Exploration of Drug Therapies for Post-Traumatic Elbow Joint Contracture

This semester I worked in the Musculoskeletal Soft Tissue Laboratory to explore the potential drug therapies for post-traumatic joint contracture (PTJC), or arthrofibrosis, in the elbow following a traumatic joint injury. To simulate the potential effects of these drugs in the elbow post-injury, this study utilized an in-vitro model using collagen gels and NIH-3T3 cells to mimick the contraction of capsule tissue in the elbow and the cells thought to contribute to disease progression in the capsule, namely fibroblasts and myofibroblasts. The first part of the study tested the effects of two drugs, losartan and simvastatin, on decreasing contraction. The standard testing procedure required that the gels be seeded with cells, then administered the appropriate drug concentration and mixture, and then observed for a period of six days. Once we narrowed down the drug formulations to a few possible candidates, we considered the issues related to timing of treatment and pharmacokinetics of these drugs if administered into the human elbow; more specifically, we wanted to understand how factors like drug clearance, or the treatment of PTJC after its onset, would affect the drug’s effectiveness. To this end, the second part of the study looked at how exposure time of the drug to the cells affected the drug’s function; more specifically, the impact of both time delay and a shorter exposure period on the performance of the drugs were explored. It quickly became apparent through these studies that simvastatin could halt contraction, but did nothing to reverse it. The third and final part of the study tested the ability of the hormone relaxing on decreasing contraction. By the end of the semester, we determined that,within the construct of our experimental set-up and parameters, simvastatin was the only promising candidate for treatment of PTJC

Role of hypogastric artery ligation in obstetrics and gynaecology: a 20-year study at tertiary care center, Ahmedabad, western India

Background: Hypogastric artery ligation (HAL) was first introduced by the end of the 19th century to control intractable haemorrhage from the uterus of women with advanced cervical cancer. Bilateral HAL is a lifesaving procedure in massive pelvic haemorrhage.Methods: This is a retrospective study of 58 cases in which HAL was performed in the obstetrics and gynecology department at tertiary care center from January 2000 to December 2020. History, operative procedure findings, immediate and late postoperative complications, morbidity and mortality data were collected and reviewed from records.Results: In this study, total of 58 women who underwent HAL s; 53 bilateral and 5 unilateral. Fifty-three women required HAL for obstetric indications, in 5 cases it was required for gynaecological indications. 20 cases (34.5%) underwent bilateral HAL for atonic PPH, 16 cases (27.6%) during obstetric hysterectomy for morbidly adherent placenta, 5 (8.6%) for colporrhexis, 2 (3.4%) for broad ligament hematoma, 1 (1.7%) for colporrhexis and left sided broad ligament hematoma, 2 cases (3.4%) for secondary PPH and 7 cases (12.1%) for the ruptured uterus. In gynecological cases 4 cases (80%) underwent after vaginal hysterectomy to control pelvic haemorrhage and 1 case (20%) underwent HAL after myomectomy.Conclusions: HAL is an important surgical procedure and should be performed to reduce blood loss when conservation of the uterus is desired. It is also useful in controlling haemorrhage after major gynaecological surgeries and secondary hemorrhage following hysterectomy.

Pleiotropic effects of simvastatin and losartan in preclinical models of post-traumatic elbow contracture

Elbow trauma can lead to post-traumatic joint contracture (PTJC), which is characterized by loss of motion associated with capsule/ligament fibrosis and cartilage damage. Unfortunately, current therapies are often unsuccessful or cause complications. This study aimed to determine the effects of prophylactically administered simvastatin (SV) and losartan (LS) in two preclinical models of elbow PTJC: a

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Natural Killer-Like T-Cell Lymphoma: A Rare Cause of Acute Liver Failure

Acute liver failure is characterized by encephalopathy and disruption of hepatic function, often requiring liver transplantation to prevent fatal consequences. We present a 33-year-old man with recurrent lymphoma presenting with acute liver failure, which was initially thought to be from drug-induced liver injury associated with his chemotherapy medication, asparaginase. However, liver biopsy revealed malignant infiltration by lymphoma. The subtype of lymphoma was natural killer-like T-cell lymphoma, which is an uncommon variant, and has rarely been associated with hepatic infiltration. His condition rapidly worsened with development of multiorgan failure leading to death

Variation of the latissimus dorsi

A typical muscle variation of latissimus dorsi - the axillary arch is represented by the muscular or fibromuscular slip detached from the anteroinferior border of the musculus latissimus dorsi passing over the axilla under the axillary fascia crossing the medial side of the brachial plexus to continue as a septum intermusculare mediale brachii distally to the medial epicondyle of humerus. The full extent of the muscle is rarely present. Slips of muscle extend from the latissimus dorsi at the inferior angle of scapula to insert into pectoralis major (Langer), coracobrachilis, biceps or coracoid process forming what is described as a common variant - the muscular axillary arch. We report three cases of variants of latissimus dorsi, one of which has not been reported in the literature before