Age, Gender, and Liver Enzyme Impact Hospital Stay in COVID-19 Minority Patient with Cancer in the USA: Does Race Matters in the Pandemic?

Patients with cancer are known to have a poor prognosis when infected with SARS-CoV-2 infection. We aimed in this study to assess health outcomes in COVID-19 patients with different cancers in comparison to non-cancer COVID-19 patients from different centers in the United States (US). We evaluated medical records of 1,943 COVID-19 Cancer patients from 3 hospitals admitted between December 2019 to October 2021 and compared them with non-cancer COVID-19 patients. Among 1,943 hospitalized COVID-19 patients, 18.7% (n=364) have an active or previous history of cancer. Among these 364 cancer patients, 222 were African Americans (61.7%) and 121 were Caucasians (33.2%). Cancer patients had significantly longer hospitalization compared to controls (8.24 vs 6.7 days). Overall, Lung cancer is associated with high mortality. Patients with a previous history of cancer were more prone to death (p=0.04) than active cancer patients. In univariate and multivariate analyses, predictors of death among cancer patients were male sex, older age, presence of dyspnea, elevated troponin, elevated AST (0.001) and ALT (0.05), low albumin (p=0.04) and mechanical ventilation (p=0.001). Patients with a previous history of cancer were more prone to death when compared to active cancer COVID-19 patients. Early recognition of cancer COVID-19 patients' death-associated risk factors can help determine appropriate treatment and management plans for better prognosis and outcome.

Insect transformation with piggyBac: getting the number of injections just right.

The insertion of exogenous genetic cargo into insects using transposable elements is a powerful research tool with potential applications in meeting food security and public health challenges facing humanity. piggyBac is the transposable element most commonly utilized for insect germline transformation. The described efficiency of this process is variable in the published literature, and a comprehensive review of transformation efficiency in insects is lacking. This study compared and contrasted all available published data with a comprehensive data set provided by a biotechnology group specializing in insect transformation. Based on analysis of these data, with particular focus on the more complete observational data from the biotechnology group, we designed a decision tool to aid researchers' decision-making when using piggyBac to transform insects by microinjection. A combination of statistical techniques was used to define appropriate summary statistics of piggyBac transformation efficiency by species and insect order. Publication bias was assessed by comparing the data sets. The bias was assessed using strategies co-opted from the medical literature. The work culminated in building the Goldilocks decision tool, a Markov-Chain Monte-Carlo simulation operated via a graphical interface and providing guidance on best practice for those seeking to transform insects using piggyBac.

Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease.

Sandhoff disease (SD) is caused by deficiency of N-acetyl-ß-hexosaminidase (Hex) resulting in pathological accumulation of GM2 ganglioside in lysosomes of the central nervous system (CNS) and progressive neurodegeneration. Currently, there is no treatment for SD, which often results in death by the age of five years. Adeno-associated virus (AAV) gene therapy achieved global CNS Hex restoration and widespread normalization of storage in the SD mouse model. Using a similar treatment approach, we sought to translate the outcome in mice to the feline SD model as an important step toward human clinical trials. Sixteen weeks after four intracranial injections of AAVrh8 vectors, Hex activity was restored to above normal levels throughout the entire CNS and in cerebrospinal fluid, despite a humoral immune response to the vector. In accordance with significant normalization of a secondary lysosomal biomarker, ganglioside storage was substantially improved, but not completely cleared. At the study endpoint, 5-month-old AAV-treated SD cats had preserved neurological function and gait compared with untreated animals (humane endpoint, 4.4±0.6 months) demonstrating clinical benefit from AAV treatment. Translation of widespread biochemical disease correction from the mouse to the feline SD model provides optimism for treatment of the larger human CNS with minimal modification of approach.

Performance of endovenous foam sclerotherapy in the USA for the treatment of venous disorders: ACP/SVM/AVF/SIR quality improvement guidelines.

