"We are Getting Those Old People Things." Polypharmacy Management and Medication Adherence Among Adult HIV Patients with Multiple Comorbidities: A Qualitative Study.

Introduction: Improvements in treatment have led to a growing population of older adults living with HIV. As this population ages, polypharmacy, or the use of more than five medications, may become more common among people living with HIV (PLWH). Methods: Two qualitative focus groups (N=7, N=8) were conducted among a sample of patients who participated in a larger study regarding differential medication adherence. Open-ended questions and probes focused on barriers and facilitators to multiple medication management as well as differential adherence. Results: Overall, patients were able to manage their polypharmacy. Social support facilitated adherence while long-term antiretroviral (ARV) use, medication-specific requirements and emotional fatigue were barriers to management. A small number of participants reported differential adherence that prioritized non-HIV medications over ARVs due to more immediate effects of non-adherence. Discussion: Findings suggest that PLWH have learned to manage their polypharmacy, but still face significant challenges adhering to multiple medications in the long-term. Future research may focus on the emotional toll of long-term ARV use and how patients' own management strategies may be leveraged to promote adherence.

Reconstruction of post-Mohs surgical wounds using a novel nanofiber matrix.

INTRODUCTION: Surgical wound healing after Mohs micrographic surgery can be challenging. Achieving an optimal aesthetic outcome is another important consideration, especially for facial lesions. OBJECTIVE: This case series evaluates the use of a novel synthetic nanofiber matrix after Mohs surgery to achieve desired results. MATERIALS AND METHODS: Four patients with NMSCs on the auricular helix underwent Mohs micrographic surgery at a single cancer center. The synthetic nanofiber matrix was applied to the prepared Mohs surgical defect and covered with a dressing. The wounds were evaluated regularly for healing progress, and an additional synthetic nanofiber matrix was applied as needed. RESULTS: Wounds were treated with an average of 1.25 applications ± 0.50 standard deviation of synthetic nanofiber matrix. The initial average wound size was 11.8 cm2. All wounds healed in 7.9 weeks ± 4.2 with excellent aesthetic results, minimal scar formation, and no skin deformity. In cases with exposed structures (cartilage and perichondrium), the synthetic nanofiber material promoted complete closure and healing. No complications were reported. Treatment using a synthetic nanofiber matrix resulted in complete wound healing in all patients. CONCLUSIONS: This study shows the synthetic nanofiber matrix is a viable option for the reconstruction of post-Mohs surgical defects.

A comparison of COVID-19 inpatients by HIV status.

COVID-19 in-hospital morbidity and mortality in people living with HIV (PLWH) were compared to HIV-negative COVID-19 patients within a New York City metropolitan health system, the hardest hit region in the United States early in the pandemic. A total of 10,202 inpatients were diagnosed with COVID-19, of which 99 were PLWH. PLWH were younger (58.3 years (SD = 12.42) versus 64.32 years (SD = 16.77), p < 0.001) and had a higher prevalence of men (73.7% versus 57.9%, p = 0.002) and Blacks (43.4% versus 21.7%, p < 0.001) than the HIV-negative population. PLWH had a higher prevalence of malignancies (18% versus 7%, p = < 0.001), chronic liver disease (12% versus 3%, p < 0.001), and end-stage renal disease (11% versus 4%, p = 0.007). Use of a ventilator, admission to the ICU, and in-hospital mortality were not different. Of the 99 PLWH, 12 were virally unsuppressed and 9 had CD4% < 14. Two of the 12 virally unsuppressed patients and 4/9 patients with CD4% < 14 died. Ninety-one of the 99 PLWH were on treatment for HIV, and 5 of the 8 not on treatment died. Among PLWH with prior values, absolute CD4 count decreased an average of 192 cells/mm3 at the time of COVID-19 diagnosis (p < 0.001). Hospitalized patients with HIV and COVID-19 coinfection did not have worse outcomes than the general population. Among PLWH, those with CD4%<14 or not on treatment for HIV had higher mortality rates. Those PLWH who received IL-6 inhibitors had lower mortality rates. PLWH given antifungal medications, hydroxychloroquine, antibiotics (including azithromycin), steroids, and vasopressors had higher mortality rates.

Structural variation of centromeric endogenous retroviruses in human populations and their impact on cutaneous T-cell lymphoma, Sézary syndrome, and HIV infection.

