Radioembolization of Intrahepatic Cholangiocarcinoma: Patient Selection, Outcomes, and Competing Therapies

Intrahepatic cholangiocarcinoma is the second most common primary hepatic malignancy and poses a therapeutic challenge owing to its late-stage presentation and treatment-resistant outcomes. Most patients are diagnosed with locally advanced, unresectable disease and are treated with a combination of systemic and local regional therapies. Transarterial radioembolization offers a survival benefit and a favorable side effect profile, with a growing body of evidence to support its use. Herein, we review patient selection and detail outcomes of radioembolization for intrahepatic cholangiocarcinoma, together with mention of competing treatments.

Miltefosine for the treatment of cutaneous leishmaniasis—A pilot study from Ethiopia

Background Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking. Methodology and principal findings In an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions. Conclusions/Significance Based on miltefosine’s good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups. Trial registration ClinicalTrials.gov NCT04004754.

Zolpidem for Insomnia: A Double-Edged Sword. A Systematic Literature Review on Zolpidem-Induced Complex Sleep Behaviors

Background: Being a nonbenzodiazepine, zolpidem is believed to have a favorable side-effect profile and is widely prescribed for insomnia. However, in the past few years, numerous neuropsychiatric adverse reactions, particularly complex sleep behaviors (CSBs), have been reported with zolpidem. Objective: To conduct a systematic review of zolpidem-associated CSBs. Data Sources: An electronic search was conducted using MEDLINE, Embase, PubMed, and Cochrane database of systematic reviews to extract relevant articles till July 2020. Study Eligibility Criteria: Any type of literature article (case report, case series, and observational or interventional study) reporting CSBs associated with zolpidem. Results: In this review, we present aggregate summarized data from 148 patients presenting with zolpidem-induced CSBs (79 patients from 23 case reports and 5 case series; 69 patients out of 1454 taking zolpidem [4.7%] from three observational clinical studies). Various types of CSBs associated with zolpidem were reported, most common being sleepwalking/somnambulism and sleep-related eating disorder. On causality assessment, around 88% of cases were found to have a probable association with zolpidem. Limitations: Extraction of data from observational studies and spontaneous reports, due to nonavailability of any randomized controlled trials relevant to the study objective. Conclusion and Implication of Key Findings: Zolpidem-induced CSBs, although not very common, may develop when the drug is used at therapeutic doses for insomnia. Doctors need to be alert to monitor such adverse effects of zolpidem and exercise caution while prescribing it.

Insect bite like rash induced by bendamustine – A common presentation with an uncommon cause

Bendamustine has become a popular cancer chemotherapeutic agent in the last couple of years. It has replaced some traditional chemotherapy regimens due to its favorable side effect profile. Various cutaneous side effects have been noted following bendamustine usage. These cutaneous eruptions are to known to occur in 15-24% of patients. Benign cutaneous events include lichenoid drug eruptions, flagellate dermatoses and polymorphic papules and plaques in exposed areas. Rarely, severe adverse cutaneous reactions such as Steven Johnson syndrome, drug rash with eosinophilia and systemic symptoms and toxic epidermal necrolysis have been reported. We report a case of a 48 year-old-female who developed an insect bite like rash after initiation of bendamustine for non-Hodgkins lymphoma.

Safe use of Interleukin-17 Inhibitors for Psoriasis and Psoriatic Arthritis in Two Patients with a History of Lymphoproliferative Disease

Psoriasis and psoriatic arthritis are chronic, inflammatory, immune-mediated diseases that affect the skin and joints, respectively. The older systemic agents that have been used to treat these conditions are associated with many side effects, including an increased risk of malignancies, specifically lymphoma. In the last few years, there has been a wave of development of novel systemic biologic therapies to target psoriasis and psoriatic arthritis. While long-term safety data is lacking, the newer therapies targeting interleukins 12, 23, and 17 reveal a much more favorable side effect profile, specifically with regards to lymphoma. Here we report two cases of patients with psoriasis and psoriatic arthritis who had histories of lymphoma, both successfully treated with an interleukin-17 inhibitor without any recurrence or worsening of lymphoproliferative disease.

