bluuebunny/crossref_metadata_2025 huggingface dataset:
Next-Generation Sequencing of Breast Cancer in the Neoadjuvant Setting
Authors: Mesquita Alexandra , Ferro Anabela , Machado José Carlos , Schmitt Fernando
Published: October 2023

Introduction: Many patients with locally advanced breast cancer are proposed to neoadjuvant chemotherapy (NAT) before surgery. Only some of them achieve a pathological complete response (pCR). The determination of gene somatic alterations using next-generation sequencing (NGS) in the non-pCR tumors is important, in order to identify potential opportunities of treatment for the patients, if targeted therapies are available. Methods: Breast cancer tissue samples of 31 patients, collected before NAT, were analyzed by NGS using the Oncomine™ Comprehensive Assay Plus (OCA-Plus) panel. Results: Twelve patients achieved pCR after NAT. ERBB2 gene alterations were the most frequent in this cohort of pCR patients, followed by BRCA 1 and 2, MYC, TP53, PIK3CA, and MET alterations. Tumors that did not achieve a pCR were mainly triple negative. In this subgroup some BRCA 1 and 2 and PIK3CA gene alterations were identified, as well as TP53 mutations. The NGS panel employed in this study also allowed for the determination of tumor mutation burden (TMB). Conclusion: This study showcases the significance of employing comprehensive genomic testing in breast cancer cases, primarily due to the scarcity of specific target assays. The detection of somatic mutations, coupled with the availability of targeted therapies, holds promise as a potential therapeutic avenue to enhance tumor response rates during NAT, or as a complementary treatment following surgery. Moreover, evaluating the TMB in non-pCR samples could serve as a valuable criterion for selecting patients suitable for immunotherapy. Further exploration through clinical trials is imperative to investigate these prospects.
Long-Time Progression-Free Survival with Trabectedin in Chemorefractory Metastatic Leiomyosarcoma of the Retroperitoneum: A Case Report
Authors: Reichinger Andreas
Published: October 2023

We present the case of a 46-year-old mother of a young child who was diagnosed with metastatic leiomyosarcoma. At diagnosis, the tumor had already infiltrated the vena cava, infiltration of the pancreas was suspected, and pulmonary metastases had been histologically confirmed. The goal of treatment was to prolong survival and gain quality time for the family. When the patient had not responded to 4 cycles of doxorubicin, trabectedin was initiated. After an initial partial remission with a reduction in the size of the primary leiomyosarcoma as well as some pulmonary metastases, the disease remained stable for a total of 10 months. Upon progression, the patient did not further respond to subsequent treatment lines. The presented case shows that second-line trabectedin may represent a promising option for patients with chemotherapy-resistant leiomyosarcoma to prolong survival while preserving quality of life.
Association between Obstructive Sleep Apnea and Intracranial Artery Calcification Stratified by Gender and Body Mass Index: A Hospital-Based Observational Study
Authors: Li Xuelong , Chen Junru , Du Heng , Zhang Yujing , Hua Jiewei , Cheng Yangyang , Li Xianliang , Chen Xiangyan
Published: October 2023

Background and Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for stroke. Furthermore, intracranial arterial calcification (IAC) has been validated as a marker for subclinical cerebrovascular disease. However, the relationship between OSA with IAC was less studied compared with its established association with coronary artery calcification. In this study, we aimed to investigate the association between the severity of OSA and the degree of IAC in hospitalized patients without preexisting cardiovascular disease. Methods: This hospital-based observational study was conducted from June 1, 2017, to May 1, 2019. In total, 901 consecutive patients who underwent head computed tomography scans and portable sleep monitoring were included. On the basis of the apnea-hypopnea index (AHI), patients were divided into four OSA severity groups (normal: AHI <5/h; mild: 5≤ AHI <15/h; moderate: 15≤ AHI <30/h; severe: AHI ≥30/h). Associations of OSA with IAC scores were assessed by using multivariate logistic regression analysis. Results: Of the 901 patients, 484 (53.7%) were men; the mean (SD) age was 66.1 (10.0) years. The non-OSA group included 207 (23.0%) patients; mild OSA, 209 (23.2%); moderate OSA, 235 (26.1%); and severe OSA, 169 (18.8%). Mean IAC scores were higher in the severe OSA group compared with non-, mild, and moderate OSA groups (4.79 vs. 2.58; 4.79 vs. 2.94; 4.79 vs. 3.39; p < 0.001). Multivariate analysis adjusted for confounding factors revealed that only severe OSA was associated with a higher IAC score (odds ratio [OR]: 1.65; 95% confidence interval [CI]: 1.43–1.91; p < 0.001). In stratified analyses by BMI, among participants with a BMI <25 kg/m2, the positive association between AHI values and IAC scores was found in the moderate OSA group (OR: 1.23; 95% CI: 1.05, 1.43; p = 0.01) and the severe OSA group (OR: 1.96; 95% CI: 1.55, 2.48; p < 0.001). When stratified by gender, in women, the positive association was found in the moderate OSA group (adjusted OR: 1.21; 95% CI: 1.02–1.51; p = 0.016) and the severe OSA group (adjusted OR: 1.76; 95% CI: 1.36–2.25; p < 0.001). For the men group, a positive association between IAC scores and AHI was only observed in the severe OSA group. Discussion: These findings suggest that OSA, in particular severe OSA (AHI ≥30), is independently associated with higher IAC scores. Women and no-obesity individuals appeared more susceptible to adverse OSA-related subclinical cerebrovascular disease as measured by IAC scores.
Preoperative Radiotherapy Does Not Change the Existing Treatment Paradigm in Stage III Breast Cancer
Authors: He Yaning , Chen Qi , Zhu Fangyuan , Liu Chaojun , Shao Yingbo , Liu Hui
Published: October 2023

