bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate Reconstruction of the Nipple-areola Complex Using Inferior Pedicle Skin for Central Tumors of the Breast
Authors: Mathew John
Published: July 2022

The nipple-areola complex (NAC) must be considered as an integral part of the breast with regard to morale and self-assurance. Achieving good aesthetic outcome is a challenge after excision of the NAC in retroareolar tumors. This article looks into immediate reconstruction of the NAC using inferior pedicle skin in patients after central excision of retroareolar tumors. Sixteen patients had breast conservation surgery for retroareolar tumors by a single surgeon between September 2016 and November 2021, and six of them had nipple-areola reconstruction with inferior pedicle skin. None of the patients having NAC reconstruction had any recorded complications and none needed reexcision of the margins. Five out of six patients undergoing NAC reconstruction had good to excellent aesthetic outcome as recorded in the patient questionnaire. There was no locoregional recurrence or distant metastasis in the whole group after a median follow-up of 17 months (2–62).
DescePrep Significantly Increases Descemet Membrane Endothelial Keratoplasty Processing Efficiency and Success Rate in Diabetic Human Donor Corneas in Comparison With Manual Dissection
Authors: Solley Katherine D. , Berges Alexandra J. , Phillips Elizabeth , Ding Andy S. , Diaz Christine M. , Pramanik Sudeep , Yazdi Youseph , Parikh Kunal S.
Published: July 2022

Purpose:

The purpose of this study was to compare the safety, efficacy, and efficiency of a Descemet membrane endothelial keratoplasty (DMEK) graft processing device, DescePrep, with a manual dissection technique through the measurement of tissue yield, processing time, and graft viability in nondiabetic and diabetic donor corneas.

Methods:

Nondiabetic (n = 20) and diabetic (n = 20) donor corneas were processed using DescePrep, which standardizes the liquid bubble technique. Nondiabetic (n = 20) and diabetic (n = 24) donor corneas were also processed through manual dissection. Corneas were stained, processed, and then evaluated for processing success rate and time. Randomly selected corneas (n = 5, each) were evaluated for cell viability using live/dead staining.

Results:

One hundred percent of nondiabetic and 95% of diabetic corneas were processed successfully with DescePrep in an average of 3.37 minutes. Ninety percent of nondiabetic and 50% of diabetic corneas were processed successfully with manual dissection in an average of 9.87 minutes. DescePrep had a significantly lower processing time (P < 0.0001) and significantly higher success rate in comparison with manual dissection. DescePrep grafts had an average cell viability of 91.1% ± 3.3% in nondiabetic and 91.5% ± 2.4% in diabetic corneas. Grafts prepared with manual dissection had an average cell viability of 89.5% ± 5.8% in nondiabetic and 88.1% ± 4.3% in diabetic corneas.

Conclusions:

DescePrep provides a more effective and efficient method of cornea preparation in comparison with the current standard, particularly in diabetic corneas, while providing comparable cell viability. Thus, DescePrep offers standardized DMEK processing that produces high-quality grafts at high yields, with the potential to expand access and improve the quality of DMEK graft preparation in a larger pool of donors.
Aortic arch plaque morphology in patients with coronary artery disease undergoing coronary computed tomography angiography with wide-volume scan
Authors: Otsuka Kenichiro , Ishikawa Hirotoshi , Kono Yasushi , Oku Shinya , Yamaura Hiroki , Shirasawa Kuniyuki , Hirata Kumiko , Shimada Kenei , Kasayuki Noriaki , Fukuda Daiju
Published: July 2022

Background

Wide-volume scanning with 320-row multidetector computed tomography coronary angiography (CTCA-WVS) enables the assessment of the aortic arch plaque (AAP) morphology and coronary arteries without requiring additional contrast volume. This study aimed to investigate the prevalence of AAPs and their association with coronary artery disease (CAD) and major adverse cardiovascular events (MACEs) in patients who underwent CTCA-WVS.

Methods

This study included 204 patients without known CAD (mean age, 65 years; 53% men) who underwent CTCA-WVS. We evaluated the presence of aortic plaques in the ascending aorta, aortic arch, and thoracic descending aorta using CTCA-WVS. Large aortic plaques were defined as plaques of at least 4 mm in thickness. A complex aortic plaque was defined as a plaque with ulceration or protrusion. MACEs were defined as composite events of cardiovascular (CV) death, nonfatal myocardial infarction, and ischemic stroke.

Results

AAPs and large/complex AAPs were identified in 51% (n = 105) and 18% (n = 36) of the study patients, respectively. The prevalence of AAPs with large/complex morphology increased with CAD severity (2.1% in no CAD, 12% in nonobstructive CAD, and 39% in obstructive CAD). The univariate Cox hazard model demonstrated that the predictors associated with MACEs were diabetes, obstructive CAD, and large/complex AAPs. Independent factors associated with large/complex AAPs were male sex [odds ratio (OR), 2.90; P = 0.025], stroke history (OR, 3.48; P = 0.026), obstructive CAD (OR, 3.35; P = 0.011), and thoracic aortic calcification (OR, 1.77; P = 0.005).

