HIV testing at visits to US emergency departments: 2021 update.

In this updated cross-sectional analysis of the National Hospital Ambulatory Medical Care Survey, we found that among the 2.5 million more weighted emergency department (ED) visits in 2021 compared with 2020, there was an insignificant increase in HIV testing per ED visit in 2021 compared with 2020 (0.81% to 0.86%). This suggests HIV testing during ED visits did not increase in line with rebounding visit volumes after the pandemic nadir.

A radiotherapy community data-driven approach to determine which complexity metrics best predict the impact of atypical TPS beam modeling on clinical dose calculation accuracy.

PURPOSE: To quantify the impact of treatment planning system beam model parameters, based on the actual spread in radiotherapy community data, on clinical treatment plans and determine which complexity metrics best describe the impact beam modeling errors have on dose accuracy. METHODS: Ten beam modeling parameters for a Varian accelerator were modified in RayStation to match radiotherapy community data at the 2.5, 25, 50, 75, and 97.5 percentile levels. These modifications were evaluated on 25 patient cases, including prostate, non-small cell lung, H&N, brain, and mesothelioma, generating 1,000 plan perturbations. Differences in the mean planned dose to clinical target volumes (CTV) and organs at risk (OAR) were evaluated with respect to the planned dose using the reference (50th-percentile) parameter values. Correlation between CTV dose differences, and 18 different complexity metrics were evaluated using linear regression; R-squared values were used to determine the best metric. RESULTS: Perturbations to MLC offset and transmission parameters demonstrated the greatest changes in dose: up to 5.7% in CTVs and 16.7% for OARs. More complex clinical plans showed greater dose perturbation with atypical beam model parameters. The mean MLC Gap and Tongue & Groove index (TGi) complexity metrics best described the impact of TPS beam modeling variations on clinical dose delivery across all anatomical sites; similar, though not identical, trends between complexity and dose perturbation were observed among all sites. CONCLUSION: Extreme values for MLC offset and MLC transmission beam modeling parameters were found to most substantially impact the dose distribution of clinical plans and careful attention should be given to these beam modeling parameters. The mean MLC Gap and TGi complexity metrics were best suited to identifying clinical plans most sensitive to beam modeling errors; this could help provide focus for clinical QA in identifying unacceptable plans.

Benefits and Risks of Medications Used in the Management of Hypotension: A Review.

This comprehensive literature review addresses the scarcity and limited study of hypotension treatments compared to abundant antihypertensive drugs. Hypotension, categorized as absolute, relative, or orthostatic, has diverse causes. This review explores various treatments, including drugs affecting the sympathetic nervous system, such as midodrine, dihydroergotamine, and ergotamine, which have shown efficacy in managing hypotension. Dopamine agonists/antagonists and other drugs such as ephedrine, norepinephrine, and fludrocortisone are also discussed, each with distinct mechanisms and applications. Additionally, adjunctive agents such as non-steroidal anti-inflammatory agents, caffeine, and monoamine oxidase inhibitors are reviewed for their effects on blood pressure. This review underscores the importance of understanding the efficacy and safety profiles of hypotension treatments to guide healthcare professionals in optimal drug selection and management, emphasizing the need for further research and comparative studies for evidence-based guidelines.

A rare case of bilateral testicular torsion in a 57-year-old man.

