bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic Status Is Related to Pubertal Development in a German Cohort
Authors: Oelkers Lea , Vogel Mandy , Kalenda Agnes , Surup Hans Christian , Körner Antje , Kratzsch Jürgen , Kiess Wieland
Published: March 2021

Introduction: Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. Objective: The goal of this study was to determine whether pubertal onset/duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. Methods: 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. Results: Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys’ age at mutation. No significant differences in boys’ and girls’ serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. Conclusion: Puberty onset/duration and boys’ age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boys.
Which Patients with Obesity Are at Risk for Renal Disease?
Authors: Sandino Justo , Luzardo Leonella , Morales Enrique , Praga Manuel
Published: March 2021

Obesity-related glomerulopathy (ORG) is an increasingly recognized cause of end-stage kidney disease. The most common clinical presentation is a slowly increasing nonnephrotic proteinuria that is followed by a progressive decline of kidney function. Key histological findings are glomerulomegaly and lesions of focal and segmental glomerulosclerosis. A central pathogenic mechanism is the increased sodium reabsorption by proximal tubules that typically accompanies obesity. This causes a decrease in the offer of sodium to the macula densa in the distal nephron, which results in a vasodilation of afferent glomerular arterioles and glomerular hyperfiltration. From a clinical point of view, it is essential to differentiate focal segmental glomerulosclerosis secondary to obesity from primary glomerular processes, which requires a careful differential diagnosis. Diet-induced weight loss, bariatric surgery, and renin-angiotensin blockers are the fundamental therapeutic measures in ORG. The recently developed sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonist represent a significant advance in renal protection and will probably improve clinical kidney outcomes in ORG.
Sonographic Evaluation of Hidradenitis Suppurativa with Smartphone-Linked Portable Ultrasound
Authors: Weigelt Maximillian A. , Hilerowicz Yuval , Leichter Jeffrey A. , Lev-Tov Hadar
Published: March 2021

Background: Clinical staging systems for hidradenitis suppurativa (HS) have poor interrater reliability and may underestimate disease activity. Sonographic staging systems may overcome these challenges, but conventional ultrasound (US) machines are expensive and bulky. Portable (p)US may facilitate the integration of sonography into routine practice. Objectives: To assess the ability of a novel smartphone-linked pUS device to identify key sonographic lesions of HS. Methods: The charts of 16 patients with HS who were assessed with pUS at the outpatient Dermatology and Wound Care Clinics of a university hospital center were retrospectively reviewed. Clinical and sonographic images of the affected areas were examined. The main outcome measures were the number of patients with identifiable sonographic lesions and the number of patients with subclinical lesions detected by pUS. Results: All 3 key sonographic lesions of HS were identifiable with pUS. Sonographic lesions were identified in 10 patients (62.5%). Subclinical lesions were identified in 2 patients (12.5%); in both cases, this affected management decisions. Conclusions: We demonstrate the ability of pUS to identify the key sonographic lesions of HS. pUS is a simple and affordable way to integrate HSUS into clinical and research settings, with clear potential benefits to patients.
Clinicopathological Characteristics of Low-Grade Appendiceal Mucinous Neoplasm
Authors: Yamaguchi Tatsuro , Murata Kohei , Shiota Tetsuya , Takeyama Hiroshi , Noura Shingo , Sakamoto Kazuhiro , Suto Takeshi , Takii Yasumasa , Nagasaki Toshiya , Takeda Takashi , Fujii Makoto , Kagawa Yoshinori , Mizushima Tsunekazu , Ohno Yuko , Yao Takashi , Kishimoto Mitsuo , Sugihara Kenichi ,   on behalf of the Study Group of Appendiceal Neoplasms in the JSCCR
Published: March 2021

Introduction: Recently, “low-grade appendiceal mucinous neoplasms” (LAMNs) have been proposed as one subtype of appendiceal mucinous neoplasms, characterized by a villous or flat proliferation of mucinous epithelium with low-grade cytologic atypia. The aim of this study was to clarify the clinicopathological characteristics of LAMN. Methods: In this multi-institutional cohort study, we retrospectively analyzed the clinicopathological characteristics in appendiceal neoplasms patients who underwent treatment from 2000 to 2017. Results: In total, 922 patients were enrolled, with 279 (30.3%) cases of LAMN, and 93 (10.1%) cases of non-LAMN disease. In comparison with patients with non-LAMN disease, those with LAMN had significantly lower levels of CA19-9 (p = 0.045), a lower frequency of T4 tumors (p < 0.0001), a lower frequency of lymph node metastasis (p < 0.0001), and a lower frequency of distant metastasis (p < 0.0001). Survival analysis revealed that patients with LAMN had a significantly better prognosis than did those with non-LAMN disease (p < 0.001). Among the patients with distant metastasis, those with LAMN had a significantly better prognosis than did those with non-LAMN disease (p = 0.0020), but among the patients without distant metastasis, the difference between the 2 groups was not significant (p = 0.26). However, among patients who underwent complete resection, the difference in prognosis between the 2 groups was not significant (p = 0.10). Conclusions: A multicenter retrospective study revealed that the clinicopathological characteristics of LAMN was different from those of non-LAMN.
Autoimmune Movement Disorders: A Video-Based Case Series of 11 Patients
Authors: Chouksey Anjali , Pandey Sanjay
Published: March 2021

