Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults.     

Ventricular fibrillation after exposure to air freshener-death just a breath away

A case of ventricular fibrillation due to butane toxicity after unintentional inhalation of air freshener is reported for its rarity and to create awareness among practitioners and the public. A 25-year-old woman collapsed in the supermarket after unintended exposure to air freshener sprayed into her nostrils. Her husband started cardiopulmonary resuscitation immediately, and she was brought to the hospital. She had coarse ventricular fibrillation. Defibrillation with 360 J was given, and the rhythm reverted to normal sinus rhythm after the third shock. Epinephrine was not administered, and she was treated with esmolol infusion for ventricular ectopy. The patient recovered completely without any sequelae and was discharged on the fifth hospital day. On thin layer chromatography, the chemical content of the spray was identified to be isobutane. Avoiding epinephrine and administering β-adrenergic blockers may protect the catecholamine-sensitized heart early during resuscitation in butane exposure cases.     

Inflammatory Markers are Associated with Outcome in Patients with Unresectable Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization

Background

The serum neutrophil–lymphocyte ratio (NLR) is associated with outcomes in several solid organ cancers, including hepatocellular carcinoma (HCC).

Methods

We reviewed our experience in patients with HCC who underwent transarterial chemoembolization (TACE) as the initial treatment. Serum complete blood counts were used to calculate the NLR before and after TACE. The Kaplan–Meier method was used to determine survival and significant differences between groups by the log-rank test.

Results

There were 103 patients identified who underwent TACE for HCC. The median age was 60.5 years. Median overall survival was 12.6 (95 % confidence interval 8.3–17) months. Median survival in patients with a high preprocedural NLR was 4.2 months compared to 15 months in those with a normal NLR (p = 0.021). In those whose NLR either rose 1 month after treatment or remained elevated, survival was worse compared to those who normalized or remained normal (18.6 vs. 10.6 months, p = 0.026). The same was true at 6 months (21.3 vs. 9.5 months, p = 0.002). An unresponsive NLR was associated with very poor outcome (median survival 3.7 months). Multivariate analysis of clinicopathologic factors showed that presence of extrahepatic disease and high NLR were independent factors associated with worse survival.

Conclusions

Our study demonstrates that periprocedural trends of serum NLR are associated with outcome in unresectable HCC undergoing TACE. Serum NLR is easy to calculate from a routine complete blood count with differential. Along with liver function, serum NLR may be helpful to clinicians in providing prognostic information and monitoring response to therapy.     

Coronavirus disease 2019: Implications of emerging infections for transplantation

The recent identification of an outbreak of 2019‐ novel Coronavirus is currently evolving, and the impact on transplantation is unknown. However, it is imperative that we anticipate the potential impact on the transplant community in order to avert severe consequences of this infection on both the transplant community and contacts of transplant patients.     

Heart transplant recipients with confirmed 2019 novel coronavirus infection: The Detroit experience

A chronic immunosuppressed state as in solid organ transplant recipients is a reported risk factor for the novel 2019 coronavirus infection. Patients with a history of orthotopic heart transplant (OHT) at a tertiary care transplant center in Detroit, Michigan were retrospectively reviewed from March until May 2020. Clinical parameters and outcomes of 5 OHT recipients and one combined heart–lung recipient with confirmed SARS-CoV-2 were obtained. The cohort was predominately African American males with median age of 59 years (interquartile range, 48.25-73.25). All patients were classified as having mild–moderate disease; none required intubation or ICU admission with no deaths. The most common presenting symptoms were fever and shortness of breath 83% (n = 5), followed by cough and chills 67% (n = 4). All admitted patients (n = 5) received hydroxychloroquine and 3 received high-dose steroids. Antimetabolites were held for 2 patients (33.3%). The calcineurin inhibitor trough goal was decreased in only 1 patient; 3 other patients, without change in goal, required calcineurin inhibitor dosage reduction. Two patients requiring readmission presented 7 and 23 days after initial symptoms onset. In conclusion, our experience with OHT patients infected by the SARS-CoV-2 virus did not have an elevated risk of severe infection. Impact of modifying immunosuppression remains unclear.     

