Older HIV-infected adults. Complex patients (III): Polypharmacy.

Polypharmacy is a well-described problem in the geriatric population. It is a relatively new problem for people living with HIV (PLWH), as this group now has a life expectancy approaching that of the general population. Defining polypharmacy for PLWH is difficult, since the most common traditional definition of at least five medications would encompass a large percentage of PLWH who are on antiretrovirals (ARVs) and medications for other medical comorbidities. Even when excluding ARVs, the prevalence of polypharmacy in PLWH is higher than the general population, and not just in resource-rich countries. Using a more nuanced approach with "appropriate" or "safer" polypharmacy allows for a better framework for discussing how to mitigate the associated risks. Some of the consequences of polypharmacy include adverse effects of medications including the risk of geriatric syndromes, drug-drug interactions, decreased adherence, and over- and undertreatment of medical comorbidities. Interventions to combat polypharmacy include decreasing pill burden-specifically with fixed-dose combination (FDC) tablets- and medication reconciliation/deprescription using established criteria. The goal of these interventions is to decrease drug interactions and improve quality of life and outcomes. Some special populations of interest within the community of PLWH include those with chronic pain, substance abuse, or requiring end of life care. A final look into the future of antiretroviral therapy (ART) shows the promise of possible two-drug regimens, which can help reduce the above risks of polypharmacy.

A Case of Lyme Carditis Presenting with Atrial Fibrillation.

We report a case of a 20-year-old man who presented to our institution with a new arrhythmia on a routine EKG. Serial EKG tracings revealed various abnormal rhythms such as episodes of atrial fibrillation, profound first degree AV block, and type I second degree AV block. He was found to have positive serologies for Borrelia burgdorferi. After initiation of antibiotic therapy, the atrial arrhythmias and AV block resolved. Here, we present a case of Lyme carditis presenting with atrial fibrillation, a highly unusual presentation of Lyme carditis.

Local Control and Toxicity of External Beam Reirradiation With a Pulsed Low-dose-rate Technique.

PURPOSE: To evaluate the efficacy and toxicity of external beam reirradiation using a pulsed low-dose-rate (PLDR) technique. METHODS AND MATERIALS: We evaluated patients treated with PLDR reirradiation from 2009 to 2016 at a single institution. Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0, and local control was assessed using the Response Evaluation Criteria In Solid Tumors, version 1.1. On univariate analysis (UVA), the χ2 and Fisher exact tests were used to assess the toxicity outcomes. Competing risk analysis using cumulative incidence function estimates were used to assess local progression. RESULTS: A total of 39 patients were treated to 41 disease sites with PLDR reirradiation. These patients had a median follow-up time of 8.8 months (range 0.5-64.7). The targets were the thorax, abdomen, and pelvis, including 36 symptomatic sites. The median interval from the first radiation course and reirradiation was 26.2 months; the median dose of the first and second course of radiation was 50.4 Gy and 50 Gy, respectively. Five patients (13%) received concurrent systemic therapy. Of the 39 patients, 9 (23%) developed grade ≥2 acute toxicity, most commonly radiation dermatitis (5 of 9). None developed grade ≥4 acute or subacute toxicity. The only grade ≥2 late toxicity was late skin toxicity in 1 patient. On UVA, toxicity was not significantly associated with the dose of the first course of radiation or reirradiation, the interval to reirradiation, or the reirradiation site. Of the 41 disease sites treated with PLDR reirradiation, 32 had pre- and post-PLDR scans to evaluate for local control. The local progression rate was 16.5% at 6 months and 23.8% at 12 months and was not associated with the dose of reirradiation, the reirradiation site, or concurrent systemic therapy on UVA. Of the 36 symptomatic disease sites, 25 sites (69%) achieved a symptomatic response after PLDR, including 6 (17%) with complete symptomatic relief. CONCLUSION: Reirradiation with PLDR is effective and well-tolerated. The risk of late toxicity and the durability of local control were limited by the relatively short follow-up duration in the present cohort.

Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy.

