Intestinal barrier functions in hematologic and oncologic diseases.

The intestinal barrier is a complex structure that not only regulates the influx of luminal contents into the systemic circulation but is also involved in immune, microbial, and metabolic homeostasis. Evidence implicating disruption in intestinal barrier functions in the development of many systemic diseases, ranging from non-alcoholic steatohepatitis to autism, or systemic complications of intestinal disorders has increased rapidly in recent years, raising the possibility of the intestinal barrier as a potential target for therapeutic intervention to alter the course and mitigate the complications associated with these diseases. In addition to the disease process being associated with a breach in the intestinal barrier functions, patients with hematologic and oncologic diseases are particularly at high risks for the development of increased intestinal permeability, due to the frequent use of broad-spectrum antibiotics and chemoradiation. They also face a distinct challenge of being intermittently severely neutropenic due to treatment of the underlying conditions. In this review, we will discuss how hematologic and oncologic diseases are associated with disruption in the intestinal barrier and highlight the complications associated with an increase in the intestinal permeability. We will explore methods to modulate the complication. To provide a background for our discussion, we will first examine the structure and appraise the methods of evaluation of the intestinal barrier.

Antibody-drug conjugates: Principles and opportunities.

Antibody-drug conjugates (ADCs) are immunoconjugates that combine the specificity of monoclonal antibodies with a cytotoxic agent. The most appealing aspects of ADCs include their potential additive or synergistic effects of the innate backbone antibody and cytotoxic effects of the payload on tumors without the severe toxic side effects often associated with traditional chemotherapy. Recent advances in identifying new targets with tumor-specific expression, along with improved bioactive payloads and novel linkers, have significantly expanded the scope and optimism for ADCs in cancer therapeutics. In this paper, we will first provide a brief overview of antibody specificity and the structure of ADCs. Next, we will discuss the mechanisms of action and the development of resistance to ADCs. Finally, we will explore opportunities for enhancing ADC efficacy, overcoming drug resistance, and offer future perspectives on leveraging ADCs to improve the outcome of ADC therapy for cancer treatment.

Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors.

INTRODUCTION: Salivary gland carcinomas (SGC) are histologically diverse cancers and next-generation sequencing (NGS) to identify key molecular targets is an important aspect in the management of advanced cases. METHODS: DNA was extracted from paraffin embedded tissues of advanced SGC and comprehensive genomic profiling (CGP) was carried out to evaluate for base substitutions, short insertions, deletions, copy number changes, gene fusions and rearrangements. Tumor mutation burden (TMB) was calculated on approximately 1.25 Mb. Some 324 genes in the FoundationOne CDX panel were analyzed. RESULTS: Mucoepidermoid carcinoma (MECa) mutations were assessed. CDKN2A and CDKN2B GA were common in mucoepidermoid carcinoma (MECa) (52.5 and 30.5%). PIK3CA was also common in MECa (16.9%). ERBB2 amplification/short variants (amp/SV) were found in MECa (5.9/0%). HRAS GA was common in MECa (14.4%) as well. Other targets, including BAP1, PTEN, and KRAS, were noted but had a low incidence. In terms of immunotherapy (IO)-predictive markers, TMB > 10 was more common in MECa (16.9%). PDL1 high was also seen in MECa (4.20%). CONCLUSION: SGC are rare tumors with no FDA-approved treatment options. This large dataset reveals many opportunities for IO and targeted therapy contributing to the continuously increased precision in the selection of treatment for these patients.

Radioimmunoconjugates in the age of modern immuno-oncology.