Autoimmune encephalitis (AIE) constitutes an important treatable cause of movement disorders. We aimed to highlight the spectrum of movement disorder and other salient features of AIE patients diagnosed at our tertiary care centre and describe their clinical symptoms, diagnostic approach, treatment, and outcome. We evaluated 11 patients who presented with movement disorder in association with AIE at our centre. Various abnormal movements observed were tremor, dyskinesias, stereotypy, dystonia, ataxia, asterixis, myoclonus, and parkinsonism. Antibodies were detected against NMDAR (n = 3), LGI-1 (n = 2), GAD-65 (n = 1), CASPR-2 (n = 1), Sox-1 (n = 1), Yo (n = 1), and thyroid peroxidase (n = 1). One patient was diagnosed with opsoclonus myoclonus syndrome associated with the suspected neuroblastic tumour. Six patients responded well to first-line immunotherapy (intravenous immunoglobulins or steroid or both). Three patients with anti-NMDAR antibodies received second-line therapy consisting of rituximab. Movement disorder is one of the most consistent features of AIE. Understanding of the ever-expanding spectrum of antibodies associated with movement disorders helps in the early diagnosis and better management of patients of autoimmune movement disorder.
Risk Factors for Mortality and Neurodevelopmental Impairment among Neonates Born at 22–23 Weeks’ Gestation
Authors: Kurimoto Tomonori , Ibara Satoshi , Kamitomo Masato , Tokuhisa Takuya , Maeda Takatsugu , Maede Yoshinobu , Ishihara Chie , Naito Yoshiki , Hirakawa Eiji , Yamamoto Tsuyoshi , Yamamoto Masakatsu , Kibe Masaya , Takayama Tatsu , Ohashi Hiroshi
Published: March 2021

Introduction: We aimed to evaluate the risk factors for mortality and neurodevelopmental impairment (NDI) among infants of 22–23 weeks’ gestational age, which currently remain unclear. Methods: This retrospective case-control study included 104 infants delivered at 22–23 weeks’ gestation at Kagoshima City Hospital from 2006 to 2015. We compared 65 and 34 cases of survival to discharge and postnatal in-hospital death (5 excluded), respectively, and 26 and 35 cases with and without NDI, respectively, using maternal, prenatal, and postnatal records. A high rate of survivors’ follow-up (61/65) was achieved in this study. Results: The survival rate was 75.0% (21/28) and 62.0% (44/71) among infants born at 22 and 23 weeks’ gestation, respectively. Infants who died weighed less (525.5 vs. 578 g, p = 0.04) and their intrauterine growth retardation (IUGR) rate (<5th percentile) was higher (14.7 vs. 1.5%, p = 0.02). Mortality was associated with an increased incidence of bradycardia on fetal heart rate monitoring (11.8 vs. 1.5%, p = 0.046), periventricular hemorrhagic infarction (PVHI; 32.4 vs. 6.2%, p = 0.001), necrotizing enterocolitis (NEC, surgery or drain tube; 14.7 vs. 0.0%, p = 0.004), and tension pneumothorax (29.4 vs. 6.2%, p = 0.004). There were significant differences in the proportion of PVHI (15.4 vs. 0%, p = 0.03) between infants with and without NDI. Conclusions: IUGR, bradycardia, PVHI, NEC, and tension pneumothorax were associated with neonatal mortality among infants born at 22–23 weeks’ gestation. NDI at 36–42 months’ chronological age was associated with PVHI.
A Prospective Multicenter Observational Study of Venous Thromboembolism after Gastric Cancer Surgery (SHISA-1601)
Authors: Kaida Sachiko , Miyake Toru , Murata Satoshi , Yamaguchi Tsuyoshi , Tatsuta Takeshi , Murakami Koichiro , Okauchi Hiroshi , Nishimura Shoichi , Ohta Hiroyuki , Tsuchihashi Hiroshi , Kawasaki Masayasu , Takebayashi Katsushi , Shimizu Tomoharu , Tani Masaji
Published: March 2021

