Platelet-Rich Plasma as a Novel, Non-invasive Method to Treat Breast Capsular Contractures: a Case Report.

We describe the first examples of breast capsular contracture amelioration using a non-surgical, transdermal treatment with platelet-rich plasma. The treated patients did not experience any complications or significant pain. This report illustrates the potential of a non-invasive treatment option for a common complication of breast augmentation.

Evaluating the effectiveness of a novel somatostatin receptor 2 antagonist, ZT-01, for hypoglycemia prevention in a rodent model of type 2 diabetes.

Elevated levels of somatostatin blunt glucagon counterregulation during hypoglycemia in type 1 diabetes (T1D) and this can be improved using somatostatin receptor 2 (SSTR2) antagonists. Hypoglycemia also occurs in late-stage type 2 diabetes (T2D), particularly when insulin therapy is initiated, but the utility of SSTR2 antagonists in ameliorating hypoglycemia in this disease state is unknown. We examined the efficacy of a single-dose of SSTR2 antagonists in a rodent model of T2D.

Identification of Hypothalamic Glucoregulatory Neurons That Sense and Respond to Changes in Glycemia.

Unlabelled: To investigate whether glucoregulatory neurons in the hypothalamus can sense and respond to physiological variation in the blood glucose (BG) level, we combined continuous arterial glucose monitoring with continuous measures of the activity of a specific subset of neurons located in the hypothalamic ventromedial nucleus that express pituitary adenylate cyclase activating peptide (VMNPACAP neurons) obtained using fiber photometry. Data were collected in conscious, free-living mice during a 1-h baseline monitoring period and a subsequent 2-h intervention period during which the BG level was raised either by consuming a chow or a high-sucrose meal or by intraperitoneal glucose injection. Cross-correlation analysis revealed that, following a 60- to 90-s delay, interventions that raise the BG level reliably associate with reduced VMNPACAP neuron activity (P < 0.

Astrocyte Glycogen Is a Major Source of Hypothalamic Lactate in Rats With Recurrent Hypoglycemia.

Unlabelled: Lactate is an important metabolic substrate for sustaining brain energy requirements when glucose supplies are limited. Recurring exposure to hypoglycemia (RH) raises lactate levels in the ventromedial hypothalamus (VMH), which contributes to counterregulatory failure. However, the source of this lactate remains unclear.

PAI-1 is a potential transcriptional silencer that supports bladder cancer cell activity.

The extracellular activity of Plasminogen activator inhibitor-1 (PAI-1) is well described, acting as an inhibitor of tissue plasminogen activator and urokinase-type plasminogen activator, impacting fibrinolysis. Recent studies have revealed a pro-tumorigenic role of PAI-1 in human cancers, via the regulation of angiogenesis and tumor cell survival. In this study, immunohistochemical staining of 939 human bladder cancer specimens showed that PAI-1 expression levels correlated with tumor grade, tumor stage and overall survival.

ZT-01: A novel somatostatin receptor 2 antagonist for restoring the glucagon response to hypoglycaemia in type 1 diabetes.

Aim: To evaluate the pharmacokinetics and efficacy of a novel somatostatin receptor 2 antagonist, ZT-01, to stimulate glucagon release in rats with type 1 diabetes (T1D).

Methods: The pharmacokinetics of ZT-01 and PRL-2903 were assessed following intraperitoneal or subcutaneous dosing at 10 mg/kg. We compared the efficacy of ZT-01 with PRL-2903 to prevent hypoglycaemia during an insulin bolus challenge and under hypoglycaemic clamp conditions.

Somatostatin Receptor Antagonism Reverses Glucagon Counterregulatory Failure in Recurrently Hypoglycemic Male Rats.

Recent antecedent hypoglycemia is a known source of defective glucose counter-regulation in diabetes; the mechanisms perpetuating the cycle of progressive α-cell failure and recurrent hypoglycemia remain unknown. Somatostatin has been shown to suppress the glucagon response to acute hypoglycemia in rodent models of type 1 diabetes. We hypothesized that somatostatin receptor 2 antagonism (SSTR2a) would restore glucagon counterregulation and delay the onset of insulin-induced hypoglycemia in recurrently hypoglycemic, nondiabetic male rats.

Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T.

Background: Combining an immune checkpoint inhibitor with a tumor vaccine may modulate the immune system to leverage complementary mechanisms of action that lead to sustained T-cell activation and a potent prolonged immunotherapeutic response in metastatic castration resistant prostate cancer (mCRPC).

Methods: Subjects with asymptomatic or minimally symptomatic mCRPC were randomly assigned in a 1:1 ratio to receive either atezolizumab followed by sipuleucel-T (Arm 1) or sipuleucel-T followed by atezolizumab (Arm 2). The primary endpoint was safety, while secondary endpoints included preliminary clinical activity such as objective tumor response and systemic immune responses that could identify key molecular and immunological changes associated with sequential administration of atezolizumab and sipuleucel-T.

Safety, Tolerability, and Long-Term Clinical Outcomes of an IL-15 analogue (N-803) Admixed with Bacillus Calmette-Guérin (BCG) for the Treatment of Bladder Cancer.

Intravesical BCG is active against non-muscle invasive bladder cancer (NMIBC), but bladder cancer will recur and even progress in a significant number of patients. To improve the response rate, N-803, an IL-15 superagonist was administered in combination with BCG. To evaluate the safety and efficacy associated with the use of intravesical N-803 and BCG in patients with BCG-naïve NMIBC.

Carvedilol prevents impairment of the counterregulatory response in recurrently hypoglycaemic diabetic rats.

Aim: It has been suggested that repeated activation of the adrenergic system during antecedent episodes of hypoglycaemia contributes to the development of counterregulatory failure. We previously reported that treatment with carvedilol, a non-specific β-blocker, prevented the development of counterregulatory failure and improved hypoglycaemia awareness in recurrently hypoglycaemic non-diabetic rats. The current study investigated whether carvedilol has similar benefits in diabetic rats.

Repeated Activation of Noradrenergic Receptors in the Ventromedial Hypothalamus Suppresses the Response to Hypoglycemia.

Activation of the adrenergic system in response to hypoglycemia is important for proper recovery from low glucose levels. However, it has been suggested that repeated adrenergic stimulation may also contribute to counterregulatory failure, but the underlying mechanisms are not known. The aim of this study was to establish whether repeated activation of noradrenergic receptors in the ventromedial hypothalamus (VMH) contributes to blunting of the counterregulatory response by enhancing local lactate production.

BRAF, hypothyroidism, and human relaxin in thyroid carcinogenesis.

Purpose: BRAF, a major driver of thyroid cancer, evaluated in the context of thyroid hormones and human relaxin.

Methods: Immunohistochemical expressions of BRAF, TSH, TSH receptor (TSHR), T4, T3 receptor (T3R), RLNH2, and its receptor, RXFP1, were evaluated in thyroid tumors from a retrospective U.S.

Associations Between the Time in Hypoglycemia and Hypoglycemia Awareness Status in Type 1 Diabetes Patients Using Continuous Glucose Monitoring Systems.

Continuous glucose monitoring (CGM) systems help reduce hypoglycemia in patients with type 1 diabetes (T1D). It remains unclear whether T1D patients with impaired awareness of hypoglycemia (IAH) continue to develop more hypoglycemia than those with normal hypoglycemia awareness (NA) despite CGM use. For this cross-sectional observational study, 99 T1D patients using real-time CGMs for ≥86% of time were recruited.

Breast tumor tissue inflammation but not lobular involution is associated with survival among breast cancer patients in the Multiethnic Cohort.

Background: This study investigated the association of breast lobular involution status and three inflammatory markers as predictors of survival among breast cancer patients in the Multiethnic Cohort.

Methods: Lobular involution was evaluated in tissue sections of normal breast tissue and COX-2, TNF-α, and TGF-β proteins were assessed by immunohistochemistry in tumor microarrays. A summary score added the expression levels of the three markers.

Plasminogen activator inhibitor-2 (PAI-2) overexpression supports bladder cancer development in PAI-1 knockout mice in N-butyl-N- (4-hydroxybutyl)-nitrosamine- induced bladder cancer mouse model.