OBJECTIVE: This report summarizes the findings of the consensus panel based on the results of the comprehensive questionnaire of US American College of Phlebology annual congress attendees and results of the systematic meta-analysis of the literature and provides quality improvement guidelines for the use of endovenous foam sclerotherapy (EFS) for the treatment of venous disorders, as well as identifies areas of needed research. METHODS: Based on the above data, quality improvement guidelines were developed and reviewed by the ten US consensus panel members and approved by their respective societies. RESULTS: EFS is effective for the treatment of truncal and tributary varicose veins, both as primary treatment and for treatment of recurrence. It may improve the signs and symptoms associated with varicose veins including pain and swelling. EFS is contraindicated in patients who have experienced an allergic reaction to previous treatment with foam or liquid sclerosant, and in patients with acute venous thrombosis events secondary to EFS. CONCLUSION: These guidelines for the use of EFS in the treatment of venous disorders provide an initial framework for the safe and efficacious use of this therapy, and the impetus to promote the evaluation of the questions remaining regarding the use of EFS through well-designed randomized and cohort studies.

MCP-1 expression is specifically regulated during activation of skeletal repair and remodeling.

Monocyte chemotactic protein-1 (MCP-1) belongs to the CC chemokine superfamily and plays a critical role in the recruitment and activation of leukocytes during acute inflammation. We hypothesize that MCP-1 is also an important chemokine that regulates the recruitment and activation of bone cells required for skeletal repair and remodeling. We used the ulnar stress fracture (SFx) model, which allows investigation of focal remodeling with a known time course and precise anatomical location. SFx were created in the right ulna of female Wistar rats using cyclic end loading. Unloaded animals were used as a control. Rats were killed 4 h and 1, 4, 7, and 14 days after loading (n = 10/group); RNA was extracted and converted to cDNA for quantitative PCR analysis using TaqMan gene expression assays. Four hours after loading, MCP-1 gene expression was increased ~30-fold (P < 0.001), remained elevated at 24 h (~12-fold, P < 0.001), then declined by day 14. Relative to the contralateral limb, expression of the receptors CCR1 and CCR2 increased over the 14 days, being significant by 4 days for CCR1 and 14 days for CCR2 (P < 0.05). Other inflammation-related chemokines (RANTES, MIP1a) were not increased at these early time points. Using in situ hybridization and immunohistochemistry in separate animal groups (n = 5/group, control, days 1, 4, 7), MCP-1 mRNA and protein were localized in periosteal osteoblasts associated with woven bone formation at the fracture exit point but not in osteocytes adjacent to the SFx. These data support an important role for MCP-1 in the early phase of SFx repair and activated remodeling.

Treatment of chronic venous disease with flavonoids: recommendations for treatment and further studies.

OBJECTIVES: A variety of studies have suggested that flavonoids are effective for the treatment of CVD. However, many questions remain about their mechanism of action and when, how, and for what signs and symptoms they should be used. METHOD: A panel of experts in CVD met in Budapest, Hungary in December 2011 to discuss the current state of knowledge of CVD and the role of flavonoids in its treatment. The discussion was based on a literature search in the current databases. The goals of this paper are recommendations for further studies on the use of flavonoids in the treatment of CVD. RESULTS: There is good evidence to recommend the use of flavonoids in the treatment of CVD. However, because of the poor quality of some older clinical trials, inadequate reporting, and insufficient information, much work is still needed to firmly establish their clinical efficacy and to determine when and how they should be employed. In particular, long-term randomized, placebo-controlled, double-blind studies are needed to establish the efficacy and safety of flavonoids. Additional studies are also needed to establish their mechanism of action, pharmacokinetics, toxicity, and cost-effectiveness. CONCLUSIONS: Aside from good evidence for the use of flavonoids in CVD further studies are indicated to establish long term treatment in this indication.

Germline transformation of the diamondback moth, Plutella xylostella L., using the piggyBac transposable element.

The diamondback moth, Plutella xylostella, is one of the most economically important agricultural pests. The larvae of this moth cause damage by feeding on the foliage of cruciferous vegetables such as cabbage, broccoli, cauliflower and rapeseed. Control generally comprises chemical treatment; however, the diamondback moth is renowned for rapid development of resistance to pesticides. Other methods, such as biological control, have not been able to provide adequate protection. Germline transformation of pest insects has become available in recent years as an enabling technology for new genetics-based control methods, such as the Release of Insects carrying a Dominant Lethal (RIDL(®) ). In the present study, we report the first transformation of the diamondback moth, using the piggyBac transposable element, by embryo microinjection. In generating transgenic strains using four different constructs, the function of three regulatory sequences in this moth was demonstrated in driving expression of fluorescent proteins. The transformation rates achieved, 0.48-0.68%, are relatively low compared with those described in other Lepidoptera, but not prohibitive, and are likely to increase with experience. We anticipate that germline transformation of the diamondback moth will permit the development of RIDL strains for use against this pest and facilitate the wider use of this species as a model organism for basic studies.