Introduction: This study aimed to clarify the frequency and risk factors of intercurrent venous thromboembolism (VTE) in patients undergoing major curative gastric cancer surgery. Methods: This prospective, multicenter, observational study included patients with gastric cancer who underwent radical gastrectomy at 5 hospitals between June 2016 and May 2018. Patients who were preoperatively administered anticoagulants were excluded. Results: A total of 126 patients were eligible to participate. VTE occurred within 9 days postoperatively in 5 cases (4.0%; 2 symptomatic and 3 asymptomatic). Postoperative day (POD) 1 plasma D-dimer and soluble fibrin (SF) levels were significantly higher in the VTE group than in the non-VTE group. Receiver-operating characteristic curve (ROC) analysis indicated a statistically significant ability of POD 1 D-dimer and SF levels to predict postoperative VTE development after gastrectomy; this finding was reflected by an area under the curve (AUC) of 0.97 (95% CI 0.92–1.0) and 0.87 (95% CI 0.74–1.0), respectively. Cutoff values of D-dimer (24.6 µg/mL) and SF (64.1 µg/mL) were determined. Intraoperative blood transfusion (odds ratio [OR] 7.86), POD 1 D-dimer ≥24.6 µg/mL (OR 17.35), and POD 1 SF ≥64.1 µg/mL (OR 19.5) were independent predictive factors for postoperative VTE (p < 0.05). Conclusion: VTE occurred in 4.0% patients (1.6% symptomatic and 2.4% asymptomatic) after gastric cancer surgery; however, with an early diagnosis and anticoagulant therapy, no patients experienced progression. Careful observation of patients with a high risk for VTE, including intraoperative blood transfusion and high POD 1 D-dimer or SF levels, would contribute to the early detection of VTE.
Pathologic Basis for the Definition of Discordant Growth in Dichorionic Twins
Authors: Ashwal Eran , Hiersch Liran , Berger Howard , Aviram Amir , Zaltz Arthur , Kingdom John , Barrett Jon , Melamed Nir
Published: March 2021

Objective: The aim of the current study was to identify the optimal cutoff that should define discordance in dichorionic twin gestations through correlation with abnormal placental pathology as a specific measure of fetal growth restriction of the smaller twin. Methods: We performed a retrospective cohort study of all women with dichorionic twin pregnancies who gave birth in a single center between 2002 and 2015. We investigated the association between the level of growth discordance and maternal vascular malperfusion (MVM) pathology in the placenta of the smaller twin, with and without adjustment for whether the smaller twin is small for gestational age (SGA). Results: A total of 1,198 women with dichorionic twin gestation met the study criteria. The rate of MVM pathology in the placenta of the smaller twin increased with the level of discordance and was most obvious for discordance ≥25% (rate of MVM 12.0% compared with 2.8% in cases with discordance <10%, adjusted relative risk [aRR] 3.71, 95% confidence interval [CI] 1.97–6.99). When the analysis was adjusted for SGA of the smaller twin, discordance was independently associated with MVM pathology only when growth discordance was ≥25% (aRR 2.18, 95%-CI 1.01–4.93), while SGA was strongly associated with MVM pathology irrespective of the level of discordance. Conclusion: Our findings suggest that discordant growth in dichorionic twins should raise the concern of fetal growth restriction of the smaller twin, irrespective of whether the smaller twin is SGA, only when the discordance s ≥25%. The association of lower levels of discordance with abnormal placental pathology is mainly driven by the confounding effect of SGA of the smaller twin.
Monitoring of COVID-19-Associated Coagulopathy and Anticoagulation with Thromboelastometry
Authors: Katz Daniel , Maher Patrick , Getrajdman Chloe , Hamburger Joshua , Zhao Shan , Madek Jonathan , Bhatt Himani , Levin Matthew , Görlinger Klaus
Published: March 2021

Introduction: Thrombosis occurs frequently in COVID-19. While the exact mechanism is unclear, 3 processes seem to play important roles in sepsis-related thrombosis and mortality: tissue factor expression on circulating monocytes and microparticles, hypercoagulability (increased clot firmness), and hypofibrinolysis. Rotational thromboelastometry is a point-of-care viscoelastic technique that uses the viscoelastic properties of blood to monitor coagulation. Using various assays, viscoelastometry could monitor this triad of changes in severely ill, COVID-19-positive patients. Similarly, with the increased incidence of coagulopathy, many patients are placed on anticoagulants, making management more difficult depending on the agents utilized. Viscoelastometry might also be used in these settings to monitor anticoagulation status and guide therapy, as it has in other areas. Case Presentation: We present a case series of 6 patients with different stages of disease and different management plans. These cases occurred at the height of the pandemic in New York City, which limited testing abilities. We first discuss the idea of using the NaHEPTEM test as a marker of tissue factor expression in COVID-19. We then present cases where patients are on different anticoagulants and review how viscoelastometry might be used in a patient on anticoagulation with COVID-19. Conclusion: In a disease such as COVID-19, which has profound effects on hemostasis and coagulation, viscoelastometry may aid in patient triage, disease course monitoring, and anticoagulation management.
Effect of a Gluten-Free Diet on Albuminuria in Children with Newly Diagnosed Celiac Disease
Authors: Levine Jeremiah , Hauptman Leora , Moy Libia , Trachtman Howard
Published: March 2021

