bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity and batokines
Authors: Ortiz Gabriela Ueta , de Freitas Ellen Cristini
Published: October 2023

Brown and beige adipose tissue share similar functionality, being both tissues specialized in producing heat through nonshivering thermogenesis and also playing endocrine roles through the release of their secretion factors called batokines. This review elucidates the influence of physical exercise, and myokines released in response, on the regulation of thermogenic and secretory functions of these adipose tissues and discusses the similarity of batokines actions with physical exercise in the remodeling of adipose tissue. This adipose tissue remodeling promoted by autocrine and paracrine batokines or physical exercise seems to optimize its functionality associated with better health outcomes.
Spinal cord injury significantly alters the properties of reticulospinal neurons: delayed repolarization mediated by potassium channels
Authors: Hough Ryan A. , McClellan Andrew D.
Published: October 2023

After spinal cord injury (SCI), lamprey reticulospinal (RS) neurons responded to subthreshold depolarizing current pulses with a transient depolarization, which included an initial depolarization that was due to passive channels followed by a delayed repolarization that was mediated by voltage-gated potassium channels. The conductance of these channels ( gK) was significantly increased for RS neurons after SCI and contributed to a reduction in excitability, which is expected to provide supportive conditions for subsequent axonal regeneration.
Visual feature tuning properties of stimulus-driven saccadic inhibition in macaque monkeys
Authors: Khademi Fatemeh , Zhang Tong , Baumann Matthias P. , Buonocore Antimo , Malevich Tatiana , Yu Yue , Hafed Ziad M.
Published: October 2023

Visual onsets dramatically reduce saccade generation likelihood with very short latencies. Such latencies suggest that stimulus-induced visual responses, normally jump-starting perceptual and scene analysis processes, can also directly impact the decision of whether to generate saccades or not, causing saccadic inhibition. Consistent with this, we found that changing the appearance of the visual onsets systematically alters the properties of saccadic inhibition. These results constrain neurally inspired models of coordination between saccade generation and exogenous sensory stimulation.
Brazilin from Caesalpinia sappan L. as a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor: Pharmacophore-Based Virtual Screening, In Silico Molecular Docking, and In Vitro Studies
Authors: Iqbal Muhammad , Hasanah Nur , Arianto Aimee Detria , Aryati Widya Dwi , Puteri Meidi Utami , Saputri Fadlina Chany
Published: October 2023

Background. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial regulator of low-density lipoprotein cholesterol (LDL-c) levels, as it binds to and degrades the LDL receptor (LDLR) in the lysosome of hepatocytes. Elevated levels of PCSK9 have been linked to an increased LDL-c plasma levels, thereby increasing the risk of cardiovascular disease (CVD), making it an attractive target for therapeutic interventions. As a way to inhibit PCSK9 action, we searched for naturally derived small molecules which can block the binding of PCSK9 to the LDLR. Methods. In this study, we carried out in silico studies which consist of virtual screening using an optimized pharmacophore model and molecular docking studies using Pyrx 0.98. Effects of the candidate compounds were evaluated using in vitro PCSK9-LDLR binding assays kit. Results. Eleven natural compounds that bind to PCSK9 were virtually screened form HerbalDB database, including brazilin. Next, molecular docking studies using Pyrx 0.98 showed that brazilin had the highest binding affinity with PCSK9 at −9.0 (Kcal/mol), which was higher than that of the other ten compounds. Subsequent in vitro PCSK9-LDLR binding assays established that brazilin decreased the binding of PCSK9 to the EGF-A fragment of the LDLR in a dose-dependent manner, with an IC50 value of 2.19 μM. Conclusion. We have identified brazilin, which is derived from the Caesalpinia sappan herb, which can act as a small molecule inhibitor of PCSK9. Our findings suggest that screening for small molecules that can block the interaction between PCSK9 and the LDLR in silico and in vitro may be a promising approach for developing novel lipid-lowering therapy.
Therapeutic Effect of Hydrodynamics-Based Delivery of Matrix Metalloproteinase-13 Gene on Thioacetamide-Induced Liver Fibrosis in Rats
Authors: Yokoo Takeshi , Kamimura Kenya , Nozawa Ryosuke , Sugita Moeno , Shibata Osamu , Kobayashi Yuji , Abe Hiroyuki , Miura Hiromi , Ohtsuka Masato , Terai Shuji
Published: October 2023

