compared to CLMA (17.07 ± 3.5 seconds) and PLMA (25 + 4.78 seconds). Least resistance was encountered in the insertion of I-gel, while maximum resistance was experienced in PLMA group (22.5% vs. 90%). The maneuver required for optimal positioning was observed in 27.5% of PLMA insertion, 2.5% in CLMA while no maneuver was required in any of the I-gel insertion. Ease of ventilation was comparable in all three SADs. The bronchoscopic view and insertion score were significantly higher with I-gel as compared to CLMA and PLMA. CONCLUSION: All three SADs were successful as rescue devices during accidental extubation in the prone position. However, the ease of insertion was maximum with I-gel, followed by CLMA and PLMA.

Management of Neglected Traumatic Bilateral Cervical Facet Dislocations Without Neurological Deficit.

INTRODUCTION: Sub axial cervical spine dislocations are common and managing these cases by closed reduction is successful in the majority of cases. However, treatment of old and neglected cases is difficult and the results may vary in terms of neurological and functional outcomes. CASE PRESENTATION: We present two cases of traumatic bilateral cervical facet dislocation with no neurological deficit (ND) who referred four months after the injury. They were managed via single stage anterior discectomy, posterior facet reduction, instrumentation, and then anterior reconstruction with bone graft and cervical plate. The patients had no ND in the postoperative period and returned to work. DISCUSSION: Patients presenting with neck pain after a history of trauma should be evaluated thoroughly with radiographs and computed tomography. The management of old neglected facet dislocations is difficult, lengthy, and fraught with potential neurological complications; operative intervention can substantially improve the quality of life in these patients.

Efficacy of contrasting background on a drug label: A prospective, randomized study.

BACKGROUND AND AIMS: Medication error can occur due to fault at any level starting from manufacturing until the administration to the patient. It can be difficult to read the drug name and other information from an ampoule, if there is poor contrast between the font color and background of the ampoule. Primary aim of this study was to evaluate the efficacy of the contrast color on the ampoule's label. MATERIAL AND METHODS: The study was conducted in a randomized blinded manner at a tertiary level trauma center. One hundred and eight resident doctors participated in the study. All the participants were divided into two groups after randomization. Group A was given the original drug ampoule while the modified ampoule with contrast was given to Group B. Total time in reading the ampoule and difficulty in reading (DR) scoring were noted for each participant. Another scoring regarding correct reading of ampoule was also noted and compared. STATISTICAL ANALYSIS: Student's t-test and Mann-Whitney test were used accordingly and P < 0.05 was considered as significant. RESULTS: It was found that mean time taken in reading the original ampoule was more compared to modified ampoule (11.64 ± 1.48 vs. 9.48 ± 1.62 seconds P < 0.05). DR score was also higher in Group A (P < 0.05) and correct reading score was more in Group B (P < 0.05). CONCLUSION: The labels on drug ampoules or vials should always have a contrasting background. This may reduce medication error and improve patient safety.

Facing the airway challenges in maxillofacial trauma: A retrospective review of 288 cases at a level i trauma center.

BACKGROUND: Maxillofacial trauma is an apt example of a difficult airway. The anesthesiologist faces challenges in their management at every step from airway access to maintenance of anesthesia and extubation and postoperative care. METHODS: A retrospective study was done of 288 patients undergoing surgery for maxillofacial trauma over a period of five years. Demographic data, detailed airway assessment and the method of airway access were noted. Trauma scores, mechanism of injury, duration of hospital stay, requirement of ventilator support were also recorded. Complications encountered during perioperative anaesthetic management were noted. RESULTS: 259 (89.93%) of the patients were male and 188 (62.85%) were in the 21-40 year range. 97.57% of the cases were operated electively. 206 (71.53%) patients were injured in motor vehicular accidents. 175 (60.76%) had other associated injuries. Mean Glasgow coma scale score (GCS), injury severity score (ISS) and revised trauma score (RTS) were 14.18, 14.8 and 12, respectively. Surgery was performed almost nine days following injury. The mean duration of hospitalization was 16 days. ICU admission was required in 22 patients with mean duration of ICU stay being two days. Majority of patients had difficult airway. 240 (83.33%) patients were intubated in the operating room and fibreoptic guided intubation was done in 159 (55.21%) patients. Submental intubation was done in 45 (14.93%) cases. CONCLUSIONS: Maxillofacial injuries present a complex challenge to the anaesthesiologist. The fibreoptic bronchoscope is the main weapon available in our arsenal. The submental technique scores over the time-honored tracheostomy. Communication between the anaesthesiologist and the surgeon must be given paramount importance.