bluuebunny/crossref_metadata_2025 huggingface dataset:
Customizing delivery nano-vehicles for precise brain tumor therapy
Authors: Miao Yang-Bao , Zhao Wang , Renchi Gao , Gong Ying , Shi Yi
Published: January 2023

Although some tumor has become a curable disease for many patients, involvement of the central nervous system (CNS) is still a major concern. The blood–brain barrier (BBB), a special structure in the CNS, protects the brain from bloodborne pathogens via its excellent barrier properties and hinders new drug development for brain tumor. Recent breakthroughs in nanotechnology have resulted in various nanovehicless (NPs) as drug carriers to cross the BBB by different strategys. Here, the complex compositions and special characteristics of causes of brain tumor formation and BBB are elucidated exhaustively. Additionally, versatile drug nanovehicles with their recent applications and their pathways on different drug delivery strategies to overcome the BBB obstacle for anti-brain tumor are briefly discussed. Customizing nanoparticles for brain tumor treatments is proposed to improve the efficacy of brain tumor treatments via drug delivery from the gut to the brain. This review provides a broad perspective on customizing delivery nano-vehicles characteristics facilitate drug distribution across the brain and pave the way for the creation of innovative nanotechnology-based nanomaterials for brain tumor treatments.
The presence of partial compaction patterns is associated with lower rates of blastocyst formation, sub-optimal morphokinetic parameters and poorer morphologic grade
Authors: Hur Christine , Nanavaty Vaani , Yao Meng , Desai Nina
Published: January 2023

Background

Compaction is an important marker of embryonic genome activation and marks a critical step in the development to blastocyst. The objective of our study was to determine whether visualization of the embryonic compaction process through time-lapse imaging (TL) can assist in predicting the kinetics of embryo development as well as the likelihood for blastocyst formation, grade, or ploidy.

Methods

This study is a retrospective review of prospectively collected data from a single academic institution. Couples included were those who underwent preimplantation genetic testing for aneuploidy (PGT-A) following in vitro fertilization between January and December 2020. Embryos were cultured in the Embrysocope. Embryo morphokinetic data was prospectively collected and analyzed. TL videos were later reviewed in detail for compaction pattern. Embryo compaction patterns (CP) were categorized as follows: 1) full compaction (CP-F), 2) partial compaction with cell extrusion (P-ext), 3) partial compaction with cell exclusion (P-exc) and 4) partial compaction with both cell extrusion and exclusion (P-both). Assessment of embryo decompaction and re-compaction was evaluated. The association between CP, morphokinetic parameters, blastocyst formation, grade and ploidy were then analyzed.

Results

A total of 349 embryos were studied. Amongst embryos which progressed to morula (n = 281), the distribution of compaction patterns were: CP-F 45.6%, P-ext 12.5%, P-exc 29.5% and P-both 12.5%. Embryos exhibiting a CP-F were more likely to proceed to blastocyst compared with those that demonstrated partial compaction patterns (p = 0.006). When compared to CP-F, partial compaction patterns were significantly associated with poorer ICM and TE grades (P < 0.001). Of the 281 morula, 59.8% (n = 168) demonstrated at least one episode of decompaction and re-compaction. Of the 249 blastocysts formed, 200 were cryopreserved for future use after undergoing PGT-A evaluation. Of those, 42.5% were diagnosed as euploid, 39.0% as aneuploid, 9.0% as mosaic and 9.5% had no result. When compared to CP-F, partial CPs exhibited a significantly greater percentage of mosaic embryos (3.6% v. 15.6%, p = 0.032). Additionally, we found that a greater percentage of embryos demonstrating CP-F exhibited morphokinetics that fell into optimal ranges for embryo development when compared to those with partial compaction patterns.

Conclusion

Time-lapse visualization of compaction patterns identified exclusions and/or extrusions as negative indicators of blastocyst formation and blastocyst grade. When compared to full compaction patterns, partial compaction patterns were associated with delayed embryonic development as well as lower rates of optimal kinetic development.
Sperm quality impairment in males of couples with pregnancy loss is correlated with sexual dysfunction: a cross-sectional study
Authors: Yu Xiaowei , Zhang Songling , Zhang Xiao Yuan , Wang Qun
Published: January 2023

Background

Erectile dysfunction is a common problem in males of couples experiencing pregnancy loss. Erectile dysfunction in males with couple infertile has been extensively investigated and found to be closely linked with semen quality impairment and psychological distress, but it is less clear if this relation exists in males of couples experiencing pregnancy loss.

Method

A cross-sectional analysis of 437 men who attended our outpatient clinic between June 2021 and October 2021 for couple pregnancy loss. All subjects underwent a complete physical examination, palpation, inspection of the male genitalia, and semen analysis. Validated assessment tools for erectile dysfunction (the International Index of Sexual Function5 -IIEF-5) and anxiety (the seven-item Generalized Anxiety Disorder Scale- GAD-7) were used.

Results

Among 437 men of couples with pregnancy loss, we found several relevant sperm parameters confirmed a significant correlation between IIEF-5 scores and sperm parameters, including: sperm progressive motility (r = 0.1627, p = 0.001), sperm normal morphology (r = 0.1373, p = 0.004) and sperm DNA fragmentation (r =—0.1248, p = 0.009). Males with an IIEF-5 scores range between 5–11 presented the worst results in terms of sperm progressive motility (p = 0.002), normal morphology (p = 0.001), and SDF levels (p = 0.003). GAD-7 score, as well as anxiety level, was significantly higher in those males with an IIEF-5 score between 5 and 11 (p = 0.000).

