bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and safety of electroacupuncture for ankylosing spondylitis: A protocol for a systematic reviews and meta-analysis
Authors: Liu Shenghui , Zheng Jiangxia , Wen Xiuzhen , Fang Qun , Zhang Xifeng
Published: November 2022

Introduction:

Ankylosing spondylitis (AS) is a type of autoimmune disease commonly characterized by joint pain and stiffness. This disease progression can exhibit common deformities and other activities with limited symptoms and significantly impacts people’s work and life. Electroacupuncture (EA) as a traditional Chinese therapy, showing several advantages (e.g., safety, economy, and less side effects), has been extensively used to treat AS. However, its curative effect is supported by limited evidence. Accordingly, the present study aims to comprehensively assess the reliability of EA in AS treatment.

Methods and analysis:

The study will conduct a systematic review and meta-analysis. Seven databases, including the Embase, Cochrane Library, Pubmed, SinoMed, CNKI, VIP, and Wanfang Data, will be searched using predefined search terms to identify relevant studies. The primary outcomes will be the clinical efficiency, the Bath AS Disease Activity Index, and the Visual Analog Scale. Eligible studies should report at least 1 of these primary outcomes. Eligible studies designed as randomized controlled trials will be included for meta-analysis, while other related clinical studies will be reviewed. The methodological quality of the included studies will be assessed with a previously established checklist. The Cochrane Collaboration’s bias risk tool will be used for assessing the bias of included randomized controlled trials. Stata 17.0 software is used for meta-analysis.

Results:

The protocol will be used to assess the efficacy and safety of EA in AS treatment.

Conclusion:

This review reliably evidences whether EA is a reliable method for the intervention of AS.
Fatigue and depression in elderly patients with poorly controlled diabetes
Authors: Esen Irfan , Akturk Esen Selin , Demirci Hakan
Published: November 2022

In this study, it was aimed to evaluate the severity of depression and fatigue in patients with type 2 diabetes mellitus (T2DM), aged ≥ 60 years, with poor diabetes control. Between December 2018 and June 2019, 310 patients aged ≥ 60 years, with hemoglobin A1C ≥ 10%, followed-up with the diagnosis of T2DM for at least 3 years in the internal medicine outpatient clinics of Bursa Yüksek İhtisas Training and research hospital were included in the study. The geriatric depression scale (GDS) and fatigue severity scale (FSS) questionnaires were administered. Patients were analyzed according to their sociodemographic and clinical characteristics, according to their GDS and FSS scores. The GDS and FSS scores were higher in the female patients than in the male patients, those with diabetes aged ≥ 21 years than those aged < 21 years, those using premixed insulin than those using basal bolus insulin and oral antidiabetic drug for + basal insulin, and those living alone than in those living with their families. The FSS score was higher in patients with vitamin D levels < 20 ng/mL. The factors affecting the GDS score were the FGS and FSS scores in the multivariate analysis. The factors affecting the FSS score were the GDS, diabetes age, hemoglobin level, and vitamin D level in the multivariate analysis. Poorly controlled diabetes affects elderly patients more in terms of their mental and physical health. Therefore, these patients should be considered in terms of psychosocial aspects to increase treatment compliance and effects.
Sensory neuronopathy in a patient with neurofibromatosis type 1: A case report
Authors: Kang You-Ri , Hong Seong-Min , Choi Jong-Hee , Lee Seung-Jin , Kim Jae-Myung , Wook Kang Kyung , Nam Tai-Seung
Published: November 2022

Rationale:

Neurofibromatosis type 1 (NF-1) can manifest with various neurological symptoms. However, sensory ataxia has not been reported.

Patient concerns:

A 44-year-old man with NF-1 presented with several weeks of unsteady gait. He was diagnosed with gastric neuroendocrine tumor with multiple hepatic metastases 6 years ago and received palliative chemotherapy. Neurological examination revealed ataxia veering to the right side with no motor weakness.

Diagnoses:

Clinical manifestations and electrodiagnostic studies suggested the dysfunction of the thoracic dorsal column (DC). Initial magnetic resonance imaging showed a lateral thoracic meningocele (LTM) located in the right paravertebral area at the T3-T4 vertebral level, but the spinal cord was unremarkable. Gait disturbance worsened after 9 months, and follow-up magnetic resonance imaging showed high signal intensity involving the right DC at the level adjacent to the LTM and spinal cord atrophy distal to the DC lesion. Tests for well-characterized paraneoplastic antibodies were negative. Ultimately, the patient was assumed to have sensory neuronopathy due to compressive damage to the dorsal root ganglia within the intervertebral foramina by LTM.

Interventions:

Empirical treatment with vitamin B12 supplementation and corticosteroids failed to improve his condition. The patient underwent decompressive laminectomy and excision of the meningocele with dura repair.

Outcomes:

The patient temporarily improved to walk with assistance postoperatively. However, he developed dyspnea and hypotension 5 weeks later. Carcinoid heart disease confined the patient to the bed. The patient died of pneumonia 3 months after the operation.