Background and Objectives: Altered gastrointestinal permeability in celiac disease (CD) is mediated by zonulin. The receptor for zonulin is expressed on podocytes. Therefore, we tested the effect of a gluten-free diet (GFD) on albuminuria in pediatric patients with newly diagnosed CD. Methods: We performed a cohort study comparing urinary albumin (μg): Cr (mg) ratio (ACR) in CD patients versus controls and in response to a GFD. Results: Children with CD (n = 46) had higher ACR than controls (n = 21), 20.2 ± 5.6 versus 8.4 ± 1.1 μg/mg, p = 0.16 and exceeded 30 μg/mg (microalbuminuria cutoff) in 7/46 cases. Seventeen patients had a follow-up assessment (interval 6.1 ± 0.7 months) on a GFD. Baseline ACR was 20.7 ± 5.2 that fell to 10.4 ± 1.5 μg/mg, p = 0.035. Conclusion: Children and adolescents with newly diagnosed CD have low-grade albuminuria that is numerically higher than controls and that declined after implementation of a GFD. CD may be associated with reversible defects in the glomerular barrier.
Physical Frailty and Future Costs of Long-Term Care in Older Adults: Results from the NCGG-SGS
Authors: Makizako Hyuma , Shimada Hiroyuki , Tsutsumimoto Kota , Makino Keitaro , Nakakubo Sho , Ishii Hideaki , Suzuki Takao , Doi Takehiko
Published: March 2021

Introduction: Frailty is associated with adverse outcomes, but few studies have determined associations between the frailty phenotype and measures of healthcare burden, including long-term care insurance (LTCI) costs, in older community-dwelling populations. Objective: The aim of this study was to examine the association between frailty status and subsequent LTCI costs in Japanese community-dwelling older adults. Methods: The prospective data were from a cohort study (National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes [NCGG-SGS]). The participants were community-dwelling older adults (mean age 71.8 years, women 50.7%) participating in an NCGG-SGS baseline examination held between August 2011 and February 2012 in Obu, Japan (N = 4,539). At baseline, we assessed the physical frailty phenotype using the Japanese version of the CHS criteria and categorized it as robust, pre-frail, or frail. We also ascertained care-needs certification and total costs using long-term care services in Japan’s public LTCI system during the 29 months. Results: During the 29-month follow-up period, 239 participants (5.3%) required the LTCI system’s care-needs certification and 163 participants (3.6%) used LTCI services. Participants classified as frail (odds ratio 5.85, 95% confidence interval 3.54–9.66) or pre-frail (2.40, 1.58–3.66) at the baseline assessment had an increased risk of requiring care-needs certification compared with robust participants. The mean total costs for LTCI services during the 29 months were ¥6,434 ($63.1) for robust, ¥19,324 ($189.5) for pre-frail, and ¥147,718 ($1,448.2) for frail participants (1 US dollar = 102 Japanese yen in July 2014). There were significantly higher costs associated with advancing frailty status. Individual frailty components (slowness, weakness, exhaustion, low activity, and weight loss) were also associated with higher total costs for using LTCI services. Discussion/Conclusion: Frail community-dwelling older adults had a higher risk of requiring the LTCI system’s care-needs certification and the subsequent total LTCI costs.
Celiac Disease Revisited
Authors: Calado João , Verdelho Machado Mariana
Published: March 2021

Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.
Die Cognitive Processing Therapy zur Behandlung Geflüchteter mit einer Posttraumatischen Belastungsstörung: Eine Machbarkeitsstudie
Authors: Steil Regina , Görg Nora , Kümmerle Stella , Lechner-Meichsner Franziska , Gutermann Jana , Müller-Engelmann Meike
Published: March 2021