Liver cirrhosis is the final stage of chronic liver disease and can be life-threatening. Despite extensive studies on its treatment, a standard therapy is yet to be developed. Considering the complex mechanism of fibrogenic and fibrolytic processes in liver cirrhosis, combined therapy may have clinically significant effects on cirrhotic livers. In this study, we used thioacetamide (TAA) administration and matrix metalloproteinase-13 (MMP13) gene delivery to induce extracellular matrix generation and degradation in rats. The aim of this study was to determine whether hydrodynamics-based gene delivery of MMP13 to cirrhotic liver has regressive and suppressive effects on fibrogenesis. MMP13-encoding plasmids were hydrodynamically delivered to TAA-induced cirrhotic livers, and intravascular pressure was monitored. Therapeutic effect with and without continuous TAA exposure was assessed 8 weeks after the gene delivery. Test results indicated successful gene delivery and gene expression in the cirrhotic livers. Furthermore, microscopic imaging showed that MMP13 delivery resulted in significant degradation of fibrotic areas. Quantitative analysis of hydroxyproline content supported the microscopic findings. These results suggest that transgene delivery of MMP13 can be a promising candidate to treat liver fibrosis and that hydrodynamics-based gene delivery can be a good option for delivery of MMP13 to cirrhotic livers.
PSGL-1 Blockade Induces Classical Activation of Human Tumor-associated Macrophages
Authors: Kauffman Kevin , Manfra Denise , Nowakowska Dominika , Zafari Mohammad , Nguyen Phuong A. , Phennicie Ryan , Vollmann Elisabeth H. , O'Nuallain Brian , Basinski Sara , Komoroski Veronica , Rooney Kate , Culyba Elizabeth K. , Wahle Joseph , Ries Carola , Brehm Michael , Sazinsky Steve , Feldman Igor , Novobrantseva Tatiana I.
Published: October 2023

The immune suppressive microenvironment is a major culprit for difficult-to-treat solid cancers. Particularly, inhibitory tumor-associated macrophages (TAM) define the resistant nature of the tumor milieu. To define tumor-enabling mechanisms of TAMs, we analyzed molecular clinical datasets correlating cell surface receptors with the TAM infiltrate. Though P-selectin glycoprotein ligand-1 (PSGL-1) is found on other immune cells and functions as an adhesion molecule, PSGL-1 is highly expressed on TAMs across multiple tumor types. siRNA-mediated knockdown and antibody-mediated inhibition revealed a role for PSGL-1 in maintaining an immune suppressed macrophage state. PSGL-1 knockdown or inhibition enhanced proinflammatory mediator release across assays and donors in vitro. In several syngeneic mouse models, PSGL-1 blockade alone and in combination with PD-1 blockade reduced tumor growth. Using a humanized tumor model, we observed the proinflammatory TAM switch following treatment with an anti-PSGL-1 antibody. In ex vivo patient-derived tumor cultures, a PSGL-1 blocking antibody increased expression of macrophage-derived proinflammatory cytokines, as well as IFNγ, indicative of T-cell activation. Our data demonstrate that PSGL-1 blockade reprograms TAMs, offering a new therapeutic avenue to patients not responding to T-cell immunotherapies, as well as patients with tumors devoid of T cells.

Significance:

This work is a significant and actionable advance, as it offers a novel approach to treating patients with cancer who do not respond to T-cell checkpoint inhibitors, as well as to patients with tumors lacking T-cell infiltration. We expect that this mechanism will be applicable in multiple indications characterized by infiltration of TAMs.
How Does Pregnancy and Type of Delivery Affect the Clinical Course of Hereditary Angioedema?
Authors: Eyice Karabacak Deniz , Can Ali , Demir Semra , Yegit Osman Ozan , Colakoglu Bahauddin , Buyukozturk Suna , Gelincik Aslı Akkor
Published: October 2023

Introduction: Knowledge on the clinical course of hereditary angioedema (HAE) during pregnancy, delivery, and breastfeeding is very limited. In this study, we aimed to evaluate the course of HAE during these periods. Methods: The HAE attacks C1-INH prophylaxis before and during pregnancy and during breastfeeding, and the delivery types were retrospectively determined. The severity of attacks was assessed by a 10-point Visual Analogue Scale (VAS). Results: We evaluated 88 pregnancies in 48 HAE patients among whom 20 were primiparous. Among those who had a HAE diagnosis during pregnancy (n = 34), the median attack numbers before pregnancy, during pregnancy, breastfeeding, and after breastfeeding were 17, 39, 24, and 14 (before pregnancy vs. pregnancy, p < 0.001; during pregnancy vs. breastfeeding, p = 0.001). The mean VASs (SD) were 6.59 (1.82), 8.33 (1.58), 7.32 (1.66), and 6.95 (1.90) (before pregnancy vs. pregnancy, p < 0.001; during pregnancy vs. breastfeeding, p = 0.016), respectively. Among those who received a HAE diagnosis after pregnancy (n = 54), the number (59.3%) and the severity (60%) of HAE attacks were high in pregnancy. 47 of the deliveries were normal vaginal delivery (NVD). Regional anesthesia was applied in 8 NVDs. 20 of caesarean deliveries were performed under general anesthesia, and 21 were under spinal anesthesia. Lowest numbers of attacks were found in patients who did not receive anesthesia during NVD (p = 0.001). Conclusion: The course of HAE can be worse during pregnancy and breastfeeding. NVD is related to fewer HAE attacks and prophylaxis with C1-INH during NVD is not necessary to prevent a HAE attack.
A Survey of Airborne Fungi and Their Sensitization Profile in Wuhan, China
Authors: Yang Lin , Li Wenjing , Qi Shanshan , Jiang Qing , Huang Nan , Yang Yaqi , Ma Dongxia , Zhang Wei , Chen Hao , Zhu Rongfei
Published: October 2023