BACKGROUND: Human Endogenous Retroviruses type K HML-2 (HK2) are integrated into 117 or more areas of human chromosomal arms while two newly discovered HK2 proviruses, K111 and K222, spread extensively in pericentromeric regions, are the first retroviruses discovered in these areas of our genome. METHODS: We use PCR and sequencing analysis to characterize pericentromeric K111 proviruses in DNA from individuals of diverse ethnicities and patients with different diseases. RESULTS: We found that the 5' LTR-gag region of K111 proviruses is missing in certain individuals, creating pericentromeric instability. K111 deletion (-/- K111) is seen in about 15% of Caucasian, Asian, and Middle Eastern populations; it is missing in 2.36% of African individuals, suggesting that the -/- K111 genotype originated out of Africa. As we identified the -/-K111 genotype in Cutaneous T-cell lymphoma (CTCL) cell lines, we studied whether the -/-K111 genotype is associated with CTCL. We found a significant increase in the frequency of detection of the -/-K111 genotype in Caucasian patients with severe CTCL and/or Sézary syndrome (n = 35, 37.14%), compared to healthy controls (n = 160, 15.6%) [p = 0.011]. The -/-K111 genotype was also found to vary in HIV-1 infection. Although Caucasian healthy individuals have a similar frequency of detection of the -/- K111 genotype, Caucasian HIV Long-Term Non-Progressors (LTNPs) and/or elite controllers, have significantly higher detection of the -/-K111 genotype (30.55%; n = 36) than patients who rapidly progress to AIDS (8.5%; n = 47) [p = 0.0097]. CONCLUSION: Our data indicate that pericentromeric instability is associated with more severe CTCL and/or Sézary syndrome in Caucasians, and appears to allow T-cells to survive lysis by HIV infection. These findings also provide new understanding of human evolution, as the -/-K111 genotype appears to have arisen out of Africa and is distributed unevenly throughout the world, possibly affecting the severity of HIV in different geographic areas.

Two Suturing Techniques for the Prevention and Treatment of Nasal Valve Collapse After Mohs Micrographic Surgery.

BACKGROUND: Tumor extirpation of nonmelanoma skin cancer (NMSC) adjacent to the alar groove, using Mohs micrographic surgery (MMS), may risk causing internal nasal valve (INV) collapse, resulting in reduced airflow during inspiration. There are many surgical options described in the literature to repair INV collapse as a postoperative corrective procedure, but few exist as an intra-operative preventative procedure. OBJECTIVE: The authors present 2 distinct methods to prevent and treat INV collapse during the repair of a perialar surgical defect caused by MMS. METHODS: A 3-point stitch method or a modified suspension suture technique was used to prevent INV collapse during the repair of MMS defects overlying the alar groove, for nonmelanoma skin cancers. The 3-point stitch was used with a complex repair. The modified suspension suture was used with flap reconstruction. RESULTS: The 3-point stitch and the modified suspension suture are simple, single-stage surgical solutions for perialar defects with collapse of the INV caused by loss of subcutaneous tissue during MMS. Once executed, patients experienced immediate subjective airflow improvement which was also supported by clinical examination. Patients were followed at 1 week and at 3 months postoperatively. Thirty-four of 35 patients reported good functional and cosmetic results and were satisfied with the final outcome. CONCLUSION: The 3-point stitch and the modified suspension suture techniques are easy and simple methods that can be incorporated into reconstruction after MMS for defects of variable depth covering any multisubunit perialar region to prevent or correct INV collapse.

Malignancies, Particularly B-Cell Lymphomas, Are a Frequent Cause of Mortality in Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy.

Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival of <2 months from time of diagnosis.

Renin modulates HIV replication in T cells.

HIV is known to subvert cellular machinery to enhance its replication. Recently, HIV has been reported to enhance TC renin expression. We hypothesized that HIV induces and maintains high renin expression to promote its own replication in TCs. Renin enhanced HIV replication in TCs in a dose-dependent manner. (P)RR-deficient TCs, as well as those lacking renin, displayed attenuated NF-κB activity and HIV replication. TCs treated with renin and Hpr displayed activation of the (P)RR-PLZF protein signaling cascade. Renin, HIV, and Hpr activated the PI3K pathway. Both renin and Hpr cleaved Agt (a renin substrate) to Ang I and also cleaved Gag polyproteins (protease substrate) to p24. Furthermore, aliskiren, a renin inhibitor, reduced renin- and Hpr-induced cleavage of Agt and Gag polyproteins. These findings indicate that renin contributes to HIV replication in TCs via the (P)RR-PLZF signaling cascade and through cleavage of the Gag polyproteins.

