Clinical and Genomic Features of Classical and Basal Transcriptional Subtypes in Pancreatic Cancer.

Purpose: Transcriptional profiling of pancreatic cancers has defined two main transcriptional subtypes: classical and basal. Initial data suggest shorter survival for patients with basal tumors and differing treatment sensitivity to FOLFIRINOX and gemcitabine plus nab-paclitaxel by transcriptional subtype.

Experimental Design: We examined 8,743 patients with RNA sequencing from pancreatic cancers performed at Caris Life Sciences.

Utility of Established Prognostic Scoring Systems for Patients with Advanced Pancreatic Adenocarcinoma Enrolled in Immunotherapy-Based Early-Phase Clinical Trials.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy for which multiagent chemotherapy is the mainstay of treatment resulting in limited survival and symptomatic benefit. Treatment with immune checkpoint inhibitors (ICI) has proven effective in a growing number of solid tumors but has yet to show clinical benefit in patients with PDAC. Given the growing number of ICI-based clinical trials in development for patients with PDAC and lack of clinical benefit thus far with ICI-based therapies in these patients, we sought to (1) determine the outcomes of patients with PDAC treated with ICI-based therapies as part of an early phase clinical trial, (2) validate the utility of established prognostic scoring systems, and (3) identify novel prognostic factors in an attempt to better identify patients that would benefit from enrollment onto an ICI-based early phase clinical trial.

Biological Stabilisation vs Mechanical Fixation: Do We Always Require Instrumentation in Anterior Decompression Surgeries for Thoracolumbar Spinal Tuberculosis?

Study Design: A retrospective cohort study.

Purpose: To compare the outcomes of anterior decompression with bone grafting alone and anterior decompression with bone grafting and fixation.

Methods: 93 patients with minimum 2 year follow-up were included in the study.

Emerging Role of Targeted Therapy in Metastatic Pancreatic Adenocarcinoma.

The aggressive biology of pancreatic ductal adenocarcinoma (PDAC), along with its limited sensitivity to many systemic therapies, presents a major challenge in the management of patients with metastatic PDAC. Over the past decade, the incorporation of combinatorial cytotoxic chemotherapy regimens has improved patient outcomes. Despite these advances, resistance to cytotoxic chemotherapy inevitably occurs, and there is a great need for effective therapies.

Immunotherapy in Gastrointestinal Malignancies.

Gastrointestinal (GI) cancers represent a heterogeneous group of malignancies, each with a unique tumor biology that in turn affects response to treatment and subsequent prognosis. The interplay between tumor cells and the local immune microenvironment also varies within each GI malignancy and can portend prognosis and response to therapy. Treatment with immune checkpoint inhibitors has changed the treatment landscape of various solid tumors including (but not limited to) renal cell carcinoma, melanoma, and lung cancer.

Outcomes of patients with metastatic pancreatic cancer who progress on first restaging imaging.

Background: Objective responses to first-line systemic chemotherapy in metastatic pancreatic cancer patients are seen in less than one third of cases. Unfortunately, a significant amount will have disease progression (PD) on their first restaging imaging. With patients' short life expectancy, it is crucial for clinicians to be prudent when deciding whom and when to treat.

Joint preservation surgery in grade 2 and 3 giant cell tumors of bone around the knee.

Objective: To evaluate the clinical and functional outcomes of joint preservation surgery in high-grade giant cell tumors (GCT) around the knee joint.

Methods: A retrospective review of 25 patients of high-grade GCT (Campanacci grade 2 and 3) involving proximal tibia or distal femur managed by extended curettage, bone grafting, and stabilization with knee spanning external fixator between 2016 and 2018 was done. The radiographic outcomes, functional outcomes (Musculoskeletal Tumor Society [MSTS] score for lower limb), and complications including donor site morbidity were evaluated.

Outcome Analysis of Dual Implant Osteosynthesis for Ipsilateral Proximal and Shaft Femur Fractures: Do We Need Cephalomedullary Nails?

Introduction Most surgeons prefer a single implant for segmental proximal and diaphyseal femur fractures, although results are controversial and still no consensus for proper management is present. This prospective study analyses the functional and radiological outcome of managing 17 patients with ipsilateral shaft and proximal femur fractures by dual implant osteosynthesis at our center. Methods Over a two-year period, we managed 17 patients with a mean age of 35 years, with cancellous cannulated screws or dynamic hip screws for intracapsular femur fractures and improvised proximal femoral nail for extracapsular proximal femur fractures.

Outcome Analysis of Fixed Angle Locking Plate in Patella Fractures: A Single Centre Experience from North India.

Background: Tension band wiring supposedly is the most commonly used technique for displaced patella fractures, but is not effective in comminuted fractures and osteoporotic bones. It often leads to loosening of wires, dislocation of fracture, hardware problem and failure of osteosynthesis, resulting in knee stiffness and post-traumatic osteoarthritis. The aim of the study is to evaluate clinical outcome in patients with acute patella fractures (< 3 week) treated with unidirectional angle fixed low-profile titanium patella locking plate.