Conclusion

Although current evidence does not demonstrate the importance of spermatozoa in the etiology of pregnancy loss, significant correlations have been observed between impaired sperm quality and low IIEF-5 scores. Also, anxiety is more likely to occur in males with sexual dysfunction.
Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis
Authors: Chen Yong , Zhu Xing-wang , Lai Wing-Fu , Liu Yong-pu , Xu Xuan-feng , Liu Li-ming , Chen Yan-juan , Zhang Chuan-fu , Wang Guang-yi , Cheng Zhi-qiang , Liu Dong-zhou
Published: January 2023

Background

Elderly rheumatoid arthritis (ERA) population faces multiple treatment dilemma. Here we aim to investigate if Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) exhibit better effects in an ERA mice model.

Methods

ERA mice model was established by adding D-galactose (Dgal) to collagen-induced arthritis (CIA) mice. The model was then assigned into control group (CIA + Dgal), MTX treatment group (MTX), GCNY treatment group (GCNY), and integrative treatment group (MTX + GCNY). Pathological scoring was performed to evaluate the severity between the groups. Proteomic analysis was applied to investigate the secretory phenotype of the ERA mouse model and the underlying mechanism of GCNY, MTX and their combination. Representative cytokines related to proteomic results were further validated by ELISAs.

Results

CIA + Dgal mice showed more aggressive joints damage than the CIA mice. Besides changes in the inflammatory pathway such as Pi3k-Akt signaling pathway in both model, differential expressed proteins (DEPs) indicated metabolism-related pathways were more obvious in CIA + Dgal mice. Low-dose MTX failed to show pathological improvement in CIA + Dgal mice, while GCNY improved joints damage significantly. Besides down-regulated inflammation-related targets, GCNY-regulated DEPs (such as Apoc1 ~ 3, Grk2 and Creb3l3) were broadly enriched in metabolism-related pathways. MTX + GCNY showed the best therapeutic effect, and the DEPs enriched in a variety of inflammatory,metabolism and osteoclast differentiation signaling pathway. Notably, MTX + GCNY treatment up-regulated Dhfr, Cbr1, Shmt1 involved in folic acid biosynthesis and anti-folate resistance pathways indicated a coincidence synergic action. ELISAs confirmed CPR and Akt that elevated in CIA + Dgal mice were significantly ameliorated by treatments, and adding on GCNY elevated folic acid levels and its regulator Dhfr.

Conclusion

Aging aggravated joints damage in CIA, which probably due to metabolic changes rather than more severe inflammation. GCNY showed significant effects in the ERA mice model especially when integrated with MTX to obtain a synergic action.
G-protein coupled estrogen receptor (GPER1) activation promotes synaptic insertion of AMPA receptors and induction of chemical LTP at hippocampal temporoammonic-CA1 synapses
Authors: Clements Leigh , Alexander Amy , Hamilton Kirsty , Irving Andrew , Harvey Jenni
Published: January 2023

It is well documented that 17β estradiol (E2) regulates excitatory synaptic transmission at hippocampal Shaffer-collateral (SC)-CA1 synapses, via activation of the classical estrogen receptors (ERα and ERβ). Hippocampal CA1 pyramidal neurons are also innervated by the temporoammonic (TA) pathway, and excitatory TA-CA1 synapses are reported to be regulated by E2. Recent studies suggest a role for the novel G-protein coupled estrogen receptor (GPER1) at SC-CA1 synapses, however, the role of GPER1 in mediating the effects of E2 at juvenile TA-CA1 synapses is unclear. Here we demonstrate that the GPER1 agonist, G1 induces a persistent, concentration-dependent (1–10 nM) increase in excitatory synaptic transmission at TA-CA1 synapses and this effect is blocked by selective GPER1 antagonists. The ability of GPER1 to induce this novel form of chemical long-term potentiation (cLTP) was prevented following blockade of N-methyl-d-aspartate (NMDA) receptors, and it was not accompanied by any change in paired pulse facilitation ratio (PPR). GPER1-induced cLTP involved activation of ERK but was independent of phosphoinositide 3-kinase (PI3K) signalling. Prior treatment with philanthotoxin prevented the effects of G1, indicating that synaptic insertion of GluA2-lacking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors underlies GPER1-induced cLTP. Furthermore, activity-dependent LTP occluded G1‐induced cLTP and vice versa, indicating that these processes have overlapping expression mechanisms. Activity‐dependent LTP was blocked by the GPER1 antagonist, G15, suggesting that GPER1 plays a role in NMDA‐dependent LTP at juvenile TA‐CA1 synapses. These findings add a new dimension to our understanding of GPER1 in modulating neuronal plasticity with relevance to age-related neurodegenerative conditions.
The complementary roles of genome-wide approaches in identifying genes linked to an inherited risk of colorectal cancer
Authors: Ahmad Olfat , Försti Asta
Published: January 2023