Introduction: Radiotherapy (RT) plays an indispensable role in postoperative breast cancer treatment. This study aimed to assess the feasibility of preoperative RT for stage III breast cancer by comparing preoperative RT with postoperative RT in terms of overall survival (OS). Methods: Based on the information in the Surveillance, Epidemiology, and End Results database from 2000 to 2018, patients with stage III breast cancer who had undergone radical surgery and RT were divided into two groups: a preoperative RT group and a postoperative RT group. OS was calculated using Kaplan-Meier analysis. The Cox proportional hazards model was used to evaluate independent factors associated with OS. Propensity score matching (PSM) was used to balance stratification factors. Results: In total, 9,605 patients were enrolled, of whom 9,456 received postoperative RT and 149 received preoperative RT. After a median follow-up of 72 months, postoperative RT was found to be superior to preoperative RT in terms of OS (p < 0.000). Compared to the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (OS: hazard ratio [HR] = 1.653, 95% confidence interval [CI]: 1.288–2.123, p < 0.000) and multivariate analyses (OS: HR = 1.409, 95% CI: 1.096–1.810, p = 0.007). After PSM, the OS of the postoperative RT group was superior to the OS in the preoperative RT group (p = 0.041). Compared with the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (HR = 1.312, 95% CI: 1.010–1.704, p = 0.042) and multivariate analyses (HR = 1.466, 95% CI: 1.127–1.906, p = 0.004). Conclusion: Preoperative RT does not improve OS in patients with stage III breast cancer and has a worse prognosis. Preoperative RT has not changed the existing treatment paradigm in the current therapeutic context for patients with stage III breast cancer.
Outcomes of Patients with Child-Pugh B and Unresectable Hepatocellular Carcinoma Undergoing First-Line Systemic Treatment with Sorafenib, Lenvatinib, or Atezolizumab Plus Bevacizumab
Authors: Kikugawa Chihiro , Uchikawa Shinsuke , Kawaoka Tomokazu , Kinami Takahiro , Yano Shigeki , Amioka Kei , Naruto Kensuke , Ando Yuwa , Yamaoka Kenji , Tsuge Masataka , Kosaka Yumi , Ohya Kazuki , Mori Nami , Takaki Shintaro , Tsuji Keiji , Kouno Hirotaka , Kohno Hiroshi , Morio Kei , Moriya Takashi , Nonaka Michihiro , Aisaka Yasuyuki , Masaki Keiichi , Honda Yohji , Naeshiro Noriaki , Hiramatsu Akira , Aikata Hiroshi , Oka Shiro
Published: October 2023

Introduction: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. Methods: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. Results: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. Conclusion: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.
CLIPB4 Is a Central Node in the Protease Network that Regulates Humoral Immunity in Anopheles gambiae Mosquitoes
Authors: Zhang Xiufeng , Zhang Shasha , Kuang Junyao , Sellens Kathleen A. , Morejon Bianca , Saab Sally A. , Li Miao , Metto Eve C. , An Chunju , Culbertson Christopher T. , Osta Mike A. , Scoglio Caterina , Michel Kristin
Published: October 2023

Insect humoral immune responses are regulated in part by protease cascades, whose components circulate as zymogens in the hemolymph. In mosquitoes, these cascades consist of clip-domain serine proteases (cSPs) and/or their non-catalytic homologs, which form a complex network, whose molecular make-up is not fully understood. Using a systems biology approach, based on a co-expression network of gene family members that function in melanization and co-immunoprecipitation using the serine protease inhibitor (SRPN)2, a key negative regulator of the melanization response in mosquitoes, we identify the cSP CLIPB4 from the African malaria mosquito Anopheles gambiae as a central node in this protease network. CLIPB4 is tightly co-expressed with SRPN2 and forms protein complexes with SRPN2 in the hemolymph of immune-challenged female mosquitoes. Genetic and biochemical approaches validate our network analysis and show that CLIPB4 is required for melanization and antibacterial immunity, acting as a prophenoloxidase (proPO)-activating protease, which is inhibited by SRPN2. In addition, we provide novel insight into the structural organization of the cSP network in An. gambiae, by demonstrating that CLIPB4 is able to activate proCLIPB8, a cSP upstream of the proPO-activating protease CLIPB9. These data provide the first evidence that, in mosquitoes, cSPs provide branching points in immune protease networks and deliver positive reinforcement in proPO activation cascades.
Clinical Manifestations of Subjective Sleep Disorders in Chinese Patients with Parkinson’s Disease and Their Relationship with Dopaminergic Drugs
Authors: Wu Dongdong , He Jing , Li Kai , Liu Huijing , Jin Ying , Du Wei , Ma Xinxin , Long Yunfei , Li Shuhua , Su Wen , Chen Haibo
Published: October 2023