Conclusion

CTCA-WVS provides a comprehensive assessment of coronary atherosclerosis and thoracic aortic plaques in patients with CAD, which may improve the stratification of patients at risk for CV events.
Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn)
Authors: Shaked Einat , Shaul Aviv A. , Perl Leor , Leshem- Lev Dorit , Sevilya Ziv , Kheifets Mark , Gutstein Ariel , Hamdan Ashraf , Kornowski Ran , Lev Eli I.
Published: July 2022

Background

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls.

Methods

We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique.

Results

Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group.

Conclusion

Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.
Relationship between intestinal flora, inflammation, BDNF gene polymorphism and generalized anxiety disorder: A clinical investigation
Authors: Cheng Yuanyuan , Wang Yue , Zhang Wen , Yin Junbo , Dong Jicheng , Liu Jintong
Published: July 2022

Introduction:

Understanding factors related to generalized anxiety disorder pathogenesis is critical for elucidating the mechanism and preventing its establishment. Intestinal flora and hereditary factors such as brain-derived neurotrophic factor (BDNF) gene polymorphism may have a role in the development of generalized anxiety disorder. This work explored the relationship between intestinal flora, inflammatory changes and BDNF gene polymorphisms and the occurrence of generalized anxiety disorder.

Methods:

Forty-eight patients with generalized anxiety disorder and 57 healthy people were included in the study. As the disease group and control group, the polymorphisms of rs10767664 and rs7124442 of the BDNF gene, differences in the distribution of intestinal flora, and changes in inflammatory and immune indicators were analyzed.

Results:

The distribution of BDNF gene alleles, genotypes and haplotypes in the disease group were different from those in the control group. The levels of TNF-α (P = .000), interleukin-4 (P = .000), interleukin-10 (P = .043) and IgG (P = .008) in patients with generalized anxiety disorder in the disease group were different from those in the control group. The distribution of gut microbes in patients with generalized anxiety disorder in the disease group was different from that in the control group.

Conclusion:

The onset of generalized anxiety disorder is related to BDNF gene polymorphism, and is accompanied by changes in intestinal flora and inflammatory immune status in the body.
The effect of acupuncture on postpartum stress urinary incontinence: A protocol for systemic review and meta-analysis
Authors: Cao Fengye , Zhang Shanshan , Huang Jingmei , Gan Lin , Zhuansun Qinshuai , Lin Xianming
Published: July 2022

Background:

Postpartum stress urinary incontinence (PSUI) is a widespread complaint in postpartum women, which significantly affects their quality of life. Acupuncture has been widely used as an alternative complementary therapy for the treatment of PSUI. This protocol is carried out to comprehensively explore the effectiveness and safety of acupuncture for treating PSUI.

Methods:

Randomized clinical trials related to acupuncture treatment of PSUI will be searched in Chinese and English literature databases: PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, and the Technology Periodical Database. Changes in pelvic floor muscle strength compared with baseline will be accepted as the primary outcomes, and secondary outcomes will be the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score, the urodynamic indexes, the incontinence quality of life questionnaire, and adverse effects of acupuncture. All publications will be screened and extracted by 2 reviewers independently. Quality of the eligible publications will be assessed according to the Cochrane Risk of Bias tool and statistical analyses will be conducted by using the Review Manager V.5.3.

Results:

This study will provide a high-quality comprehensive evaluation for the clinical efficacy and safety of acupuncture for PSUI.

Conclusion:

This systematic review will provide comprehensive evidence of acupuncture treatment on specific outcomes for PSUI.

Ethics and Dissemination:

Because of the study will not collect personal information, ethical approval will not be required. The results will be published in a peer-reviewed journal.

Trial registration:

INPLASY 202220045.
Risk factors of non-sentinel lymph node metastasis in 443 breast cancer patients with sentinel lymph node-positive
Authors: Cai Shuang-long , Wei Ran-mei , Han Lei , Chen Xiao-geng , Gong Guo-xian , Lin Xiu-quan , Zhang Jin , Chen Hong-dan
Published: July 2022