CONTEXT: Testicular torsion, the twisting of the testis or spermatic cord, places the testis at risk of vascular compromise and is a surgical emergency. Testicular torsion is predominantly unilateral (98% of torsion cases) and primarily affects neonates and adolescents in a bimodal distribution. Bilateral testicular torsion is exceedingly rare (2% of cases) and is associated with neonates. To the authors' best knowledge, there have been no reports of bilateral torsion in adult males over the age of 24. CASE DETAILS: A 57-year-old man presented to the emergency department 9 days after developing testicular pain while lifting his lawnmower. Ultrasonography performed at an outside facility was unremarkable. He was encouraged to followup with urology as an outpatient. Despite outpatient analgesia, he continued to experience pain and returned to the ED, where repeat ultrasonography demonstrated bilateral torsion with hypoperfusion. DISCUSSION: Although testicular torsion is uncommon, the clinician must recognize torsion; if left untreated, torsion leads to infertility. Previous publications suggest that ultrasonographic findings of bilateral testicular torsion should be attributed to "technical failure" rather than a plausible diagnosis. However, this case demonstrates the importance of maintaining a high index of suspicion, especially with an atypical age range and pathological presentation, particularly among men during their reproductive years.

Survival Outcomes of Adjuvant Chemotherapy Combined With Radiation Versus Chemotherapy Alone After Pancreatectomy for Distal Pancreatic Adenocarcinoma: A Single-Institution Experience.

OBJECTIVE: We evaluated survival outcomes in patients with distal pancreatic ductal adenocarcinoma (D-PDAC) after distal pancreatectomy (DP) and adjuvant chemotherapy or chemoradiation. METHODS: A retrospective analysis of patients who underwent DP for D-PDAC from 2000 to 2015 at the Johns Hopkins Hospital was performed. Demographics, baseline risk factors, and type of adjuvant treatment were assessed for associations with overall survival (OS) and disease-free survival (DFS). Comparisons were made with log-rank tests and Cox proportional hazards regression models. RESULTS: A total of 294 patients underwent DP for D-PDAC. Of these, 105 patients were followed at the Johns Hopkins Hospital. Forty-five patients received chemotherapy only and 60 patients received chemoradiation. The median OS with chemoradiation was 33.6 months and 27.9 months (P = 0.54) with chemotherapy only. The median DFS was 15.3 months with chemoradiation and 19.8 months with chemotherapy only (P = 0.89). Elevated carbohydrate antigen 19-9, stage II to III disease, splenic vein involvement, and vascular invasion were significant risk factors in multivariate analyses. CONCLUSIONS: In this retrospective analysis, there were no significant differences in OS or DFS with chemoradiation compared with chemotherapy alone after DP in patients with D-PDAC.

Gastric cancer following pancreaticoduodenectomy: Experience from a high-volume center and review of existing literature.

BACKGROUND: Prolonged survival of patients after pancreaticoduodenectomy can be associated with late complications due to altered gastrointestinal anatomy. The incidence of gastric cancer is increasingly reported. We set out to examine our experience with gastric cancer as a late complication after pancreaticoduodenectomy with a focus on incidence, risk factors, and outcomes. METHODS: We queried our prospectively collected institutional database for patients that developed gastric cancer after pancreaticoduodenectomy and conducted a systematic review of the literature. RESULTS: Our database revealed 6 patients who developed gastric cancer following pancreaticoduodenectomy, presenting with a mean age of 62.2 years and an even sex distribution. All of those patients underwent pancreaticoduodenectomy for malignant indications with an average time to development of metachronous gastric cancer of 8.3 years. Four patients complained of gastrointestinal discomfort prior to diagnosis of secondary malignancy. All of these cancers were poorly differentiated and were discovered at an advanced T stage (≥ 3). Only half developed at the gastrointestinal anastomosis. Four underwent surgery with a curative intent, and 2 patients are currently alive (mean postgastrectomy survival = 25.5 months). In accordance with previous literature, biliopancreatic reflux from pancreaticoduodenectomy reconstruction, underlying genetic susceptibility, and adjuvant therapy may play a causative role in later development of gastric cancer. CONCLUSION: Long-term survivors after pancreaticoduodenectomy who develop nonspecific gastrointestinal complaints should be evaluated carefully for complications including gastric malignancy. This may serve as an opportunity to intervene on tumors that typically present at an advanced stage and with aggressive histology.

Microwave ablation of the liver in a live porcine model: the impact of power, time and total energy on ablation zone size and shape.