Immunotherapy was first investigated as a therapeutic option for treating cancer more than a century ago. During this period, it has gone through numerous disappointments when the successes obtained in the laboratory were not matched clinically. However, recent advances in immuno-oncology have provided the impetus to revisit this therapeutic option. Unlike previous efforts, modern immunotherapy is now a realistic and formidable therapeutic option for patients with relapsed/refractory malignancies. Unfortunately, most of the successes obtained thus far have primarily been in patients with hematologic malignancies. While the results of immunotherapy with immune check-point inhibitors for solid tumors such as non-small cell lung cancer and melanoma are encouraging, more effective treatment methods are desirable. Many intrinsic and extrinsic factors pose as obstacles to successful immunotherapy of solid tumors. They include heterogeneity of tumor antigens, limitation in the trafficking and accessibility of the effector mechanisms to the tumor sites, the adverse anti-inflammatory tumor microenvironment, and the on-target off tumor and off-target off-tumor effects of some of these approaches. In this review, we will discuss these obstacles and examine the evidence that support the notion that radioimmunotherapy, using radioimmunoconjugates, may be the answer to overcome these obstacles in patients with metastatic cancer. Finally, we will discuss how the efficacy of radioimmunotherapy using radioimmunoconjugates might further be harnessed to maximize successes in these patients.

Kocuria kristinae pneumonia and bacteremia.

Kocuria kristinae is an aerobic gram-positive bacterium that is part of the normal skin flora and not a common cause of infection. Here, we present the first reported case of community-acquired pneumonia and bacteremia caused by K. kristinae. The pneumonia was complicated by acute on chronic diastolic heart failure, resulting in acute hypoxic respiratory failure requiring intubation and mechanical ventilation.

The Role of Ischemia Modified Albumin as a Biomarker in Patients with Chronic Liver Disease.

INTRODUCTION: Chronic Liver Disease (CLD) is characterised by gradual destruction of liver tissue over time. Ischemia Modified Albumin (IMA) is an upcoming biomarker shown to be elevated in conditions associated with ischemia and oxidative stress. Albumin levels are greatly reduced in patients with CLD and studying its alterations will provide essential information regarding the molecular changes occurring to it. AIM: The study aims to estimate IMA and IMA/Albumin ratio in patients with CLD and to correlate it with parameters assessing liver function and the Model for End Stage Liver Disease (MELD) score. MATERIALS AND METHODS: The study consisted of 43 CLD patients as test subjects and 28 apparently healthy individuals as controls. Multiple parameters assessing liver function like albumin, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), Gamma Glutamyl Transpeptidase (GGT), alkaline phosphatase (ALP), Prothrombin Time (PT) INR and creatinine were estimated and the MELD score calculated. Serum IMA expressed as Absorbance Units (ABSU) was estimated using the Albumin Cobalt Binding test (ABT). Student's t-test and correlation coefficient was used for statistical analysis. RESULTS: Serum IMA was significantly higher in CLD patients (0.5320 ± 0.1677) as compared to the control group (0.3203 ± 0.1257) with a p-value of <0.0001. The IMA/Albumin ratio was also significantly higher (0.2035 ± 0.0970) in patients with CLD compared to control group (0.0714 ± 0.0283) with a p-value of <0.0001. IMA has a negative correlation with albumin. The IMA/Albumin ratio shows positive correlation with MELD score, bilirubin and ALP. There was no correlation with ALT, AST, GGT and PT INR. CONCLUSION: Decreased serum albumin correlates with increase in IMA in CLD could indicate a qualitative change and not merely a quantitative reduction of albumin. IMA can serve as a biomarker to assess the disease severity and prognosis of CLD patients.

Pancreatic Tuberculosis: A Puzzle for Physicians. A Rare Case and Review of Literature.

Pancreatic Tuberculosis is an uncommon form of extra pulmonary tuberculosis that resembles malignancy of pancreas and serve as a diagnostic challenge for physicians. Conservative management with Anti Tuberculosis Therapy (ATT) will suffice for pancreatic tuberculosis whereas a malignancy may require major surgeries which may lead to significant morbidity. Here, we discuss the case of a female patient who presented with abdominal pain and vomiting and is a known case of chronic calcific pancreatitis. Radiological findings were that of malignancy of the pancreas. Enteroscopy showed pus flowing out from the duodenum. Endoscopic Ultrasound (EUS) guided Fine Needle Aspiration Cytology (FNAC) of the pancreas revealed acid fast bacilli. The patient was treated successfully with ATT. Timely diagnosis of this rare form of extra pulmonary tuberculosis can thus help avoid unwanted resections done for presumed malignancy, for which a high index of suspicion is needed.