A phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects.

BACKGROUND: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. METHODS: Patients with stage I-III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. RESULTS: Of 126 patients approached, 56 (44%) enrolled. Forty-five (80%) received ≥1 dose of memantine and completed pre-post assessments. Seventy-six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across objective cognitive domain composite measures. Sixty-six percent self-reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. CONCLUSIONS: Memantine was well-tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre- to post-assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033419.

Primary amoebic meningoencephalitis in children- report of two cases from South India.

Primary Amoebic meningoencephalitis is a rare and fatal neuro-infection caused by free-living fresh-water amoeba Naegleria fowleri. It is a ubiquitous organism and the infection occurs usually via contact with warm water-bodies. The clinical presentation is often indistinguishable from acute bacterial meningitis and the diagnosis can be made by CSF wet smear examination if there is a high index of suspicion. The disease progresses rapidly compared to pyogenic meningitis and usually has a fatal outcome. Reports of two confirmed cases of primary amoebic meningoencephalitis in children from different centres in Kerala state of India are presented here. In spite of early diagnosis and treatment, both these patients demised. Primary amoebic meningoencephalitis should be considered in the differential diagnosis of acute meningitis, especially in patients with recent freshwater exposure. Implementation of chlorination of pools of water bodies, especially if re-opened for recreational purpose after prolonged periods of non-use, needs vigorous implementation.

Activation of Supraspinatus and Infraspinatus Partitions and Periscapular Musculature During Rehabilitative Elastic Resistance Exercises.

OBJECTIVE: The purpose of this study was to quantify the activation of partitions within supraspinatus and infraspinatus and some periscapular muscles during four resistance exercises with elastic bands. DESIGN: Twenty-seven right-handed healthy volunteers (age, 22.5 ± 2.7 yrs) were recruited. Intramuscular electromyography from supraspinatus (anterior and posterior) and infraspinatus (superior and middle) and surface electromyography data from the upper, middle, and lower trapezius and serratus anterior were recorded during four elastic resistance exercises (Y, T, W, L). Kinematics were recorded synchronously. Electromyography values were presented as percentage of maximal voluntary isometric contraction and compared across exercises using analysis of variance. Muscle activation ratios were also calculated. RESULTS: The mean activations of all rotator cuff partitions were more than 40% maximal voluntary isometric contraction, except middle infraspinatus during the T exercise (29.3% maximal voluntary isometric contraction). Serratus anterior activity was significantly higher during the Y exercise (P < 0.008). Lower trapezius was activated more than 80% maximal voluntary isometric contraction in all four exercises with higher contributions compared with the upper trapezius. CONCLUSIONS: The investigated exercises induced moderate to high activation in supraspinatus and infraspinatus partitions and very high activation in lower trapezius. YTWL exercises are appropriate for strengthening of some rotator cuff and periscapular muscles and for late stages of shoulder rehabilitation.

Review of checkpoint immunotherapy for the management of non-small cell lung cancer.

Checkpoint immunotherapy uses highly selective humanized monoclonal antibodies against checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1). By blocking these receptors and signals, the immune system can be reactivated to fight the tumor. Immunotherapy for advanced non-small cell lung cancer (NSCLC) has resulted in a new paradigm of treatment options resulting in improved survival and response rates and has a less severe yet unique toxicity profile when compared to chemotherapy. PD-1 inhibitors, nivolumab and pembrolizumab, and PD-L1 inhibitor, atezolizumab, are currently approved by regulatory authorities for the treatment of advanced NSCLC. This article provides a detailed review of these newer agents, their mechanism of action, side-effect profile, therapeutic indications and current evidence supporting their use in the management of NSCLC.

Plasma exchange for the management of refractory pruritus of cholestasis: A report of three cases and review of literature.

BACKGROUND: Intractable pruritus of cholestasis leads to significant morbidity. Therapeutic plasma exchange (TPE) has been shown to be an effective alternative in the setting of refractory pruritus associated with cholestatic liver disease based on several individual reports. Due to rarity of this approach to intractable pruritus, the literature is sparse and therefore TPE, as a treatment for refractory pruritus is currently not in the apheresis guidelines. We present three additional patients with severe intractable pruritus of cholestasis successfully treated with plasma exchange to add to the mounting literature showing this as an effective and safe adjunctive therapy. METHODS: Three patients underwent serial plasma exchange procedures to control pruritus. Frequency of plasma exchange was three times a week, with slow taper upon improvement of pruritus. Total bile acid levels were assessed before procedures. RESULTS: All three patients had an intractable pruritus with different underlying etiologies of cholestasis. All three patients showed significant improvement in pruritus, with none or minimal pruritus in one patient with primary biliary cirrhosis. Pre procedure bile acids levels were decreased initially, but showed rebound increase upon tapering of plasma exchange, without increased pruritus. No serious side effects or complications were observed. CONCLUSION: Our results in conjunction with the published literature show that severe and intractable pruritus associated with cholestasis could be successfully treated with TPE, irrespective of the underlying disease, and can be done safely.