Introduction: Sleep disorders are common in Parkinson’s disease (PD) and significantly impact quality of life. Herein, we surveyed the incidence and severity of sleep disorders in Chinese PD patients and observed their relationship with dopaminergic drugs. Methods: We collected the demographic and disease information of 232 PD patients. The incidence and severity of sleep disorders were surveyed with the Parkinson’s disease sleep scale (PDSS) Chinese version. Data on dopaminergic drug intake were collected and converted to levodopa equivalent doses (LED). Results: The average total score of PDSS in 232 patients was 119.3 ± 19.7. There was a significant difference in PDSS scores between groups classified by the Hoehn-Yahr (H&Y) stage, but not between the groups classified by the type of dopaminergic drugs. Stepwise regression analysis revealed that the LED of dopaminergic drugs taken before bedtime (p < 0.00), LED of dopaminergic drugs taken over a 24-h period (p < 0.00), and scores of the Hamilton Rating Scale for Depression (HAMD) (p = 0.01) were determinants of PDSS. Conclusion: Sleep disorders in PD patients may be multifactorial. High dosage of dopaminergic drugs taken prior to sleep, daily total high dosage of dopaminergic drugs, and depression exert negative effects on subjective sleep. The timing and dosage of dopaminergic drugs taken before bedtime should be considered in PD management.
The Association between Vitamin D Deficiency and Hepatosteatosis in Children and Adolescents with Obesity
Authors: Korkmaz Hüseyin Anıl , Arya Ved Bhushan , Barisik Vatan , Atila Dincer , Coskunol Fulya , Alci Serra , Cekdemir Yasin Ertug , Torlak Derun , Özkan Behzat
Published: October 2023

Introduction: Increasingly, research groups have been studying the association of serum vitamin D and metabolic health indicators, especially in patients with obesity. We compared the serum 25-hydroxyvitamin D (25(OH)D) concentrations in children and adolescents who had obesity and hepatosteatosis with children and adolescents who had obesity without hepatosteatosis and investigated the relationship between serum 25(OH)D concentrations and severity of hepatosteatosis. We also aimed to assess the effect of vitamin D treatment after 6 months on hepatosteatosis and liver biochemistry. Methods: One hundred thirty-three patients with obesity (body mass index [BMI] >+2 standard deviations [SDs] for their age and gender) and vitamin D deficiency (serum 25(OH)D <12 ng/mL) were recruited. Anthropometric measurements, biochemical parameters (serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25(OH)D, glucose and insulin concentrations), and ultrasonographic findings of hepatosteatosis were recorded before and 6 months after Vitamin D treatment. χ2, Student’s t tests, and multivariate analysis were performed. Results: Grade 1, 2, and 3 hepatosteatosis at baseline was present in 51 (38.4%), 43 (32.3%), and 10 (7.5%) subjects, respectively. Mean (± SD) serum 25(OH)D concentrations were significantly lower in those with hepatosteatosis (8.4 ± 2.4 ng/mL) compared with those without hepatosteatosis (9.9 ± 2.4 ng/mL, p < 0.005). Multivariable logistic regression analysis showed serum 25(OH)D concentration was the independent predictor for hepatosteatosis (p < 0.005), whereas age, sex, weight SD, BMI SD, and homeostasis model of assessment (HOMA)-insulin resistance (IR) were not (p > 0.05). There was no significant difference in BMI SD, HOMA-IR, and liver enzymes between subjects with and without hepatosteatosis (p > 0.05). Despite improvement in serum 25(OH)D concentrations at 6 months post-treatment (34.7 ± 10.6 ng/mL vs. 8.7 ± 2.4 ng/mL; p < 0.0001), there was no significant difference in the proportion of patients with different severity of hepatosteatosis as compared to before treatment (p = 0.88). Conclusion: Serum 25(OH)D concentrations were lower in children and adolescents with obesity and hepatic steatosis as compared to those without hepatic steatosis, with an inverse association between the severity of hepatosteatosis and serum 25(OH)D concentrations. Vitamin D treatment in children and adolescents with obesity and hypovitaminosis D did not improve severity of hepatic steatosis on ultrasonography at 6 months.
Sorafenib-Induced Capillary Leak Syndrome
Authors: Kwon Hyunwoo , Odackal John , Husain Marium , Liebner David A.
Published: October 2023