Objective: To explore various microwave (MW) time/power combinations to achieve maximum single-probe system performance in a live pig liver model.Methods: Fifty-one microwave ablations performed in 12 female pigs using the following time/power combinations: 65 W for 10 min (65W 10MIN), ramped from 20 to 65 W (RAMPED), 95 W pulses with cooling periods (95W PULSED), 40 W for 16 min 15 s (LOW POWER), 1 min 95 W pulse then 8 min 65 W then a second 1 min 95 W pulse (BOOKEND 95W) and 65 W for 15 min (65W 15MIN). Temperatures 1.5 cm from the antenna were measured. Livers were excised, and ablations were measured and compared.Results: At fixed overall energy, LOW POWER produced ablation zones with the smallest volume compared to 65W 10MIN, RAMPED and 95W PULSED. At a fixed time of 10-min, BOOKEND 95W protocol achieved wider and larger ablation zones than 65W 10MIN (p = 0.038, p = 0.008) and 95W PULSED (p = 0.049, p = 0.004). The 65W 15MIN combination had significantly larger diameters (p = 0.026), larger lengths (p = 0.014) and larger volumes (p = 0.005) versus 65W 10MIN. Maximum temperatures were highest with BOOKEND 95W (62.9 °C) and 65 W 15 MIN (63.0 °C) and lowest with LOW POWER (45.9 °C), p = 0.009.Conclusions: Low power ablations, even if controlled for total energy delivery, create small ablation zones. High peak powers are associated with larger ablation zones and high margin temperatures if cooling pauses are avoided. Ramping and pulsing protocols with interleaved cooling appear to be of no benefit versus continuous 65 W for creating large ablation zones.

Evaluation of usefulness of smart device-based testing: a survey study of Korean medical students / 한국의학교육

Purpose@#This study aims to understand the characteristics of smart device-based testing (SBT) by comparing the typical characteristics of students’ satisfaction with SBT, its usefulness, advantages, and disadvantages when compared with existing testing methods. @*Methods@#A total of 250 students from the first to third year were selected as the final targets of the study and the questionnaire was developed by faculty members who participated in the survey from the start of the SBT. The total number of questions is 12, and the questionnaire used a 4-point scale. The data obtained were analyzed using the IBM SPSS ver. 23.0 (IBM Corp., Armonk, USA). @*Results@#Answers to the “satisfaction with SBT” were generally negative, while answers to the “usefulness of SBT” were generally positive. There was no difference in satisfaction across gender and smart device ownership, whereas there were significant differences across years. With reference to the usefulness of SBT, students responded positively, while about the overall configuration and completeness of SBT, students responded negatively. Students also seemed to show a greater preference toward the pencil-paper test. @*Conclusion@#On the other hand, students generally thought that SBT helped to assess medical knowledge better and was a more objective method of knowledge assessment than a pencil-paper test. We believe that students preferred the traditional paper-pencil test due to their unfamiliarity with SBT. We believe that an appropriate and careful remedy for drawbacks of the SBT will have a significant impact in the accumulation of actual clinical knowledge and in the improvement of practical skills for medical students.

Zoonosis: Update on Existing and Emerging Vector-Borne Illnesses in the USA.

PURPOSE OF REVIEW: This review describes mosquito- and tick-borne diseases found in the Western Hemisphere. It focuses on emerging diseases and recent geographic shifts in the presence of disease vectors. RECENT FINDINGS: Mosquito and tick vectors have become more widespread as environmental conditions have become more favorable. Zika recently has emerged as a concern for fetal anomalies. West Nile Virus has become widespread. Lyme disease and other tick-borne diseases are more prevalent in areas previously inhospitable to these ticks. SUMMARY: Healthcare providers must consider the possibility of mosquito- and tick-borne diseases in broader geographic areas and council patients traveling to endemic areas on precautions against these diseases. Treatment for suspected cases of serious tick-borne illnesses should not be delayed pending culture results.

