Perioperative Plasma Exchange and Intravenous Immunoglobulin Use for Refractory Heparin-Induced Thrombocytopenia in a Liver Transplant Recipient.

BACKGROUND Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin, which can lead to a prothrombotic state. Prompt cessation of heparin and initiation of non-heparin anticoagulation is the standard of care for HIT. Nevertheless, the treatment can pose challenges, particularly in refractory HIT, in patients with contraindications to anticoagulation, or those requiring urgent surgery. Additionally, in rare cases, conventional anticoagulation therapy is not effective, necessitating alternative treatments such as plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). CASE REPORT Here, we report the case of a 57-year-old male patient who developed mild acute cellular rejection, refractory HIT, and disseminated intravascular coagulation after liver transplant surgery. Heparin was stopped and argatroban was initiated for thromboembolism treatment, but hepatic artery thrombosis occurred in the setting of refractory HIT and caused transplant failure. The patient underwent a second liver transplant 1 month after the first surgery. He had 2 sessions of PLEX and received 1 dose of IVIG before and 1 dose during the operation. Despite advanced treatment with PLEX and IVIG, the refractory HIT persisted. Hepatic artery thrombosis recurred within 2 weeks and the transplant failed again despite catheter-directed intra-arterial thrombolysis and argatroban therapy. CONCLUSIONS Recently perioperative PLEX and IVIG have been used a few times for the treatment of refractory HIT. This is the first reported case of a liver transplant recipient with refractory HIT who underwent this treatment strategy. Further investigation is required to determine the efficacy and safety of preoperative and intraoperative administration of PLEX and IVIG, especially in liver transplant recipients with HIT.

Fecal microbiota transplantation in hematopoietic cell transplant and cellular therapy recipients: lessons learned and the path forward.

Disruptions to the gut microbiota have been associated with adverse outcomes including graft-versus-host disease, infections, and mortality after hematopoietic cell transplantation and cellular therapy. Evidence for causal links is accumulating, thus supporting therapeutic interventions targeting the microbiota with the goal of preventing and treating adverse outcomes. One such intervention is fecal microbiota transplantation (FMT) by which an entire community of gut microbiota is transferred to the patient with dysbiosis. As this approach in transplant and cellular therapy recipients is still in its infancy, no best approach has been defined and many open questions need to be addressed before FMT becomes a standard treatment. In this review, we highlight microbiota-outcome associations with the highest level of evidence, provide an overview of the main FMT trials, and suggest some paths forward.

Unusual stroke-like symptoms with oxaliplatin use.

INTRODUCTION: Oxaliplatin has become the mainstay of treatment for many cancers, but its use can be accompanied by unusual side effects. CASE REPORT: We describe herein a 74-year-old patient with pancreatic cancer who developed severe motor weakness affecting lower extremities after starting treatment with oxaliplatin on three separate occasions. Our patient also experienced slurred speech, with decreased ability to phonate and word-finding difficulty. Brain imaging studies did not suggest recent brain ischemia, and the symptoms resolved within 15-20 h. MANAGEMENT AND OUTCOME: Oxaliplatin had to be discontinued due to suboptimal tolerance and a short-lived clinical response. After discontinuation of oxaliplatin, she did not experience any more similar symptoms. A score of 9 on the Naranjo nomogram supported a definite causality relationship between oxaliplatin and the observed neurologic toxicity. DISCUSSION: Rare reports of stroke-like events have previously been described with oxaliplatin. While the exact mechanism of these phenomena is not known, alterations in neuronal sodium channels might be involved. Clinicians, pharmacists, and patients need to be aware of these rare but important side effects of oxaliplatin. Nonetheless, work-up for a cerebrovascular accident is still warranted as hypercoagulability related to malignancy can also predispose the patients to strokes.

Immune checkpoint inhibition in advanced colorectal cancer with inherited and acquired microsatellite instability: Current state and future directions.