VDR hypermethylation and HIV-induced T cell loss.

Epigenetics contributes to the development of variety of diseases by modulation of gene expression. We evaluated the effect of HIV-induced VDR methylation on loss of TCs. HIV/TC displayed enhanced VDR-CpG methylation and increased expression of Dnmt3b but attenuated expression of VDR. A demethylating agent, AZA, inhibited this effect of HIV. HIV/TC also displayed the activation of the RAS, which was reversed by EB (a VDA). Further, HIV/TCs displayed enhanced generation of ROS and induction of DSBs but attenuated DNA repair response. However, in the presence of AZA, EB, LOS (a RAS blocker), Cat, and tempol (free radical scavengers), HIV-induced TC ROS generation and induction of DSBs were attenuated but associated with enhanced DNA repair. Additionally, AZA, EB, and LOS provided protection against HIV-induced TC apoptosis. These findings suggested that HIV-induced TC apoptosis was mediated through ROS generation in response to HIV-induced VDR methylation and associated activation of the RAS.

Giant fibrous hamartoma of infancy: a report of two cases and review of the literature.

We present two unique cases of fibrous hamartoma of infancy defined by giant-sized and/or multicentric cutaneous and subcuticular lesions--features not, to our knowledge, reported to coexist. We review the nature of such tumors and examine the clinical implications of tumor size and multicentricity on risk for recurrence and likelihood of visceral involvement.

Noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), treatment eliminates estrogenic effects on song responsiveness in female zebra finches (Taeniopygia guttata).

Female songbirds use male songs as an important criterion for mate selection. Several studies have reported that female songbirds prefer complex songs to other song types. In a recent study, the authors found that song responsiveness in female zebra finches (Taeniopygia guttata) is strongly modulated by circulating estrogen levels. The behavioral effects of estrogen are often mediated via norepinephrine (NE). The current study administered the noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) to estradiol-treated female zebra finches to investigate if estrogenic effects on song responsiveness are mediated via NE. The authors tested song responsiveness of adult female zebra finches for three acoustically different song types--simple, long-bout, and complex--under three treatment conditions, untreated, estradiol-treated, and estradiol + DSP-4-treated. Females only showed differential song responsiveness when treated with estradiol alone, responding more to complex songs. DSP-4 treatment eliminated this differential responsiveness. The results are discussed in the light of evidence from functional, neurochemical, and neuroanatomical studies that suggest that estrogenic effects on song processing might be mediated by NE.

Multiple primary acral melanomas in African-Americans: a case series and review of the literature.

BACKGROUND: Although melanoma accounts for only 4% to 5% of all skin cancers in the United States, it causes most skin cancer-related deaths. We describe a unique group of African-American patients with multiple primary acral lentiginous melanomas (ALMs). OBJECTIVE: The purpose of this study was to review the case histories and management of a cohort of patients in the Mohs practice of our dermatologic surgeon with multiple primary ALM. METHODS: This is a case series of patients with multiple ALM identified by chart review from 2000 to 2005. A thorough review of the literature was performed. RESULTS: Four patients, all African-American, were identified with multiple ALM. All patients were managed with excision or Mohs micrographic surgery utilizing permanent sections. None of the patients with ALM had melanomas at nonacral sites or other types of skin cancer. Several had acral melanosis. Information in the literature on patients with multiple primary acral melanomas was insufficient. CONCLUSION: Patients with multiple acral melanomas have not, to our knowledge, been reported thus far. It can be extrapolated from current literature, however, that appropriate management of these patients, including staging work and surgical intervention, is to be determined by the individual characteristics of the melanoma and the patient's concomitant risk factors, if any.

Proliferative nodules with balloon-cell change in a large congenital melanocytic nevus.

The balloon-cell nevus was first described over 100 years ago. Since then, balloon-cell changes of melanocytes have been noted in numerous tumors, including melanoma, blue nevus, and Spitz nevus. Whether these changes reflect cellular deterioration or proliferative changes is a matter of debate. We report a case in which balloon-cell changes were found within proliferative nodules occurring in a large congenital melanocytic nevus.

Cryptococcal fungemia in a neutropenic patient with AIDS while receiving caspofungin.