Axillary lymph node dissection is the standard surgical procedure for breast cancer patients with sentinel lymph node (SLN) positive. In clinical practice, axillary lymph node dissection may be an unnecessary treatment for some breast cancer patients with non-sentinel lymph node (NSLN) negative. The aim of this study was to analyze the risk factors of NSLN metastasis in breast cancer patients with SLN positive. Four hundred fifty-six clinical early stage breast cancer patients with SLN positive were collected and analyzed in the oncological surgery department of Fujian Provincial Hospital during 2013 to 2018. All these patients underwent surgical treatment. The average age and tumor size of 443 patients with SLN positive breast cancer were (49.8 ± 10.8) years and (2.42 ± 0.94) cm. Univariate analysis showed that the size of primary tumor, the number of positive SLN, the number of negative SLN, the ratio of positive SLNs, and the type of metastases in SLN were the influencing factors of NSLN metastasis. Multivariate regression analysis showed that primary tumor size T > 2 cm (P < .001, OR = 2.609), the positive number of SLNs ≥3 (P = .002, OR = 5.435), the ratio of positive SLNs ≥ 50% (P = .017, OR = 1.770), and SLN macrometastases (P < 0.001, OR = 16.099) were independent risk factors for NSLN metastasis. Combined with the 4 independent risk factors, the area under the curve to predict NSLN metastasis was 0.747 > 0.7. For clinical early breast cancer with positive SLN, primary tumor size T > 2 cm,the positive number of SLNs ≥ 3, the ratio of positive SLNs ≥ 50%, and SLN macrometastases could predict NSLN metastasis well, and guide surgery to avoid overtreatment.
Association between smoking and COVID-19 severity: A multicentre retrospective observational study
Authors: He Yue , He Yangai , Hu Qinghui , Yang Sheng , Li Jun , Liu Yuan , Hu Jun
Published: July 2022

The relationship between smoking and coronavirus disease 2019 (COVID-19) severity remains unclear. This study aimed to investigate the effect of smoking status (current smoking and a smoking history) on the clinical severity of COVID-19. Data of all enrolled 588 patients, who were referred to 25 hospitals in Jiangsu province between January 10, 2020 and March 14, 2020, were retrospectively reviewed. Univariate and multivariate regression, random forest algorithms, and additive interaction were used to estimate the importance of selective predictor variables in the relationship between smoking and COVID-19 severity. In the univariate analysis, the proportion of patients with a current smoking status in the severe group was significantly higher than that in the non-severe group. In the multivariate analysis, current smoking remained a risk factor for severe COVID-19. Data from the interaction analysis showed a strong interaction between the number of comorbidities in patients with COVID-19 and smoking. However, no significant interaction was found between smoking and specific comorbidities, such as hypertension, diabetes, etc. In the random forest model, smoking history was ranked sixth in mean decrease accuracy. Active smoking may be significantly associated with an enhanced risk of COVID-19 progression towards severe disease. However, additional prospective studies are needed to clarify the complex relationship between smoking and COVID-19 severity.
Do antihypertensive drugs really have antitumor effects? Baseline differences in hypertensive and non-hypertensive patients with advanced pancreatic cancer
Authors: Iede Kiyotsugu , Yamada Terumasa , Ueda Masami , Tsuda Yujiro , Nakashima Shinsuke , Ohta Katsuya , Tanida Tsukasa , Matsuyama Jin , Ikenaga Masakazu , Tominaga Shusei
Published: July 2022

Although the antitumor effects of antihypertensive drugs for patients with advanced pancreatic cancer (APC) have been investigated, their efficacy remains unclear. Previous studies suggest that hypertensive (HT) patients with APC are significantly older than non-HT patients with APC, and that other major baseline differences in patient characteristics which may affect prognosis exist between HT and non-HT patients. It is also possible that antihypertensive drugs lack antitumor activity. Therefore, we herein retrospectively investigated the baseline differences between HT and non-HT patients with APC. From January 2015 to April 2020, 56 patients with APC received nab-paclitaxel plus gemcitabine as first-line chemotherapy at Higashiosaka City Medical Center (Higashiosaka, Japan). Of these 56 patients, 30 were diagnosed with hypertension (HT group); the remaining 26 did not have hypertension (non-HT group). Differences between the two groups were compared and prognostic factors were evaluated. Patients in the HT group had significantly less sarcopenia, a significantly larger body mass index, were significantly older, and significantly more likely to have a regular doctor and primary site in the body and tail of the pancreas than those in the non-HT group. Although no significant difference was found in the treatment response, patients in the HT group were significantly more likely to move to second-line chemotherapy than those in the non-HT group. Survival curves showed that median overall survival (OS) in the HT group was significantly longer (10.5 months) than in the non-HT group (6.8 months, P = .04). Multivariate analysis did not identify the use of antihypertensive drugs as an independent prognostic factor of OS. We identified key baseline differences in the characteristics of APC patients with and without HT, suggesting that major selection bias could occur when investigating the efficacy of antihypertensive drugs in all populations. Therefore, it is possible that antihypertensive drugs lack antitumor activity. To determine the true efficacy of antihypertensive drugs for APC, HT, and non-HT patients in another population should be investigated, or a prospective, randomized, controlled trial conducted that is stratified by HT or non-HT status.
Serum adipocyte fatty acid-binding protein level is positively associated with aortic stiffness in nondialysis chronic kidney disease patients: A cross-sectional study
Authors: Su Hsiao-Yuan , Hsu Bang-Gee , Lin Yu-Li , Wang Chih-Hsien , Lai Yu-Hsien
Published: July 2022

Aortic stiffness (AS) is a major predictor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD) and adipocyte fatty acid-binding protein (A-FABP) is a novel adipokine that is positively correlated with AS in the general population. Therefore, we investigated the correlation between serum A-FABP levels and AS in nondialysis CKD patients.