The current understanding of the inherited risk of colorectal cancer (CRC) started with an observational clinical era in the late 19th century, which was followed by a genetic era starting in the late 20th century. Genome-wide linkage analysis allowed mapping several high-risk genes, which marked the beginning of the genetic era. The current high-throughput genomic phase includes genome-wide association study (GWAS) and genome-wide sequencing approaches which have revolutionized the conception of the inherited risk of CRC. On the one hand, GWAS has allowed the identification of multiple low risk loci correlated with CRC. On the other, genome-wide sequencing has led to the discovery of a second batch of high-to-moderate-risk genes that correlate to atypical familial CRC and polyposis syndromes. In contrast to other common cancers, which are usually dominated by a polygenic background, CRC risk is believed to be equally explained by monogenic and polygenic architectures, which jointly contribute to a quarter of familial clustering. Despite the fact that genome-wide approaches have allowed the identification of a continuum of responsible high-to-moderate-to-low-risk variants, much of the predisposition and familial clustering of CRC has not yet been explained. Other genetic, epigenetic and environmental factors might be playing important roles as well. In this review we aim to provide insights on the complementary roles played by different genomic approaches in allowing the current understanding of the genetic architecture of inherited CRC.
Developing an Outcome Measures in Rheumatology (OMERACT) Core set of Outcome Measures for FOot and ankle disorders in RheumaTic and musculoskeletal diseases (COMFORT): core domain set study protocol
Authors: Chapman Lara S. , Redmond Anthony C. , Flurey Caroline A. , Richards Pamela , Smith Toby O. , Arnold John B. , Beaton Dorcas , Conaghan Philip G. , Golightly Yvonne M. , Hannan Marian T. , Hofstetter Catherine , Maxwell Lara J. , Menz Hylton B. , Shea Beverley , Tugwell Peter , Helliwell Philip , Siddle Heidi J.
Published: January 2023

Background

Foot and ankle involvement is common in rheumatic and musculoskeletal diseases (RMDs). High-quality evidence is lacking to determine the effectiveness of treatments for these disorders. Heterogeneity in the outcomes used across clinical trials and observational studies hinders the ability to compare findings, and some outcomes are not always meaningful to patients and end-users. The Core set of Outcome Measures for FOot and ankle disorders in RheumaTic and musculoskeletal diseases (COMFORT) study aims to develop a core outcome set (COS) for use in all trials of interventions for foot and ankle disorders in RMDs. This protocol addresses core outcome domains (what to measure) only. Future work will focus on core outcome measurement instruments (how to measure).

Methods

COMFORT: Core Domain Set is a mixed-methods study involving the following: (i) identification of important outcome domains through literature reviews, qualitative interviews and focus groups with patients and (ii) prioritisation of domains through an online, modified Delphi consensus study and subsequent consensus meeting with representation from all stakeholder groups. Findings will be disseminated widely to enhance uptake.

Conclusions

This protocol details the development process and methodology to identify and prioritise domains for a COS in the novel area of foot and ankle disorders in RMDs. Future use of this standardised set of outcome domains, developed with all key stakeholders, will help address issues with outcome variability. This will facilitate comparing and combining study findings, thus improving the evidence base for treatments of these conditions. Future work will identify suitable outcome measurement instruments for each of the core domains.

Trial registration

This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database, as of June 2022: https://www.comet-initiative.org/Studies/Details/2081
Vibrio vulnificus sepsis after shrimp shelling in a patient with preexisting primary biliary cholangitis: a case report
Authors: Sakihara Eishi , Noge Ikuma , Suzuyama Hiroki , Takeoka Hiroaki , Nabeshima Shigeki
Published: January 2023

Background

Vibrio vulnificus is typically present in seawater, fish, and shellfish, and is known to cause severe sepsis, particularly in patients with liver diseases such as cirrhosis. V. vulnificus is one of the most dangerous waterborne pathogens, and infection mainly occurs in western Japan during the summer, with an increased fatality rate. Herein, we report the case of a patient with primary biliary cholangitis and sepsis caused by V. vulnificus infection sustained through shrimp shelling.

Case presentation

An 82-year-old Japanese Asian woman with no medical history or underlying disease developed redness, swelling, and pain, which extended from the right fingers to the upper arm. A diagnosis of sepsis due to cellulitis was made. Blood culture detected V. vulnificus; thus, minocycline was administered in addition to meropenem. The disease course was uneventful, and the patient was discharged on day 28 of hospitalization. Symptoms in the right upper arm developed 1 day after the patient shelled a large number of shrimp; therefore, the infection route was assumed to be through wounds sustained during shrimp shelling. We suspected liver disease and measured serum anti-mitochondrial M2 antibody levels, leading to the diagnosis of primary biliary cholangitis.

Conclusions

As in this case, small wounds caused by handling fish and shrimp are a potential source of infection. Patients with severe V. vulnificus infection should be thoroughly assessed for the presence of liver diseases such as primary biliary cholangitis.
The global prevalence of methicillin-resistant Staphylococcus aureus colonization in residents of elderly care centers: a systematic review and meta-analysis
Authors: Hasanpour Amir Hossein , Sepidarkish Mahdi , Mollalo Abolfazl , Ardekani Ali , Almukhtar Mustafa , Mechaal Amal , Hosseini Seyed Reza , Bayani Masoumeh , Javanian Mostafa , Rostami Ali
Published: January 2023

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a difficult to treat infection, particularly in residents of elderly care centers (ECCs). Despite the substantial burden of MRSA, an inadequate number of studies have analyzed MRSA prevalence in ECCs.

Objectives

We conducted a worldwide systematic review and meta-analysis on the prevalence and risk factors of MRSA in ECCs.