Higher Tumor Burden Neutralizes Negative Margin Status in Hepatectomy for Colorectal Cancer Liver Metastasis.

OBJECTIVE: The aim of this study was to examine if the prognostic significance of margin status in hepatectomy for colorectal cancer liver metastasis (CRLM) varies for different levels of tumor burden because hepatectomy indications for CRLM have been recently expanded to include patients with a higher tumor burden in whom achieving an R0 resection is difficult. METHODS: Clinicopathological variables in an exploration cohort of 290 patients receiving hepatectomy in Japan for CRLM were investigated. R0 resection was defined as a margin width > 0 mm. Tumor burden was assessed using the recently introduced Tumor Burden Score (TBS), which was calculated as TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2. The principal findings were validated using a cohort from the United States. RESULTS: R1 resection rates significantly increased as TBS increased: 4/86 (4.7%) in patients with TBS < 3, 29/171 (17.0%) in patients with TBS ≥ 3 and < 9, and 9/33 (27.3%) in patients with TBS ≥ 9 (p < 0.001). R0 resection was significantly superior to R1 resection in patients with TBS ≥ 5; however, this was not the case for TBS ≥ 6, as confirmed by both univariate and multivariate analyses. Furthermore, prehepatectomy chemotherapy was associated with significantly improved survival for patients with TBS ≥ 8. Analysis of the validation cohort yielded similar results. CONCLUSIONS: R0 resection appeared to have a positive impact on prognosis among patients with low tumor burden; however, this was not the case for patients with high tumor burden. As such, systemic treatment, in addition to surgery, may be central to achieving satisfactory outcomes in the latter patient population.

CDK activity provides temporal and quantitative cues for organizing genome duplication.

In eukaryotes, the spatial and temporal organization of genome duplication gives rise to distinctive profiles of replication origin usage along the chromosomes. While it has become increasingly clear that these programs are important for cellular physiology, the mechanisms by which they are determined and modulated remain elusive. Replication initiation requires the function of cyclin-dependent kinases (CDKs), which associate with various cyclin partners to drive cell proliferation. Surprisingly, although we possess detailed knowledge of the CDK regulators and targets that are crucial for origin activation, little is known about whether CDKs play a critical role in establishing the genome-wide pattern of origin selection. We have addressed this question in the fission yeast, taking advantage of a simplified cell cycle network in which cell proliferation is driven by a single cyclin-CDK module. This system allows us to precisely control CDK activity in vivo using chemical genetics. First, in contrast to previous reports, our results clearly show that distinct cyclin-CDK pairs are not essential for regulating specific subsets of origins and for establishing a normal replication program. Importantly, we then demonstrate that the timing at which CDK activity reaches the S phase threshold is critical for the organization of replication in distinct efficiency domains, while the level of CDK activity at the onset of S phase is a dose-dependent modulator of overall origin efficiencies. Our study therefore implicates these different aspects of CDK regulation as versatile mechanisms for shaping the architecture of DNA replication across the genome.

Attitudes and barriers to the use of donation after cardiac death livers: Comparison of a United States transplant center survey to the united network for organ sharing data.

Transplantation of liver grafts from donation after cardiac death (DCD) is limited. To identify barriers of DCD liver utilization, all active US liver transplant centers (n = 138) were surveyed, and the responses were compared with the United Network for Organ Sharing (UNOS) data. In total, 74 (54%) centers responded, and diversity in attitudes was observed, with many not using organ and/or recipient prognostic variables defined in prior studies and UNOS data analysis. Most centers (74%) believed lack of a system allowing a timely retransplant is a barrier to utilization. UNOS data demonstrated worse 1- and 5-year patient survival (PS) and graft survival (GS) in DCD (PS, 86% and 64%; GS, 82% and 59%, respectively) versus donation after brain death (DBD) recipients (PS, 90% and 71%; GS, 88% and 69%, respectively). Donor alanine aminotransferase (ALT), recipient Model for End-Stage Liver Disease (MELD), and cold ischemia time (CIT) significantly impacted DCD outcomes to a greater extent than DBD outcomes. At 3 years, relisting and retransplant rates were 7.9% and 4.6% higher in DCD recipients. To optimize outcome, our data support the use of DCD liver grafts with CIT <6-8 hours in patients with MELD ≤ 20. In conclusion, standardization of donor and recipient criteria, defining the impact of ischemic cholangiopathy, addressing donor hospital policies, and developing a strategy for timely retransplant may help to expand the use of these organs. Liver Transplantation 23 1372-1383 2017 AASLD.