Introduction: Airborne fungi induce allergic symptoms in 3–10% of the population worldwide. To better prevent and manage fungi-related allergic diseases, it is essential to identify the genus and the distribution profile of airborne fungi. Methods: With this purpose in mind, we carried out a 12-month volumetric sampling study to monitor the airborne fungi and retrospectively analyzed the sensitization profile of four dominant fungi (Cladosporium, Alternaria, Aspergillus, and Penicillium) among respiratory allergies during the same study period in Wuhan, China. Results: A total of 29 different fungal genuses were identified, and the peak fungal concentration period was found to be in September and October, followed by May and June. The most prevalent fungi in this area were Cladosporium (36.36%), Ustilago (20.12%), and Alternaria (13.87%). In addition, the skin prick test data from 1,365 respiratory allergies patients showed that 202 (14.80%) of them were sensitized to fungi. The sensitization rates to Cladosporium, Alternaria, Aspergillus, and Penicillium were 11.72%, 4.69%, 1.98%, and 4.76%, respectively. The seasonal fluctuation of Alternaria and Aspergillus correlated with their sensitization rates. Among the fungal sensitized patients, 76 (37.62%) were sensitized to two or more kinds of fungi. The serum-specific IgE tests suggested low to high correlations existed between these fungi; however, these correlations were not found between fungi and other allergens. Conclusion: Our study provides the distribution profile and reveals the clinical significance of the airborne fungi in Wuhan, which will facilitate the precise management of fungal allergy.
Endovascular Treatment plus Medical Treatment versus Medical Treatment Alone in Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Toubasi Ahmad A. , Al-Sayegh Thuraya N. , Albustanji Farah H. , Al-Harasis Layla M.
Published: October 2023

Introduction: This study was conducted to assess the hypothesis that endovascular treatment in addition to medical treatment improve stroke mortality and post-stroke disability. Methods: In this systematic review and meta-analysis, the studies were included if they were randomized controlled trials in design and compared between endovascular treatment and medical therapy versus medical therapy alone in stroke management. Results: The search yielded 22 articles that included 5,049 patients. The analysis showed significant association between the intervention and reduction in disability measured by Modified Rankin Scale (mRS) (mRS = 0–2) (odds ratio [OR] = 1.61; 95% confidence intervals [95% CI]: 1.27–2.06) and National Institute of Health Stroke Scale (NIHSS) (NIHSS = 0–15) (OR = 2.13; 95% CI: 1.04–4.34). Also, we found a significant difference in disability scores between the intervention and the medical therapy group (mRS weighted mean difference [WMD] = −0.59; 95% CI: −1.15 to −0.02, NIHSS WMD = −4.52; 95% CI: −6.32 to −2.72). Additionally, there was significant reduction in mortality in the intervention group (OR = 0.79; 95% CI: 0.68–0.92). There was no significant difference in the rate of any serious adverse effects between the two study groups except for asymptomatic intracerebral hemorrhage. Conclusion: Our study provides strong evidence stemmed from randomized clinical trials that endovascular treatment combined with medical therapy is superior to medical therapy alone in the management of stroke.
Immune Checkpoint Inhibitor-Associated Nephrotoxicity
Authors: Mamlouk Omar , Danesh Farhad R.
Published: October 2023

Context: The clinical indications for immune checkpoint inhibitors (ICIs) are rapidly expanding. However, adverse events affecting multiple organs, including kidneys leading to ICI-associated acute kidney injury (AKI), remain a significant challenge with ICI therapy. Although AKI is considered a rare complication, it can be severe and result in treatment interruption or discontinuation of ICIs. Despite a generally favorable kidney prognosis, the possibility of re-challenging ICI therapy remains a subject of debate, particularly for patients who have exhausted other treatment options or experienced severe AKI. Subject of Review: In a recent review article, Sprangers et al. provide a comprehensive overview of the possible mechanisms and clinical manifestations of ICI-associated AKI [Nat Rev Nephrol. 2022;18(12):794–805]. The authors propose a practical strategy for diagnosing and managing suspected cases of ICI-associated AKI, which includes identifying a subset of eligible patients who may be re-exposed to ICIs following an episode of AKI. Second Opinion: The authors of the review article offer several recommendations on the diagnosis and treatment of ICI-associated nephrotoxicity. While we generally agree with the recommendations proposed by the authors, it is important to acknowledge that the available data primarily rely on small retrospective studies, as the authors have recognized. In addition, there are two key questions that need be carefully addressed in future studies: (1) the optimal dose and duration of corticosteroids and the use of alternative immunosuppressive agents in patients with ICI-associated nephrotoxicity and (2) a clear guideline for restarting ICI treatment in patients with AKI who have not fully recovered their kidney function.
Comparison of Different Internal Limiting Membrane Peeling Sizes for Idiopathic Macular Holes: A Systematic Review and Meta-Analysis
Authors: Qi Biying , Zhang Ke , Yang Xiaohan , Wu Xijin , Wang Xinbo , Liu Wu
Published: October 2023