Methods

We searched MEDLINE/PubMed, EMBASE, Web of Science, and Scopus databases and the gray literature sources for all studies published between January 1980 and December 2022 on the prevalence of MRSA in ECCs. A random-effects model was utilized to estimate pooled prevalence rates at 95% confidence intervals (CI). Moreover, the data were analyzed based on World Health Organization-defined regions, income, and human development index levels.

Results

In total, 119 studies, including 164,717 participants from 29 countries, were found eligible for meta-analysis. The pooled global prevalence of MRSA was 14.69% (95% CI 12.39–17.15%; 16,793/164,717). Male gender [prevalence ratio (PR) = 1.55; 95% CI 1.47–1.64], previous MRSA infection (PR = 3.71; 95% CI 3.44–4.01), prior use of antibiotics (PR = 1.97; 95% CI 1.83–2.12), hospitalized within the previous year (PR = 1.32; 95% CI 1.20–1.45), have had any wound (PR = 2.38; 95% CI 2.23–2.55), have used urinary catheter (PR = 2.24; 95% CI 2.06–2.43), have used any medical device (PR = 1.78; 95% CI 1.66–1.91), and those with diabetes (PR = 1.55; CI 1.43–1.67) were more likely to be colonized by MRSA than other patients.

Conclusion

Screening programs and preventive measures should target MRSA in ECCs due to the high global prevalence rates.
Rheological, Mechanical, Microstructural and Radiation Shielding Properties of Cement Pastes Containing Magnetite (Fe3O4) Nanoparticles
Authors: Sikora Pawel , El-Khayatt Ahmed M. , Saudi H. A. , Liard Maxime , Lootens Didier , Chung Sang-Yeop , Woliński Paweł , Abd Elrahman Mohamed
Published: January 2023

This work examines the influence of iron oxide nanoparticles (Fe3O4 NPs) on neutron and gamma-ray radiation shielding characteristics of Portland cement paste. Experimental evaluations were supplemented with theoretical studies using NXCom program. Portland cement pastes with 5, 10, 15, 20, and 30 wt% of nanomagnetite cement replacement were produced. Moreover, rheological, early strength development, compressive strength, and mercury intrusion porosimetry (MIP) tests were performed. The results showed that increasing the amount of Fe3O4 NPs in a mix leads to a gradual increment in measured viscosity and yield stress. High nano-Fe3O4 content substantially impeded the early strength development process and led to a decrement in the 7- and 28-day compressive strength of cement paste. The MIP studies exhibited a gradual increment in total porosity, and average pore volume, as nano-Fe3O4 content was increased. All the macroscopic cross-sections of slow, fast and thermal neutrons constantly increased as a result of the addition of magnetite nanoparticles, with their variations being markedly linear. Similarly, gamma attenuation test results indicated that the addition of Fe3O4 powder enhances the shielding capability of paste in the energy range of interest (0.08–2.614 MeV). In conclusion, Fe3O4 nanoparticles can be successfully used in producing lead-free cementitious composites with improved gamma-ray and neutron shielding properties. However, certain drawbacks related to an increment in matrix porosity and thus a decrement in mechanical performance should be taken into account.
An exploration into EFL learners’ perspectives on online computerized listening comprehension dynamic assessment
Authors: Ebadi Saman , Karimi Elham , Vakili Shokoufeh
Published: January 2023

As a part of a more extensive computerized dynamic assessment (CDA) project delivered through a dedicated website, www.lingeli.com, this study explores EFL learners’ perspectives on an online listening comprehension dynamic assessment software focusing on inferential listening skills while trying to minimize the guessing effect. The study participants were 94 Iranian EFL learners selected through convenience sampling to participate in a 1-month dynamic assessment targeting EFL learners listening comprehension using the developed software. The researchers involved half of the study participants in semi-structured interviews held in their native language (Persian) to shed light on the pros and cons of the software. Six major themes emerged from the interviews’ content analysis, encapsulating participant’’ generally positive perceptions and some negative perspectives about the software. They perceived the CDA software as novel and interesting, stress-relieving, supportive, convenient, and cost-effective in terms of time and money, and removing the time and location limitations. In contrast, a few others assumed it was time-consuming and stressful, with limited learning and ignoring the benefits of social aspects of teaching. The study’s findings recommend that learners’ perspectives be considered when developing future CDA listening comprehension software to increase the validity of CDA projects by addressing their drawbacks and fully implementing the CDA test's potential to enhance EFL learners’ listening comprehension abilities.
Error and optimism bias regularization
Authors: Sohaee Nassim
Published: January 2023

In Machine Learning, prediction quality is usually measured using different techniques and evaluation methods. In the regression models, the goal is to minimize the distance between the actual and predicted value. This error evaluation technique lacks a detailed evaluation of the type of errors that occur on specific data. This paper will introduce a simple regularization term to manage the number of over-predicted/under-predicted instances in a regression model.
Association of serum electrolyte changes during haemodialysis with stimulation of premature ventricular contractions
Authors: Anno Emi , Sato Yukihiro , Hoshimoto Ainori , Harano Makiko , Hagiwara So , Imai Eri , Kaneko Shuzo , Tsukamoto Yusuke
Published: January 2023

Background

Patients on haemodialysis are predisposed to heart rhythm disorders, including bradyarrhythmia, atrial fibrillation (AF)/atrial flutter, supraventricular/ventricular arrhythmias and sudden cardiac death (SCD) (Turakhia et al. in Eur Heart J 39:2314–2325, 2018). In addition to the fact that patients on haemodialysis have a high prevalence of underlying cardiac disease, the stress of haemodialysis itself might also contribute to increased rates of arrhythmias and SCD (Samanta et al. in Can J Cardiol 35:1228–1240, 2019).