Hintergrund: Metaanalysen zeigen die Wirksamkeit traumafokussierter Verfahren für Geflüchtete. Für die Cognitive Processing Therapy (CPT) liegt bei dieser Population in Deutschland bisher keine empirische Machbarkeitsprüfung vor. Patient*innen und Methoden: Im Rahmen einer Machbarkeitsstudie erhielten 16 Geflüchtete mit einer Posttraumatischen Belastungsstörung (PTBS) unter klinischen Routinebedingungen drei diagnostische Vorgespräche, fünf probatorische Sitzungen, zwölf Doppelsitzungen (100 Minuten) CPT sowie bis zu vier optionale Krisensitzungen. Vor und nach der Therapie wurde die PTBS-Symptomatik erhoben. Qualitative Nachbefragungen mit Patient*innen und Therapeut*innen wurden durchgeführt. Ergebnisse: Insgesamt neun von 16 Patient*innen brachen die Therapie vorzeitig ab. Innerhalb der Completer-Stichprobe (Per-protocol-Analyse) zeigten sich mittelgroße, aber nicht signifikante Effekte auf die PTBS-Symptomatik (d = 0,75; M[CAPSprä] = 39,33 [SD = 10,89]; M[CAPSpost] = 22,50 [SD = 15,16]). Patient*innen und Therapeut*innen berichteten eine Reihe von Hürden in der Therapiedurchführung. Diskussionen: Die vorliegende Machbarkeitsstudie verzeichnete eine für die CPT ungewöhnlich hohe Abbruchquote. Diese lässt sich möglicherweise auf die mangelnde Passung des Verfahrens für Patient*innen mit geringer Schreib- und Lesekompetenz oder hoher psychosozialer Belastung zurückführen. Implikationen für die Behandlung Geflüchteter bezüglich der Wahl des Behandlungsverfahrens, der Motivationsklärung und der Rahmenbedingungen werden diskutiert. Schlussfolgerungen: Während breite empirische Evidenz für traumafokussierte Verfahren bei Geflüchteten vorliegt, ist die Standard-CPT möglicherweise nur für Subgruppen dieser Population geeignet. Eine Vereinfachung der CPT-Materialien und eine vorherige Motivationsklärung erscheinen notwendig.
Adjuvant Treatment of the Salivary Duct Carcinoma with Her2 Overexpression
Authors: Berendika Jelena , Jungić Saša , Tubić Biljana , Malčić Kecman Gordana , Rakita Ivanka , Gojković Zdenka , Vještica Milka , Nikić Gordan , Babić Božana
Published: March 2021

Malignant salivary gland tumors form 11% of all head and neck tumors. Salivary duct carcinoma (SDC) of the parotid gland is an uncommon and highly aggressive tumor accounting for 2% of all salivary gland malignancies. The fourth edition of the WHO Classification of Head and Neck Tumors reported global annual incidence of 0.4–2.6/100,000 people. Standard treatment for SDC is wide surgical resection along with lymph node dissection followed by adjuvant radiation therapy. The role of adjuvant chemotherapy is not known. Here, we present a case of an SDC of the parotid gland in a 55-year-old female. She presented with a painless swelling behind her right ear. Surgery was performed, and total right parotidectomy was done along with selective neck dissection (levels II, III, VA). The pathology report concluded that it was a G3 (poorly differentiated) SDC (micropapillary variant) with lymphovascular and perineural invasion. The clinical stage of the disease was T4aN2bM0. Adjuvant therapy consisted of concurrent radiation (TD 66 Gy) and chemotherapy with weekly paclitaxel (45 mg/m2), carboplatin (AUC 1.5), and trastuzumab (2 mg/kg; THC) for 6 weeks followed by 4 cycles of THC every 3 weeks. Adjuvant trastuzumab was continued for a total of 1 year. She is still without the evidence of the disease 7 years later. The consensus regarding the use of adjuvant chemotherapy does not exist. Based on all the data that have been presented before, the conclusion is that we need new treatment modalities to improve the outome of this aggressive disease.
Cardiac Melanoma Metastasis with ERBB2 Gene Amplification: A Potential for Future Targeted Therapy
Authors: Gams Polona , Dolenc Stražar Zvezdana , Šoštarič Maja , Bošnjak Matic , Kšela Juš
Published: March 2021

Cardiac tumors are rare, and their treatment differs interindividually regarding the histopathological proprieties and the stage of disease. Authors present a case of symptomatic cardiac melanoma metastasis that expressed an ERBB2 (HER2) gene amplification in a course of the disease that has not yet been reported. The frail patient with a history of pulmonary and renal carcinoma, was admitted to the hospital due to a symptomatic left atrial tumor mass. The patient underwent a tumor-resecting cardiac surgery. At first mistaken for myxoma on echocardiography, the histopathological examination of the tumor revealed a melanoma of acral or mucosal origin. The melanoma metastasis was negative for common genetic mutations in BRAF, NRAS or KIT genes, and for the presence of NTRK genes fusions, but carried ERBB2 (HER2) gene amplification. The absence of standard gene mutations rendered it unresponsive to treatment with BRAF and MEK inhibitors. This molecular finding is rare in melanomas and represented a therapeutic target for off-label systemic treatment with drugs, primarily aimed at ERBB2 positive breast, gastric, and gastroesophageal junction cancers. A rare finding like this justifies molecular genetic analysis of unusual tumor specimen and guarantees optimal treatment for uncommon types of cardiac metastatic tumors.
Genotypic Sex and Severity of the Disease Determine the Time of Clinical Presentation in Steroid 17α-Hydroxylase/17,20-Lyase Deficiency
Authors: Kurnaz Erdal , Kartal Baykan Emine , Türkyılmaz Ayberk , Yaralı Oğuzhan , Yavaş Abalı Zehra , Turan Serap , Bereket Abdullah , Çayır Atilla , Guran Tulay
Published: March 2021