Background: Although internal limiting membrane (ILM) peeling facilitates macular hole (MH) closure and reduces late hole reopening, it brings some detrimental consequences to the retinal microstructure and functional outcomes. So far, previous studies have not reached a consensus on the optimal ILM peeling size. Objectives: The objective of this study was to evaluate the outcomes of different ILM peeling sizes for idiopathic MHs. Methods: PubMed, Embase, Cochrane Library, Web of Science, CNKI, and WANFANG were searched until April 10, 2022. Studies in English or Chinese that compare the effects of two ILM peeling sizes (>2 disk diameters [DDs] vs. ≤2DD) for idiopathic MHs were included. The overall closure rate, postoperative best-corrected visual acuity (BCVA), type 1 closure, and adverse events were extracted. BCVA was converted to logarithm of the minimum angle of resolution (LogMAR). Results: Seven eligible studies (560 eyes) including 3 randomized clinical trials, 3 prospective trials, and one retrospective cohort were included. Pooled results showed a significantly better postoperative BCVA (mean difference = −0.16; 95% confidence interval [CI]: −0.27 to −0.04; LogMAR) and higher type 1 closure rate (risk ratio [RR] = 1.24; 95% CI: 1.08–1.43) in eyes with ILM peeling >2DD than those with peeling ≤2DD. No significant difference was found in overall closure rate and adverse events between the two groups. Subgroup analysis indicated that in MHs >400 μm, peeling >2DD helped obtain a better postoperative BCVA (mean difference = −0.17; 95% CI: −0.29 to −0.04; LogMAR) and higher frequency of type 1 closure (RR = 1.25; 95% CI: 1.03–1.51). Conclusions: Peeling >2DD shares similar safety level with peeling ≤2DD and has a superiority of facilitating visual recovery. Larger ILM peeling may be more beneficial for large MHs.
Hepatic Fibrosis Evaluated in Patients with Type 2 Diabetes with and without Chronic Kidney Disease
Authors: Adrian Therese , Hornum Mads , Knop Filip Krag , Christensen Karl Bang , Almdal Thomas , Rossing Peter , Lídaa Lisa Í , Heinrich Niels Søndergaard , Boer Vincent Oltman , Marsman Anouk , Petersen Esben Thade , Siebner Hartwig Roman , Feldt-Rasmussen Bo
Published: October 2023

Background: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population. Methods: Cross-sectional study including patients with type 2 diabetes with CKD stages 3–5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) >0.675. Results: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p < 0.0009 and p < 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007). Conclusion: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively.
Case Report of Seronegative Cancer-Associated Retinopathy in a Patient with Small Cell Lung Carcinoma
Authors: Thomas Miles , Benfield John , Morales Joshua
Published: October 2023

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome characterized by autoimmune destruction of photoreceptor cells. It is associated with several tumor types, including small cell lung carcinoma (SCLC). Corticosteroids have been the mainstay treatment for CAR, although no therapeutic standard has truly been established. A 66-year-old female with significant smoking history and age-related macular degeneration (ARMD) presented with rapidly declining bilateral visual acuity. Ophthalmologic examination findings appeared consistent with the known diagnosis of ARMD but did not otherwise present a clear alternative etiology. Imaging with a computed tomography (CT) scan revealed a right hilar mass which was confirmed to be limited stage SCLC based on a subsequent biopsy and further imaging with a positron emission tomography/computed tomography (PET/CT) scan. Antibody testing was negative for anti-recoverin antibodies. The patient experienced a complete response to chemoradiation with cisplatin and etoposide; however, her ocular symptoms did not respond to a combined treatment approach with corticosteroids, plasmapheresis, and intravenous immunoglobulin (IVIG). While CAR represents a rare condition in SCLC, cases that are seronegative for anti-recoverin are even less common. Further, the diagnosis of CAR by ophthalmologic examination may be more challenging in patients with pre-existing ocular diseases, such as macular degeneration. Clinicians should have suspicion for paraneoplastic blindness in patients with known risk factors for malignancy, whose ocular symptoms are inconsistent with exam findings.
A Retrospective Descriptive Analysis of the Saudi Clinical Trials Registry from 2010 to 2021
Authors: Aljahmi Abdullah , Balkhi Bandar , Al Hassan Haitham A. , Hafiz Radwan A.
Published: October 2023