Performance of endovenous foam sclerotherapy in the USA.

PURPOSE: To assess practice patterns of endovenous foam sclerotherapy (EFS) use in the USA. METHODS: A multidisciplinary panel of US experts was convened and developed a questionnaire to assess use of EFS. US attendees at the American College of Phlebology 2009 Annual Congress were asked to complete the questionnaire. RESULTS: Of 776 questionnaires distributed, 239 were completed (31%). The majority of respondents (87%) reported using EFS for the treatment of venous disorders. Foam sclerotherapy was used by a wide variety of specialists in every region of the USA. The most common indication was sclerosis of recurrent truncal or tributary veins of the leg. There was variation among practitioners in the indications for use, pre- and postprocedural evaluation and procedure methodology. CONCLUSIONS: The results of this questionnaire show widespread usage of EFS and are important in the development of national quality improvement guidelines for the performance of EFS.

Experiments and Lagrangian simulations on the formation of droplets in drop-on-demand mode.

The creation and evolution of millimeter-sized droplets of a Newtonian liquid generated on demand by the action of pressure pulses were studied experimentally and simulated numerically. The velocity response within a model, large-scale printhead was recorded by laser Doppler anemometry, and the waveform was used in Lagrangian finite-element simulations as an input. Droplet shapes and positions were observed by shadowgraphy and compared with their numerically obtained analogues.

Experiments and Lagrangian simulations on the formation of droplets in continuous mode.

Experimental and computational studies on the dynamics of millimeter-scale cylindrical liquid jets are presented. The influences of the modulation amplitude and the nozzle geometry on jet behavior have been considered. Laser Doppler anemometry (LDA) was used in order to extract the velocity field of a jet along its length, and to determine the velocity modulation amplitude. Jet shapes and breakup dynamics were observed via shadowgraph imaging. Aqueous solutions of glycerol were used for these experiments. Results were compared with Lagrangian finite-element simulations with good quantitative agreement.

Familial Kleefstra syndrome due to maternal somatic mosaicism for interstitial 9q34.3 microdeletions.

The Kleefstra syndrome (Online Mendelian Inheritance in Man 607001) is caused by a submicroscopic 9q34.3 deletion or by intragenic euchromatin histone methyl transferase 1 (EHMT1) mutations. So far only de novo occurrence of mutations has been reported, whereas 9q34.3 deletions can be either de novo or caused by complex chromosomal rearrangements or translocations. Here we give the first descriptions of affected parent-to-child transmission of Kleefstra syndrome caused by small interstitial deletions, approximately 200 kb, involving part of the EHMT1 gene. Additional genome-wide array studies in the parents showed the presence of similar deletions in both mothers who only had mild learning difficulties and minor facial characteristics suggesting either variable clinical expression or somatic mosaicism for these deletions. Further studies showed only one of the maternal deletions resulted in significantly quantitative differences in signal intensity on the array between the mother and her child. But by investigating different tissues with additional fluorescent in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) analyses, we confirmed somatic mosaicism in both mothers. Careful clinical and cytogenetic assessments of parents of an affected proband with an (interstitial) 9q34.3 microdeletion are merited for accurate estimation of recurrence risk.

Incidence of side effects using carbon dioxide-oxygen foam for chemical ablation of superficial veins of the lower extremity.