Methods

A Holter 24-h electrocardiogram was set up immediately before the start of haemodialysis for 72 haemodialysis patients (dialysis vintage: 6–8734 days) to record premature ventricular contractions (PVCs) as a marker of arrhythmogenesis for 24 h. Blood samples were also collected every hour during haemodialysis treatment. Each patient was dialyzed against a dialysate consisting of Na+140 mEq/L, K+ 2.0 mEq/L, Ca+ 3.0 mEq/L, Mg2+ 1.0 mEq/L, Cl− 110 mEq/L, CH3COO− 8 mmol/L and HCO3− 30 mEq/L.

Results

The frequency of PVCs significantly increased in the 4th (80 ± 34 beats/hour, mean ± S.E.), 5th (79 ± 31 beats/hour) and 6th (105 ± 36 beats/hour) hours (F = 5.24, p < 0.00001, n = 72). The lowest left ventricular ejection fraction (LVEF, p = 0.001) and the highest b-type natriuretic peptide (BNP) levels (p = 0.049) were found in patients with the highest PVC counts. There was an association of positive changes in both serum K+ (β ± S.E., 9.7 ± 2.4, p = 0.0002), Mg2+ (43.2 ± 10.3, p = 0.0001) and HCO3− (5.3 ± 1.8, p = 0.005) with the frequency of PVCs for 4 h immediately after dialysis. During the same period, there was an association of lower serum K+ (− 8.37 ± 2.16, p = 0.0003) and higher Ca2+ (73.4 ± 18.0, p = 0.0002) with the frequency of PVCs.

Conclusions

Haemodialysis stimulated PVC generation, and this effect was especially prominent during the period immediately after haemodialysis. Some serum electrolyte changes affected this PVC stimulation. A positive change in serum K+ or Mg2+ and a negative change in serum Ca2+ during dialysis are risk factors for stimulating PVCs, particularly in patients with lower serum K+ or higher serum Ca2+ levels at the start of dialysis.
A newly developing case of adrenal insufficiency developing after Coronavirus disease
Authors: Özer Özge , Yorulmaz Göknur , Tekin Melisa Şahin
Published: January 2023

Introduction

Although some short and long-term effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection on the endocrine system are shown, there are still much more remaining to be clarified. A few case reports have shown that adrenal insufficiency can develop after COVID-19 infection due to adrenal hemorrhage or infarction. However, the exact effects of infection on cortisol dynamics are still poorly understood. This case report highlights an unusual case of acute adrenal insufficiency in a Covid-19.

Clinical Case

A 30-year-old female patient with no history of chronic disease applied with complaints of nausea, abdominal pain, and weakness for nearly 2 weeks. She was hospitalized. Her vitals were stable at the admission. Her initial laboratory evaluation showed serum sodium: 119 mEq/L, potassium: 5.38 mEq/L, creatinine: 1.35 mg/dL, aldosterone 2.33 ng/dL (1.46–17.4), plasma renin activity 40.56 ng/ml/h (0.06–4.69). Hemogram and liver function tests were normal. The basal ACTH value was measured 1142 pg/mL (7.2–63.3), and cortisol was 0.29 (6.24–18).The diagnosis of tuberculosis was ruled out with the quantiferon and the PPD test performed. In the detailed questioning of the patient, it was learned that she had Covid-19 infection about 3 months before the onset of symptoms. In this process, the patient's skin color was significantly darkened, and it was confirmed in comparison with the old photographs and from the patient's declaration. She was diagnosed with adrenal crisis, and corticosteroid therapy (80 mg/day intravenous methylprednisolone) and intravenous hydration were started. On the other hand, imaging and endoscopic evaluations were performed to exclude other intra-abdominal pathologies. No pathology was detected. Adrenal glands were normal in abdominal tomography. Stress dose steroid therapy was adjusted by reducing the daily dose. In the follow-up, the patient's complaints decreased and disappeared. Fludrocortisone was added to her treatment because electrolyte disturbances continued as hyponatremia and hyperkalemia. In the first week of treatment the patient's electrolyte disturbances improved and she was discharged with oral hydrocortisone and fludrocortisone treatment. The patient's skin color was observed lighter than before in the control examination, one week after discharge.

Conclusion

Although cases of adrenal insufficiency due to Covid-19 infection are found in the literature, their number is limited. The underlying causes are usually shown as hemorrhage and thrombosis. The absence of these findings in our case supports that the underlying cause is autoimmune and brought a different perspective to the issue. Our case also drives attention to the evaluation of patients in terms of adrenal insufficiency not only in the acute period but also in the later periods, since the diagnosis was made 3 months after the disease.
How the algorithms can change during the COVID-19 pandemic: A case of primary hyperaldosteronism
Authors: Iremli Burcin Gonul , Sendur Suleyman Nahit , Yildiz Bulent Okan
Published: January 2023

Introduction

Primary hyperaldosteronism (PA) is an important reason of secondary endocrine hypertension. The etiology is either an aldosterone producing adenoma or bilateral adrenal hyperplasia in 90% of cases. The diagnosis is based on specific algorithms starting with screening the population at risk and continues with confirmatory testing of positive resulted individuals. According to current recommendations, adrenal vein sampling (AVS) and imaging should both be used to classify the subtypes of PA; but during the COVID-19 pandemic, the algorithms may have to be changed. Here, we present a case diagnosed with PA and successfully treated during pandemic.