Capillary leak syndrome is a rare life-threatening disorder of acute endothelial hyperpermeability. It consists of initial fluid extravasation resulting in hypotension, hypoalbuminemia, and hemoconcentration, followed by noncardiogenic pulmonary edema from rapid fluid remobilization into intravascular compartment. Drug-induced etiology is an important diagnostic consideration in cancer patients, particularly with use of antimetabolites, immunostimulants, and monoclonal antibodies. Sorafenib-mediated capillary leak syndrome has never been reported. Here, we present the case of a 29-year-old female patient with a desmoid tumor of the thigh, who was admitted for acute hypoxic respiratory failure after recent initiation of sorafenib. She was found to have extensive pulmonary edema, bilateral pleural effusions, and hemoconcentration, all of which stabilized on supportive care with noninvasive mechanical ventilation and intravenous diuresis. Her infectious and cardiac work-up were negative. Given the temporal relationship between sorafenib use and symptom onset as well as a lack of an alternative etiology of her findings, patient was deemed to have sorafenib-induced acute capillary leak syndrome. Importantly, she did not become hypotensive prior to or during this hospitalization. To our knowledge, we reported for the first time an atypical presentation of acute capillary leak syndrome due to sorafenib use without hemodynamic instability.
A Rare Presentation of Homozygous Pathogenic Variant in MC2R Gene with Salt-Wasting Crisis in a Neonate
Authors: Kardas Yildiz Aysenur , Bulbul Ali , Ozer Bekmez Buse , Turkyilmaz Ayberk , Terali Kerem , Dagdeviren Cakir Aydilek , Ucar Ahmet
Published: October 2023

Introduction: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from isolated glucocorticoid deficiency or unresponsiveness to adrenocorticotropic hormone. Patients with FGD usually present in infancy or early childhood with hyperpigmentation, recurrent infections, and hypoglycemia. The salt-wasting crisis is rare. Case Presentation: A term female neonate was admitted to the neonatal intensive care unit due to respiratory distress. On physical examination, she had generalized hyperpigmentation. Initial laboratory work-up yielded normal serum electrolytes and glucose. Hyponatremia and hyperkalemia emerged on follow-up. The patient was diagnosed as having primary adrenal insufficiency (PAI) with elevated plasma adrenocorticotropin hormone and reduced cortisol levels and hydrocortisone. We started on oral sodium (5 mEq/kg/day) and fludrocortisone (FC) (0.2 mg/day) treatment to the patient. Ultrasonography revealed hypoplastic adrenal glands. Molecular genetic analysis revealed a previously reported homozygous pathogenic variant NM_000529.2: c.560delT (p.V187fs*29) in the MC2R gene. FC dose was tapered to 0.05 mg/day on the third month of life and was stopped at tenth months of age with maintenance of normal serum electrolytes and clinical findings. Conclusion: FGD due to MC2R gene mutation may rarely present with a salt-wasting crisis in the neonatal period. Identifying the causative gene with the pathogenic variant in PAI may serve to individualize a treatment plan.
Acute Kidney Injury and Rehabilitation Outcomes among Elderly Patients with Chronic Kidney Disease
Authors: Nacasch Naomi , Sarel Erez , Rozenberg Ilan , Ayzenfeld Rachel Heffez , Greenberg Meidad , Erez Daniel , Benchetrit Sydney , Cohen-Hagai Keren
Published: October 2023

Introduction: The incidence of chronic kidney disease (CKD) is growing rapidly, along with the increasing geriatric population. CKD patients have higher incidence of fractures, stroke, and hospitalizations requiring rehabilitation. This is accompanied with the need for suitable rehabilitation programs to decrease disability and improve functionality to help elderly CKD patients maintain independence in activities of daily living. Considering that survivors of acute kidney injury (AKI) tend to experience decreased quality of life with increased frailty, rehabilitation in the elderly with kidney injury becomes even more complex. The aim of this study was to examine the impact of AKI on the outcomes of rehabilitation among elderly patients with CKD. Methods: For this retrospective, observational study, the electronic medical records of all patients who were hospitalized in the rehabilitation department were reviewed. We assessed functional status at the beginning and end of rehabilitation, renal outcome, and all-cause mortality among elderly patients with CKD who experienced an AKI and compared them to those who did not have an AKI. Results: The study cohort included 183 elderly patients with non-dialysis-dependent CKD. Patients with AKI (23% of study cohort) had a higher prevalence of heart failure and lower baseline estimated glomerular filtration rate, as compared with patients who did not have AKI. They were admitted to rehabilitation at a poorer functional capacity and were also discharged with lower functional independence measure scores. Overall odds ratio for all-cause death among patients with AKI versus without AKI was 3.2 (95% CI: 1.6–6.5; p = 0.001). Conclusion: AKI and CKD are interrelated syndromes. AKI was prevalent among elderly CKD patients and was associated with worse rehabilitation outcomes and higher mortality compared to similar patients without AKI.
Tracing the Evolution of Prostate Brachytherapy in the 20th Century
Authors: Schaulin Michael  S. , Delouya Guila , Zwahlen Daniel , Taussky Daniel
Published: October 2023