Introduction: To date, the number and type of drug trials undertaken in Saudi Arabia have yet to be assessed comprehensively. This study aims to give a holistic view and describe the patterns of drug clinical studies registered and conducted in Saudi Arabia from 2010 to 2021, including the most common study phases, study site distribution, most commonly studied diseases, study sponsorship, and statistics about contract research organization (CRO) use. Methods: A descriptive cross-sectional study of all completed drug clinical study applications submitted to the Saudi Clinical Trials Registry at the Saudi Food and Drug Authority (SCTR-SFDA) database from February 2010 to December 2021. Results: The SCTR received 477 drug clinical trial applications from February 2010 to December 2021. Of these, 151 (31.7%) were accepted and completed their studies, while 214 (44.9%) were accepted but had ongoing studies. Most submitted trials (62.7%) were international multicenter studies, while 37.3% were conducted only in Saudi Arabia. Phase 3 and 4 trials were the most submitted study phases, followed by phase 2 and phase 1. The most studied therapeutic areas were oncology, endocrinology/metabolism, cardiology, and infectious diseases. Pharmaceutical companies sponsored most studies (62.7%) compared to local investigator (non-pharmaceutical) studies (37.3%). The Riyadh region had the most clinical study sites, followed by the Makkah region and the Eastern Province region. Of the 151 completed studies, 46.4% were published, with multinational studies being more likely to be published than local studies. Pharmaceutical companies were more likely to sponsor multinational studies, while studies conducted in Saudi Arabia only were more likely to be sponsored by local investigators. Only 33.3% of the studies employed CRO services, with 6.5% of studies conducted locally in Saudi Arabia using CROs and 26.8% of studies delegated CROs for multinational studies. Conclusions: SCTR has shown an increase in evaluated applications over time. The number of completed trial reviews in Saudi Arabia had increased from 18 in 2010 to 55 in 2021. This indicates the SFDA’s ability to monitor and regulate more studies in the future, with the majority of submitted trials being international multicenter studies. The most studied therapeutic areas were oncology, endocrinology/metabolism, cardiology, and infectious diseases, with pharmaceutical companies sponsoring most studies. The Riyadh region had the most clinical study sites, and only a third of the studies employed CRO services.
Social Protection Supports and Management of Non-Communicable Diseases in Ghana: A Qualitative Cross-Sectional Perspective of Health Stakeholders
Authors: Brenyah Joseph Kwasi , Dassah Ebenezer , Yeboah Georgina
Published: October 2023

Introduction: Africa faces a double burden of communicable and non-communicable diseases (NCDs). Already, health systems in Africa are overwhelmed with a high burden of communicable diseases with perennial outbreaks of highly infectious diseases. The rise in NCDs comprises an already fragile health system challenging its ability to provide comprehensive care to people living with these diseases. Without responsive social support systems, NCDs will draw more people into catastrophic health financing, worsening health outcomes, and poverty. This study explores how vulnerable people negotiate major disease burdens with the social protection supports available in Ghana. Methods: The study applied a cross-sectional design with a qualitative approach involving healthcare professionals and non-healthcare professionals in 4 regions in Ghana with a total of 32 qualitative interviews analyzed thematically. Results: The main social protection support for the health sector in Ghana is the National Health Insurance Scheme. Other social protection supports such as free maternal healthcare, Livelihood Empowerment Against Poverty, and conventional informal social protection mechanisms do not directly target people afflicted with NCDs. Even though national health insurance covers about 90% of diseases, the quality of care is questionable. Again, the exclusion of diagnostic investigations makes national health insurance a setback to NCD disease management. Also, NCD patients still do out-of-pocket expenses though they have valid national health insurance. Informal social protection supports which used to be effective sometime back are dwindling due to the rising cost of living, gradual breakdown of the African system of reciprocity, and infiltration of Western lifestyles. Conclusion: NCD patients have very limited social protection for the management of their condition. Health insurance which is the only option for many has limited applications. A multidisciplinary body is established by the government to outline more effective ways of offering social protection support for health services, especially chronic conditions such as NCDs which affect a greater proportion of the population.
Venous Excess Doppler Ultrasound: A Visual Guide to Decongestion in Cardiorenal Syndrome
Authors: Gudlawar Sirisha , Koratala Abhilash
Published: October 2023

Promptly recognizing congestion, both clinical and hemodynamic, is paramount in the management of patients with heart failure. The pathophysiology of congestion involves a complex interplay of absolute fluid gain, volume redistribution from venous capacitance beds to the central venous circulation, inadequate excretion due to renal dysfunction, salt and water retention, and endothelial dysfunction. While congestive nephropathy is gaining wider recognition as a distinct variant of hemodynamic acute kidney injury (AKI), there are limited bedside diagnostic tools for proper evaluation of these patients. In this manuscript, we describe a case of AKI where POCUS helped us diagnose clinically silent congestion as well as monitor the response to therapy. A patient with heart failure with mildly reduced ejection fraction was initially administered intravenous fluids for rise in serum creatinine attributed to volume depletion. However, POCUS demonstrated a completely different scenario with severe venous congestion. Both sonographic stigmata of congestion and serum creatinine improved with diuretic therapy. Furthermore, serial venous excess Doppler ultrasound scans facilitated the visualization of decongestion in real time.
Transarterial Selective Internal Radiation Therapy with Yttrium-90 for Liver Metastatic Urothelial Carcinoma of the Ureter as a Bridging Therapy to Immunotherapy: A Case Report with a 10-Year Follow-Up
Authors: Schmid Bruno Pagnin , Silva Cunha Marcela Juliano , Moreira Valle Leonardo Guedes , Galastri Francisco Leonardo , Affonso Breno Boueri , Falsarella Priscila Mina , Kaliks Guendelmann Rafael Aliosha , Garcia Rodrigo Gobbo , Nasser Felipe
Published: October 2023