Fasting blood samples and baseline characteristics were obtained in 270 patients with nondialysis CKD. Serum A-FABP concentrations were determined by enzyme immunoassay and carotid–femoral pulse wave velocity (cfPWV) measurements were acquired using a validated tonometry system. Patients with cfPWV >10 m/s formed the AS group, while those with values ≤10 m/s comprised the comparison group.

Among 270 CKD patients, 92 patients (34.1%) were in the AS group. Compared to those in the comparison group, patients in the AS group were older (P< .001), had a higher prevalence of diabetes, along with higher serum A-FABP level (P< .001), larger waist circumference (P= .004), and lower estimated glomerular filtration rate (P= .001) but higher levels of body fat mass (P= .010), systolic blood pressure (P< .001), fasting glucose (P= .014), blood urea nitrogen (P= .009), and serum creatinine (P= .004). The serum log-A-FABP level was positively associated with log-cfPWV (β = 0.178,P= .001) in nondialysis CKD patients and multivariable logistic regression analysis identified serum A-FABP (P= .006), age (P= .001), and systolic blood pressure (P= .015) as independent predictors of AS in nondialysis-dependent CKD patients.

Elevated A-FABP levels may be a significant predictor of AS in nondialysis CKD patients.
Effect of buttonhole cannulation versus rope-ladder cannulation in hemodialysis patients with vascular access: A systematic review and meta-analysis of randomized/clinical controlled trials
Authors: Wang Li-Ping , Tsai Li-Hwa , Huang Hisang-Yun , Okoli Chizimuzo , Guo Su-Er
Published: July 2022

Background:

Safe and effective arteriovenous fistula (AVF) puncture techniques must be used to reduce harm to hemodialysis patients. The relative benefits of buttonhole (BH) cannulation over those of rope ladder (RL) cannulation for AVF remain unclear and inconsistent.

Methods:

This systematic review and meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Literature searches were conducted in June 2020 in multiple scientific databases including Cochrane library, CINAHL, PubMed/ Medline, Airiti Library, National Digital Library of Theses and Dissertations in Taiwan, Google scholar, Embase, and ProQuest. We included all randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that explored the efficacy of BH cannulation in hemodialysis patients. These included reports published in either English or Chinese that enrolled adults aged 18 years or older who underwent hemodialysis using an autogenous AVF. Studies that showed poor design, such as use of a self-control group or no control group, were excluded from analysis. The critical appraisal skills program checklist for RCTs were used to assess the quality of the evidence and RevMan software were used to perform the meta-analysis.

Results:

Fifteen studies (11 RCTs and 4 CCTs) met the inclusion criteria and were used for the meta-analysis. Meta-analysis showed that BH cannulation significantly reduced aneurysm formation (RR = 0.18, 95% confidence interval [CI] [0.1, 0.32]), stenosis (RR = 0.44, 95% CI [0.25, 0.77]), thrombosis formation (RR = 0.4, 95% CI [0.2, 0.8]), and hematoma (RR = 0.63, 95% CI [0.40, 0.99]) and showed no differences in AVR infection (≦6 months, RR = 2.17, 95% CI [0.76, 6.23]; >6 months, RR = 2.7, 95% CI [0.92, 7.92]) compared to RL cannulation.

Conclusions:

Given the benefits of BH, this meta-analysis found that BH cannulation should be recommended as a routine procedure for hemodialysis but that hospitals and hemodialysis clinics should strengthen staff knowledge and skills of BH cannulation to reduce the risk of AVF infection.
Clinical application of gastrointestinal decompression in anastomotic fistula after McKeown esophagectomy for esophageal cancer
Authors: Lu Yanhong , Ren Zixue
Published: July 2022

AbstractCervical anastomotic fistula is one of the most common complications after McKeown esophagectomy for esophageal cancer, leading to septic shock and even death. It is therefore very important to provide effective symptom management after diagnosis of anastomotic fistula. Placing the gastrointestinal decompression tube beside the anastomotic site and connecting the tube to a gastrointestinal decompression disk could support the prevention and treatment of anastomotic fistula after surgical treatment of esophageal cancer.

Thirty-eight patients with anastomotic fistula after undergoing McKeown esophagectomy for esophageal cancer in our hospital from April 2017 to January 2021 were divided equally into control and observation groups according to the gastrointestinal decompression method used. Gastrointestinal decompression tubes were placed 45 to 50 cm from the incisors in the control group or 25 to 30 cm from the incisors in the observation group. The treatment efficacy was compared between the 2 groups.

The drainage time, length of hospital stay after anastomotic fistula detection, and fistula healing time in the observation group were significantly shorter than those in the control group (P < .05 for all).