OBJECTIVES: To determine the incidence of side effects following treatment of varicose veins with carbon dioxide-oxygen (CO(2)/O(2)) foam sclerotherapy, and to compare results with historical controls using CO(2)- or air-based foams. DESIGN: Cohort study with prospective data collection, private clinic setting. PATIENTS: The patient population consisted of one hundred patients, 95% women, age 52 SD 13 years-old, CEAP class C(2)EpAsPr. METHODS: Patients underwent ultrasound-guided foam sclerotherapy following thermal ablation of saphenous trunks; 1-3% polidocanol and 70%CO(2)-30%O(2) gas were mixed in a 1:4 proportion. Volume injected averaged 22 SD 11 (range: 2-46) mL. Vital signs were monitored for 1 h; side effects were recorded up to 24 h post treatment. Incidence of side effects was compared to CO(2)- and air-based foam data. RESULTS: Heart rate decreased from 73 SD 11 at the start to 68 SD 9 bpm (p < 0.001, paired t-test) following the procedure. Systolic and diastolic pressures, 127/75 SD 18/14 mmHg, respiratory rate, 15 SD 4 rpm and pO(2), 98 SD 2%, did not change significantly. Itching (7) or leg pain (24) reporting was similar to that for air-based foam (p = NS). Lack of reported chest tightness and/or dry cough was superior to our previous data with CO(2) or air foam (p < 0.05). Reporting of dizziness (1) was less than that for air-based foam (p = 0.002). The incidence of visual disturbance (2%), was comparable with that for CO(2) (3%) or air (8%) foam, but too few cases were available for meaningful statistical analysis. CONCLUSIONS: Foam sclerotherapy using CO(2)/O(2) foam was well tolerated by patients and resulted in fewer side effects than similar treatment using air foams.

Information about the weight of grasped objects from vision and internal models interacts within the primary motor cortex.

When grasping and lifting different objects, visual cues and previously acquired knowledge enable us to prepare the upcoming grasp by scaling the fingertip forces according to the actual weight of the object. However, when no visual information is available, the weight of the object has to be predicted based on information learned from previous grasps. Here, we investigated how changes in corticospinal excitability (CSE) and grip force scaling depend on the presence of visual cues and the weight of previously lifted objects. CSE was assessed by delivering transcranial magnetic stimulation (TMS) at different times before grasp of the object. In conditions in which visual information was not provided, the size of motor evoked potentials (MEP) was larger when the object lifted was preceded by a heavy relative to a light object. Interestingly, the previous lift also affected MEP amplitude when visual cues about object weight were available but only in the period immediately after object presentation (50 ms); this effect had already declined for TMS delivered 150 ms after presentation. In a second experiment, we demonstrated that these CSE changes are used by the motor system to scale grip force. This suggests that the corticospinal system stores a "sensorimotor memory" of the grasp of different objects and relies on this memory when no visual cues are present. Moreover, visual information about weight interacts with this stored representation and allows the corticospinal system to switch rapidly to a different model of predictive grasp control.

Foam sclerotherapy: cardiac and cerebral monitoring.

OBJECTIVES: To investigate and review collected and reported transcutaneous ultrasound, transthoracic echocardiography (TTE) and transcranial Doppler (TCD) data obtained during ultrasound-guided foam sclerotherapy (USGFS) of incompetent saphenous, tributary and perforating veins of the lower extremities. METHODS: TTE and/or middle cerebral artery TCD were performed during USGFS. Ultrasound (US) findings and adverse events were recorded. Existing literature was reviewed. RESULTS: Ultrasound detected emboli circulating in superficial, perforating, communicating and deep veins and into the central circulation. TTE detected bright echoes in the right heart after every injection and in the left heart in up to 65% of selected patients. TCD high-intensity transient signals (HITS) were detected in 14-42% of the patients. Incidence of HITS was higher than patient reports of adverse events. Incidence of HITS was independent of foam volumes injected. CONCLUSION: Echogenic signals were detected in non-treated veins, in heart chambers and in the cerebral circulation by transcutaneous US, TTE and TCD. Pathological consequences of such findings remain to be investigated.

Dual-energy X-ray absorptiometry overestimates bone mineral density of the lumbar spine in persons with spinal cord injury.