OBJECTIVE: This paper reviews comprehensively the most relevant data on single-agent and combination therapies for advanced colorectal cancer with inherited and acquired microsatellite instability (MSI). DATA SOURCES: We performed a systematic search on PubMed and MEDLINE articles published from inception to December 2022. We have also searched independent websites including U.S. Food and Drug Administration and ClinicalTrials.gov. DATA SUMMARY: Performing microsatellite stability testing, tumor mutational burden (TMB), and germline mutation analysis could identify patients with metastatic colorectal cancer that benefit from immune checkpoint inhibitor (ICI) therapy. Single-agent pembrolizumab has proven superiority over traditional chemotherapy in these patients. The nivolumab-ipilimumab is the only combination ICI therapy approved in this space. Recently, the anti-PD-1 antibody dostarlimab was granted Food and Drug Administration approval in refractory tissue-agnostic advanced solid cancers with deficient mismatch repair (dMMR). ICIs are also being studied in the adjuvant/neoadjuvant setting in colon cancer patients with dMMR. Newer agents are being scrutinized in this space as well. More solid data on biomarkers predicting responses in patients with MSI-high or TMB-H to various therapies are needed. Given its both clinical and financial toxicity, it is imperative to determine the optimal duration of ICI therapy in individual patients. CONCLUSIONS: Overall, the outlook in advanced colorectal cancer patients with MSI appears optimistic as new and efficacious ICI drugs and combinations are being added to the existing therapeutic armamentarium.

Acquired angioedema late in the course of nivolumab treatment.

INTRODUCTION: Although programmed cell death-1 inhibitors have become the mainstay of treatment for many cancers, their use can at times be accompanied by unusual side effects. CASE REPORT: We describe herein a 43-year-old patient with Lynch syndrome and colon cancer who developed facial swelling 18 months after starting nivolumab therapy. Our patient also experienced a grade 1 maculopapular rash due to this agent. Naranjo nomogram assessment showed a probable causality between nivolumab and angioedema (score of 8). MANAGEMENT & OUTCOME: Given the modest intensity of symptoms and the excellent response of metastatic colon cancer to nivolumab, this agent was continued without interruptions. She was prescribed prednisone 20 mg orally daily as needed to be taken if the swelling progressed, or if respiratory symptoms developed. The patient experienced another two similar episodes over the next months; however, they were self-limiting and did not require steroids. Subsequently, she had no further similar symptoms. DISCUSSION: Rare reports of angioedema associated with immune checkpoint inhibitor (ICI) treatment have previously been described. The exact mechanism of these phenomena is unknown, but bradykinin release leading to increased vascular permeability might be involved. Clinicians, pharmacists, and patients should be aware of this rare side effect of ICIs as it can be life-threatening when involving the respiratory tract and causing impending airway obstruction.

Cycle-dependent eosinophilia due to adjuvant nivolumab for malignant melanoma.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have been widely used in the contemporary anticancer armamentarium. However, new side effects due to these agents have continued to emerge. CASE REPORT: We describe herein a 71-year-old patient who received nivolumab as adjuvant therapy for malignant melanoma of the skin. He developed eosinophilia starting at 4 weeks of therapy. Eosinophilia increased progressively during the first six nivolumab cycles, then stabilized. Cycle-dependent increments were observed. Subsequently, the patient experienced well-known side effects of ICIs such as grade 1 diarrhea, arthralgias, and erythematous papular rash. MANAGEMENT AND OUTCOME: Nivolumab was continued, and absolute eosinophil counts were monitored. Prednisone 10 mg PO daily was required for moderate gastroenteritis, dermatitis, and arthritis, which all subsequently improved. Eosinophil levels gradually downtrended after starting prednisone. Causality assessment between nivolumab and eosinophilia via adverse drug reaction (ADR) probability scale revealed a score of 9. DISCUSSION: Physicians and pharmacists need to be aware of this important side effect of ICI therapy. Eosinophilia in the context of ICI use has been previously reported in clinical trials. Our case is unique as eosinophilia was cumulative, showed increments every 8 weeks, and exhibited a trend toward cycle dependency. Extensive and expensive workup does not appear warranted, and simple monitoring of complete blood count is appropriate in most patients. Further studies are necessary to assess the true incidence, pattern, and severity of eosinophilia related to ICIs as well as its association with clinical outcomes.