Background: Prostate brachytherapy (BT) techniques have evolved over the past century. This paper aimed to preserve our collective memory of history and the early development of its technique. We searched articles in PubMed and Google Scholar using keywords referring to authors, dates, and BT technical details, including different radioactive sources and country-specific publications. We reviewed the work published by Holm and Aronowitz. The digital library Internet Archives was used to retrieve original journal articles, science newspaper printings, and government reports, which allowed us to situate the development of BT in its sociopolitical context in Europe and the USA. Our search was conducted in English, French, and German languages. Summary: Early BT methods were developed by European physicians with early access to radium. Technical advancements were made by HH Young, who brought this practice to the USA, where Barringer pioneered the use of radon seeds and low-dose interstitial brachytherapy. While centralized radiotherapy centers, such as Memorial Hospital in New York, emerged for training and research, the high cost of radium and opposing interests made brachytherapy harder to implement in Germany. After World War II, the introduction of man-made radioisotopes allowed experiments with colloidal solutions and new seeds, including I-125. In the 1980s, transrectal ultrasound allowed for more accurate radioactive seed insertion and replaced the transrectal finger guidance.
Hypothalamic-Pituitary Axis Function and Adrenal Insufficiency in COVID-19 Patients
Authors: Durcan Emre , Hacioglu Aysa , Karaca Zuleyha , Unluhizarci Kursad , Gonen Mustafa Sait , Kelestimur Fahrettin
Published: October 2023

The outbreak of COVID-19 has affected more than half a billion people worldwide and caused more than 6 million deaths since 2019. The responsible virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the lungs, but it has multisystemic effects. It is well known that dysfunction of multiple endocrine organs may occur during or after COVID-19. Impairment of the hypothalamic-pituitary-adrenal (HPA) axis is of utmost importance as it may lead to death if went undiagnosed. SARS-CoV-2 may cause both primary and secondary adrenal insufficiencies (AIs). The clinical manifestations of AI are generally non-specific and might be attributed to the complications caused by the infection itself. The underlying pathogenetic mechanisms were explained by the immunogenic, vascular effects of the infection or the direct effects of the virus. The diagnosis of AI in critically ill patients with COVID-19 is not straightforward. There is lack of consensus on the cut-off values of basal serum cortisol levels and stimulation tests during the disease. Here we review the literature with a special regard on the evaluation of the HPA axis in patients with COVID-19. We conclude that the possibility of AI should always be kept in mind when dealing with patients with COVID-19, and repeated basal cortisol measurements and the ACTH stimulation test results could guide the clinician during the diagnostic process.
Thyroid Incidentalomas: Incidence and Oncological Implication in Patients with Esophageal Cancer
Authors: van Doesburg Jasmijn R. , Kalff Marianne C. , Voeten Daan M. , Engelsman Anton F. , Jol Saskia , van Berge Henegouwen Mark I. , Daams Freek , Gisbertz Suzanne S.
Published: October 2023

Introduction: Thyroid incidentalomas are often encountered during imaging performed for the workup of esophageal cancer. Their oncological significance is unknown. This study aimed to establish incidence and etiology of thyroid incidentalomas found during the diagnostic workup of esophageal cancer. Methods: All esophageal cancer patients referred to or diagnosed at the Amsterdam UMC between January 2012 and December 2016 were included. Radiology and multidisciplinary team meeting reports were reviewed for presence of thyroid incidentalomas. When present, the fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) or CT was reassessed by a radiologist. Primary outcome was the incidence and etiology of thyroid incidentalomas. Results: In total, 1,110 esophageal cancer patients were included. Median age was 66 years, most were male (77.2%) and had an adenocarcinoma (69.4%). For 115 patients (10.4%), a thyroid incidentaloma was reported. Two thyroidal lesions proved malignant. One was an esophageal cancer metastasis (0.9%) and one was a primary thyroid carcinoma (0.9%). Only the primary thyroid carcinoma resulted in treatment alteration. The other malignant thyroid incidentaloma was in the context of disseminated esophageal disease and ineligible for curative treatment. Conclusion: In this study, thyroid incidentalomas were only very rarely oncologically significant. Further etiological examination should only be considered in accordance with the TI-RADS classification system and when clinical consequences are to be expected.
Impact of Serotonin Pathway Gene Polymorphisms and Serotonin Levels in Suicidal Behaviour
Authors: Sivaramakrishnan Sneha , Venkatesan Vettriselvi , Paranthaman Sampath Kumar , Sathianathan Ramanathan , Raghavan Swetha , Pradhan Priyadarshee
Published: October 2023

Objective: Suicide is a significant public health issue and a major cause of death in all ages worldwide. Previous studies have shown the involvement of genetics in suicidal behaviour. This study aimed to assess the role of the genetic variants of the serotonin transporter genes (5HTTLPR, SLC6A4 intron 2) and receptor gene (5HTR2AT102C) in individuals who died of suicide. The study compares the serum levels of serotonin between the cases and controls. Methods: We conducted a case-control study with 120 cases and 126 controls. Socio-economic details of the subjects were collected using a semi-structured proforma, and psychological autopsy was used to collect details of medical and other clinical conditions. Blood was drawn after taking informed consent and serum levels of serotonin were estimated by enzyme-linked immunosorbent assay. Genotyping was performed using appropriate primers followed by polymerase chain reaction and a restriction fragment length polymorphism. Results: Mean age was 32.59 ± 12.58 for cases and 33.64 ± 9.78 for controls. The risk-associated LL genotype of 5HTTLPR was higher among cases. The heterozygous 12/10 genotype of SLC6A4 intron 2 polymorphism was increased among controls. Serum levels of serotonin were lower among cases. Variant genotypes of all the 3 polymorphisms showed significant interaction (OR = 39.26) indicating that this model may increase suicidal tendency. Conclusion: The findings of this study suggest that low serum levels of serotonin and two variants of the serotonin gene may influence suicide behaviour in a south Indian population.
Continuous Erythropoietin Receptor Activator for the Treatment of Chronic Dialysis Patients with Renal Anemia in Daily Clinical Practice in Poland: A Non-Interventional, Multi-Center, Pragmatic NAVIGO Trial
Authors: Nowicki Michał , Drożdż Maciej , Wajda Jarosław , Klatko Wiesław , Segiet-Święcicka Agnieszka
Published: October 2023

