Evaluation of tumor-infiltrating lymphocytes (TILs) in molecular subtypes of an Indian cohort of breast cancer patients.

OBJECTIVES: Evaluation of tumor-infiltrating lymphocytes (TILs) distribution in an Indian cohort of breast cancer patients for its prognostic significance. METHODS: A retrospective cohort of breast cancer patients from a single onco-surgeon's breast cancer clinic with a uniform treatment strategy was evaluated for TILs. Tumor sections were H&E stained and scored for the spatial distribution and percent stromal TILs infiltration by a certified pathologist. The scores were analysed for association with treatment response and survival outcomes across molecular subtypes. RESULTS: Total 229 breast cancer tumors were evaluated. Within spatial distribution categories, intra-tumoral TILs were observed to be associated with complete pathological response and lower recurrence frequency for the entire cohort. Subtype-wise analysis of stromal TILs (sTILs) re-enforced significantly higher infiltration in TNBC compared to HER2-positive and ER-positive tumors. A favourable association of higher stromal infiltration was observed with treatment response and disease outcomes, specifically in TNBC. CONCLUSION: Intra-tumoral TILs showed a higher proportion with favourable association with better patient outcomes in an Indian cohort, unlike western cohorts where both stromal and intra-tumoral TILs show similar association with prognosis. With further validation, TILs can be developed as a cost-effective surrogate marker for treatment response, especially in a low-resource setting such as India.

A Multicenter Qualitative Analysis of Medical Student Narratives After a Palliative Care Elective.

BACKGROUND: The medical student experience of a clinical elective in palliative care (PC) remains understudied. Reflective narrative interventions can help students hone narrative competency skills, make sense of their clinical experiences and shed light on their perception of the rotation. OBJECTIVES: To evaluate medical student written reflections after a PC clinical elective. DESIGN: Students were asked to write a short reflective essay after PC clinical electives using open-ended writing prompts. SETTING: Essays were collected from third and fourth-year medical students after completion of a PC elective at three geographically diverse academic medical centers in the United States. MEASUREMENTS: Essays were coded for themes using a conventional content qualitative method of analysis. RESULTS: Thirty-four essays were analyzed and four major themes emerged: reflection on the mission of medicine or motivation for being in medicine, reflection on professional skills or lessons learned, reflection on patient's experience and personal responses to PC rotation. Sub-themes were also identified. CONCLUSIONS: Themes underscore the utility of the PC clinical elective as a meaningful experience that imparts useful skills, builds empathy, reminds students of their own motivations for being in medicine and serves as a catalyst for reflection on their own lives and relationships with their patients. Awareness of medical students' personal and emotional responses to a PC elective can help inform educators as they support their students and provide opportunities for reflection and education.

Tumescent Anesthesia for Dermatosurgical Procedures Other Than Liposuction.

CONTEXT: Tumescent local anesthesia is a form of local anesthesia, which is a technique in which a dilute local anesthetic solution is injected into the subcutaneous tissue until it becomes firm and tense. Originally developed to facilitate liposuction, the use of tumescent anesthesia has expanded to other dermatological and plastic surgery procedures, as well as to other disciplines, including endocrine and vascular surgeries. For infiltration local anesthesia, the conventional dosage of lidocaine is up to 4.5 mg/kg, and that with adrenaline is up to 7 mg/kg; however, in liposuction using tumescent anesthesia, the recommended maximum dose of lidocaine with adrenaline is up to 55 mg/kg. There are several important pharmacological, pharmacokinetic, and pharmacodynamic factors that need to be considered in the administration of tumescent anesthesia leading to considerable interdisciplinary differences of opinion with respect to the maximum dose of local anesthetic permissible. Although several studies and publications have studied these issues in liposuction extensively, the role of tumescent anesthesia in other indications has not been reviewed adequately. AIMS AND OBJECTIVES: The aim of this study was to discuss the science behind tumescent anesthesia, its applications, and safety considerations in different dermatosurgical procedures other than liposuction. MATERIALS AND METHODS: For this review, a systematic literature search in PubMed, Embase, Web of Science, Cochrane Library, Central, Emcare, Academic Search Premier, and ScienceDirect was conducted for safety studies on tumescent anesthesia. CONCLUSION: Tumescent anesthesia is generally very well accepted by patients and is relatively safe at the recommended doses. Nonetheless, one must be vigilant about the signs and symptoms of LAST, as they may not manifest until several hours after the procedure. Lipid emulsion therapy should be readily available and could prove life-saving in such situations.

Small synthetic hyaluronan disaccharides afford neuroprotection in brain ischemia-related models.

High molecular weight (HMW) glycosaminoglycanes of the extracellular matrix have been implicated in tissue repair. The aim of this study was to evaluate if small synthetic hyaluronan disaccharides with different degrees of sulfation (methyl 2-acetamido-2-deoxy-3-O-(ß-d-glucopyranosyluronic acid)-O-sulfo-α-d-glucopyranoside, sodium salt (di0S), methyl 2-acetamido-2-deoxy-3-O-(ß-d-glucopyranosyluronic acid)-6-di-O-sulfo-α-d-glucopyranoside, disodium salt (di6S) and methyl 2-acetamido-2-deoxy-3-O-(ß-d-glucopyranosyluronic acid)-4,6-di-O-sulfo-α-d-glucopyranoside, trisodium salt (di4,6S)) could improve cell survival in in vitro and in vivo brain ischemia-related models. Rat hippocampal slices subjected to oxygen and glucose deprivation and a photothrombotic stroke model in mice were used. The three hyaluran disaccharides, incubated during the oxygen and glucose deprivation (15min) and re-oxygenation periods (120min), reduced cell death of hippocampal slices measured as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, being the most potent di4,6S; in contrast, high molecular hyaluronan was ineffective. The protective actions of di4,6S against oxygen and glucose deprivation were related to activation of the PI3K/Akt survival pathway, reduction of p65 translocation to the nucleus, inhibition of inducible nitric oxide oxidase induction and reactive oxygen species production, and to an increase in glutathione levels. Administered 1h post-stroke, di4,6S reduced cerebral infarct size and improved motor activity in the beam walk test. In conclusion, di4,6S affords neuroprotection in in vitro and in vivo models of ischemic neuronal damage. Our results suggest that its neuroprotective effect could be exerted through its capability to reduce oxidative stress during ischemia. Its small molecular size makes it a more potential druggable drug to target the brain as compared with its HMW parent compound hyaluronan.