Because molecular mechanisms underlying refractory focal epilepsy are poorly defined, we performed transcriptome analysis on human epileptogenic tissue. Compared with controls, expression of Circadian Locomotor Output Cycles Kaput (CLOCK) is decreased in epileptogenic tissue. To define the function of CLOCK, we generated and tested the Emx-Cre; Clockflox/flox and PV-Cre; Clockflox/flox mouse lines with targeted deletions of the Clock gene in excitatory and parvalbumin (PV)-expressing inhibitory neurons, respectively. The Emx-Cre; Clockflox/flox mouse line alone has decreased seizure thresholds, but no laminar or dendritic defects in the cortex. However, excitatory neurons from the Emx-Cre; Clockflox/flox mouse have spontaneous epileptiform discharges. Both neurons from Emx-Cre; Clockflox/flox mouse and human epileptogenic tissue exhibit decreased spontaneous inhibitory postsynaptic currents. Finally, video-EEG of Emx-Cre; Clockflox/flox mice reveals epileptiform discharges during sleep and also seizures arising from sleep. Altogether, these data show that disruption of CLOCK alters cortical circuits and may lead to generation of focal epilepsy.

Acellular Dermal Matrix Versus Inferior Deepithelialized Flap Breast Reconstruction: Equivalent Outcomes, with Increased Cost.

BACKGROUND: Approximately 250,000 new cases of breast cancer are diagnosed yearly in the U.S. resulting in more postmastectomy breast reconstructions (PMBRs). The acellular dermal matrix (ADM) expander-implant method became popular in the mid-2000s, but newer techniques such as the inferior deepithelialized flap (IDF) has more recently been described. We hypothesize that ADMs and IDFs provide comparable aesthetic outcomes, with no difference in complication rates and operative characteristics. METHODS: A retrospective, single-institution study was performed between July 1, 2012, and June 30, 2014, examining all PMBR's (ADM and IDF). Outcomes were categorized as clinical (e.g., complications requiring surgical intervention) or aesthetic. RESULTS: A total of 65 patients (41 ADM; 24 IDF; mean age, 53.4 ± 10.7 years) were included, with 101 PMBR's evaluated (63 ADM and 38 IDF). Patients who underwent IDFs had higher body mass index (32 versus 25; P < 0.01) and higher grades of breast ptosis. Major complication rates were similar between ADM and IDF groups (22% versus 31.5%; P = 0.34). There were no differences in aesthetic outcomes between groups (rater intraclass correlation, 0.92). The average IDF breast reconstruction took nearly 30 minutes longer per reconstructed side (192 minutes versus 166 minutes; P = 0.02), but operative costs were more expensive for the ADM breast reconstruction. CONCLUSIONS: The IDF procedure took 30 minutes longer for each reconstructed side, without significant differences in complications or aesthetic outcomes between the 2 PMBRs. IDF reconstructions may be more suitable for patients with grade 3 breast ptosis and higher body mass index. Further studies should focus on long-term outcomes and value-based approaches to PMBR.

Characteristics of lymph node metastasis in resected adenosquamous lung cancer.

The aim of this study was to retrospectively analyze the clinical data of resected adenosquamous lung cancer (ASLC) and to explore the influencing factors and clinicopathological characteristics of the metastasis lymph nodes. A total of 1156 consecutive patients with surgically resected lung cancer from January 2009 to June 2014 were studied. Fifty-four previously diagnosed ASLC patients were re-evaluated by experienced pathologists. IHC and H&E staining were employed to examine the primary focus and metastasis lymph nodes. The relationship between lymph node metastasis and clinicopathological characteristics of ASLC patients was then analyzed and the pathological type of metastasis lymph node was also determined. Forty-nine cases of typical ASLC were included in the study. Of the 49 ASLC patients, 26 cases presented lymph node metastasis. Lymph node metastasis was not associated with gender, smoking, tumor distribution, histological type of primary focus, and preoperative CEA level, but was associated with age ≥ 65 (P < .05) and tumor size ≥ 3 cm (P < .05). Lymph node metastasis adenocarcinoma was the main type in ASLC patients, and was related to the age and tumor size of the primary focus. Further large sample studies are necessary to identify influencing factors and clinicopathological characteristics of metastasis lymph nodes.