Context: Steroid 17α-hydroxylase/17,20-lyase deficiency (17OHD) is characterized by decreased sex steroids and cortisol, and excessive mineralocorticoid action. The clinical symptoms of hypocortisolemia are subtle. Aim: The clinical, biochemical, and molecular characteristics of patients with 17OHD were evaluated to determine the factors influencing the time of diagnosis and the management. Patients and Methods: Clinical data, steroid profiles by liquid chromatography-tandem mass spectrometry, and Sanger sequencing of the CYP17A1 gene was evaluated in 12 patients with 17OHD diagnosed between 2004 and 2020. Results: Median age of diagnosis was 13.9 (range: 0.04–29.5) years. Ten of 12 patients had 46,XY karyotype. Except for one boy with partial 17OHD, all patients had female external genitalia hence raised as females. The clinical presentation of 17OHD was earlier (median age: 7 years) in patients, who presented with severe hypertension, atypical genitalia, or positive family history (n = 6, 50%) than those without (median age: 15.3 years; p = 0.0005). The latter group presented with amenorrhea (n = 6, 50%). Steroid profile of patients uniformly showed a typical pattern of 17OHD regardless of the age at diagnosis. Serum gonadotropin concentrations were elevated in patients >12 years (n = 7), normal in pre-adolescents (n = 4), and low in a patient, who had a digenic inheritance of homozygous CYP17A1 and KISS1R mutations. Conclusions: Early clinical presentation and diagnosis in 17OHD are associated with symptomatic hypertension in both 46,XX and 46,XY patients or inadequate virilization of external genitalia in 46,XY partial 17OHD. In the absence of these, the clinical presentation is at late pubertal ages at which time amenorrhea and elevated gonadotropins are the hints for diagnosis.
Erythema Ab Igne with Histological Features of Keratosis Lichenoides Chronica
Authors: Prohic Asja , Poparic Selma , Cemerlic Adem , Kapetanovic Aida
Published: March 2021

Erythema ab igne (EAI) is a localized, hyperpigmented and reticulated dermatosis at sites of chronic heat exposure. Within longstanding skin lesions of EAI, hyperkeratotic lesions may emerge and can potentially transform into pre-malignant or malignant skin lesions. A 55-year-old woman presented for the evaluation of multiple hyperkeratotic lesions along with a reticular patterned hyperpigmentation on her right knee, an area that had repeated and prolonged exposure to a heat source over a period of several months. Based on her clinical history and the physical examination of her lesions, she was diagnosed as having a hyperkeratotic form of EAI. A skin biopsy was performed to rule out malignant alteration, but the histopathological findings were supportive of keratosis lichenoides chronica.
Eosinophilic Esophagitis and Achalasia: Two Distinct Nosologic Entities or a Possible Etiopathogenic Association?
Authors: Schizas Dimitrios , Syllaios Athanasios , Vailas Michail , Sotiropoulou Maria , Triantafyllou Tania , Tsapralis Dimitrios , Papanikolaou Ioannis S. , Theodorou Dimitrios
Published: March 2021

Background: Despite the fact that researchers have made significant progress in elucidating the pathophysiology of esophageal diseases, the understanding of esophageal motility alterations in patients with eosinophilic esophagitis (EoE) is in its infancy and current published medical literature remains rather scarce on this topic. A growing body of scientific data regarding associations between esophageal motor disorders, such as achalasia and EoE, exists nowadays. Summary: It seems that the association of EoE and achalasia does not constitute a cause and effect relationship, as it is not clear whether esophageal motility abnormalities are the result of EoE or vice versa. As such, there is no universally accepted treatment algorithm for patients presenting with both of these entities. Key Messages: The aim of this article is to review the existing data on achalasia-like motility disorders in patients with EoE, highlighting a possible association between these 2 esophageal disorders. Moreover, we seek to describe the clinical presentation in such cases, diagnostic modalities to be used, and current treatment strategies in patients suspected to suffer from both disorders.
Alternative Flicker Glass: A New Anti-Suppression Approach to the Treatment of Anisometropic Amblyopia
Authors: Yuan Ying , Zhu Chengcheng , Wang Peng , Hu Xiaojun , Yao Wenbo , Huang Xinhui , Ke Bilian
Published: March 2021