SAT-278 Vaginal Cabergoline: A Simple Solution to a Challenging Problem

Introduction: Prolactinomas is a common endocrine disorder that can be associated with significant morbidity. Generally, prolactinomas are more responsive to pharmacologic treatment than any other types of pituitary adenoma. Dopamine agonists (DA), including cabergoline and bromocriptine, are the first line of treatment in all sizes of prolactinomas and they decrease both the secretion and size of these adenomas. However, treatment remains challenging for patients who are intolerance to those medications. Case: We report a 32-year-old Hispanic woman who presented with secondary amenorrhea, she was found to have hyperprolactinemia of 1496 mcg/L. MRI of the brain showed a pituitary adenoma measuring 2.7 cm with sella turcica invasion and mass effect on the optic chiasma. She failed the lowest doses of oral cabergoline and bromocriptine and underwent TSS and gamma knife radiosurgery. Given her persistent symptoms (marked depression, insomnia, fatigue, short-term memory loss, and lack of concentration along with constipation) and elevation of prolactin, she was started on low dose vaginal cabergoline leading to a marked improvement of her symptoms and a steady decrease in serum prolactin. Discussion: Despite the availability of DA as a first-line treatment of Prolactinoma, treatment remains challenging, given the commonly reported side effects for all DA. Cabergoline is oftentimes the treatment of choice due to efficacy and favorable side-effect profile. However, intolerance to those medications can lead to discontinuation of therapy and increase morbidity. Other strategies, including transsphenoidal surgery (TSS) or radiation therapy, have been considered for the minority of patients whose adenomas are resistant to DA or who cannot tolerate these drugs. Interestingly, tolerance to DA can be improved by administering the drug intravaginally, which can have similar efficacy to the oral route and a more favorable side-effect profile. However, only a few studies assessed the effectiveness and tolerance of vaginal DAs in hyperprolactinemic patients intolerant to oral medications, little evidence supports the use of intravaginal DA to improve drug tolerance, and further studies are necessary to determine the safety and efficacy of vaginal cabergoline.

Drug Rash With Eosinophilia and Systemic Symptoms (DRESS) Syndrome Probably Related to Cefpodoxime: A Case Report

Cefpodoxime is a common antibiotic with a favorable side effect profile. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome has been described with several cephalosporins but not cefpodoxime. We report the probable first case of cefpodoxime-induced DRESS syndrome in a 52-year-old female patient. In our case, the patient presented with symptoms of DRESS syndrome 16 days after initiation of cefpodoxime. This case highlights the necessity of consideration of an iatrogenic reason for presenting signs and symptoms at all times. Reinforcing the importance of taking a thorough drug history and considering drug reactions even if onset of symptoms are delayed.

Remission of Severe, Relapsed, and Refractory TTP after Multiple Cycles of Bortezomib

Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by autoantibodies against a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Uncleaved von Willebrand factor (VWF) multimers accumulate and bind to platelets which causes spontaneous microthrombi ultimately causing microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemia. Plasma exchange (PEX) with or without steroids constitutes standard first-line therapy with rituximab typically reserved for refractory cases. Therapies beyond rituximab lack strong evidence for routine use. Recently, bortezomib, a proteasome inhibitor used commonly in patients with multiple myeloma, was shown to induce remission in patients with refractory TTP. Here, we report a case of severe, relapsed TTP that was refractory to PEX, steroids, and rituximab that underwent remission following three cycles of bortezomib. We discuss the salient features of our case, the mechanism of action of bortezomib, and the very few other similar reports that exist in the literature. We conclude that bortezomib should be considered for patients with TTP refractory to PEX, steroids, and rituximab due to its efficacy and relatively favorable side effect profile.

Cambia® (Diclofenac Potassium for Oral Solution) in the Management of Acute Migraine

Migraine is a prevalent and disabling disorder involving central and peripheral neurologic processes that generate inflammatory mediated pain. Cambia® (diclofenac potassium for oral solution), a novel patented form of the anti-inflammatory medication diclofenac potassium, has been approved by the US Food and Drug Administration for the acute treatment of migraine. Clinical trial data have demonstrated that this formulation offers a four-fold decrease in time of onset of relief compared with conventional diclofenac, which has comparable efficacy to triptan medication. It has also proven effective in a real-world setting. Over the past few years, it has been established that migraine treatment that is administered early may prevent central sensitization and improve treatment outcomes. Given the importance of early intervention in migraine treatment, this medication offers rapid, convenient, and effective relief with a favorable side-effect profile. This review describes migraine pathophysiology, treatment rationale, clinical trial results, and real-world experience with the use of this new medication.