Placing the gastrointestinal decompression tube connected to a gastrointestinal decompression disk next to the anastomotic site is a simple procedure and may significantly improve the drainage time, length of hospital stay, and fistula healing time of patients who develop anastomotic fistula resulting from McKeown esophagectomy for esophageal cancer.
Evaluation Methods in Community Microgrant Programs for Health Promotion: A Scoping Review
Authors: Conlin Michèle P. , McLaren Dorothy , MacDermott Sean , Spelten Evelien
Published: July 2022

Context:

Evaluating community-based health promotion programs is an essential aspect of public health programming to ensure evidence-based practices, justify limited resource allocation, and share knowledge about promising strategies. Community microgrant schemes represent a viable strategy to strengthen local health promotion, yet limited guidance exists surrounding the evaluation of such programs.

Objective:

This research aimed to map methods used in evaluating community microgrants programs for health promotion.

Design:

A scoping review in accordance with Joanna Briggs Institute methodology.

Eligibility Criteria:

Peer-reviewed academic and gray literature, which evaluated processes and/or outcomes of nonprescriptive community-based microgrant program for health promotion in high-income countries.

Study Selection:

Literature was identified through MEDLINE, Scopus, CINAHL, and EMBASE databases, Google and DuckDuckGo browsers, and hand-searching key reference lists. Articles were screened by title, abstract, and then full-text.

Main Outcome Measure(s):

Review findings were mapped according to included sources' evaluation methodologies.

Results:

Eighteen academic publications describing 14 microgrant programs met the inclusion criteria. These spanned the years 1996 to 2020 and were located across 5 countries. Evaluation methods were very similar in terms of design (mixed-methods case studies) and focus (both processes and outcomes) and yet varied widely with regard to measurements and data collection. Few made explicit the use of an evaluation framework, chose to involve stakeholders in the evaluation process, or discussed application and dissemination of evaluation findings.

Discussion:

Community-based microgrant programs for health promotion are a promising model in diverse settings and with various health priorities and targets, yet robust evaluations of their implementation and effectiveness are lacking. The review highlights the need to further develop and support evaluation practices in public health, even in small-scale programs with limited budgets.
Readying the Applied Epidemiology Workforce for Emerging Areas of Public Health Practice
Authors: Daly Elizabeth R. , Arrazola Jessica , Umble Karl
Published: July 2022

Context:

Epidemiologists are key professionals within the public health workforce. As the role of public health agencies changes over time, epidemiologists will need to adapt and develop new skill sets to work in emerging areas of (public health) practice (EAoPs), which are areas of practice that are new or are growing in interest and use.

Objective:

This mixed-methods research study sought to explore the role and readiness of state health department epidemiologists in the United States to work in EAoPs.

Design:

Three phases of data collection and analysis were conducted including secondary analysis of the Public Health Workforce Interests and Needs Survey, a survey of the designated state epidemiologist in all 50 states and the District of Columbia, and focus groups with early-, mid-, and senior-career epidemiologists working in state health departments.

Setting:

Fifty state health departments and the District of Columbia.

Participants:

Epidemiologists working in state health departments.

Main Outcome Measures:

Identification of EAoPs relevant to epidemiologists, the role of epidemiologists in these EAoPs, and readiness of epidemiologists to work in EAoPs.

Results:

Participant state health department epidemiologists indicated that the studied EAoPs were important to their work and that epidemiologists have some role in them. Key facilitators identified to working in EAoPs included supportive organizational strategy and leadership, dedicated time for training and work, cross-training across programs, and the development of crosscutting skills.

Conclusions:

There is much opportunity for epidemiologists to be more engaged in current EAoPs. Not only can epidemiologists supply relevant data but they can also bring skills and expertise to help improve the overall success of population health improvement work. Workforce development strategies should be implemented to ensure a nimble epidemiology workforce that can readily adapt to the needs of future public health practice.
The Role of Local Health Departments in Strengthening the Alignment Between Nonprofit Hospitals' Community Health Needs Assessments and Their Implementation Strategies
Authors: Singh Simone R. , Cronin Cory E. , Yeager Valerie , Burns Ashlyn , Franz Berkeley
Published: July 2022

Nonprofit hospitals frequently partner with their local health department on developing community health needs assessments (CHNAs); yet, little is known about the role that such partnerships play in strengthening the alignment between needs identified in hospitals' assessments and the strategies adopted by hospitals to address identified needs. Using data for 486 hospitals from the third round of CHNAs (spanning the years 2018-2021), this study showed strong alignment between the health needs identified in the CHNAs and those addressed in hospitals' implementation strategies, independent of collaboration with the local health department. One noteworthy exception to this finding was that hospital-public health collaboration remained important for improved alignment of needs related to substance use. Involvement of the local health department may strengthen hospitals' capacity to address needs outside their traditional areas of expertise, such as substance use.
Postacute sequelae and adaptive immune responses in people with HIV recovering from SARS-COV-2 infection
Authors: Peluso Michael J. , Spinelli Matthew A. , Deveau Tyler-Marie , Forman Carrie A. , Munter Sadie E. , Mathur Sujata , Tang Alex F. , Lu Scott , Goldberg Sarah A. , Arreguin Mireya I. , Hoh Rebecca , Tai Viva , Chen Jessica Y. , Martinez Enrique O. , Yee Brandon C. , Chenna Ahmed , Winslow John W. , Petropoulos Christos J. , Sette Alessandro , Weiskopf Daniella , Kumar Nitasha , Lynch Kara L. , Hunt Peter W. , Durstenfeld Matthew S. , Hsue Priscilla Y. , Kelly J. Daniel , Martin Jeffrey N. , Glidden David V. , Gandhi Monica , Deeks Steven G. , Rutishauser Rachel L. , Henrich Timothy J.
Published: July 2022