Introduction: Amblyopia always presents with monocular and binocular dysfunction. In this study, we aim to investigate the efficacy of alternative occlusion using liquid crystal glasses versus continuous occlusion therapy using traditional patches for treating amblyopia. Methods: Eligible subjects with anisometropic amblyopia were randomized into 2 groups: alternative flicker glass (AFG) or patching group. In the AFG group, subjects were instructed to wear the flicker glasses for 1 h a day. The AFG is a lightweight spectacle frame with liquid crystal lenses that provide direct square-wave alternating occlusion, which were preprogrammed at a temporal frequency of 7 Hz. In the patching group, the patients were prescribed to wear traditional patches for 2 h a day. The best-corrected visual acuity (BCVA), contrast sensitivity function (CSF), and stereoacuity were measured at the baseline and 3 and 12 weeks. Results: In this pilot study, a total of 40 children were recruited, with 20 in the AFG group. Mean BCVA improved by 0.17 ± 0.14 logMAR (95% CI = 0.10–0.23) in the AFG group and 0.18 ± 0.18 logMAR (95% CI = 0.09–0.26) in the patching group from baseline to 12 weeks. The improvement in BCVA in both groups was significant (both p < 0.01), while there was no significant difference between the groups (p = 0.82). The CSF of both low and high spatial frequencies exhibited significant improvement at 12 weeks in the AFG group (p < 0.01, respectively) and just had a significant improvement at low spatial frequency in the patching group (p < 0.01). The stereoacuity significantly improved by 504.00 ± 848.00 (95% CI = 107.12 to 900.88) arc seconds in the AFG group (p < 0.05), while it was 263.50 ± 639.55 (95% CI = –35.82 to 562.82) arc seconds in the patching group (p > 0.05). Conclusion: Alternative flicker glass was effective in improving both monocular and binocular function, which was most likely achieved by reducing suppression and promoting binocular fusion. This therapy exhibited promise as an alternative method for amblyopia treatment.
COVID-19 y enfermedad pulmonar pediátrica: Experiencia en un centro de atención terciaria en Sudáfrica
Authors: Gray Diane M. , Davies Mary-Ann , Githinji Leah , Levin Michael , Mapani Muntanga , Nowalaza Zandiswa , Washaya Norbertta , Yassin Aamir , Zampoli Marco , Zar Heather J. , Vanker Aneesa
Published: March 2021

La pandemia de COVID-19 resultó en una rápida diseminación global, con profundos impactos en los sistemas de salud. Aunque los datos pediátricos muestran de manera consistente un cuadro clínico más leve, se ha identificado que la enfermedad pulmonar crónica es un factor de riesgo para la hospitalización y para desarrollar una enfermedad grave. En África, continente formado predominantemente por países con ingresos bajos o medios (LMIC), la elevada prevalencia de VIH, tuberculosis, desnutrición y hacinamiento aumenta aún más los riesgos a la salud. En este trabajo se revisa la literatura sobre COVID-19 y enfermedad pulmonar crónica en niños, y relata nuestra experiencia en un centro de atención pulmonar pediátrico en Ciudad del Cabo, Sudáfrica. Los datos epidemiológicos en Sudáfrica confirman una baja prevalencia de la enfermedad grave, donde los pacientes < 18 años comprenden 8% de todos los casos diagnosticados de COVID-19 y 3% de todas las admisiones por esa causa. Se encontró una reducción en la admisión hospitalaria por otras infecciones del tracto respiratorio inferior. Aunque el servicio de pulmonología atiende niños con una amplia variedad de condiciones respiratorias crónicas, incluyendo bronquiectasias, fibrosis quística, asma, enfermedad pulmonar intersticial y pacientes con traqueostomías, no se observó un incremento significativo en las admisiones por COVID-19, y en quienes desarrollaron COVID-19, el curso de la enfermedad no fue grave. La evidencia actual sugiere que la preexistencia de una enfermedad respiratoria en niños no parece ser un factor de riesgo significativo para el COVID-19 grave. Aún se requieren datos longitudinales para evaluar el riesgo en niños con inmunosupresión y enfermedades pulmonares intersticiales. Los impactos indirectos de la respuesta a la pandemia en la salud respiratoria de los niños son notables, y es muy probable que aún deban comprenderse y cuantificarse. Garantizar el acceso de los niños a servicios preventivos y de cuidado completos durante este tiempo es prioritario.
Zitronensamenallergie: ein Fallbericht
Authors: Kayode O. Stephanie , Prado Nuevalynne , Thursfield David J. , Till Stephen J. , Siew Leonard Q.C.
Published: March 2021

Hintergrund: Wir berichten über einen Fall von IgE-vermittelter Hypersensitivität auf Zitronensamen. Wir zeigen erstmals ein Muster der Kreuzsensibilisierung zwischen Samen von Zitrus-Hybridarten, die von ähnlichen Vorfahrenspezies abstammen. Fallbericht: Es wird der Fall einer 26-jährigen Frau mit rezidivierender Anaphylaxie nach Exposition gegenüber Zitronensamen und nachgewiesener Sensibilisierung im Prick-to-Prick-Test beschrieben. Darüber hinaus erfolgten Prick-to-Prick-Tests auch für verschiedene Samen von Zitrusfrüchten und essbaren Nahrungsmittel aus anderen wichtigen Familien aus der Ordnung der Seifenbaumartigen (Sapindales). Schlussfolgerung: In Fällen von unklarer oder rezidivierender Anaphylaxie bei erwachsenen Patienten sollte eine Allergie gegen Zitrusfrüchtesamen in Betracht gezogen werden.
Establishment and Verification of a Nomogram for Predicting Survival in Patients with Small Intestinal Gastrointestinal Stromal Tumors
Authors: Lu Guangrong , Li Jiajia , Wu Limin , Shi Yuning , Zhang Xuchao , Xia Yushan , Li Lili
Published: March 2021