Background: Renal anemia is one of the most common complications of chronic kidney disease (CKD). This real-life study assessed the effectiveness of methoxy polyethylene glycol-epoetin beta, a continuous erythropoietin receptor activator (C.E.R.A.), for the treatment of CKD-associated anemia in patients receiving dialysis in daily clinical practice. Methods: 247 patients receiving chronic intermitted dialysis in 26 centers in Poland with CKD-associated symptomatic anemia, ESA-naïve, and with balanced iron stores in the investigators’ opinion were enrolled this real-life study. Over 12 months, the following data were collected: hemoglobin (Hb) concentration and dosage, route of administration and dosing scheme of C.E.R.A., dialysis adequacy, adverse events, iron therapy, and blood transfusions. Results: During the treatment, a Hb concentration of ≥10 g/dL was noted in 90.9% of hemodialysis patients (n = 224) and 96.0% of peritoneal dialysis patients (n = 23). At baseline, 7.8% of patients had a Hb concentration of 10–12 g/dL, which increased to 63.3% after 12 months. The median time when Hb concentration was maintained within 10–12 g/dL was 115.2 (interquartile range 49.1–188.7) days. A Hb concentration ≥12 g/dL was observed after 7 months of treatment in a maximum of 24.1% of hemodialysis patients, and 31.8% of peritoneal dialysis patients. The median time elapsed between the start of treatment and the first Hb concentration >10 g/dL was 42.0 (21.0–78.2) days. C.E.R.A. was well tolerated. Conclusions: C.E.R.A. corrects CKD-associated anemia in dialysis patients, and maintains Hb levels within the recommended target range. The study also confirmed the acceptable safety profile of the drug.
Metabolism and Nutrition in Sepsis: In Need of a Paradigm Shift
Authors: Collins Kristina , Huen Sarah C.
Published: October 2023

Background: Sepsis continues to cause significant morbidity and mortality despite technological advancements in medical management. While sepsis is defined as organ dysfunction owing to the dysregulated host response to infection, our understanding of the dysregulation of the host response remains incomplete. Summary: Many metabolic derangements that occur during sepsis, including those associated with anorexia, hyperglycemia, and proteolysis, have largely been considered maladaptive. Supportive medical and nutritional interventions targeted at correcting these metabolic derangements have not led to improved outcomes, suggesting a reappraisal of our approach to metabolism and nutrition in critically ill septic patients is needed. Key Messages: Explanations of the lack of efficacy of these clinical interventions may include targeting the wrong metric or patient population, or the possibility that some of these metabolic changes could be protective. In this mini-review, we propose a paradigm shift that is needed in metabolism and nutrition management in sepsis.
Perilipin 1 Deficiency Prompts Lipolysis in Lipid Droplets and Aggravates the Pathogenesis of Persistent Immune Activation in Drosophila
Authors: Wang Lei , Lin Jiaxin , Yang Kaiyan , Wang Weina , Lv Yan , Zeng Xiangkang , Zhao Yaya , Yu Junjing , Pan Lei
Published: October 2023

Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs’ reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.
Paclitaxel-Induced Periarticular Thenar Erythema with Onycholysis Syndrome
Authors: Kaur Japnoor , Gaurav Vishal , Tyagi Mehul
Published: October 2023

Introduction: Periarticular thenar erythema with onycholysis (PATEO) syndrome is a rare subtype of hand-foot syndrome seen in patients undergoing taxane-based chemotherapy. It presents as erythematous to violaceous plaques on the dorsum of hands, feet, and around the Achilles tendon along with nail changes, particularly onycholysis. Case Presentation: A 39-year-old female on paclitaxel chemotherapy for stage IIIA (T3N2aM0) invasive ductal breast carcinoma, presented with mildly tender erythematous to violaceous plaques involving the dorsa of bilateral hands and feet, in the periarticular areas of the Achilles tendon, with facial involvement. All fingernails showed shortening, orange-red chromonychia, Beau’s lines, onychoschizia, and subungual debris. The toenail involvement was relatively less severe, with distal onycholysis being the predominant finding. The patient showed significant improvement in cutaneous lesions with topical steroid therapy and was advised cold water immersion during subsequent chemotherapy infusions. Discussion: A shorter interval between cycles and a higher cumulative number of cycles correlate with severity of dermatitis and nail involvement. Rarely, periocular and facial involvement can occur concurrently with PATEO syndrome. This case is being reported to increase awareness about this entity facilitating early diagnosis and treatment.
The Effects and Outcomes of the COVID-19 Pandemic on Pregnant Women in Kuwait
Authors: Akbar Zahraa , Al Azmi Eman , Husain Eelaf , Aldarweesh Mariam , AlMuzayen Khaled , Alhadhoud Fatemah , Al Harmi Jehad
Published: October 2023