Correlation Between Modic Changes and Bacterial Infection: A Causative Study.

Study Design: Prospective nonrandomized study.

Objective: Objective of the study was to ascertain etiological correlation between Modic changes (MC) and bacterial infection through 16s DNA sequencing in patients with chronic low backache.

Summary Of Background Data: Modic changes are common on magnetic resonance imaging (MRI) of patients with low back pain and are strongly associated with low back pain.

Phase II Study of Ipilimumab in Men With Metastatic Prostate Cancer With an Incomplete Response to Androgen Deprivation Therapy.

Phase 3 studies of immune checkpoint inhibitors have not shown a survival benefit in prostate cancer, but some patients have a profound anticancer response. We evaluated the efficacy of the CTLA-4 targeted agent, ipilimumab, in metastatic prostate cancer patients who had an incomplete biochemical response to initial androgen deprivation therapy (ADT) alone. Ten patients were enrolled, each treated with ipilimumab 10 mg/kg (every 3 weeks for up to 4 doses) with maintenance ipilimumab every 12 weeks for non-progressing patients.

Pancreatic cancer.

Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10% in the USA, and it is becoming an increasingly common cause of cancer mortality. Risk factors for developing pancreatic cancer include family history, obesity, type 2 diabetes, and tobacco use. Patients typically present with advanced disease due to lack of or vague symptoms when the cancer is still localised.

RNA interference screening methods to identify proliferation determinants and mechanisms of resistance to immune attack.

We have used RNA interference (RNAi) screening technology to reveal unknown components of biological signaling pathways including survival mechanisms of estrogen-independent breast cancer cell growth and cancer cell resistance to immune attack. In this chapter, a detailed protocol describing the use of RNAi screening to identify factors important for the proliferation of estrogen-independent MCF7 breast cancer cells will be described. Resistance to therapies that target the estrogen pathway remains a challenge in the treatment of estrogen receptor-positive breast cancer.

Ecstasy induced acute systolic heart failure and Non-Ischemic Cardiomyopathy in a young female: a rare case report and literature review.

Ecstasy or 3,4-methylenedioxymethamphetamine (MDMA) is an illicit recreational drug. Effects include euphoria, increased sensory awareness, and central stimulation. Although various arrhythmias, as well as dilated cardiomyopathy, have been previously noted to occur with chronic use, cardiac toxicities are seldom reported in an acute setting.

Too Many Biopsies Performed to Rule Out Hirschsprung's Disease: But It is Worth Doing Them.

Introduction:  The U.K. National Institute for Health and Clinical Excellence (NICE) specify the following indications for performing rectal biopsy to rule out Hirschsprung's disease (HSD): (1) passage of meconium > 48 hours; (2) constipation since first few weeks of life; (3) chronic abdominal distension with vomiting; (4) family history of HSD; and (5) faltering growth in addition to any other indication.

Cross cultural comparison of constipation profiles at tertiary care centers between India and USA.

Background: Despite potential differences in patient perception of chronic constipation (CC) in geographically and culturally distinct regions, head-to-head studies comparing the clinical profile, constipation severity, impact on quality of life (QOL) and economic impact are lacking.

Methods: We conducted a cross-sectional cohort study of patients presenting with CC to tertiary care centers in the USA and India. Standardized instruments were used to assess constipation subtype, disease severity, disease-specific QOL, somatization, and psychiatric comorbidities.

RNA Interference Screening to Identify Proliferation Determinants in Breast Cancer Cells.

RNAi screening technology has revealed unknown determinants of various biological signaling pathways in biomedical studies. This protocol provided detailed information about how to use RNAi screening to identify proliferation determinants in breast tumor cells. siRNA-based libraries targeting against Estrogen receptor (ER)-network, including 631 genes relevant to estrogen signaling, was constructed for screening in breast cancer cells.

Yes-associated protein mediates immune reprogramming in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high degree of inflammation and profound immune suppression. Here we identify Yes-associated protein (Yap) as a critical regulator of the immunosuppressive microenvironment in both mouse and human PDAC. Within Kras:p53 mutant pancreatic ductal cells, Yap drives the expression and secretion of multiple cytokines/chemokines, which in turn promote the differentiation and accumulation of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo.

Acquisition of estrogen independence induces TOB1-related mechanisms supporting breast cancer cell proliferation.

Resistance to therapies targeting the estrogen pathway remains a challenge in the treatment of estrogen receptor-positive breast cancer. To address this challenge, a systems biology approach was used. A library of small interfering RNAs targeting an estrogen receptor (ER)- and aromatase-centered network identified 46 genes that are dispensable in estrogen-dependent MCF7 cells, but are selectively required for the survival of estrogen-independent MCF7-derived cells and multiple additional estrogen-independent breast cancer cell lines.

Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2.

Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm" and extensive lymphocyte infiltration.