Lessons:

This case with NF-1 shows asymmetric sensory ataxia of subacute progression. LTM may contribute to the development of sensory neuronopathy by damaging sensory neurons of the dorsal root ganglia. The comorbidities of the patient, including gastric neuroendocrine tumor and LTM, made it challenging to investigate the pathomechanism.
Laboratory markers at admission to predict the presence of totally occluded culprit artery in NSTEMI
Authors: Yildirim Ufuk , Balaban Fuatcan
Published: November 2022

A significant proportion of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) have a totally occluded culprit artery (OCA). If these patients do not meet very high-risk criteria, they may be deprived of an immediate invasive strategy. Therefore, there is a need for markers that can predict OCA in patients with NSTEMI. A total of 357 consecutive patients with NSTEMI but without very high-risk criteria were included in this retrospective study. Two groups were formed: NSTEMI with OCA (n = 106) and NSTEMI with patent culprit artery (PCA) (n = 251). Complete blood count (CBC) and serum biochemical parameters obtained immediately at admission were compared between the groups. Receiver operating characteristic (ROC) analysis to predict the presence of OCA was performed for the parameters that were significantly different between the groups, and an area under the curve (AUC) > 0.7 was considered to suggest acceptable discrimination. Neutrophil count [8.13 (2.82‐27.88) × 103/µL vs 5.59 (1.85‐19.71) × 103/µL, P < .001] and aspartate aminotransferase (AST) level [45 (12‐405) U/L vs 25 (5‐143) U/L, P < .001] were significantly higher in patients with OCA. The AUC was 0.750 for neutrophil count and 0.731 for AST level. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of elevated neutrophil and/or AST levels for the presence of OCA were 77.4%, 70.1%, 52.2%, and 88.0%, respectively. More strikingly, the specificity was 95.2% in the presence of both neutrophil and AST elevation. Elevated neutrophil and/or AST levels at admission were strongly associated with the presence of OCA in patients with NSTEMI.
Biosafety protection and workflow of clinical microbiology laboratory under COVID-19: A review
Authors: Zhou Wenjun , Zou Limin , Zhu Fenyong , Yang Jie
Published: November 2022

This paper mainly discusses how to do a good job of daily biosafety protection measures in clinical microbiology laboratories during the epidemic of COVID-19, so as to ensure the safe development of routine clinical microbiology testing items. According to the microbiological and epidemiological characteristics of the novel coronavirus, this paper analyzed the potential risks of the laboratory from the perspective of personal protection before, during, and after testing. Combined with the actual work situation, the improved biosafety protection measures and optimized work flow are introduced to ensure the safety of medical staff and the smooth development of daily work. Danyang People’s Hospital of Jiangsu Province, clinical microbiology laboratory of clinical laboratory in strict accordance with the relevant laws and regulations, technical specifications and the expert consensus, combined with their own conditions, the biosafety measures to perfect the working process was optimized, effectively prevent the laboratory exposure, and maintain strict working condition for a long time, continue to improve. We found that the biosafety protection measures of clinical microbiology laboratory have good prevention and control effect on preventing infection of medical staff, which will greatly reduce the risk of infection of medical staff, form good working habits, and provide reference for biosafety protection of microbiology laboratory during the epidemic of COVID-19.
Laparoscopic hepatectomy for the treatment of pyogenic liver abscess: A retrospective case-control study
Authors: Zeng Xintao , Luo Hua , Yang Pei
Published: November 2022

Percutaneous catheter drainage is the first-line treatment for pyogenic liver abscess (PLA). Some patients need hepatectomy because of underling hepatobiliary pathology or unresponsiveness to nonoperative treatment, the traditional method is open hepatectomy (OH). Laparoscopic hepatectomy (LH) for PLA is rarely reported. The purpose of this study is to describe our experience of LH for treating PLA and to compare LH with OH. The medical records of patients who underwent LH for treating PLA were retrospectively analyzed, and the results were compared with those of patients with OH. From January 2015 to December 2021, 61 patients with PLA underwent hepatectomy, and 28 patients who underwent LH (LH group) were compared with 33 patients who underwent OH (OH group). There were no significant differences in the basic data between the 2 groups. Two patients in the LH group were converted to open surgery due to hemorrhage and dense perihepatic adhesions, there was no significant difference between the 2 groups in the operation time (186.2 ± 85.6 vs. 175.9 ± 76.7 minutes, P = .239), Institut Mutualiste Montsouris classification, extent of hepatectomy and drainage tube removal time, however, the blood loss (200.0 ± 100.5 vs. 470.9 ± 120.1 mL, P = .003), numerical rating scale (5.2 ± 1.8 vs. 9.1 ± 1.6, P = .042), the time to resume oral diet (12.3 ± 6.5 vs. 24.6 ± 10.2 hours, P = .005), the ambulant time (20.2 ± 7.3 vs. 40.2 ± 10.8 hours, P = .010), incidence of postoperative complications (14.3% vs.33.3%, P = .002), comprehensive complication index (46.2 vs. 60.6, P = .013), postoperative hospital stay (8.5 ± 7.3 vs. 13.5 ± 10.2 days, P = .025) in the LH group was significantly less than that in the OH group. Wit experience laparoscopic surgeons, treating PLA by LH is safe and feasible and compares favorably with OH.
A Bayesian network analysis of immunotherapy and taxane chemotherapy as second- or later-line treatments in non-small cell lung cancer
Authors: Liu Xin-Xiu , Lin Guo-He , Wang Bi-Cheng
Published: November 2022

Background:

Taxane chemotherapy represents the standard of care in the second-line setting for non-small cell lung cancer (NSCLC) patients, but immunotherapy agents pose great challenges. Whether immunotherapy/chemotherapy alone or combination therapy has more benefits remains controversial. In this study, we provided comparisons to integrate the efficacy of immunotherapy and taxane chemotherapy as second- or later-line treatments in advanced NSCLC.

Methods:

PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to September 1, 2020. Randomized controlled trials comparing immunotherapy and taxane chemotherapy were enrolled in the Bayesian network analysis. Overall survival (OS) and progression-free survival (PFS) with hazard ratios (HRs) were investigated.