Objectives: This retrospective study reports the effects of COVID-19 among hospitalized pregnant women infected with COVID-19 and compares them to a control group. Methods: We performed a multicenter retrospective cohort study, in which data of pregnant women with COVID-19, admitted to five different hospitals in Kuwait, were collected. Two groups were included; the first group was women with COVID-19 who were admitted between March 22, 2020, and December 31, 2020. The second (control) group included pregnant women without COVID-19 who were admitted between March 1, 2019, and March 21, 2020. Data were collected using a standardized data collection survey, entered using Excel software, and analyzed using analysis of variance. Results: We compared 764 patients, with confirmed COVID-19 with 765 uninfected control subjects. The majority of pregnant women were diagnosed with COVID-19 infection during the third trimester. Tachycardia was the most frequent sign at admission, and dry cough and fever were the most common presenting symptoms. ICU admission and respiratory failure were significantly higher in the COVID-19 group. Cesarean section (CS) rate was higher in the COVID-19 group, with obstetric and maternal complications being the most common indications in comparison to fetal indications in the control group. Conclusions: This study was conducted to identify the effects of COVID-19 in pregnancy. Most patients were asymptomatic. The rate of normal vaginal delivery was higher in the control group. The main indications for CS in the COVID-19 group were obstetrical and maternal complications compared to fetal complications in the control group.
Olfactory Bulbs in Arthritis Model Mouse Persistently Express Interleukin-6 before the Onset of Arthritis: Relationship to Food Intake
Authors: Otani Kazuhiro , Yoshiga Masayuki , Hirano Masashi , Matsushita Takayuki , Noda Kentaro , Kurosaka Daitaro
Published: October 2023

Introduction: Rheumatoid arthritis (RA) can be comorbid with psychiatric symptoms. Brain abnormalities in RA patients and in arthritis models have been reported. However, it remains unclear when these abnormalities occur and where they are distributed. In this study, we analyzed spatiotemporal changes in gene expression in the brains of mice with collagen-induced arthritis (CIA). Methods: Mice were divided into three groups: (i) CIA (all mice developed arthritis on day 35): complete Freund’s adjuvant (CFA) and type II collagen at initial immunization, and incomplete Freund’s adjuvant (IFA) and type II collagen at booster immunization; (ii) C(+/−) (50% mice developed arthritis on day 35): only IFA at booster immunization; and (iii) C(−/−) (no arthritis): only CFA at initial immunization and only IFA at booster immunization. Whole brains were collected at ten stages of arthritis and divided into six sections. Real-time polymerase chain reaction was performed using RNA extracted from the brain, and the expression of proinflammatory cytokines and glial markers was semi-quantified. Arthritis score, body weight, and food and water intakes were recorded and analyzed for correlations with brain gene expression. We also investigated the effect of interleukin-6 (IL-6) injection in the olfactory bulbs (OBs) on the food intake. Results: After booster immunization, a transient increase in Integrin subunit α-M and IL-1β was observed in multiple areas in CIA. IL-6 is persistently expressed in the OB before the onset of arthritis, which is correlated with body weight loss and decreased food intake. This change in the OB was observed in the C(+/−) but not in the C(−/−) groups. In the C(+/−) group, non-arthritic mice showed the same changes in the OB as the arthritic mice. This elevation in IL-6 levels persisted throughout the chronic phase until day 84. In addition, IL-6 injection into the OB reduced food intake. Conclusion: Persistent elevation of IL-6 in the OB from the early stage of arthritis may be an important finding that might explain the neuropsychiatric pathophysiology of RA, including appetite loss, which is present in the early stages of the disease and manifests as a variety of symptoms over time.
Involving Voters and Consumers in Decision-Making about the Health Care System – The Swiss Case: A Review
Authors: Jütte Robert
Published: October 2023

Background: Behind the principle of involving users and voters directly in decision-making about the health care system are ideas relating to empowerment. This implies a challenge to the traditional view that scientific knowledge is generally believed to be of higher value than empirical knowledge, as it is the case with CAM. The objectives of this review are (a) to show that this assumption disregards the fact that CAM is as scientific as conventional medicine but has different basic assumptions what the world is being made of and consequently uses different/adapted scientific methods; (b) to demonstrate how a perspective of the history of medicine and science as well as direct democracy mechanisms such as stipulated in the Swiss constitution can be used to achieve the acceptance of CAM in a modern medical health care system. A public health care system financed by levies from the population should also reflect the widely documented desire in the population for medical pluralism (provided that therapeutical alternatives are not risky). Otherwise, the problem of social inequality arises because only people with a good financial background can afford this medicine. Summary: From the perspective of scientific theory and the history of science, the answer to the question of whether complementary medicine and conventional medical procedures must provide proof of efficacy according to a uniform scientific is quite controversial according to epistemologically oriented studies on this issue. Key Messages: This review found strong evidence for involving voters and consumers directly in decision-making about the provision of CAM in the health care system. It also seems necessary to step back in the debate on evidence-based medicine, taking a history of medicine and science perspective, as the role which the proper method occupies and plays in medicine is defined by the scientific nature of the world view.
Rapid Initiation of Peritoneal Dialysis by Automated Peritoneal Dialysis or Hemodialysis: A Randomized Clinical Trial
Authors: Zhang Qianying , Wu Pei , Xie Jingyuan , Li Xiao , Xu Tian , Huang Xiaomin , Zhang Chunyan , Chen Nan , Ren Hong
Published: October 2023