Personalized Nanoparticles for Cancer Therapy: A Call for Greater Precision.

Nanotechnology has brought about the advent of personalized medicine in the era of targeted therapeutic strategies for cancer therapy. The ability to exploit tumor features for therapeutic gain has made it possible to manufacture more effective nanomedicines for cancer treatment. However, known obstacles, including the inability to overcome pathophysiological barriers of tumors, have impeded disease management. In spite of this, recent efforts have been made to develop more functionalized nanosystems that utilize the active-targeting approach. This article reviews the FDA-approved cancer drug delivery systems in the general framework of personalized nanomedicine. We discuss the latest efforts in the development of functionalized nano-systems, and summarize relevant ongoing preclinical and clinical trials.

Fingolimod (Gilenya) and melanoma.

The Food and Drug Administration (FDA) had approved fingolimod usage for multiple sclerosis in 2010. Melanoma after the usage of fingolimod immunomodulation was reported rarely in clinical trials, and only two case reports exist in the published literature, both occurring in Europe. Most of the incidences reported in clinical trials were in-situ, whereas both case reports were of malignant melanoma. Fingolimod has been found to inhibit metastatic melanoma growth in a mouse model that depends on vascular endothelial growth factor (VEGF)-induced angiogenesis for metastasis. However, there are numerous pathways of angiogenesis and tumour growth found in vivo by which melanoma can expand that do not mandate VEGF. We report a case of superficial spreading malignant melanoma occurring after fingolimod therapy in the USA.

The high-affinity human IgG receptor Fc gamma receptor I (FcγRI) is not associated with vascular leakage of dengue.

BACKGROUND: Dengue is a major public health problem in many tropical and sub-tropical countries. Vascular leakage and shock are identified as the major causes of deaths in patients with severe dengue. Studies have suggested the potential role of Fc gamma receptors I (FcγRI) in the pathogenesis of dengue. We hypothesized that the circulating level of Fcγ receptor I could potentially be used as an indicator in assisting early diagnosis of severe dengue. RESULTS: A selected cohort of 66 dengue patients including 42 dengue with signs of vascular leakage, and 24 dengue without signs of vascular leakage were identified and were afterwards referred to as 'cases' and 'controls' respectively. Thirty seven normal healthy controls were also recruited in this study. The circulating level of FcγRI was quantified from the serum using enzyme-link immunosorbent assay (ELISA). The levels of FcγRI in both groups of patients with and without vascular leakage were found to be significantly higher than the normal healthy controls (P < 0.001). However, there was no significant difference found between patients with vascular leakage and those without vascular leakage (p = 0.777). CONCLUSION: We suggest that FcγRI is not associated with the vascular leakage in dengue. However, further studies are necessary to delineate the role of FcγRI in antibody-dependent enhancement (ADE) mechanism.

A novel approach to sterile pharmaceutical freeze-drying.