Background:

Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).

Methods:

We measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 (n = 39 and n = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing postacute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T-cell responses, as well as differences in the prevalence of PASC.

Results:

Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T-cell responses as compared with a well matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8+ T cells (P = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4+ T cells (P = 0.007). Higher CD4+/CD8+ ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8+ T cells (0.34-fold effect, P = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, P = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.

Conclusion:

We identified potentially important differences in SARS-CoV-2-specific CD4+ and CD8+ T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.
Cerebellar Metastasis From Thyroid Carcinoma With Prominent 123I Uptake But Less Impressive MRI Findings in a Pediatric Patient
Authors: Gupta Neetika , Fleury Anilawan , Zhuang Hongming
Published: July 2022

Papillary thyroid carcinoma in childhood frequently presents with locoregional lymph node metastases. The distant metastases often involve lungs and the bone, whereas brain metastasis is rare. We report a case of classic variant–papillary thyroid carcinoma with right cerebellar metastasis in a 7-year-old girl on a 123I SPECT/CT study. A brain MRI on the same day shows a tiny millimetric enhancing nodule in the right cerebellum with no perceivable perilesional edema, confirming the 123I scan findings.
Perforation and Fistula of the Gastrointestinal Tract in Patients With Necrotizing Pancreatitis
Authors: Timmerhuis Hester C. , van Dijk Sven M. , Hollemans Robbert A. , Umans Devica S. , Sperna Weiland Christina J. , Besselink Marc G. , Bouwense Stefan A.W. , Bruno Marco J. , van Duijvendijk Peter , van Eijck Casper H.J. , Issa Yama , Mieog J. Sven D. , Molenaar I. Quintus , Stommel Martijn W.J. , Bollen Thomas L. , Voermans Rogier P. , Verdonk Robert C. , van Santvoort Hjalmar C. ,   for the Dutch Pancreatitis Study Group
Published: July 2022

Objective:

The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal (GI) tract in a large unselected cohort of patients with necrotizing pancreatitis.

Background:

Perforation and fistula of the GI tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes, and treatment are lacking.

Methods:

We performed a post hoc analysis of a nationwide prospective database of 896 patients with necrotizing pancreatitis. GI tract perforation and fistula were defined as spontaneous or iatrogenic discontinuation of the GI wall. Multivariable logistic regression was used to explore risk factors and to adjust for confounders to explore associations of the GI tract perforation and fistula on the clinical course.

Results:

A perforation or fistula of the GI tract was identified in 139 (16%) patients, located in the stomach in 23 (14%), duodenum in 56 (35%), jejunum or ileum in 18 (11%), and colon in 64 (40%). Risk factors were high C-reactive protein within 48 hours after admission [odds ratio (OR): 1.19; 95% confidence interval (CI): 1.01–1.39] and early organ failure (OR: 2.76; 95% CI: 1.78–4.29). Prior invasive intervention was a risk factor for developing a perforation or fistula of the lower GI tract (OR: 2.60; 95% CI: 1.04–6.60). While perforation or fistula of the upper GI tract appeared to be protective for persistent intensive care unit-admission (OR: 0.11, 95% CI: 0.02–0.44) and persistent organ failure (OR: 0.15; 95% CI: 0.02–0.58), perforation or fistula of the lower GI tract was associated with a higher rate of new onset organ failure (OR: 2.47; 95% CI: 1.23–4.84). When the stomach or duodenum was affected, treatment was mostly conservative (n=54, 68%). Treatment was mostly surgical when the colon was affected (n=38, 59%).

Conclusions:

Perforation and fistula of the GI tract occurred in one out of six patients with necrotizing pancreatitis. Risk factors were high C-reactive protein within 48 hours and early organ failure. Prior intervention was identified as a risk factor for perforation or fistula of the lower GI tract. The clinical course was mostly affected by involvement of the lower GI tract.
Ten-Year Survival and Recurrence Patterns After Three-Field Lymph Node Dissection for Squamous Cell and Adenocarcinoma of the Esophagus
Authors: Altorki Nasser , Mynard Nathan , Nasar Abu , Spinelli Cathy , Villena-Vargas Jonathan , Chow Oliver , Lee Benjamin , Harrison Sebron , Port Jeffrey
Published: July 2022

Objective:

The aim was to determine the prevalence of metastases to the cervical and recurrent laryngeal cervicothoracic (CT) nodes as well as survival and recurrence patterns after esophagectomy with three-field lymph node dissection (TFD) in patients with predominately adenocarcinoma (AC) of the esophagus.