Background: Accumulating evidence suggests that plasminogen activator inhibitor-1 (PAI-1) plays an important role in bladder tumorigenesis by regulating cell cycle. However, it remains unclear whether and how inhibition of PAI-1 suppresses bladder tumorigenesis.

Methods: To elucidate the therapeutic effect of PAI-1 inhibition, we tested its tumorigenicity in PAI-1 knockout (KO) mice exposed to a known bladder carcinogen.

Alarm Settings of Continuous Glucose Monitoring Systems and Associations to Glucose Outcomes in Type 1 Diabetes.

Context: Little evidence exists regarding the positive and negative impacts of continuous glucose monitor system (CGM) alarm settings for diabetes control in patients with type 1 diabetes (T1D).

Objective: Evaluate the associations between CGM alarm settings and glucose outcomes.

Design And Setting: A cross-sectional observational study in a single academic institution.

Prognostic Significance of Lymphocyte Infiltration and a Stromal Immunostaining of a Bladder Cancer Associated Diagnostic Panel in Urothelial Carcinoma.

We set out to expand on our previous work in which we reported the epithelial expression pattern of a urine-based bladder cancer-associated diagnostic panel (A1AT, ANG, APOE, CA9, IL8, MMP9, MMP10, PAI1, SDC1, and VEGFA). Since many of the analytes in the bladder cancer-associated diagnostic signature were chemokines, cytokines, or secreted proteins, we set out to report the stromal staining pattern of the diagnostic signature as well as CD3 (T-cell) cell and CD68 (macrophage) cell staining in human bladder tumors as a snapshot of the tumor immune landscape. Immunohistochemical staining was performed on 213 tumor specimens and 74 benign controls.

An Unlikely Route: Metastatic Ovarian Malignancy within the Duodenum.

The small bowel is an uncommon site for cancer metastasis. Despite this, cases have reported the duodenum as a metastatic site from local organs. However, duodenal involvement from more distant organs, such as the ovaries, has rarely been reported.

Proctitis and Abdominal Aortic Aneurysm: Six Degrees of Separation.

Cytomegalovirus (CMV) is an aggressive virus responsible for a considerable amount of case fatalities. In the overwhelming majority of cases, this affects only the immunocompromised. Herein, we present a 76-year-old immunocompetent female who presented with gastrointestinal bleeding found to have rectal ulceration secondary to CMV infection.

Outlasting a Rare Duodenal Angiosarcoma.

With current life expectancies exceeding 78 years on average, to be confronted with the discovery of a rare cancer often found in advanced stages is a startling devastation. Angiosarcoma of the intestine is a rare and aggressive tumor that is not often considered in the differential diagnosis of intestinal obstruction. Once found and accurately diagnosed, it is a bewildering race against time as its median survival time is 150 days from diagnosis.

Altered Central Nutrient Sensing in Male Mice Lacking Insulin Receptors in Glut4-Expressing Neurons.

Insulin signaling in the central nervous system influences satiety, counterregulation, and peripheral insulin sensitivity. Neurons expressing the Glut4 glucose transporter influence peripheral insulin sensitivity. Here, we analyzed the effects of insulin receptor (IR) signaling in hypothalamic Glut4 neurons on glucose sensing as well as leptin and amino acid signaling.

Underlying liver disease and advanced stage liver cancer are associated with elevated neutrophil-lymphocyte ratio.

Background/aims: Inflammation-based scores, such as the neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis in hepatocellular carcinoma (HCC); but variable cut-off values and potential lack of specificity have limited the utility of NLR. This study evaluates NLR in a large cohort of HCC patients.

Methods: We retrospectively reviewed 789 HCC cases (1993-2017) for demographics, tumor characteristics, treatment, and survival.

Human papillomavirus DNA detection, p16, and oral cavity cancer in a U.S. population.

Objectives: The role of HPV in oral cavity cancers was investigated using two markers of viral exposure.

Materials And Methods: HPV DNA and p16 expression were evaluated in tumor tissue from a U.S.