Results:

Eight trials in 13 studies with 4398 patients comparing seven treatments were identified. Pembrolizumab 10 mg/kg was associated with the best improved OS, with significant differences versus docetaxel (HR 0.81, 95% credible interval [CrI] 0.74‐0.88), avelumab (HR 0.84, 95% CrI 0.75‐0.95), and pembrolizumab 200 mg plus docetaxel (HR 0.75, 95% CrI 0.56‐1.00). Although pembrolizumab 200 mg plus docetaxel ranked the last in terms of OS, the combination therapy showed the most favorable PFS. Additionally, the anti-programmed death-ligand 1 (PD-L1) agent, avelumab, was associated with the least improvement in PFS.

Conclusion:

As second- or later-line therapeutic strategies, pembrolizumab 10 mg/kg provided the largest OS benefits and pembrolizumab 200 mg plus docetaxel improved PFS to the greatest extent. Considering that immunotherapy has been recommended to the first-line setting of NSCLC, advanced patients who have not received immunotherapy previously might be the suitable population for our findings.
Coexistence of condyloma acuminatum and extramammary Paget’s disease on penis and scrotum: A rare case report
Authors: Kang Inho , Lee Joon Ho , Lee Jong Im , Hong Joon Shik , Mo Young Woong , Jung Gyu Yong
Published: November 2022

Rationale:

Extramammary Paget’s disease (EMPD) is a rare skin cancer that commonly occurs in sites rich in apocrine glands, such as perineum, vulva, axilla, scrotum, and penis. On the other hand, condyloma acuminatum (CA; also referred to as anogenital warts) is a common benign neoplasm caused by human papillomavirus. Few cases of coexistent EMPD and CA have been reported because of the rarity of the condition.

Patient concerns and diagnosis:

A 72-year-old man with a genital mass, which appeared to be composed of multiple papillomatous masses, was referred for surgical resection. The lesion was first noticed 6 months previously and grew rapidly. CO2 ablative laser therapy was performed twice at a primary clinic, but the mass recurred.

Intervention and outcomes:

Excisional biopsy revealed the presence of coexistent EMPD and CA. Additional wide excision was performed, and postoperative biopsy confirmed no residual tumor. Two years after surgery, no recurrence had occurred.

Lessons:

CA can co-occur with several types of skin malignancies, and a skin malignancy coexisting with CA is difficult to diagnose visually. Therefore, even if a skin lesion in the genital region is considered to be CA, we recommend punch biopsy before treatment because it can benefit prognosiss.
Septic pulmonary embolism and subsequent bilateral pneumothorax in patients undergoing chemoradiotherapy for head angiosarcoma: An autopsy case report and literature review
Authors: Ikejiri Kaoru , Goto Hiroyuki , Usui Miki , Nakayama Yuichi , Sugioka Kyoko , Ito Asami , Suzuki Kei , Hirokawa Yoshifumi , Yamanaka Keiichi , Imai Hiroshi
Published: November 2022

Rationale:

Septic pulmonary embolism (SPE) and subsequent pneumothorax are rare but serious conditions. We report a case of SPE and pneumothorax caused by central venous port (CV port) infection.

Patient concerns:

A 73-year-old woman, who underwent chemoradiotherapy for a head angiosarcoma and a CV port placement, presented with general malaise and myalgia.

Diagnosis:

A laboratory examination showed high levels of inflammatory markers. Chest computed tomography showed fluid collection around the CV port and multiple ground-glass opacities and nodular shadows in the bilateral lung field. She was admitted with a diagnosis of SPE due to CV port infection. The port was removed, and antibiotic administration was initiated; however, she was intubated because of refractory septic shock. Methicillin-susceptibleStaphylococcus aureuswas detected in the blood and pus around the port site.

Interventions:

Her respiratory status did not improve despite recovering from septic shock, and radiologic findings showed a left pneumothorax and exacerbation of SPE on day 9. Her condition was judged ineligible for surgery for pneumothorax, and chest tube thoracostomy was continued.

Outcomes:

Air leaks persisted after chest tube thoracostomy, and her respiratory status did not improve despite ventilator management and recruitment maneuvers. Moreover, a right pneumothorax developed on day 19. Her respiratory status gradually worsened, and she died on day 21. Autopsy showed multiple cavitary lesions in the bilateral lungs and emboli containing organization and inflammatory cells that obstructed the pulmonary arterioles.

Lessons:

This case indicates that CV port-related infections are infrequent and difficult to diagnose; understanding the clinical features of SPE is important because of its high mortality rate; and pneumothorax secondary to SPE is a rare but serious condition and is difficult to treat during ventilator management.
Risk factors for infection in older adults who receive home healthcare and/or home help: A protocol for systematic review and meta-analysis
Authors: Liljas Ann E.M. , Agerholm Janne , Schön Pär , Burström Bo
Published: November 2022

Background:

The shift towards home-based care has resulted in increased provision of home healthcare and home help to older adults. Infections acquired in older adults while receiving home care have increased too, resulting in unplanned yet avoidable hospitalizations. In recent years, several studies have reported an array of factors associated with risk of infection; however, no previous systematic review has compiled such evidence, which is important to better protect older adults. Therefore, we have outlined the work of a systematic review that aims to identify risk factors for infection in older adults receiving home healthcare and/or home help.

