Treatment Targets in Ulcerative Colitis: Is It Time for All In, including Histology?

The main therapeutic goal of ulcerative colitis (UC) is to induce and maintain remission to prevent long-term disease progression. Treat-to-target strategies, first introduced by the STRIDE consensus and updated in 2021, have shifted focus from symptomatic control toward more stringent objective endpoints. Today, patient monitoring should be based on a combination of biomarkers and clinical scores, while patient-reported outcomes could be used as short-term targets in monitoring disease activity and therapeutic response. In addition, endoscopic healing was the preferred long-term goal in UC. A Mayo endoscopic score (MES) ≤ 1 can be recommended as a minimum target. However, recent evidence suggests that more stringent endoscopic goals (MES of 0) are associated with superior outcomes. Recently, emerging data support that histological remission (HR) is a superior prognostic factor to endoscopic healing in predicting long-term remission. Despite not yet being recommended as a target, HR may become an important potential therapeutic goal in UC. However, it remains questionable if histological healing should be used as a routine assessment in addition to clinical, biomarker, and endoscopic targets in all patients. Therefore, in this review, our aim was to discuss the current evidence for the different treatment targets and their value in everyday clinical practice.

The Abscopal Effect: A Review of Pre-Clinical and Clinical Advances

Radiotherapy has been used for more than a hundred years to cure or locally control tumors. Regression of tumors outside of the irradiated field was occasionally observed and is known as the abscopal effect. However, the occurrence of systemic anti-tumor effects was deemed too rare and unpredictable to be a therapeutic goal. Recent studies suggest that immunotherapy and radiation in combination may enhance the abscopal response. Increasing numbers of cases are being reported since the routine implementation of immune checkpoint inhibitors, showing that combined radiotherapy with immunotherapy has a synergistic effect on both local and distant (i.e., unirradiated) tumors. In this review, we summarize pre-clinical and clinical reports, with a specific focus on the mechanisms behind the immunostimulatory effects of radiation and how this is enhanced by immunotherapy.

Achieving Physiologic 17-ẞ-Estradiol Levels in Transgender Females on Estradiol Transdermal Patches and Optimal Dosing

Purpose: Gender dysphoria is defined as a significant incongruence between an individual’s experienced gender and the gender assigned at birth, leading to persistent distress. Hormone therapy and gender affirmation surgery improve gender dysphoria by mitigating or completely removing undesirable primary/secondary sexual characteristics which would better align with one’s physical and psychological features. Maintaining cross-sex hormone levels in the physiologic range for the preferred gender is the basis of transgender hormonal therapy. For trans females (MTF), estradiol is most commonly administered orally, and studies have shown this route is often successful in achieving therapeutic hormone levels. However, there is wide individual variability in the dose response to oral estradiol, and approximately 25% of patients will not reach therapeutic goal on maximum oral estradiol. Furthermore, high dose oral estrogen has been associated with increased thrombotic risk, especially in older individuals. The efficacy or optimal dose of adding or switching to the transdermal route is not known. We investigated the efficacy of estradiol transdermal patches and the optimal dose to reach therapeutic goal. Methods: A chart review was conducted of all MTF patients who were treated with estradiol transdermal patches in our transgender clinic from 2006 through 2020. We looked at the success of achieving physiologic serum 17-β-estradiol levels (with and without antiandrogens spironolactone and finasteride) on various doses of estradiol transdermal patches. Target serum level for estradiol >100 pg/mL is recommended (but may be lower in certain clinical circumstances). Results: 371 MTF patients were identified, 41 received an estradiol transdermal patch. Of these 41 patients, 16 of them were placed on a transdermal patch due to failure to achieve target 17-β-estradiol levels on maximal oral therapy. We found that 9 of these 16 patients achieved goal estrogen levels, as well as one patient very near goal. Of the 7 who did not reach goal, only 2 were on patch doses >60 mcg/day. The majority who reached goal serum estradiol levels were taking a dose of 100 mcg/daily. When considering all MTF patients on the highest dose (100 mcg) of transdermal estrogen, 11 of 18 attained goal level, as well as one just under goal. Of the 41 MTF patients taking a transdermal patch, only 6 of them had serum estrogen levels lowered from being at goal on oral therapy. Thirteen patients had their estrogen levels improve to reach goal when placed on patch (4 as add-on therapy). Conclusions: Our study supports the findings that using an estradiol transdermal patch can help MTF patients achieve goal 17-β-estradiol levels. This delivery method can be useful for patients unable to reach goal on oral agents and for patients at higher thrombotic risk. The highest dose patch available is often needed to achieve therapeutic goal.

Methotrexate and Cardiovascular Disease in Patients With Rheumatoid Arthritis: Insights and Novel Speculations

Rheumatoid arthritis (RA) increases the risk for cardiovascular disease (CVD) and the risk is related to disease activity1,2,3,4. Groundbreaking studies on the etiology of CVD have shown that there is a strong relationship with inflammation5,6. Given that a core therapeutic goal in RA is to control inflammation, it is appropriate to determine if therapeutic interventions for disease activity may also favorably affect the incidence of CVD.

FETO-MATERNAL OUTCOME OF INTRAVENOUS LABETALOLAND ORAL NIFEDIPINE IN SEVERE PRE-ECLAMPSIA- A COMPARATIVE STUDY

Introduction: Pre-eclampsia (PE) is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. Aims and objectives: 1. to determine the efficacy and safety of oral nifedipine for treatment of severe hypertension of pregnancy compared with intravenous labetalol. 2. To compare the time taken to reach the therapeutic goal blood pressure after using intravenous labetalol & oral nifedipine in severe pregnancy induced hypertension. 3. The time taken to achieve a blood pressure of less than 150/100 mmHg. 4. To compare the maternal and perinatal outcome among the subjects using nifedepine over labetalo. Material and method: PROSPECTIVE RANDOMISED INTERVENTIONAL COMPARITIVE TRAIL. One and half year. Conclusion: Our present study compares the efficacy of oral Nifedipine and IV Labetalol in reaching the therapeutic goal. From the results of our study we can conclude that nifedipine required less time for reaching target BP as compare to labetalol. Less no of dose of nifedipine was used for the rapid control of blood pressure in severe hypertension in pregnancy. So, Nifedipine may be preferable as it is a simple, less time and is an oral regimen.

Beyond Growth Factors: Macrophage-Centric Strategies for Angiogenesis

Functional angiogenesis is a critical therapeutic goal in many pathological conditions. Logically, the use of pro-angiogenic growth factors has been the mainstay approach despite obvious limitations and modest success. Recently, macrophages have been identified as key regulators of the host response to implanted materials. Particularly, our understanding of dynamically plastic macrophage phenotypes, their interactions with biomaterials, and varied roles in different stages of angiogenic processes is evolving rapidly. In this review, we discuss changing perspectives on therapeutic angiogenesis, in relation to implantable materials and macrophage-centric strategies therein. Harnessing the different mechanisms through which the macrophage-driven host response is involved in angiogenesis has great potential for improving clinical outcome.