Nattamol Hosiriluck

Sex-Driven Differences in Immunological Responses: Challenges and Opportunities for the Immunotherapies of the Third Millennium

Purpose of the study: Male-based studies, both at the biochemical and at the pre-clinical/clinical trial levels, still predominate in the scientific community. Many studies are based on the wrong assumption that both sexes are fundamentally identical in their response to treatments. As a result, findings obtained mainly in males are applied to females, resulting in negative consequences female patients. In cancer immunotherapy, there is still a scarce focus on this topic. Here we review the main differences in immune modulation and immune system biology between males and females with a particular focus on how these differences affect cancer immunotherapy and cancer vaccines. Methods: We reviewed articles published on PubMed from 1999 to 2014, using the keywords: sex hormones, immune response, estrogen, immunotherapy, testosterone, cancer vaccines, sex-based medicine. We also present new data wherein the expression of the cancer testis antigen, Ropporin-1, was determined in patients with multiple myeloma, showing that the expression of Ropporin-1 was influenced by sex. Results: Male and female immune systems display radical differences mainly due to the immune regulatory effects of sex hormones. These differences might have a dramatic impact on the immunological treatment of cancer. Moreover, the expression of tumor antigens that can be targeted by anti-cancer vaccines is associated with sex. Conclusion: Future clinical trials focusing on cancer immunotherapy will need to take into account the differences in the immune response and in the frequency of target antigen expression between male and females, in order to optimize these anti-cancer immunotherapies of the third millennium.

Galectins as therapeutic targets for hematological malignancies: a hopeful sweetness.

Galectins are family of galactose-binding proteins known to play critical roles in inflammation and neoplastic progression. Galectins facilitate the growth and survival of neoplastic cells by regulating their cross-talk with the extracellular microenvironment and hampering anti-neoplastic immunity. Here, we review the role of galectins in the biology of hematological malignancies and their promise as potential therapeutic agents in these diseases.

Meta-analysis of the effect of proton pump inhibitors on obstructive sleep apnea symptoms and indices in patients with gastroesophageal reflux disease.

This study was designed to assess evidence for an association between the treatment of gastroesophageal reflux disease (GERD) with proton pump inhibitors (PPIs) and improvement in obstructive sleep apnea (OSA). We conducted a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies to evaluate the treatment effect of PPIs on OSA symptoms and indices in patients with GERD. EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were reviewed up to October 2014. From 238 articles, two randomized trials and four prospective cohort studies were selected. In four cohort studies there were no differences in the apnea-hypopnea indices before and after treatment with PPIs (standard mean difference, 0.21; 95% confidence interval, −0.11 to 0.54). There was moderate heterogeneity among these studies. Two cohort studies revealed significantly decreased apnea indices after treatment (percent change, 31% and 35%), but one showed no significant difference. A significant improvement in the Epworth Sleepiness Scale was observed in three cohort studies and one trial. The frequency of apnea attacks recorded in diaries was decreased by 73% in one trial. In conclusion, available studies do not provide enough evidence to make firm conclusions about the effects of PPI treatment on OSA symptoms and indices in patients with concomitant GERD. Controlled clinical trials with larger sample sizes are needed to evaluate these associations. We recommend PPIs in OSA patients with concomitant GERD to treat reflux symptoms. This treatment may improve the quality of sleep without any effect on apnea-hypopnea indices.

Reactive Thrombocytosis Associated with Acute Myocardial Infarction following STEMI with Percutaneous Coronary Intervention.

The etiology of thrombocytosis can be classified into reactive and essential forms. The rate of thromboembolic events is higher in essential thrombocytosis, and these events include strokes, transient ischemic attacks, retinal artery or retinal vein occlusions, digital ischemia, and acute coronary syndrome. In a study of 732 medical and surgical patients with thrombocytosis, 88% had reactive thrombocytosis. Patients with reactive thrombocytosis do not require cytoreductive medications or antiplatelet treatment. We report a healthy 40-year-old man without any medical problems who developed a new episode of myocardial infarction associated with thrombocytosis after an episode of myocardial infarction followed by percutaneous coronary intervention. He had thrombocytosis, and his platelet function test did not reveal adequate inhibition. To treat his acute coronary syndrome, therapeutic enoxaparin was added, and clopidrogel was substituted with ticagrelor. We decided to start hydroxyurea to reduce platelets counts. Enoxaparin and hydroxyurea were discontinued when platelet count returned to baseline. JAK-2 and BCR/ABL mutations were negative. This case report highlights a clinical dilemma (reactive thrombocytosis), which is challenging in terms of management and pathophysiology.

Post-infectious encephalomyelitis in an orthopedic surgeon with motor and cognitive impairment following Campylobacter gastroenteritis with complete recovery

Acute disseminated encephalomyelitis, also known as post-infectious encephalomyelitis, is an acute central nervous system demyelinating disorder which typically follows an autoimmune response secondary to a post-viral infection/syndrome. Although uncommon, the outcome can be devastating; mortality is not high but the morbidity may be catastrophic. Survival is anticipated but return to full function of highly motor skilled and cognitive individuals may not be expected. An orthopedic surgeon developed an acute autoimmune encephalitis presumed to be due to Campylobacter jejuni and despite initial significant cognitive and motor deficits was able to recover fully and ultimately return to his specialty surgical occupation.

Reversal of liver function without exchange transfusion in sickle cell intrahepatic cholestasis

Sickle cell intrahepatic cholestasis (SCIC) is a rare but fatal complication of sickle cell disease. It is found mainly in homozygous sickle cell disease. To date, there are no standard diagnostic criteria or well-established therapeutic approaches to this condition. Herein, we report this case of a 48-year-old man with sickle cell anemia and a total bilirubin of 78.5 mg/dL without evidence of extrahepatic biliary obstruction or viral hepatitis. The patient had a hemoglobin S level of 87.9%, acute renal failure, and mild coagulopathy. Despite the disease severity, he refused exchange transfusion (ET) with packed red blood cells. He was transfused with 2 units of blood and treated mainly with supportive measures. His total bilirubin levels trended down to normal days after discharge. Multiple studies have shown a significant decrease in the mortality rate in SCIC after ET. To date, only two reported adult cases have survived SCIC without aggressive treatment. Our case is the third case that demonstrates recovery of severe SCIC without ET.