Methods:

Searches for relevant studies will be conducted in five databases [MEDLINE, EMBASE (Excerpta Medica Database), Web of Science Core Collection, Cinahl (Cumulative Index to Nursing & Allied Health Literature) and Sociological Abstracts]. All types of studies will be included. Exposures considered refer to medical, individual, social/behavioral and environmental risk factors for infection (outcome). Two researchers will independently go through the records generated. Eligible studies will be assessed for risk of biases using the Cochrane risk of bias assessment tool and an overall interpretation of the biases will be provided. If the data allow, a meta-analysis will be conducted. It is possible that both quantitative and qualitative studies will be identified and eligible. Therefore, for the analysis, the Joanna Briggs Institute Reviewers’ Manual for mixed methods systematic reviews will be used as it allows for two or more single method reviews (e.g., one quantitative and one qualitative) to be conducted separately and then combined in a joint overarching synthesis.

Results:

The findings of the planned systematic review are of interest to healthcare professionals, caregivers, older adults and their families, and policy- and decisions makers in the health and social care sectors as the review will provide evidence-based data on multiple factors that influence the risk of infection among older adults receiving care in their homes.

Conclusion:

The results could guide future policy on effective infection control in the home care sector.
Type 2 diabetes mellitus and cognitive function: understanding the connections
Authors: Dao Lisa , Choi Sarah , Freeby Matthew
Published: November 2022

Purpose of review

To review the connection between type 2 diabetes and cognitive dysfunction, including its epidemiology, potential mechanisms of pathophysiology, risk factors, possible prevention, and treatment considerations.

Recent findings

Diabetes is a risk factor for mild cognitive decline, in addition to Alzheimer's disease and vascular dementia. Duration of diabetes, concomitant vascular or associated co-morbidities, hyper- and hypoglycemia may lead to worsening cognitive dysfunction. Unfortunately, there is a lack of evidence-based guidance on the prevention of cognitive dysfunction in the diabetes population. Studies of diabetes medications, including metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2) have shown some benefit with cardiovascular morbidity and may affect cognition. In the absence of clearly defined preventive tools, diabetes practice guidelines recommend annual cognitive screening as standard of care in adults with diabetes aged 65 years or older.

People living with diabetes are at risk for significant decline in cognitive function. Epidemiology and risk factors are well defined. Prevention and treatment strategies are limited and require further study.
The Natural Course of Pancreatic Cysts in Inflammatory Bowel Disease
Authors: Abou Saleh Mohannad , Alkhayyat Motasem , Habash Alaa , Almomani Ashraf , Qayyum Farhan , Kim Woan , Bena James , Martin Charles , Regueiro Miguel , Rieder Florian , Simons-Linares Carlos Roberto , Chahal Prabhleen
Published: November 2022

Objectives

The natural course of pancreatic cysts in inflammatory bowel disease (IBD) is unknown. We aim to describe the natural course of pancreatic cysts in IBD and evaluate long-term outcomes.

Methods

A database of patients with abdominal imaging diagnosis of pancreatic cysts (2008–2019) was reviewed. Patients with IBD and pancreatic cysts (study group) and pancreatic cysts without IBD (controls) were selected. Outcomes were measured at 1, 3, 5, and 10 years. Several logistic regression models were used for analysis.

Results

Of the 1789 patients evaluated, 1690 had pancreatic cysts without IBD, and 78 had IBD and pancreatic cysts. Majority of cysts were intraductal papillary mucinous neoplasms. Patients with IBD and pancreatic cysts were more likely to be diagnosed with pancreatic cysts at a younger age (P < 0.001) and were more likely to undergo surgical intervention at a younger age (P < 0.001).

Conclusions

This is the first study to evaluate the natural course of pancreatic cysts in IBD patients. Patients with IBD were more likely to have pancreatic cysts detected at a younger age. Despite the early presentation, there were no differences in long-term outcomes. Patients with IBD with pancreatic cysts should be managed similarly to those without IBD.
A Real-World, Population-Based Study for the Incidence and Outcomes of Neuroendocrine Neoplasms of Nondigestive, Nonpulmonary Primary
Authors: Abdel-Rahman Omar , Ghosh Sunita
Published: November 2022

Objectives

The aim of this study was to assess incidence and outcomes of neuroendocrine neoplasms (NENs) arising from primary sites other than digestive organs, lung, or thymic gland.

Methods

Surveillance, Epidemiology, and End Results database (1975–2016) was accessed, and cases of NENs arising from primary sites other than digestive organs, lung, or thymic gland were reviewed. Overall and cancer-specific survival outcomes for NENs arising from different organs compared with small intestinal NENs were evaluated.

Results

A total of 4405 patients were included in the study. Compared with small intestinal NENs, some NENs arising from uncommon sites in the current study have worse cancer-specific survival (hazard ratio [HR] for genitourinary vs small intestinal NENs, 1.80; 95% confidence interval [CI], 1.44–2.25; HR for gynecological vs small intestinal NENs, 1.88; 95% CI, 1.52–2.33). When the analysis was limited for patients with distant stage only, small intestinal NENs have better outcomes compared with genitourinary and gynecological NENs (HR for genitourinary NENs with distant stage vs small intestinal NENs with distant stage, 1.38; 95% CI, 1.01–1.88; HR for gynecological NENs with distant stage vs small intestinal NENs with distant stage, 2.02; 95% CI, 1.54–2.66).