Clinical Case

A fifty-one-year-old male patient was referred to our department from internal medicine clinic with hypertension and hypokalemia. He was hypertensive since 30 years old, but he had no history or clinical symptoms of hypokalemia or hypertension associated organ injury. His blood pressures (BP) were under control with 10 mg of amlodipine. But for the last 2 years, his blood pressures couldn't be managed with just amlodipine. Despite losing weight, BP was still higher than 160/100 mmHg. When he evaluated by his internal medicine physician, K level was significantly low (2.57 mEq/L). After oral potassium replacement and discontinuation of thiazide, it increased to only the lower limit (3.4 mEq/L). Abdominal CT showed bilateral adrenal thickness with 13 HU on the right and 10 HU on the left. On physical examination, he had no characteristic findings of hypercortisolemia or acromegaly. His BP was 180/100 mmHg, even he adopted salt-free diet and antihypertensive therapy with candesartan, thiazide, amlodipine. His echocardiography and retinal examination were normal. His catecholamine excretion on 24h urine was normal. After discontinuing aldosterone receptor blocker and thiazide, aldosterone and plasma renin activity were 73 ng/dL and 0.59 ng/mL/h respectively. The ratio was 123.7 and suspected highly of PA. The patient didn't want to be admitted to hospital for saline infusion test. He was directed to AVS. After medically controlling his BP, AVS was performed successfully in May 2022. His results are shown in Table-1. After this result, right adrenal gland was considered as PA source and right adrenalectomy was performed. The patient is on follow-up with single dose of candesartan within normal BP limits and normal K levels.

Conclusion

COVID-19 pandemic has indisputably changed certain algorithms in every field. On this matter, patient specific approaches have become more important. Most specifically for this case, even when the hypertension started early-on-set, clinicians should seek the hypertensive end-organ injuries to understand the onset of the secondary reasons of hypertension. It should be remembered that not every early-on-set hypertension is secondary, and not every late-on-set hypertension is essential.
Cushing's syndrome, pheochromocytoma, or both?
Authors: Kullamaa Liisa , Ryhänen Eeva , Söderlund Sanni , Bärlund Milla Rosengård , Viukari Marianna , Muona Kirsi , Pekkarinen Tuula , Matikainen Niina , Jäntti Camilla Schalin
Published: January 2023

Clinical Case

A 45-year-old woman presented to the emergency department with weakness and was found to have a Hb level of 68 g/l. She was also tachycardic (pulse 118 x/min) and hypertensive with a BP of 210/108 mmhg.

She had a history of ulcerative colitis, menorrhagia and seronegative arthritis for which she had been using 5mg prednisolone daily for several years. The patient had suffered and episode of heart failure 4 years earlier of unknown etiology, during which she was tachycardic, hypertensive and her LVEF was decreased to 35%. In 2016 the patient had undergone an abdominal CT that had shown an incidental finding of a mass in the right adrenal gland, but she did not show up for additional investigations.

During the previous year, the patient had developed symptoms of decreased physical fitness, increased weight, livedo reticularis-type skin changes (Figure), agitation, hirsutism and swelling on the neck.

Gastroscopy revealed esophageal candidiasis and abdominal CT-scan showed a mass in the right adrenal gland that had increased in size from 2 cm to 3.8 cm compared to the previous CT in 2016 with a density of 21 HU.

The patient had clinical Cushing's syndrome, that was confirmed in the lab tests (Table). In addition, lab tests showed an excess production of catecholamines.

MRI of the sellar region was performed, that showed a 3×4×3 mm size Rathke's cleft cyst/microadenoma.

A CRH stimulation test with inferior petrosal sinus sampling was performed and results were consistent with ectopic ACTH production.

The clinical studies were consistent with pheochromocytoma that was also producing ACTH.

The patient underwent unilateral adrenalectomy after having been treated with metyrapone and phenoxybenzamine preoperatively.

Histopathology was compatible with pheochromcytoma. ACTH staining was negative, but CRH staining was not available. MIB-1 proliferation index was ≤3%.

Postoperatively hypercortisolism and catecholamine excess have subsided. The patient has stopped diabetic and antihypertensive medication and she also been cured of the notable livedo reticularis-type skin changes (Figure).

Conclusion

The clinical presentation of pheochromocytoma in our patient was atypical with coexistence of ACTH-dependent Cushing's syndrome. Furthermore, the patient had a mass in the hypophysis that could have been a potential cause for ACTH-secretion. The clinical and biochemical signs were completely reversed with adrenalectomy, compatible with ectopic Cushing's syndrome due to a pheochromytoma that produced both catecholamines and most probably CRH.