Background:

Although esophagectomy with TFD is commonly practiced in Japan and Southeast Asia for squamous cell cancer (SCC) of the esophagus, there are only a handful of reports about its’ utilization and survival benefit in North American patients.

Methods:

This is a retrospective case series of patients who had an esophagectomy with TFD. The primary outcomes of interest were the prevalence of nodal metastases to the CT nodes as well as overall survival (OS) and disease-free survival. Secondary outcomes included time to recurrence, recurrence patterns, operative morbidity as well as 30 and 90-day mortality.

Results:

Two hundred forty-two patients with esophageal cancer (AC: 67%) underwent esophagectomy with TFD. Metastases to the CT nodes were present in 56 patients (23%: AC 20% and SCC 30%). Positive CT nodes were present in 14% of pT1/T2 tumors and 30% of pT3 tumors. For the 56 patients with CT positive nodes, 5-year OS was 25% (AC:16%; SCC:39%). Fifteen of 56 (26.7%) patients with metastases to the CT nodes were alive and disease-free at a minimum of 5 years postoperatively. Ten-year OS was 43% for all patients with SCC and 28% for patients with AC.

Conclusions:

Metastases to the CT nodes are common in both SCC and AC of the esophagus and may be present in at least 14% of early lesions. Five-year survival is encouraging particularly for patients with esophageal SCC cancer.
Simultaneously screening for methicillin-resistant Staphylococcus aureus and its susceptibility to potentiated penicillins
Authors: Ba Xiaoliang , Raisen Claire L. , Zhou Zhen-Chao , Harrison Ewan M. , Peacock Sharon J. , Holmes Mark A.
Published: July 2022

Introduction. We recently revealed that a significant proportion of clinical methicillin-resistant

Staphylococcus aureus

(MRSA) isolates are susceptible to pencillins and clavulanic acid (potentiated penicillins), including widely available combinations such as co-amoxiclav. These isolates also showed increased susceptibility to oxacillin on Iso-Sensitest Agar (ISA).

Hypothesis/Gap Statement. The increased susceptibility to oxacillin displayed on ISA by these MRSA isolates may be used to distinguish them from the resistant ones.

Aim. We aimed to develop a method to simultaneously screen a

S. aureus

clinical isolate for its susceptibility to methicillin and potentiated penicillins.

Methodology. A double-disc diffusion method using 10 µg cefoxitin and 1 µg oxacillin discs on ISA was developed and tested against a panel of 120 whole genome-sequenced MRSA isolates. The sensitivity of the method was compared with that of previously published genotypic and phenotypic methods. In addition, double-disc diffusion was performed for all isolates on Müller–Hinton agar (MHA) following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) protocol.

Results. All isolates (120/120) were reconfirmed to be phenotypically MRSA, as indicated by the result of cefoxitin disc diffusion testing. All isolates (40/40) that had a pencillins and clavulanic acid (Pen–Clav)-resistant genotype were not inhibited by oxacillin, while 77/80 (96.3 %) isolates that had a Pen–Clav-susceptible genotype were inhibited by oxacillin on ISA. The results also showed that the EUCAST method using MHA correctly identified all isolates as MRSA but failed to distinguish the Pen–Clav-susceptible isolates from the Pen–Clav-resistant isolates.

Conclusions. This double-disc diffusion method using ISA could be used to accurately screen for clinical MRSA isolates and determine their susceptibility to Pen–Clav simultaneously, rapidly identifying MRSA infections that might be suitable for treatment with potentiated penicillins.
Clinical case study meets population cohort: Identification of a BRCA1 pathogenic founder variant in Orcadians
Authors: Kerr Shona M. , Cowan Emma , Klaric Lucija , Bell Christine , O’Sullivan Dawn , Buchanan David , Grzymski Joseph J. , Center Regeneron Genetics , van Hout Cristopher V. , Tzoneva Gannie , Shuldiner Alan R. , Wilson James F. , Miedzybrodzka Zosia
Published: July 2022