BACKGROUND: Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal or increased in persons with chronic spinal cord injury (SCI). OBJECTIVE: To determine BMD of the L-spine by dual-energy X-ray absorptiometry (DXA) and quantitative computerized tomography (qCT) in men with chronic SCI compared with able-bodied controls. DESIGN: Cross-sectional, comparative study. SETTING: Clinical research unit, Veterans Affairs Medical Center, Bronx, NY, USA and Kessler Institute of Rehabilitation, West Orange, NJ, USA. METHODS: Measurements of the L-spine were made in 20 men with SCI and compared with 15 able-bodied controls. The DXA images were acquired on a GE Lunar DPX-IQ. The qCT images of the L-spine were acquired on a Picker Q series computerized tomographic scanner. RESULTS: The mean ages for the SCI and control groups were 44+/-13 vs 42+/-9 years, and the duration of injury of the group with SCI was 14+/-11 years. There were no significant differences between the SCI and control groups for L-spine DXA BMD (1.391+/-0.210 vs 1.315+/-0.178 g/m(2)) or for L-spine DXA T-score (1.471+/-1.794 vs 0.782+/-1.481). L-spine qCT BMD was significantly lower in the SCI compared with the control group (1.296+/-0.416 vs 1.572+/-0.382 g/m(2), P=0.05); the T-score approached significance (-1.838+/-1.366 vs -0.963+/-1.227, P=0.059). Subjects with moderate degenerative joint disease (DJD) had significantly higher T-scores by DXA than those without or with mild DJD. CONCLUSION: Individuals with SCI who have moderate to severe DJD may have bone loss of the L-spine that may be underestimated by DXA, reducing awareness of the risk of fracture.

17q21.31 microdeletion syndrome: further expanding the clinical phenotype.

Microdeletions of the 17q21.31 region are associated with hypotonia, oromotor dyspraxia, an apparently characteristic face, moderate learning disability and have an estimated prevalence of approximately 1 in 16,000. Here we report 3 individuals who extend further the phenotypic spectrum observed with microdeletions of the 17q21.31 region. They all have learning disability, hypotonia, and craniofacial dysmorphism in keeping with previous reported cases. One case has iris-choroid coloboma and partial situs inversus, 2 features that are newly recorded phenotype abnormalities. These deletions were detected from a cohort of 600 individuals with learning disability and congenital anomalies, reflecting that 17q21.31 microdeletions are a common finding in such cases. FISH analysis demonstrated that each of the deletions occurred as de novo events. The deleted region in our cases encompasses the previously defined critical region for 17q21.31, and includes CRHR1 and MAPT, putative candidate genes for the 17q21.31 phenotype. The 17q21.31 microdeletion phenotype is perhaps more variable than previously described despite haploinsufficiency for the same genes in many cases.

Abbreviated method of determining vein volume in balloon-controlled vein ablation.

Traditional surgical ligation and stripping for the treatment of saphenous vein incompetence has been replaced by minimally invasive alternative treatments during the last five years. Endovenous ablation with radiofrequency (RP) and laser (EVL) have proven to be safe, durable, and widely accepted by patients. Catheter-delivered sclerotherapy (CDS) with foam and liquid for ablation of the great saphenous vein is also under investigation. In this technique, vein volume must be measured accurately by ultrasound just prior to the procedure and can require up to 11 diameter measurements. The purpose of this study was to identify an abbreviated method of determining vein volume to expedite associated endovenous procedures. Seventy-five veins were treated in 55 subjects with catheter-directed sclerotherapy in a three-center clinical study using a standardized protocol. Vein volume was carefully calculated by determining vein diameter over the Treatment Length in 4 cm intervals. These measurements were compared to vein volume calculations where only three measurements were taken. Our results suggest that the abbreviated method is capable of significantly reducing the number of diameter measurements without sacrificing accuracy. We found the method produced a vein volume that fell within 1 mL or 15% of the actual vein volume in 80% of cases. The abbreviated method cannot be used with accuracy in veins that are Erratic.

Peptide phage display: opportunities for development of personalized anti-cancer strategies.

Personalized medicine is critical for cancer patients, because (1) cancer is a highly heterogeneous disease with major molecular differences in the expression and distribution of tumor cell surface markers among patients with the same type and grade of cancer, (2) cellular mutations tend to accumulate as cancer progresses, further increasing tumor heterogeneity, and (3) currently used cancer therapies often are toxic to normal cells, causing severe side effects rarely seen in other diseases. To prevent side effects and to improve effectiveness, cytotoxic therapies should be targeted and each patient should be profiled for the presence of cancer targets before the therapy is administered. Phage display technology utilizes combinatorial libraries of proteins expressed on phage particles that can be selected for specific binding to cancer cells. Such cancer-specific molecules can be used in a variety of applications, including identification of cell-specific targeting molecules; identification of cell surface biomarkers; profiling of specimens obtained from individual cancer patients, and the design of peptide-based anti-cancer therapeutics for personalized treatments. This review is focused on peptide phage display strategies that target cell surfaces because many biomarkers important in cancer are differentially expressed molecules located on the outside of the cell membranes.