In summary pheochromocytomas can rarely also secrete other hormones such as interleukins, calcitonin, ACTH or CRH and this can significantly alter the clinical presentation of both Cushing's syndrome and pheochromocytoma. A recent meta-analysis (Elliott, JCEM 2021) reported 99 published cases of ACTH/CRH-producing pheochromocytomas.
A rare case of concomitant hypophosphatemic osteomalacia and neurofibromatosis type 1
Authors: Şehit Kara Canan , Hacıoğlu Ayşa , Karaca Züleyha , Ünlühızarcı Kürşad
Published: January 2023

Introduction

Neurofibromatosis type 1 is a rare genetic disorder with an increased susceptibility to develop skeletal abnormalities. However, the association of hypophosphatemic osteomalacia and neurofibromatosis type 1 is extremely rare. Herein, we report a case of hypophosphatemic osteomalacia in concomitant with neurofibromatosis type 1.

Clinical Case

A 45-year-old Turkish female patient, who was followed up in another hospital due to osteoporosis and kyphoscoliosis, applied to us with the complaints of persistent bone pain and inability to walk. She had no chronic diseases other than osteoporosis. The physical examination revealed widespread freckling over her trunk and proximal parts of upper and lower extremities and multiple neurofibromas and cafe au lait spots all over her body (figure 1). It was learned that her 2 brothers, mother and daughter also had the widespread freckling. They have no known chronic diseases. She had a severe degree of kyphoscoliosis. She had not have any complaints up to 24 years of age, and low back pain started after delivery. She was diagnosed with osteoporosis at the age of 29. In about 15 years, her height decreased from 167 cm to 135 cm. She had a severe degree of kyphoscoliosis and severe bone pain and was unable to walk on her own because of pain. Bilateral ophthalmic examination revealed no Lisch nodules. Audiometer revealed no abnormalities. Laboratory findings were as follows: Ca: 9.4 (8.4–10.6 mg/dl), phosphorus: 1.8 (2.3–4.7 mg/dl), albumin: 4.2 g/dl, parathormone: 88.3 (11–80 pg/ml), 25 hydroxy vitamin D: 26.1 ug/L, creatinine: 0.4 mg/dl, alkaline phosphatase: 79 (35–105 U/L), the 24-hour urinary excretion of calcium: 187.5 mg/24 h, the 24-hour urinary excretion of phosphorus: 253 mg/24 h, fractional excretion of phosphate: %8.5 and maximum transport of phosphorus in the renal proximal tubules (TmP/GFR): 0.74 (0.88–1.42 mmol/L). According to laboratory data there was a hyperphosphaturia. On the basis of the physical examination, laboratory and radiological findings, she was diagnosed with neurofibromatosis type 1 and hypophosphatemic osteomalacia. Oral phosphate solution (1.5 gram as elemantary phosphorus per day in 3 divided doses) and calcitriol (1 microgram per day in 2 divided doses) were started. After 6 months of therapy, bone pain was significantly decreased and her serum phosphorus level increased. The results of genetic analysis are awaited.

Conclusion

The coexistence of hypophosphatemic osteomalacia and neurofibromatosis type 1 have been reported in less than 50 cases in the literature. The underlying mechanism is not clarified. The diagnosis of hypophosphatemic osteomalacia should be kept in mind in patients with neurofibromatosis type 1, as they will benefit greatly from oral phosphorus solution and active vitamin D.
Primary hyperparathyroidism: Brown tumor in hand, foot, and femur
Authors: Pekkolay Zafer
Published: January 2023

Introduction

Bone fractures due to primary hyperparathyroidism/brown tumor can still be seen today, albeit rarely.

Clinical Case

A 47-year-old migrant woman had a right femur fracture after a simple fall. The patient's laboratory values were found as calcium 16.3 (8.4–10.2) mg/dl, phosphorus 2.5 (3.2–5.5) mg/dl, Alkaline phosphatase: 1131 (40–150) U/L, Parathormone 1711 (15–65) pg/ml. A 40×30 mm parathyroid adenoma was detected in the lower left side of the patient, who was suspected of having primary hyperparathyroidism. Parathyroid adenoma in the same localization was also observed in neck tomography. At the same time, a brown tumor was detected on the hand and foot bones. The patient underwent a left parathyroid adenomectomy. Intravenous calcium infusion was given to the patient who developed hungry bone syndrome in the postoperative period. Calcium, phosphorus, and parathormone levels of the patient who was treated for hungry bone syndrome returned to normal. Later on, the patient underwent a right femoral prosthesis operation.

Conclusion

Brown tumor is often seen in the bones of the hands, feet, and long bones.
Mask parathyroid adenoma in morbid obese woman with secondary adrenal insufficiency
Authors: Altemimi Mahmood Thamer , Mansour Abbas Ali
Published: January 2023

Introduction

Primary hyperparathyroidism (PHPT) and metabolic syndrome (MS) are independently increase cardiovascular morbidities; however, this association is still controversial. The pathogenic mechanisms of MS among PHPT are not completely clear and the association with calcium metabolism is being studied, since calcium is pivotal for many metabolic processes. The association between these entities is complex and may be a source of additional morbidity and mortality. Objective is to highlight the mask features of parathyroid adenoma in morbid obese woman with secondary adrenal insufficiency.

Clinical case

A 33-year-old female presented with discomforting polyarthralgia and weight gain for the last 2 years that was labelled as nonspecific arthritis and treated by multiple intra-articular injections of glucocorticoids. After a careful history and examination with baseline analysis, she was discovered to have MS (dysglycemia, high insulin resistance and hypertension). A feature glucocorticoid induced adrenal insufficiency was documented and work up for any evidence of osteoporosis was initiated. A high parathyroid hormone with hypercalcemia was documented and an established osteoporosis was evident. Furthermore, a large left side parathyroid adenoma was observed by a neck sonography and confirmed by a four-dimension computed tomography of the neck. Surgical exploration with excision of the parathyroid adenoma was performed, following which the patient recovered uneventfully.