Conclusions

Compared with small intestinal NENs, NENs arising from uncommon sites (such as genitourinary, gynecological) have worse survival outcomes.
Giant Pancreatic Myoepithelial Hamartoma in a Patient With Familial Insulin-Dependent Diabetes Mellitus
Authors: Sharib Jeremy , Ord Jeffrey R. , Bentley Rex C. , Shi Chanjuan , Blazer Dan G.
Published: November 2022

Pancreatic myoepithelial hamartoma is a rare, benign solid and cystic lesion of the pancreas. We present the first case of an adult with a giant myoepithelial hamartoma extending throughout the pancreas in a patient with diabetes in 4 immediate family members. The patient is a 46-year-old man presented with recurrent acute pancreatitis. Computed tomographic imaging showed that the head and body of the pancreas were replaced by a solid-cystic mass with focal calcification. Medical history includes insulin-dependent diabetes mellitus (IDDM) diagnosed at age 30. Endoscopic ultrasound-guided fine-needle aspiration showed pancreatic acinar tissue and smooth muscle without evidence of malignancy. Total pancreatectomy was performed because of the diffuse nature of the cystic disease and preexisting IDDM. The histopathologic diagnosis was consistent with myoepithelial hamartoma. In addition, there was a family history of IDDM and hamartomatous cyst resection in the paternal grandmother. We report the first case of diffuse pancreatic myoepithelial hamartoma with near total replacement of the entire pancreatic parenchyma, and the first reported case associated with a family history of heritable IDDM. Improved knowledge of the genetics, development, and malignant potential of such rare diseases is critical to determine appropriate management for patients.
Assuring a Continuum of Care for Heart Failure Patients Through Postacute Care Collaboration
Authors: Krishna Purnima
Published: November 2022

Purpose/Objectives:

This review evaluates the published studies on how postacute care collaboration ensures a continuum of care and reduces heart failure (HF) readmissions.

Primary Practice Setting:

An integrated literature review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. PubMed and Cumulative Index to Nursing and Allied Health were searched for the keywordsheart failure AND (post-acute care OR transitional care OR skilled nursing facility OR rehabilitation facility OR home healthagency)AND (readmission) AND (care coordination OR collaboration OR interprofessional OR partnerships).Seventy-nine studies were returned, and a reverse reference search yielded four studies. Of those studies, 14 were selected for critical appraisal of evidence. The practice settings of these studies were hospitals, homes, home health agencies, and skilled nursing facilities.

Findings/Conclusions:

Multidisciplinary management of HF patients, high-impact transitional care interventions, and integration with postacute care facilities decreased HF 30-day readmissions. Collaborative models involving a skilled HF team, primary care physicians, and postacute care partners, and targeting postdischarge follow-ups positively impacted outcomes. Bundling interventions, such as home visits, follow-ups (telephone and/or clinic follow-up), and telecare, significantly impacted outcomes compared with their delivery in isolation.

Implications for Case Management Practice:

Case management leaders are vital decision-makers and key stakeholders in building the collaboration with community partners. As case management roles extend to outpatient and ambulatory care, better opportunities emerge to coordinate services across settings. Key takeaways for the case management practice is to build a robust case management program spanning postacute care facilities, evidence-based treatment protocols, and infrastructure that supports seamless information sharing between sites.
Fibromyxoid Nephrogenic Adenoma
Authors: Li Lin , Williamson Sean R. , Castillo Rosa P. , Delma Katiana S. , Gonzalgo Mark L. , Epstein Jonathan I. , Kryvenko Oleksandr N.
Published: November 2022

Nephrogenic adenoma is a benign epithelial lesion of the genitourinary tract that arises from the reimplantation and proliferation of shed renal tubular cells in areas of urothelial injury and denudation. Fibromyxoid nephrogenic adenoma is a rare variant that consists of compressed spindle-shaped renal epithelial cells in a fibromyxoid background. Only 14 observations of this variant are reported in the literature. We performed a retrospective analysis of fibromyxoid nephrogenic adenomas from 3 large reference centers. We identified 43 lesions in 6 women and 36 men (2 in 1 man) with a median age of 72 years (range, 31 to 94 y). Median lesion size was 0.7 cm (range, 0.2 to 5 cm). Nephrogenic adenomas were in the bladder (n=15), prostate/prostatic urethra (n=14), kidney (n=7), ureter (n=3), penile urethra (n=3), and urethral diverticulum (n=1). One of the kidney lesions developed in an end-stage kidney and radiologically mimicked cancer. Of 37 patients with information, 36 had predisposing conditions including prior biopsy, transurethral resection of bladder tumor, resection, Foley catheter, BCG treatment, urinary stones, (chemo)radiation, or diverticulum. Only 4/37 (10.8%) had a history of prior irradiation. Fifteen lesions had pure fibromyxoid morphology and 28 were admixed classic and fibromyxoid patterns. Three nephrogenic adenomas involved prostatic stroma, 3 renal sinus fat, 2 muscularis propria (1 bladder, 1 renal pelvis), 1 perinephric fat, and 1 corpus spongiosum. Ten fibromyxoid nephrogenic adenomas were intermixed with urothelial carcinoma, 1 with prostate adenocarcinoma, and 1 with malignant melanoma. By immunohistochemistry, PAX8 was positive in all the examined lesions (n=31). Napsin A was negative in all examined fibromyxoid nephrogenic adenomas (n=30). Twenty of them had classic nephrogenic adenoma component which was positive for napsin A. Similar to classic nephrogenic adenoma, fibromyxoid nephrogenic adenoma can occur anywhere along the urinary tract and is associated with a prior history that causes urothelial injury. In nearly a quarter of the cases, fibromyxoid nephrogenic adenoma extended beyond the lamina propria. Unlike previously suggested, fibromyxoid nephrogenic adenoma is not specifically related to prior radiation therapy. Awareness of this variant is important to avoid misdiagnosis and overtreatment.
TRAF7-mutated Fibromyxoid Spindle Cell Tumors Are Associated With an Aggressive Clinical Course and Harbor an Undifferentiated Sarcoma Methylation Signature
Authors: Dermawan Josephine K. , Villafania Liliana , Bale Tejus , Singer Samuel , D’Angelo Sandra P. , Tap William D. , Antonescu Cristina R.
Published: November 2022