Multidisciplinary Approach to the Management of Esophageal Malignancies.

INTRODUCTION: A multidisciplinary approach in the management of complex malignancies is becoming more common, and likewise, adopting such an approach to the care of patients with locally advanced esophageal is recommended in order to optimize clinical outcomes. METHODS: In this review, we discuss both the surgical and medical oncology perspectives in the management of patients with locally advanced esophageal cancer. We review the data supporting the current standard-of-care approach, namely trimodality therapy with neoadjuvant chemo-radiotherapy followed by surgery. Other aspects of managing these patients including the control of dysphagia and pain as well as nutritional support are discussed. Finally, we review data that support the importance of incorporating a multidisciplinary streamlined approach in the management of these patients. RESULTS: Rather than having patients see each provider separately, a multidisciplinary approach to esophageal cancer allows for the seamless flow of communication and proactive management of the patient's symptoms. These benefits include increasing the likelihood of evidence-based decision making, shorter time to treatment, and increased patient quality of life, all of which can result in improved patient outcomes. CONCLUSION: The use of a multidisciplinary team can lead to a more accurate staging paradigm and thereby, better management decisions that translate to improved clinical outcomes. Therefore, optimizing the multidisciplinary approach for the care of patients with locally advanced esophageal cancer is essential for successful and individualized patient care.

Comparison of Spectra Optia and COBE Spectra apheresis systems' performances for red blood cell exchange procedures.

BACKGROUND: Spectra Optia (Terumo BCT, Lakewood, CO) was FDA approved for red blood cell exchange (RBCx) procedures in January 2014 and is expected to replace COBE spectra (Terumo BCT) very soon in the USA. The performance characteristics of these devices for Isovolemic Hemodilution (IHD-RBCx) procedure were compared in this study. METHODS: A total of 114 IHD-RBCx procedures from 19 patients were analyzed. For every patient, three procedures on each device with similar pre-procedure hematocrits were compared. Pre and post procedure laboratory parameters compared were hemoglobin S (HbS), hematocrits (Hct), platelet counts and fraction of cells remaining (FCR). Statistical analysis was performed using t-test adjusted by the Holm-Bonferroni method to reduce family-wise error rate. RESULTS: There were no significant differences between these two devices in regards to HbS, Hct, FCR and platelet counts (p = > 0.05). However, rinseback volume (124.2 ± 8.9 ml) and normal saline replacement volume during IHD phase (296.1 ± 97.2 ml) were lower in Spectra Optia as compared to COBE Spectra (337 ± 33.8 ml and 326.6 ± 105.2 ml, p value <0.001 and 0.030 respectively). Spectra Optia had a longer run time (107.1 ± 15.9 min vs 123.8 ± 19.6 min, p value <0.001) overall. CONCLUSIONS: Performance characteristics of Spectra Optia for HbS, Hct and FCR were similar to COBE Spectra for IHD-RBCx. IHD-RBCx procedure on Optia required less normal saline replacement volume and rinse back volume but with overall longer procedure run time.

Thromboembolic outcomes after use of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal in a real-world setting.

BACKGROUND: A four-factor prothrombin complex concentrate (4F-PCC) was recently licensed in the United States for urgent vitamin K antagonist (VKA) reversal based on two randomized clinical trials. These studies excluded patients at high risk of thrombosis; therefore, the risk of thrombotic complications in unselected patients remains a concern. STUDY DESIGN AND METHODS: This study retrospectively evaluated the incidence of thromboembolic events (TEEs) and death in patients who received 4F-PCC for VKA reversal. The study included 113 consecutive patients who were 18 years of age and older and were administered 4F-PCC for VKA reversal. The incidence of TEE and deaths was evaluated for up to 60 days after PCC administration or until the end of hospitalization, whichever came later. RESULTS: Seven (6.2%) patients developed TEEs and 17 (15%) patients died. PCC administration was probably related to TEE and subsequent death in two (1.8%) patients. Multivariate analysis revealed that a diagnosis of Factor V Leiden or antiphospholipid syndrome was predictive of TEE, and active malignancy was predictive of death. CONCLUSION: This study supports the safety of 4F-PCC for urgent VKA reversal even in unselected patients. The underlying type of hypercoagulable state and the dose of PCC may influence the incidence of TEE.

Cardiac tamponade complicating purulent pericarditis due to community acquired methicilin resistant Staphylococcus aureus (CA-MRSA).

Community acquired methicillin resistant Staphylococcus aureus(CA-MRSA) is a global pathogen capable of causing life-threatening infections with increasing prevalence since the 1990s. Purulentpericarditis, characterized by accumulation of purulent fluid in the pericardial space was historically a disease of the pediatric and early adult population, but through the years the median age of diagnosis has increased from 21 to 49. Mortality rates are as high as 40% even in the treated population. We report a case of purulent pericarditis due to CA-MRSA that was complicated by cardiac tamponade. Early diagnosis and intervention proved to be life-saving. A brief review of the literature and current management options are discussed.