The patient was initially managed as a case of MS with secondary adrenal insufficiency due to glucocorticoid misuse. Although not suspected initially, an extensive work up for osteoporosis screening and accidental hypercalcemia increase the chance of high index of suspicion for hyperparathyroidism. Further investigations then revealed the presence of a solitary parathyroid adenoma with coexistent hyperparathyroidism which was then managed surgically.

Conclusion

Despite the majority of PHPT is asymptomatic and over masked by MS, Active surveillance for any evidence of hypercalcemia and bone metabolism have to be judged carefully to reduce further morbidity and mortality.
Acute Charcot neuropathy: A devastating consequence of diabetes mellitus
Authors: Iremli Burcin Gonul , Sendur Suleyman Nahit , Yildiz Bulent Okan
Published: January 2023

Introduction

Acute Charcot neuropathy (ACN) is a complication of diabetes mellitus. The prevalence of ACN may be up to 13% in diabetic individuals. ACN has a complex etiology. Although it mostly affects middle of the foot, hind-foot joints, the ankle, and forefoot joints; upper limp may also be affected. Here, we present a case with ACN, whose diagnosis was hard to differentiate and manage.

Clinical Case

A fifty-nine-year-old female admitted to our emergency department with a complaint of pain, numbness, swelling, edema and erythema on left arm. When questioned, she had a history of type 2 diabetes for 22 years and had impaired glycemic regulation with 12.2% HbA1c level. She had all macro and micro vasculary complications of diabetes. On physical examination, her left arm was swollen, pulses were not palpabl. With a suspicion of acute thromboembolism, doppler ultrasound was performed and USG showed no arterial occlusion, but thrombosis from the basilic vein to the proximal brachial vein was seen. She initiated anticoagulant therapy with heparin. After 2 weeks, her complaints increased and pallor, coldness, and pain with passive movements on the left arm were added. She admitted to our intensive care unit with a diagnosis of compartment syndrome. She was followed in ICU with stable hemodynamics and without oxygen supplementation. She had transient acute kidney injury due to rhabdomyolysis but resolved without hemodialysis. Despite fasciotomy, myonecrosis developed on left arm and transhumeral resection was performed. After this devastating result, the patient transferred to endocrinology clinic. Intensive insulin therapy and appropriate antibiotic treatment were continued. During her stay in our clinic, she had the same complaints and physical examination findings on her left foot. Imaging studies (X-ray, bone scintigraphy) showed no osteomyelitis but acute charcot arthropathy was seen. Her glucose levels were regulated, and antibiotics completed. The physical strengthening and ROM exercises for lower extremity and oral total calorie intake was adjusted. Her HbA1c level was decreased to 6.2% without hypoglycemia and she is stable on follow-up.

Conclusion

ACN is a devastating complication of diabetic neuropathy with its consequences. The diagnosis may mislead clinicians to cellulitis, acute venous thrombosis, arthritis or gout. Misdiagnosis or delay in diagnosis may result in serious consequences such as infection, ulceration even amputation as in our case. A multidisciplinary approach and close monitoring of the findings may provide huge benefit for the patient.
A rare case report: Werner syndrome
Authors: Uysal Serhat , Demir Ahmet Numan , Sulu Cem , Kara Zehra , Muradov Ilkin , Kadıoğlu Pınar
Published: January 2023

Introduction

Werner syndrome (WS), also known as adult progeria, is a rare autosomal recessive syndrome caused by pathogenic loss of function of the WRN gene on chromosome 8p12. WS is characterized by signs of premature aging in young adults, including short stature, graying of hair, bilateral cataracts, and scleroderma-like skin changes. A thin, high-pitched voice is characteristic of patients. In addition, diabetes mellitus, cardiovascular disease and osteoporosis can also be seen at an increased rate. Patients have an increased thyroid neoplasms, malignant melanoma and meningioma. There is no specific or effective treatment for this rare syndrome. In this case, we aimed to present our patient with this rare syndrome.

Clinical case

A 28-year-old male patient was admitted for diabetes regulation and foot ulcers. In the patient's history, it was learned that he did not gain weight and did not gain sufficient height since the age of 14. He had been receiving insulin therapy for uncontrolled diabetes for about 10 years. He had cataract surgery at the age of 18. In our evaluation, there were scleroderma-like skin changes on the distal parts of both lower extremities. The patient's hair turned gray. His voice was high-pitched. Two of his siblings looked like him. One sibling who looked like him died at the age of 34. In the laboratory tests; FPG:306 mg/dL and HbA1C:11. The patient had hypergonadotropic hypogonadism. Rheumatological disease examination was normal. No pathological features were observed in lower extremity doppler examinations. Werner syndrome was considered in the patient who did not have sufficient height growth during adolescence, graying of the hair, a history of cataracts, scleroderma-like skin changes, and an elderly appearance. Malignancy scans of the patient were found to be normal. Genetic counseling was given to the patient and his family. The patient was taken to outpatient follow-up.

Conclusion

Werner syndrome is a rare disease. It is important to recognize patients in the early period, to prevent disease-related complications, especially in terms of the risk of malignancy development.