Mechanism of antithrombin III inhibition of factor VIIa/tissue factor activity on cell surfaces. Comparison with tissue factor pathway inhibitor/factor Xa-induced inhibition of factor VIIa/tissue factor activity

Recent studies have shown that antithrombin III (AT III)/heparin is capable of inhibiting the catalytic activity of factor VIIa bound either to relipidated tissue factor (TF) in suspension or to TF expressed on cell surfaces. We report studies of the mechanism of which by AT III inhibits factor VIIa bound to cell surface TF and compare this inhibitory mechanism with that of tissue factor pathway inhibitor (TFPI)-induced inhibition of factor VIIa/TF. AT III alone and AT III/heparin to a greater extent reduced factor VIIa bound to cell surface TF. Our data show that the decrease in the amount of factor VIIa associated with cell surface TF in the presence of AT III was the result of (1) accelerated dissociation of factor VIIa from cell surface TF after the binding of AT III to factor VIIa/TF complexes and (2) the inability of the resultant free factor VIIa-AT III complexes to bind effectively to a new cell surface TF site. Binding of TFPI/factor Xa to cell surface factor VIIa/TF complexes markedly decreased the dissociation of factor VIIa from the resultant quaternary complex of factor VIIa/TF/TFPI/factor Xa. Addition of high concentrations of factor VIIa could reverse the AT III-induced inhibition of cell surface factor VIIa/TF activity but not TFPI/factor Xa-induced inhibition of factor VIIa/TF activity.     

Multivessel coronary thrombosis treated with abciximab (reopro®) in a patient with essential thrombocythemia

A 50-year-old man was admitted with acute inferior and anterior myocardial infarction. The patient was diagnosed with essential thrombocythemia (ET) based on the findings of marked thrombocytosis of 1,113 × 10³/mm³, splenomegaly, and numerous clumping megakaryocytes on bone marrow biopsy. Emergent coronary angiography revealed extensive multivessel thrombosis involving the left main coronary artery and completely occluding the proximal right coronary artery. In addition to standard therapy with aspirin, heparin, and primary angioplasty of the right coronary artery, the patient received additional antiplatelet therapy with ticlopidine, hydroxyurea, and the platelet glycoprotein IIb/IIIa receptor-inhibiting monoclonal antibody drug abciximab (ReoPro®). Serial coronary angiograms 1 and 5 days following the infarction showed progressive thrombus resolution. The pathophysiologic mechanisms and therapeutic challenges of ET-associated coronary thrombosis are discussed in this report.     

A Multidimensional Measure of Sexual Orientation,Use of Psychoactive Substances,and Depression: Results of a National Survey on Sexual Behavior in France

Using data from a large national representative survey on sexual behavior in France (Contexte de la Sexualité en France), this study analyzed the relationship between a multidimensional measure of sexual orientation and psychoactive substance use and depression. The survey was conducted in 2006 by telephone with a random sample of the continental French speaking population between the ages of 18 and 69 years. The sample used for this analysis consisted of the 4,400 men and 5,472 women who were sexually active. A sexual orientation measure was constructed by combining information on three dimensions of sexual orientation: attraction, sexual behavior, and self-definition. Five mutually exclusive groups were defined for men and women: those with only heterosexual behavior were divided in two groups whether or not they declared any same-sex attraction; those with any same-sex partners were divided into three categories derived from their self-definition (heterosexual, bisexual or homosexual). The consumption of alcohol and cannabis, which was higher in the non-exclusively heterosexual groups, was more closely associated with homosexual self-identification for women than for men. Self-defined bisexuals (both male and female) followed by gay men and lesbians had the highest risk of chronic or recent depression. Self-defined heterosexuals who had same-sex partners or attraction had levels of risk between exclusive heterosexuals and self-identified homosexuals and bisexuals. The use of a multidimensional measure of sexual orientation demonstrated variation in substance use and mental health between non-heterosexual subgroups defined in terms of behavior, attraction, and identity.