Coronary artery tortuosity: a narrative review.

Coronary artery tortuosity (CAT) is a prevalent angiographic finding commonly associated with aging, hypertension, atherosclerosis and other conditions. Preliminary evidence suggests that degradation of elastin, a key component of extracellular matrix in the vascular wall, may be responsible for the development of CAT. The clinical significance of CAT should be considered in several aspects. First, coronary flow alteration associated with CAT may result in myocardial ischemia owing to reduced perfusion pressure distal to the tortuous segment. Second, increased and oscillatory shear stress in the tortuous vessel may promote atherosclerotic plaque formation and acute coronary syndrome. Third, as one of the criteria for coronary lesion complexity, the presence of severe tortuosity proximal to the culprit lesion may pose a challenge to wiring and stent or balloon delivery, thereby increasing the risk of periprocedural complications. Last, the presence of CAT may serve as a diagnostic clue of concurrent vasculopathy such as fibromuscular dysplasia or spontaneous coronary artery dissection. In general, CAT represents a benign entity that does not require specific treatment or intervention. Further research is warranted to elucidate the pathogenesis and prognostic effect of coronary tortuosity.

Mechanic hands: clinical and capillaroscopy manifestations of patients with connective tissue diseases presented with and without mechanic hands.

OBJECTIVES: The condition known as 'Mechanic's Hands' is a thickened, hyperkeratotic eruption, which is bilaterally symmetric along the fingers, and often occurs in patients with some connective tissue diseases. Nail fold capillaroscopy is a non-invasive technique for evaluation of connective tissue diseases. We evaluated the prevalence of mechanic hands in patients with connective tissue diseases and compared the clinical manifestations and capillaroscopic changes in the patients with and without mechanic hands. METHODS: The clinical manifestations and capillaroscopy of 576 patients with scleroderma, dermatomyositis, systemic lupus erythematosus, Sjogren's syndrome, undifferentiated and mixed connective tissue diseases were evaluated and compared in patients with and without mechanic hands. RESULTS: A total of 576 patients were enrolled. Mechanic hands were observed in 17.2% of patients: 50% of mixed connective tissue disease, 35% of dermatomyositis, 15.4% of scleroderma, 14.9% of undifferentiated connective tissue disease, 14.3% of Sjogren's syndrome, and no patient with SLE. Among them, 80.8% had abnormal capillaroscopic findings. In dermatomyositis patients, Raynaud's phenomenon, anti-Jo-1 positivity, and some capillaroscopy findings were detected more frequently in patients with mechanic hand. In scleroderma, positive Scl70 and capillary loss were observed more frequently in patients without mechanic hands. CONCLUSIONS: Mechanic hands can be a presenting sign of some systemic connective tissue diseases. Probably, finding this sign on examination, especially together with Raynaud's phenomenon or abnormal capillaroscopy, can be helpful in the early diagnosis of the connective tissue diseases and can be used as a predictive and prognostic tool in future studies.

A Review on Glycosylated Hemoglobin in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders among women of reproductive age, with a variety of complications and consequences mostly due to hyperandrogenism and insulin resistance (IR). PCOS patients with IR are at risk for metabolic syndrome and diabetes mellitus (DM) along with its complications such as cardiovascular events. There are several methods for screening IR in patients with PCOS to predict DM and other complications. Fasting plasma glucose test, oral glucose tolerance test, and insulin and glycosylated hemoglobin (HbA1c) levels are some available screening tools for IR. The American Diabetes Association recommended HbA1c to screen for DM because HbA1c is not affected by day-to-day plasma glucose levels and reflects the plasma glucose status during 2-3 months before measurement. Some studies have evaluated the role of HbA1c as a screening method to predict DM in PCOS patients, however, there are still controversies in this matter. Also some studies reported that HbA1c has a correlation with complications of PCOS such as metabolic syndrome and cardiovascular events. We found that HbA1c could be a suitable screening test for IR in PCOS patients but more studies are recommended, omitting confounding factors that could affect IR in patients with PCOS, such as antihyperglycemic agents like metformin, or lifestyle modification, which can be effective in reducing IR in patients with PCOS.