TRAF7 somatic mutations are rare and have been reported in meningiomas, intraneural perineuriomas, and mesotheliomas. Triggered by an index case of an unclassified low-grade mesenchymal tumor with TRAF7 mutation as the only genetic alteration, we searched our files and identified 2 additional cases with similar features. The tumors arose in 2 females and 1 male, aged 63 to 75 years old (median: 67 y). They were infiltrative deep soft tissue masses involving the shoulder, chest wall, and thigh, measuring 7.0 to 9.1 cm in greatest dimensions. One tumor was locally aggressive, and 2 were associated with lung and bone metastases. The tumors displayed alternating fibrous and myxoid stroma with mild to moderate cellularity and consisted of uniform spindle cells with open chromatin, inconspicuous nucleoli and scant cytoplasm. Significant mitotic activity or necrosis were not present. However, the metastatic tumor of 1 case showed an epithelioid morphology and brisk mitotic activity. Immunohistochemically, the tumors showed nonspecific and focal smooth muscle actin or CD34 expression. By DNA sequencing, all 3 cases harbored TRAF7 missense mutations involving the C-terminal WD40 domains as the only somatic mutations, showed nonrecurrent focal copy number alterations, and were negative for gene fusions by targeted RNA sequencing. On methylation profiling, the tumors clustered with the undifferentiated sarcoma and myxofibrosarcoma methylation classes and were distinct from morphologic mimics. On follow-up (5 to 36 mo), 2 patients died of disease following aggressive chemotherapeutic regimens. We describe a novel TRAF7-mutated mesenchymal tumor characterized by aggressive clinical behavior despite the histologic appearance of a low-grade fibromyxoid spindle cell tumor.
Localization Evaluation of Primary Middle Ear Cholesteatoma With Fusion of Turbo Spin-Echo Diffusion-Weighted Imaging and High-Resolution Computed Tomography
Authors: Fan Xiaoxue , Ding Changwei , Liu Zhaoyu
Published: November 2022

Objective

The aim of the study is to evaluate the application of high-resolution computed tomography (HRCT) and turbo spin-echo diffusion-weighted imaging (TSE-DWI) fusion imaging for localization of middle ear cholesteatomas.

Methods

Eighty-six patients with clinically suspected middle ear cholesteatomas were enrolled prospectively. Ear TSE-DWI and HRCT scans were performed using a postprocessing workstation to generate a TSE-DWI-CT fusion image. Subsequently, all the enrolled patients received surgical treatment. According to the STAM system (difficult access sites [S], the tympanic cavity [T], the attic [A], and the mastoid [M]), the agreement between the localization of lesions evaluated by HRCT, TSE-DWI, and TSE-DWI-CT fusion images and the intraoperatively recorded localization were computed using Cohen κ statistic.

Results

Based on the pathological results, the enrolled patients were divided into a cholesteatoma (n = 50) and a noncholesteatoma group (n = 36). The area under the receiver operator characteristic curve for diagnosis of cholesteatoma with TSE-DWI-CT fusion imaging was identical to that using the TSE-DWI images (0.924 vs 0.924, P > 0.05), but was significantly higher than that with HRCT imaging (0.924 vs 0.767, P = 0.0005). Furthermore, the diagnostic sensitivity and specificity of TSE-DWI-CT fusion imaging for cholesteatomas were 96.0% and 88.9%, respectively. Depending on whether the cholesteatoma extended to the mastoid, TSE-DWI-CT fusion imaging demonstrated good agreement with the intraoperative record for localization of lesions (κ = 0.808) and had a high accuracy of localization by the STAM system.

Conclusions

Turbo spin-echo–DWI–CT fusion images have a very high diagnostic value for the preoperative localization of cholesteatomas.
DETERMINANTS OF PRETERM BIRTH IN PUBLIC HOSPITALS OF HORRO GUDURU WOLLEGA ZONE, WESTERN ETHIOPIA: UNMATCHED CASE CONTROL STUDY
Authors: Duresa Warkisa Bayisa , Atomssa Emiru Merdassa , Wakuma Bizuneh , Ebi Worku Etafa
Published: November 2022

Background

Preterm birth is one of a public health issue worldwide. It is a single most important cause of death in the first month of life and second leading cause of death in children aged less than five years. The cause of preterm birth is multifactorial and not well identified. Therefore, the aim of this study was to identify determinants of preterm birth in public hospitals of Horro Guduru Wallaga zone, Western Ethiopia.

Methods

Hospital-based unmatched case-control study design was carried out in public hospitals of Horro Guduru Wallaga zone which involved 78 cases and 155 controls. Data were collected using pre-tested questionnaires from three hospitals. Data were entered in to EpiData and exported to SPSS version 25 for analysis. Frequency and proportion were computed to summarize the data. Ethical approval was made by Wollega University Research Ethical Review Committee before the study was started. Multivariable binary logistic regression analysis was used to determine the association of predictor and response variable at P < 0.05. Adjusted odds ratio with 95% CI was used to show the strength of association between predictors and outcome variables.