Primary transitional cell carcinoma of the ureter is a rare type of cancer with metastasis presented in approximately 25% at diagnosis. Due to its rarity and poor prognosis, the management of this neoplasm is still controversial, and the development of new therapies is of uttermost importance. Herein, we describe a case of a 54-year-old patient diagnosed with transitional cell carcinoma of the left ureter submitted to left nephroureterectomy (pT3N2M0) and methotrexate, vinblastine, doxorubicin, and cisplatin adjuvant chemotherapy. A single liver metastasis was detected and combination chemotherapy with gemcitabine and carboplatin was initiated along with stereotactic body radiation therapy. Despite these 2 previous chemotherapy regimens, the patient presented disease progression and transarterial selective internal radiation therapy (SIRT) with yttrium-90 was indicated. This locoregional treatment was performed with the administration of 1.2 GBq yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, NSW, Australia) into the right hepatic artery. Another systemic treatment was immunotherapy using nivolumab with excellent tolerability. After 10 years of follow-up, at the last clinical evaluation, the patient had no clinical symptoms and the last imaging follow-up using positron emission tomography-computed tomography scan showed complete response. This report introduces upper urinary tract urothelial carcinoma as a distinct type of malignancy in which SIRT can be safely implemented. As a transition method to nivolumab, it was successful. There might be a potential therapeutic synergism between these 2 treatment modalities.
Malignant Mesothelioma of the Testes with Retroperitoneal Recurrence and Resection in an 80-Year-Old Male and Review of the Literature
Authors: Janes W.C. Ian , Al-Asaaed Sohaib , Johnston Paul H.
Published: October 2023

Malignant mesothelioma of the testes is an aggressive, yet rare urogenital malignancy, accounting for an infinitesimally small number of oncologic diagnoses. This infrequent occurrence is accompanied by a relative lack of knowledge surrounding this disease, thus limiting management options beyond surgical intervention. Oftentimes, these malignancies present with a poor prognosis despite early intervention and only worsen in the event of metastatic spread with poor survival and limited response to treatment, if any. Our case documents positive patient outcomes following the use of aggressive surgical intervention in the management of a metastatic testicular mesothelioma. A healthy 80-year-old male with sudden painless testicular swelling requiring radical orchidectomy following failed initial conservative management. Pathologically, the specimen was diagnosed as malignant mesothelioma of the right testis with involvement of the tunica albuginea and tunica vaginalis. Following disease recurrence at 82 years of age, the patient subsequently opted for an open right-sided template non-nerve sparing retroperitoneal lymph node dissection which was undertaken without complication. Malignant mesothelioma of the testes remains an ominous diagnosis with historically poor outcomes and for which surgical intervention remains the mainstay of treatment. The retroperitoneal lymphatic drainage represents the most common route of metastatic spread for testicular tumours; however, retroperitoneal lymph node dissection has rarely been employed in this patient population and never in an individual of this age. Our findings contribute to the growing literature surrounding these rare malignancies and outline the importance of considering both patient autonomy and the clinical picture in disease management.
Successful Treatment with Osimertinib Based on Therapeutic Drug Monitoring in a Hemodialysis Patient with Non-Small Cell Lung Cancer: A Case Report
Authors: Tabata Keisuke , Aoki Masaya , Miyata Ryo , Umehara Tadashi , Harada-Takeda Aya , Kamimura Go , Nagata Toshiyuki , Okizono Ryuya , Terazono Hideyuki , Takeda Yasuo , Suetsugu Takayuki , Ueda Kazuhiro , Sato Masami
Published: October 2023

Although osimertinib is a key drug in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, the safety in hemodialysis patients has not been established. A 76-year-old man was diagnosed with NSCLC with EGFR deletion mutation in exon 19. After treatment failure with first- and second-generation EGFR tyrosine kinase inhibitors, a T790M mutation was revealed by liquid biopsy. Hemodialysis was started three times a week because chronic renal failure worsened during treatment. Although the subsequent administration of osimertinib (80 mg daily) resulted in a tumor shrinkage and a gradual increase in the plasma concentration of osimertinib, which resulted in grade 3 general fatigue, reducing the dosage of osimertinib decreased its plasma concentration, leading to an improvement in his adverse event. Subsequently, with by adjusting the dosage while periodically measuring the plasma concentration of osimertinib, a stable therapeutic effect was sustained over the long term with no symptoms. Periodic plasma concentration measurements may be indispensable for successful treatment with osimertinib in hemodialysis patients.
Isolated Pancreatic Metastasis from a Lung Adenocarcinoma Primary: A Case Report and Literature Review
Authors: Akpoviroro Ogheneyoma , Pramick Michelle , Adjei Abdul
Published: October 2023