The BRCA1 pathogenic missense variant c.5207T>C; p.Val1736Ala (V1736A) was multiply ascertained in the clinical investigation of breast and ovarian cancer families from Orkney in the Northern Isles of Scotland, UK. Oral history and birth, marriage and death registrations indicated genealogical linkage of the clinical cases to ancestors from the Isle of Westray, Orkney. Further clinical cases were identified through targeted testing for V1736A in women of Orcadian ancestry attending National Health Service (NHS) genetic clinics for breast and ovarian cancer family risk assessments. Fourteen mutation carriers were identified from predictive tests in relatives of affected members of the index kindred, nine more from NHS diagnostic testing plus a further six obligate carrier females. The variant segregates with female breast and ovarian cancer in clinically ascertained cases. Separately, exome sequence data from 2,090 volunteer participants with three or more Orcadian grandparents, in the ORCADES research cohort, was interrogated to estimate the population prevalence of V1736A in Orcadians. The effects of the variant were assessed using Electronic Health Record (EHR) linkage. Twenty out of 2,090 ORCADES research volunteers (∼1%) carry V1736A, with a common haplotype around the variant. This allele frequency is ∼480-fold higher than in UK Biobank participants. Cost-effectiveness of population screening for a single BRCA1 founder mutation has been demonstrated at a carrier frequency below the ∼1% observed here. Thus we suggest that Orcadian women should be offered testing for the BRCA1 V1736A founder mutation, starting with those with ancestry from Westray.
The Potential Clinical Impact of Implementing Different COVID-19 Boosters in Fall 2022 in the United States
Authors: Kohli Michele A. , Maschio Michael , Lee Amy , Fust Kelly , Van de Velde Nicolas , Buck Philip O. , Weinstein Milton C.
Published: July 2022

Objective

Emerging SARS-COV-2 variants are spurring the development of adapted vaccines as public health authorities plan for the fall vaccination strategy. We aimed to estimate the number of infections and hospitalizations prevented by three potential booster strategies in those ≥18 years of age in the United States: Boosting with Moderna’s licensed first generation monovalent vaccine mRNA-1273 (ancestral strain) starting in September 2022, boosting with Moderna’s candidate bivalent vaccine mRNA-1273.214 (ancestral + BA.1 variant of concern [VOC]) starting in September 2022, or boosting with Moderna’s updated candidate bivalent vaccine mRNA-1273.222 (ancestral + BA.4/5 VOC) starting 2 months later in November 2022 due to longer development timeline.

Methods

An age-stratified, transmission dynamic, Susceptible-Exposed-Infection-Recovered (SEIR) model, adapted from previous literature, was used to estimate the number of infections over time; the model contains compartments defined by both SEIR status and vaccination status. A decision tree was subsequently used to estimate the clinical consequences of those infections. Calibration was performed so the model tracks the actual course of the pandemic up to the present time.

Results

Vaccinating with mRNA-1273(Sept), mRNA-1273.214(Sept), and mRNA-1273.222(Nov) is predicted to reduce infections by 34%, 40%, and 18%, respectively, over a 6-month time horizon (September-February) compared to no booster. Similarly, boosting in September prevents substantially more hospitalizations than starting to boost in November with a more effective vaccine (42%, 48%, and 25% for mRNA-1273, mRNA-1273.214, and mRNA-1273.222, respectively, at 6 months compared to no booster). Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning of natural and vaccine-induced immunity changed the magnitude of cases prevented but boosting with mRNA-1273.214 in September consistently prevented more cases of infection and hospitalization than the other two strategies.

Limitations and Conclusions

With the emergence of new variants, key characteristics of the virus that affect estimates of spread and clinical impact also evolve, making estimation of these parameters difficult, especially in heterogeneous populations. Our analysis demonstrated that vaccinating with the bivalent mRNA-1273.214 booster was more effective over a 6-month period in preventing infections and hospitalizations with a BA.4/5 subvariant than the tailored vaccine, simply because it could be deployed 2 months earlier. We conclude that there is no advantage to delay boosting until a BA.4/5 vaccine is available; earlier boosting with mRNA-1273.214 will prevent the most infections and hospitalizations.
Validation of SeptiCyte RAPID to discriminate sepsis from non-infectious systemic inflammation
Authors: Balk Robert , Esper Annette M. , Martin Greg S. , Miller Russell R. , Lopansri Bert K. , Burke John P. , Levy Mitchell , Opal Steven , Rothman Richard E. , D’Alessio Franco R. , Sidhaye Venkataramana K. , Aggarwal Neil R. , Greenberg Jared A. , Yoder Mark , Patel Gourang , Gilbert Emily , Parada Jorge P. , Afshar Majid , Kempker Jordan A. , van der Poll Tom , Schultz Marcus J. , Scicluna Brendon P. , Klein Klouwenberg Peter M.C. , Liebler Janice , Blodget Emily , Kumar Santhi , Navalkar Krupa , Yager Thomas D. , Sampson Dayle , Kirk James T. , Cermelli Silvia , Davis Roy F. , Brandon Richard B.
Published: July 2022

(1) Background

SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospective banked and prospectively collected patient samples.

(2) Methods

The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ∼1 hour. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N=356) and prospective (N=63) samples were tested from adult patients in ICU either having the systemic inflammatory response syndrome (SIRS), or suspected of / diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework.

(3) Results

Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Area Under the ROC Curve (AUC) ranging from 0.82 to 0.85, negative predictive value 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and positive predictive value 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. Comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3.

(4) Conclusions

This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.