Results

Out of 233 mothers, 231(78 cases and 153 controls) were participated with response rate, 99.14%. The result of this study showed that not attending ANC (AOR= 4.61, 95%CI; 1.54, 13.79), history of abortion(AOR =3.88, 95% CI; 1.62, 9.30), Premature rupture of the membrane (AOR=3.91,95% CI;1.15,13.25), Sexually transmitted illness (AOR=3.51,95% CI; 1.26,9.76) and physical violence (AOR=2.78, 95%CI;1.19,6.52) had significant association with preterm birth.

Conclusions

The result of this study showed that not attending antenatal care, history of abortion, premature rupture of membrane, sexually transmitted illness and physical violence identified as potential risk factors of preterm birth. Therefore, it is important to encourage pregnant mothers to have optimum antenatal care follow-up. Healthcare providers should also focus on screening and counseling pregnant mother on obstetric complications and limiting physical violence.
Aerosolization of viableMycobacterium tuberculosisbacilli by tuberculosis clinic attendees independent of sputum-GeneXpert status
Authors: Patterson Benjamin , Dinkele Ryan , Gessner Sophia , Koch Anastasia , Hoosen Zeenat , January Vanessa , Leonard Bryan , McKerry Andrea , Seldon Ronnett , Vazi Andiswa , Hermans Sabine , Cobelens Frank , Warner Digby F. , Wood Robin
Published: November 2022

The potential for bioaerosol release ofMycobacterium tuberculosis(Mtb) during different tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolizedMtbfrom presumptive TB patients on diagnosis and, thereafter, through six months’ standard chemotherapy. At presentation, TB clinic attendees (n=102) were classified by laboratory, radiological, and clinical features into Group A: Sputum-GeneXpert-positive TB (n=52), Group B: Sputum-GeneXpert-negative TB (n=20), or Group C: TB not diagnosed (n=30). All were assessed forMtbbioaerosol release at baseline, and subsequently at two weeks, two months, and six months. In Groups A and B, comprising notified TB cases,Mtbwas isolated from 92% and 90% of participants at initial presentation; 87% and 74% at two weeks; 54% and 44% at two months; and 32% and 20% at six months, respectively. Surprisingly, similar numbers were detected in Group C: 93%, 70%, 48%, and 22% at the same timepoints. We also observed a temporal association betweenMtbbioaerosol release and TB symptoms in all three groups, with 30% of participants remainingMtbbioaerosol positive at six months irrespective of TB chemotherapy. CapturedMtbbacilli were predominantly acid-fast stain-negative and poorly culturable; however, followingin vitroincubation, one sputum-GeneXpert-positive and two sputum-GeneXpert-negative aerosol samples yielded sufficient biomass for whole-genome sequencing, revealing two differentMtblineages. The detection of viable aerosolizedMtbin most clinic attendees at presentation, independent of TB diagnosis, suggests that unidentifiedMtbtransmitters could account for a significant attributable proportion of community exposure. However, longitudinal studies are required to investigate this possibility.

One Sentence Summary:M. tuberculosisbacilli are detected in bioaerosols of presumptive tuberculosis (TB) patients irrespective of final TB diagnosis and clear over time.
A Machine Learning Algorithm to Predict Hypoxic Respiratory Failure and risk of Acute Respiratory Distress Syndrome (ARDS) by Utilizing Features Derived from Electrocardiogram (ECG) and Routinely Clinical Data
Authors: Marshall Curtis Earl , Narendrula Saideep , Wang Jeffrey , De Souza Vale Joao Gabriel , Jeong Hayoung , Krishnan Preethi , Yang Phillip , Esper Annette , Kamaleswaran Rishi
Published: November 2022

The recognition of Acute Respiratory Distress Syndrome (ARDS) may be delayed or missed entirely among critically ill patients. This study focuses on the development of a predictive algorithm for Hypoxic Respiratory Failure and associated risk of ARDS by utilizing routinely collected bedside monitoring. Specifically, the algorithm aims to predict onset over time. Uniquely, and favorable to robustness, the algorithm utilizes routinely collected, non-invasive cardiorespiratory waveform signals. This is a retrospective, Institutional-Review-Board-approved study of 2,078 patients at a tertiary hospital system. A modified Berlin criteria was used to identify 128 of the patients to have the condition during their encounter. A prediction horizon of 6 to 36 hours was defined for model training and evaluation. Xtreme Gradient Boosting algorithm was evaluated against signal processing and statistical features derived from the waveform and clinical data. Waveform-derived cardiorespiratory features, namely measures relating to variability and multi-scale entropy were robust and reliable features that predicted onset up to 36 hours before the clinical definition is met. The inclusion of structured data from the medical record, namely oxygenation patterns, complete blood counts, and basic metabolics further improved model performance. The combined model with 6-hour prediction horizon achieved an area under the receiver operating characteristic of 0.79 as opposed to the first 24-hour Lung Injury Prediction Score of 0.72.
Dynamic modulation of genomic enhancer elements in the suprachiasmatic nucleus mediates daily timekeeping in mammals
Authors: Bafna Akanksha , Banks Gareth , Hastings Michael H. , Nolan Patrick M.
Published: November 2022