Isolated pancreatic metastasis is a rare occurrence and is commonly misdiagnosed as primary pancreatic malignancy. We present a case of a 65-year-old female patient with a history of stage IIIA lung adenocarcinoma, who developed significant epigastric pain 27 months after diagnosis and treatment of a primary lung adenocarcinoma. This patient was found to have a pancreatic head lesion initially suspected to be a primary pancreatic neoplasm but eventually discovered to be a metastatic lesion from the previously treated primary lung adenocarcinoma.
Localized Donor Area Acute Telogen Effluvium following Follicular Unit Extraction: Key Trichoscopic Findings
Authors: Guerrero-González Guillermo Antonio , González-Martínez Gerardo , Valdez-Zertuche Jair Alejandro
Published: October 2023

Introduction: Telogen effluvium is a form of non-scarring alopecia characterized by an increased hair shedding rate induced by mechanical or inflammatory factors. Case Report: A 27-year-old healthy male patient presented with several itchy alopecic patches in the occipital region. The patient had undergone a follicular unit extraction 6 weeks before with complete recovery after 1 week. Upon trichoscopy, we found empty follicular openings, short regrowing hairs, and coudability hairs. A diagnosis of acute telogen effluvium was made, and the patient was started on betamethasone lotion for daily use as a means to treat pruritus. After 1 month, the patient presented an almost complete response. Conclusion: While acute telogen effluvium is commonly seen in the receptor area after a hair transplant, the incidence of the donor region as a presentation is unknown. Common trichoscopic findings in telogen effluvium include empty follicular openings, short regrowing hairs, and lack of other signs usually seen in other types of alopecia. This description was consistent with what we found in our patient. Trichoscopic findings can help in the diagnosis, and understanding its natural course, physicians can reassure the patient about the self-resolutive outcome of this condition.
Dasatinib-Induced Transverse Melanonychia
Authors: Tyagi Mehul , Gaurav Vishal , Kaur Japnoor
Published: October 2023

Introduction: Transverse melanonychia, characterized by grey to black pigmented bands traversing the nail plate, can occur as a side-effect of certain medications. While no documented reports specifically associate dasatinib, a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia, with nail changes, we present a case of transverse melanonychia possibly related to dasatinib therapy. Case Report: A 54-year-old male with CML, receiving dasatinib for 1.5 years, presented with transverse pigmented lines involving all fingernails and toenails. Clinical examination revealed discrete bands of transverse melanonychia in the nails. Onychoscopy of all finger- and toenails revealed multiple longitudinal grey lines within transverse grey bands of homogeneous chromonychia. Based on clinical presentation, onychoscopic features, and temporal association with dasatinib therapy, a provisional diagnosis of dasatinib-induced transverse melanonychia was made. Discussion: The exact mechanisms underlying melanonychia are not fully understood but may involve nail matrix or toxicity, stimulation of nail-matrix melanocytes, or drug deposition within the nail plate. This case highlights the possibility of dasatinib-induced transverse melanonychia and underscores the importance of monitoring and evaluating nail changes in patients undergoing dasatinib treatment.
Low Blood Glucose Index Associated with Cardiovascular Events in Diabetic Hemodialysis Patients
Authors: He Ruibin , Xuan Yingli , Zhu Lingling , Pang Shiqing , Qin Li , Tian Jingyan , Yuan Jiangzi
Published: October 2023

Introduction: Blood glucose monitoring was vitally important in diabetic kidney disease (DKD) patients for preventing complications and improving survival rates. The associations between glycemic variability and blood biochemical indicators were underestimated in patients with DKD undergoing hemodialysis. Therefore, we primarily aimed to investigate the glycemic variability and 1-year risk of cardiovascular disease events in diabetic hemodialysis patients. And we secondarily aimed to explore the association between glycemic variability and blood biochemical indicators. Methods: In total, 27 patients were included in the final analysis. Continuous glucose monitoring (CGM) was used to evaluate glucose variability for 14 days. Patients were divided into two groups by the cutoff level of time in range (TIR; >70% or ≤70%). The three-point major adverse cardiovascular event (3P MACE) was recorded within 1 year. Results: After 1 year of follow-up, 4 patients in the high-TIR group and 3 patients in the low-TIR group had 3p MACE. Higher low blood glucose index (LBGI) level in diabetic hemodialysis patients increased the risk of 3p MACE outcomes (HR = 2.37, p = 0.018). And the level of albumin was positively associated with LBGI (β = 0.51, p = 0.036). The plasma levels of albumin, glycosylated hemoglobin, and hemoglobin were positively associated with other CGM parameters. Conclusion: LBGI during 14 days was positively associated with the risk of cardiovascular events in diabetic hemodialysis patients.
Novel Approach to Intradialytic Progressive Resistance Exercise Training
Authors: Cardoso Daniela Filipa , Leal Diogo Vaz , Martins Pedro , Abade Eduardo Andre , Rocha Henrique Coelho , Ferreira Manuel , Baker Luke Alexander , Smith Alice C. , Viana João L.
Published: October 2023