Empiric choice of anti-fungal therapy in febrile neutropenia should be based upon a host's susceptibility to specific fungal pathogens. We present a case of a patient with multiple risk factors for fungemia including HIV infection, Hodgkin's disease, corticosteroid use and chemotherapy-induced neutropenia who developed disseminated cryptococcal infection while receiving caspofungin.

Effective gene therapy for an inherited CNS disease in a large animal model.

Genetic diseases affecting the brain typically have widespread lesions that require global correction. Lysosomal storage diseases are good candidates for central nervous system gene therapy, because active enzyme from genetically corrected cells can be secreted and taken up by surrounding diseased cells, and only small amounts of enzyme (<5% of normal) are required to reverse storage lesions. Injection of gene transfer vectors into multiple sites in the mouse brain has been shown to mediate widespread reversal of storage lesions in several disease models. To study a brain closer in size to the human brain, we evaluated the extent of storage correction mediated by a limited number of adeno-associated virus vector injections in the cat model of human alpha-mannosidosis. The treated cats showed remarkable improvements in clinical neurological signs and in brain myelination assessed by quantitative magnetic resonance imaging. Postmortem examination showed that storage lesions were greatly reduced throughout the brain, even though gene transfer was limited to the areas surrounding the injection tracks. The data demonstrate that widespread improvement of neuropathology in a large mammalian brain can be achieved using multiple injection sites during one operation and suggest that this could be an effective treatment for the central nervous system component of human lysosomal enzyme deficiencies.

Treatment of pyoderma gangrenosum with etanercept.

UNLABELLED: We describe a patient with pyoderma gangrenosum (PG) whose lesions responded to etanercept therapy. This disease has been recognized for diverse underlying pathology and associated immune disturbances. Although the role of cytokines in pathogenesis is not fully understood, tumor necrosis factor alpha (TNF-alpha) may facilitate induction and maintenance of the disease. This is supported by the successful use of infliximab, a recombinant anti-TNF-alpha monoclonal antibody, in cases of PG associated with inflammatory bowel disease (IBD). Etanercept is a divalent recombinant fusion protein that binds soluble TNF-alpha. To our knowledge, the utility of etanercept for PG has not been reported. A patient with recalcitrant and widespread PG that was unresponsive to systemic corticosteroids was treated with etanercept. Rapid and complete clearing of the skin lesions was observed, and steroid taper to 5 mg/day was sustained for two months. Treatment was well-tolerated with no adverse reactions reported. CONCLUSIONS: Etanercept therapy offered rapid and complete resolution of all PG lesions. Such response supports the use of etanercept as a steroid-sparing agent in recalcitrant disease and suggests the role of TNF-alpha in pathogenesis of PG.

Risk behavior for transmission of human immunodeficiency virus (HIV) among HIV-seropositive individuals in an urban setting.

We conducted interviews with 256 human immunodeficiency virus (HIV)-infected patients who attended an HIV clinic in New York City to assess ongoing risk behaviors for HIV transmission. After learning that the result of an HIV test was positive, 106 subjects (41%) had unprotected sex, 63 (25%) had a new sexually transmitted disease diagnosis, and 38 (15%) used injection drugs. Unprotected sex was reported by 50% of women, 29% of heterosexual men (P=.006, compared with women), and 42% of men who have sex with men, and it was reported more often by persons with a history of trading sex for money or drugs (P<.001). In multivariate analysis, unprotected sex was associated with a history of trading sex for money or drugs (adjusted odds ratio [AOR], 4.0; 95% confidence interval [CI], 2.2-7.0) and use of highly active antiretroviral therapy (AOR, 1.8; 95% CI, 1.1-3.1). Ongoing risk-reduction counseling and substance abuse treatment for HIV-infected persons are needed to reduce behaviors associated with HIV transmission.

Prevalence and characteristics of hepatitis C virus coinfection in a human immunodeficiency virus clinical trials group: the Terry Beirn Community Programs for Clinical Research on AIDS.

The baseline prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection among 2705 patients enrolled in HIV clinical trials in the Community Programs for Clinical Research on AIDS (CPCRA) was 16.6%. For men, multivariate logistic regression showed that the baseline prevalence of HIV-HCV coinfection was positively associated with history of injection drug use, older age, antiretroviral therapy naive status, African American or Latino ethnicity, and no history of having sex with men. No association was found with baseline CD4+ cell count or HIV RNA level. The prevalence of HCV coinfection in a diverse HIV clinical trials cohort provides additional information about risk behaviors and demographic factors that can be used in the analysis of clinical and virologic outcomes.