The mammalian suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, is crucial for synchronising and resetting all cellular rhythms in accordance with critical environmental and visceral cues. Consequently, the systematic regulation of spatiotemporal gene transcription in the SCN is vital for daily timekeeping. Here, we sought to identify SCN enriched gene regulatory elements that enable temporal gene expression using histone-ChIP-seq. We found a vast majority of SCN enhancers not only exhibit robust 24-hour rhythmic modulation in H3K27ac occupancy, but also possess canonical E-box (CACGTG) motif, potentially influencing downstream cycling gene expression. In parallel, we conducted RNA-Seq at six distinct times to establish enhancer-gene relationships in the SCN. Surprisingly, around 35% of cycling H3K27ac abundance is seen adjacent to rhythmic gene transcripts, often preceding the rise in mRNA levels. We also noted that enhancers encompass non-coding actively transcribing enhancer RNAs (eRNAs), that in turn oscillate along with cyclic histone acetylation to direct gene transcription. Taken together, these findings shed light on genome-wide pre-transcriptional regulation operative in the central clock that enables its orchestration of daily timekeeping mechanisms in mammals.
Autism-specific PTEN p.I135L mutation and an autism genetic background combine to dysregulate cortical neurogenesis
Authors: Fu Shuai , Bury Luke , Eum Jaejin , Wynshaw-Boris Anthony
Published: November 2022

Alterations in cortical neurogenesis are implicated in neurodevelopmental disorders including autism spectrum disorders (ASDs). The contribution of genetic backgrounds, in additional to ASD risk genes, on cortical neurogenesis remain understudied. Here, using isogenic induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) and cortical organoid models, we report that a heterozygousPTENp.I135L mutation found in an ASD patient with macrocephaly activates PI3K/AKT and dysregulates cortical neurogenesis in an ASD genetic background-dependent fashion. Transcriptome analysis at both bulk and single cell level revealedPTENp.I135L mutation and ASD genetic background affected genes involved in neurogenesis, neural development and synapse signaling. We also found that thisPTENp.I135L mutation led to overproduction of NPC subtypes as well as neuronal subtypes including both deep and upper layer neurons in its ASD background, but not when introduced into a control genetic background. These findings provide experimental evidence that both aPTENp.I135L mutation and ASD genetic background contribute to cellular features consistent with ASD associated with macrocephaly.
Rapid, automated and experimenter-free assessment of cognitive flexibility reveals learning impairments following recovery from activity-based anorexia in female rats
Authors: Huang Kaixin , Milton Laura K , Dempsey Harry , Power Stephen J , Conn Kyna-Anne , Andrews Zane B , Foldi Claire J
Published: November 2022

Anorexia nervosa (AN) has among the highest mortality rates of any psychiatric disorder and is characterised by cognitive inflexibility that persists after weight recovery and contributes to the low rates of recovery. What remains unknown is whether cognitive inflexibility predisposes individuals to AN, a question that is difficult to determine from human studies. Our previous work using the most well-established animal model of AN, known as activity-based anorexia (ABA) identified a neurobiological link between cognitive inflexibility and susceptibility to pathological weight loss in female rats. However, testing flexible learning prior to exposure to ABA in the same animals has been thus far impossible due to the length of training required and the necessity of daily handling, which can itself influence the development of ABA.

Here we describe experiments that validate and optimise the first fully-automated and experimenter-free touchscreen cognitive testing system for rats (n=20) and use this novel system to examine the reciprocal links between reversal learning (an assay of cognitive flexibility) and weight loss in the ABA model (n=60). Firstly, we show substantially reduced testing time and increased throughput compared to conventional touchscreen testing methods because animals engage in test sessions at their own direction and can complete multiple sessions per day without experimenter involvement. We also show that, contrary to expectations, cognitive inflexibility does not predispose rats to pathological weight loss in ABA but instead that rats subsequently susceptible to weight loss performed better on the reversal learning task. Intriguingly, we show reciprocal links between ABA exposure and cognitive flexibility, with ABA exposed (but weight recovered) rats performing much worse that ABA naïve rats on the reversal learning task. On the other hand, animals that had been trained on reversal learning were better able to resist weight loss upon subsequent exposure to the ABA model. We also uncovered some stable behavioural differences between ABA susceptible versus resistant rats during touchscreen test sessions using machine learning tools that highlight possible predictors of anorectic phenotypes.

These findings shed new light on the relationship between cognitive inflexibility and pathological weight loss and provide a robust target for future studies using the ABA model to investigate potential novel pharmacotherapies for AN.
Tumor proliferation and invasion are coupled through cell-extracellular matrix friction
Authors: Crawford Ashleigh J. , Gomez-Cruz Clara , Russo Gabriella C. , Huang Wilson , Bhorkar Isha , Muñoz-Barrutia Arrate , Wirtz Denis , Garcia-Gonzalez Daniel
Published: November 2022

Cell proliferation and invasion are two key drivers of tumor progression and are traditionally considered two independent cellular processes regulated by distinct pathways. Throughin vitroandin silicomethods, we provide evidence that these two processes are intrinsically coupled through matrix-adhesion friction. Using novel tumor spheroids, we show that both tumor cell proliferation and invasion are limited by a volumetric carrying capacity of the system, i.e. maximum spatial cell concentration supported by the system’s total cell count, nutrient consumption rate, and collagen gel mechanical properties. To manipulate these phenotypes in breast cancer cells, we modulate the expression of E-cadherin and its associated role in adhesion, invasion, and proliferation. We integrate these results into a mixed-constitutive formulation to computationally delineate the contributions of cellular and extracellular adhesion, stiffness, and mechanical properties of the extracellular matrix (ECM) to the proliferative and invasive fates of breast cancer tumor spheroids. Both approaches conclude that the dominant drivers of tumor fate are system properties modulating cell-ECM friction, such as E-cadherin dependent cell-ECM adhesion and matrix pore size.