Physical activity levels are typically undesirably low in chronic kidney disease patients, especially in those undergoing haemodialysis, and particularly on dialysis days. Intradialytic exercise programmes could be a solution to this issue and have been reported to be safe and relatively easily implemented in dialysis clinics. Nevertheless, such implementation has been failing in part due to barriers such as the lack of funding, qualified personnel, equipment, and patient motivation. Intradialytic aerobic exercise has been the most used type of intervention in dialysis clinics. However, resistance exercise may be superior in eliciting potential benefits on indicators of muscle strength and mass. Yet, few intradialytic exercise programmes have focused on this type of intervention, and the ones which have report inconsistent benefits, diverging on prescribed exercise intensity, absent or subjective load progression, equipment availability, or exercise supervision. Commonly, intradialytic resistance exercise interventions use free weights, ankle cuffs, or elastic bands which hinder load progression and exercise intensity monitoring. Here, we introduce a recently developed intradialytic resistance exercise device and propose an accompanying innovative resistance exercise training protocol which aims to improve the quality of resistance exercise interventions within dialysis treatment sessions.
Factors Influencing Genetic Screening Enrollment among a Diverse, Community-Ascertained Cohort
Authors: Rao Nandana D. , Kaganovsky Jailanie , Fullerton Stephanie M. , Chen Annie T. , Shirts Brian H.
Published: October 2023

Introduction: Genetic screening for preventable adult-onset hereditary conditions has been proposed as a mechanism to reduce health disparities. Analysis of how race and ethnicity influence decision-making to receive screening can inform recruitment efforts and more equitable population screening design. A study at the University of Washington Medicine that invited unselected patients to participate in genetic screening for pathogenic variation in medically important genes provided an opportunity to evaluate these factors. Methods: We analyzed screening enrollee survey data to understand factors most important and least important in decision-making about screening overall and across different race and ethnicity groups. Electronic health record race and ethnicity and survey-reported race and ethnicity were compared to assist with interpretation. Comments provided about reasons for not enrolling in screening were analyzed using content analysis. Results: Overall, learning about disease risk and identifying risk early for prevention purposes were important factors in decision-making to receive screening, and regrets about screening and screening being against one’s moral code were not viewed as important. Although racial identity was challenging to assign in all cases, compared to other enrollees, African-American and Asian enrollees considered test accuracy and knowing more about the test to be of greater importance. Three themes emerged related to nonparticipation: benefits do not outweigh risks, don’t want to know, and challenges with study logistics. Conclusion: Our results highlight important motivators for receiving screening and areas that can be addressed to increase screening interest and accessibility. This knowledge can inform future population screening program design including recruitment and education approaches.
Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study
Authors: Lin Chuwen , Tan Miaoqin , Wang Dongmei , Gu Chunping , Wu Yongming , Wang Shengnan
Published: October 2023

Introduction: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs. Methods: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without. Results: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline. Conclusion: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment.
Protease-Activated Receptor 2 Controls Vascular Smooth Muscle Cell Proliferation in Cyclic AMP-Dependent Protein Kinase/Mitogen-Activated Protein Kinase Kinase 1/2-Dependent Manner
Authors: Williams Madison D. , Bullock Michael T. , Johnson Sean C. , Holland Nathan A. , Vuncannon Danielle M. , Oswald Joani Zary , Adderley Shaquria P. , Tulis David A.
Published: October 2023

Introduction: Cardiovascular disorders are characterized by vascular smooth muscle (VSM) transition from a contractile to proliferative state. Protease-activated receptor 2 (PAR2) involvement in this phenotypic conversion remains unclear. We hypothesized that PAR2 controls VSM cell proliferation in phenotype-dependent manner and through specific protein kinases. Methods: Rat clonal low (PLo; P3–P6) and high passage (PHi; P10–P15) VSM cells were established as respective models of quiescent and proliferative cells, based on reduced PKG-1 and VASP. Western blotting determined expression of cytoskeletal/contractile proteins, PAR2, and select protein kinases. DNA synthesis and cell proliferation were measured 24–72 h following PAR2 agonism (SLIGRL; 100 nM–10 μm) with/without PKA (PKI; 10 μm), MEK1/2 (PD98059; 10 μm), and PI3K (LY294002; 1 μm) blockade. Results: PKG-1, VASP, SM22α, calponin, cofilin, and PAR2 were reduced in PHi versus PLo cells. Following PAR2 agonism, DNA synthesis and cell proliferation increased in PLo cells but decreased in PHi cells. Western analyses showed reduced PKA, MEK1/2, and PI3K in PHi versus PLo cells, and kinase blockade revealed PAR2 controls VSM cell proliferation through PKA/MEK1/2. Discussion: Findings highlight PAR2 and PAR2-driven PKA/MEK1/2 in control of VSM cell growth and provide evidence for continued investigation of PAR2 in VSM pathology.