A novel approach has been developed that enables sterile pharmaceutical products to be freeze-dried in the open laboratory without specialist facilities. The product is filled into vials, semi-stoppered and sealed inside one, followed by a second, sterilization pouch under class 100 conditions. The product is then freeze-dried in the laboratory where the vials are shelf-stoppered before being returned to class 100, unwrapped and crimped. The sterilization pouches increased the resistance to water vapor movement during sublimation, thereby increasing the sublimation time and product temperature. Ovine immunoglobulins were double wrapped and lyophilized (as above) adjusting the primary drying time and shelf temperature for increased product temperature and, therefore, prevention of collapse. Ovine immunoglobulin G formulations freeze-dried to ≤ 1.1% residual moisture with no effect on protein aggregation or biological activity. The process was simulated with tryptone soya broth and no growth of contaminating microbial cells was observed after incubation at 35 °C for 2 weeks. Although increasing lyophilization time, this approach offers significant plant and validation cost savings when sterile freeze-drying small numbers of vials thereby making the manufacture of treatments for neglected and orphan diseases more viable economically.

Local functional overconnectivity in posterior brain regions is associated with symptom severity in autism spectrum disorders.

Although growing evidence indicates atypical long-distance connectivity in autism spectrum disorder (ASD), much less is known about local connectivity, despite conjectures that local overconnectivity may be causally involved in the disorder. Using functional connectivity MRI and graph theory, we found that local functional connectivity was atypically increased in adolescents with ASD in temporo-occipital regions bilaterally. Posterior overconnectivity was found to be associated with higher ASD symptom severity, whereas an ASD subsample with low severity showed frontal underconnectivity. The findings suggest links between symptomatology and local connectivity, which vary within the autism spectrum.

Metabolic abnormalities in adult HIV infected population on antiretroviral medication in Malaysia: a cross-sectional survey.

BACKGROUND: In the current two decades, dyslipidemia and increased blood glucose as metabolic abnormalities are the most common health threats with a high incidence among HIV/AIDS patients on antiretroviral (ARV) treatment. Scientific investigations and reports on lipid and glucose disorders among HIV infected communities are inadequate especially in those developing such as Malaysia. This cross-sectional survey was mainly aimed to evaluate the prevalence of metabolic abnormalities and associated risk factors among HIV infected population patients on ARV medication. METHODS: In a single reference health center in Malaysia, 2739 adult HIV positive patients on antiretroviral therapy (ART) were studied cross-sectionally using medical records. Besides demographic variables and associated health disorders, those factors which can change the lipid and glucose levels were collected. Logistic Regression was used to find the potential risk factors (p < 0.05). RESULTS: Majority of the studied population were male (81.1%) and aged between 30-49 (68.6%). Mean CD4 count was 474.25 (cells/mm3) while undetectable RNA viral load was common among 83.3 (%) of subjects. Among 1,583 patients with the recent blood lipid and glucose tests, increased levels of triglyceride (TG) and total cholesterol (TC) were frequently prevalent in half of the population as 59 (%) and 54.2 (%) while 28.7 (%), 35.1 (%) and 38.2 (%) had declined level of high-density lipoprotein (HDL), raised low-density lipoprotein (LDL) and fasting plasma glucose (FPG) which were less common. Dyslipidemia was common in 82.3 (%) of the subjects. Notably, medication with protease inhibitor (PI) was a potential risk for elevated triglyceride (odds ratio (OR) = 2.309, 95% confidence interval (CI) = 1.605-3.324, P = 0.001), high TC (OR = 1.561, 95% CI = 1.123-2.169, P = 0.008) and low HDL (OR = 1.449, 95% CI = 1.037-2.024, P = 0.029). As lifestyle factor, alcohol consumption results as significant risk factor for raised TG (OR = 2.653, 95% CI = 1.353-5.202, P = 0.004). Also having hepatitis raised risk of high FPG level (OR = 1.630, 95% CI = 1.197-2.220, P = 0.002) in this sample population. CONCLUSIONS: Dyslipidemia is highly common in Malaysian HIV subjects receiving ARV medication. Lifestyle modification, changing PI and switch to other ARV regimen can help in reduction of these abnormalities. Also suitable strategies and plans are necessary to prevent cardiovascular diseases in future.