Methotrexate therapy leading to a rapid progression of a previously indolent prostate cancer: is immunosuppression to blame?

Methotrexate therapy has been associated with occurrence and/or accelerated progression of malignancies. We describe a patient who developed widespread bone metastases of a previously confined to the prostate gland prostate cancer shortly after starting methotrexate therapy for rheumatoid arthritis and large granular lymphocyte leukemia. We believe an immunosuppressive milieu brought on by the methotrexate use in this case is responsible for the rapid progression of prostate cancer leading to the patient's demise. To the best of our knowledge, no association has been made to date between the therapy with methotrexate and a fulminant course of a previously indolent prostate cancer. Given its utilization in a variety of benign and malignant conditions and the ageing population, caution is advised with the use of this agent, especially in the presence of an underlying malignancy.

A curious case of oxaliplatin-induced neurotoxicity: recurrent, self-limiting dysarthria.

This report presents a unique case of oxaliplatin-induced neurotoxicity featuring acute, recurrent, self-limiting dysarthria following multiple subsequent infusions of oxaliplatin. A 65-year-old man started chemotherapy for metastatic pancreatic adenocarcinoma with oxaliplatin-irinotecan-leucovorin-5-fluorouracil (FOLFIRINOX). During the first and subsequent infusions of oxaliplatin, the patient developed episodes of dysarthria that lasted between 2 and 4 h after oxaliplatin infusions, followed by their complete and uneventful resolution. A thorough neurological examination showed no new neurologic deficits except for very fine tongue fasciculations. Recognizing this self-limiting toxic effect of oxaliplatin is important in order to avoid dose reductions that may affect clinical outcomes.

Acute skin graft-versus-host disease with molecular features mimicking herpes simplex virus-associated erythema multiforme: report of three cases.

BACKGROUND: Acute skin erythematous lesions that follow allogeneic hematopoietic stem cell transplantation (HSCT) and are histologically diagnosed as graft-versus-host disease (GVHD) are often associated with reactivation of latent herpes simplex virus (HSV). OBJECTIVE: To further examine the relationship between reactivated HSV and GVHD development. METHODS: We present 3 patients with acute skin GVHD after allogeneic HSCT who were studied prospectively for expression of the HSV antigen Pol, which is involved in HSV-associated erythema multiforme. RESULTS: Pol was expressed in the GVHD lesions but not the pre-HSCT normal skin or peripheral blood mononuclear cells. Lesion severity correlated with the Pol levels but not the histopathologically defined GVHD grade. Lesion development was accompanied by increased numbers of Pol+ circulating/skin-infiltrating CD34+ stem cells and CD1a+ and other dermal dendritic cells. CONCLUSIONS: Subclinical HSV infection of circulating CD34+ cells can contribute to some post-HSCT skin lesions histologically diagnosed as GVHD, with potential preventive and therapeutic implications.

Frequent detection of herpes simplex virus antigen in skin and peripheral blood CD34+ mononuclear cells from patients with graft-versus-host disease.

Viruses are implicated in the initiation or flare of graft-versus-host disease (GVHD) by virtue of their ability to activate antigen-presenting dendritic cells (DC). Herpes simplex virus (HSV) infects circulating CD34+ stem cell progenitors, favoring their differentiation into skin homing DC (CD1a+ Langerhans cells) that contribute to the development of an inflammatory skin rash known as HSV-associated erythema multiforme (HAEM). Following on these findings, we conducted a prospective study to examine whether HSV is also associated with GVHD. Skin biopsies and peripheral blood mononuclear cells (PBMC) were collected from 37 consecutive patients on admission before and after allogeneic hematopoietic stem cell transplantation (HSCT) and examined for HSV antigen (Pol) expression and the presence of Pol+CD34+ and Pol+CD1a+ cells. Sixteen patients developed a skin rash that was histopathologically consistent with GVHD (group I), 3 patients had a rash that was not GVHD (group II, EM-like) and 18 patients did not develop any rash after HSCT (group III). Skin biopsies from the group I patients were Pol negative pre-HSCT (baseline) but became Pol+ after the diagnosis of GVHD. The GVHD biopsies also contained Pol+CD34+ and Pol+CD1a+ cells, and these patients had a significant percentage of circulating Pol+CD34+ and Pol+CD1a+ PBMC. By contrast, the group II patients had Pol+ skin cells and Pol+CD34+ circulating PBMC at baseline that decreased post-HSCT. The group III patients had Pol negative skin and very few circulating Pol+CD34+ and Pol+CD1a+ PBMC at baseline that were not significantly changed post-HSCT. The data associate skin GVHD with HSV reactivation during conditioning and its propensity for nonreplicative infection of CD34+ PBMC that induces DC activation. Further studies are needed to better elucidate this association.