Introduction: It is still controversial whether automated peritoneal dialysis (APD) or hemodialysis (HD) is a more favorable choice for the rapid initiation of peritoneal dialysis (PD). Methods: A pilot randomized prospective controlled trial was carried out in Shanghai Ruijin Hospital. Sixty-seven patients who chose long-term PD treatment and needed unplanned dialysis were enrolled and randomized into HD-CAPD group (33 cases) or APD-CAPD group (34 cases) based on the dialysis modality during the transition period (within 14 days from the day PD catheter was implanted). Continuous ambulatory PD started after the transition period. The primary outcome was the decline rates of residual glomerular filtration rate (GFR). Secondary outcomes included the rates of mechanical complications, the rates of infectious complications, and complications of end-stage renal disease. Results: We found residual GFR decline was faster in HD-CAPD group than in APD-CAPD group (0.06 mL/min/w vs. 0.03 mL/min/w, p < 0.01). The incidences of mechanical complications were similar in APD-CAPD group comparing with HD-CAPD group, including hernia (2.9% vs. 3.0%, p = 1.00), catheter malposition (0.02 episodes/patient-months vs. 0.02 episodes/patient-months, p = 0.70), leakage (5.9% vs. 6.1%, p = 1.00), and omental wrap (0 episode vs. 3 episodes, p = 0.368). Though the 1-year overall infection rates were similar (0.03 episodes/patient-months vs. 0.05 episodes/patient-months, p = 0.10), APD-CAPD group had lower rate of bacteremia compared to HD-CAPD group (0 episodes/patient-months vs. 0.02 episodes/patient-months, p < 0.01). Conclusions: Both APD and HD could be used for patients who need to start dialysis in an unplanned manner. APD may have the advantage in protecting residual renal functions among these patients.
Relapse Primary Central Nervous System Lymphoma Successfully Consolidated with Allogeneic Stem Cell Transplantation with Thiotepa/Busulfan/Fludarabine Conditioning
Authors: Noij Daniel P. , van den Bent Martin , Doorduijn Jeannette K. , Wlazlo Nick
Published: October 2023

Primary central nervous system lymphoma (PCNSL) is generally characterized by a poor prognosis and frequent relapsing disease. Consolidation therapy in the upfront setting usually consists of an autologous stem cell transplantation. We report the case of a 19-year-old Caucasian male who had previously undergone an allogeneic stem cell transplantation with complete engraftment for the treatment of juvenile myelomonocytic leukemia when he was 1 year old. He presented with two episodes of (donor-derived) PCNSL from allogeneic stem cells; however, after induction chemotherapy, he failed to harvest stem cells for the consolidation with autologous stem cell transplantation. He was consolidated successfully with a second allogeneic stem cell transplantation with another donor after conditioning with thiotepa, busulfan, and fludarabine.
Chronic Kidney Disease Risk in Living Kidney Transplant Donors: A Long-Term Follow-Up Study
Authors: Haberal Guldehan , Yildirim Tolga , Yilmaz Seref Rahmi , Altun Bulent , Aki Fazil Tuncay , Erdem Yunus , Arici Mustafa
Published: October 2023

Background: Living kidney donors (LKD) may experience some untoward consequences following donation such as development of chronic kidney disease (CKD). In this study, we aimed to investigate the rate of development of CKD and factors affecting the development of CKD in LKDs during long-term follow-up from a center in Turkey. Methods: This study was a retrospective analysis of LKDs followed between January 2000 and December 2017. Pre-transplant and post-transplant clinical data of the 338 LKDs were recorded and compared. Factors affecting the development of stage 3 and later stages of CKD were analyzed. Results: Majority of the donors were females (64.2%), and the median age of all donors was 47 (39–54) years. Stage 3 CKD developed in 50 donors during the median follow-up of 71 months. Older age at the time of transplantation and a low pre-transplant estimated glomerular filtration rate (eGFR) were determined as the factors affecting the development of stage 3 CKD (p < 0.001, p < 0.001). The receiver operating characteristic analysis showed that the cut-off age for the development of stage 3 CKD was 50.5 years. Newly diagnosed hypertension was detected in 57 patients (16.8%) after the transplantation. While hypertension was seen at a rate of 42% in those with an eGFR <60 mL/min/1.73 m2, it was detected at 19.4% in the group with an eGFR >60 mL/min/1.73 m2 (p < 0.001). Conclusion: These results reveal that being a LKD is associated with the development of CKD and hypertension. Age and eGFR values at the time of transplantation were the determinants for the development of CKD.