Background: This study aimed to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in small intestinal gastrointestinal stromal tumors (SI GISTs). Methods: Patients diagnosed with SI GISTs were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further randomly divided into training and validating cohorts. Univariate and multivariate Cox analyses were conducted in the training set to determine independent prognostic factors to build nomograms for predicting 3- and 5-year OS and CSS. The performance of the nomograms was assessed by using the concordance index (C-index), calibration plot, and the area under the receiver operating characteristic curve (AUC). Results: Data of a total of 776 patients with SI GISTs were retrospectively collected from the SEER database. The OS nomogram was constructed based on age, surgery, imatinib treatment, and American Joint Committee for Cancer (AJCC) stage, while the CSS nomogram incorporated age, surgery, tumor grade, and AJCC stage. In the training set, the C-index for the OS nomogram was 0.773 (95% confidence interval [95% CI]: 0.722–0.824) and for the CSS nomogram 0.806 (95% CI: 0.757–0.855). In the internal validation cohort, the C-index for the OS nomogram was 0.741, while for the CSS nomogram, it was 0.819. Well-corresponded calibration plots both in OS and CSS nomogram models were noticed. The comparisons of AUC values showed that the established nomograms exhibited superior discrimination power than the 7th Tumor-Node-Metastasis staging system. Conclusion: Our nomogram can effectively predict 3- and 5-year OS and CSS in patients with SI GISTs, and its use can help improve the accuracy of personalized survival prediction and facilitate to provide constructive therapeutic suggestions.
Prognostic Role of Prior Heart Failure Hospitalization Among Patients Hospitalized for Worsening Chronic Heart Failure
Authors: Blumer Vanessa , Mentz Robert J. , Sun Jie-Lena , Butler Javed , Metra Marco , Voors Adriaan A. , Hernandez Adrian F. , O’Connor Christopher M. , Greene Stephen J.
Published: March 2021

Background:

Hospitalization for heart failure (HF) is associated with increased risk of death among patients with chronic HF. The degree to which hospitalization for HF is a distinct biologic entity with independent prognostic value versus a marker of higher risk chronic HF patients is unclear.

Methods:

After excluding patients with new-onset HF, the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) included 4205 patients hospitalized for worsening chronic HF with reduced or preserved ejection fraction. The present analysis compared patients by presence or absence of prior HF hospitalization within 12 months and by timing of prior HF hospitalization relative to index hospitalization. Associations with 180-day all-cause mortality were assessed, including adjustment for 27 prespecified clinical factors.

Results:

Overall, 2241 (53.3%) patients had a HF hospitalization within the prior 12 months and 1964 (46.7%) did not. Mortality rates at 180 days were 15.5% and 11.9%, respectively. In unadjusted analyses, prior HF hospitalization was associated with increased risk of 180-day mortality (HR, 1.35 [95% CI, 1.14–1.59];
P
<0.01). After adjustment, the point estimate was attenuated and the association not statistically significant (HR, 1.18 [95% CI, 0.99–1.40];
P
=0.064). Similarly, after adjustment, compared with patients without prior hospitalization, prior HF hospitalization was not associated with mortality, irrespective of timing (0–4 months: HR, 1.10 [95% CI, 0.87–1.39],
P
=0.41; 4–8 months: HR, 0.95 [95% CI, 0.70–1.27];
P
=0.72; 8–12 months: HR, 1.06 [95% CI, 0.74–1.51],
P
=0.77; >12 months: HR, 0.81 [95% CI, 0.63–1.06],
P
=0.12).

Conclusions:

In this cohort of patients hospitalized for worsening HF, prior HF hospitalization was not associated with 180-day mortality after comprehensively accounting for patient characteristics measured during the index patient visit. Clinical confounders measured at the point-of-care may explain previously observed associations between prior HF hospitalization and mortality, and these clinical factors may be a more direct means of predicting patient survival.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00475852.
Comprehensive Comparative Effectiveness and Safety of First-Line β-Blocker Monotherapy in Hypertensive Patients
Authors: Chan You Seng , Krumholz Harlan M. , Suchard Marc A. , Schuemie Martijn J. , Hripcsak George , Chen RuiJun , Shea Steven , Duke Jon , Pratt Nicole , Reich Christian G. , Madigan David , Ryan Patrick B. , Woong Park Rae , Park Sungha
Published: March 2021

Evidence for the effectiveness and safety of the third-generation β-blockers other than atenolol in hypertension remains scarce. We assessed the effectiveness and safety of β-blockers as first-line treatment for hypertension using 3 databases in the United States: 2 administrative claims databases and 1 electronic health record–based database from 2001 to 2018. In each database, comparative effectiveness of β-blockers for the risks of acute myocardial infarction, stroke, and hospitalization for heart failure was assessed, using large-scale propensity adjustment and empirical calibration. Estimates were combined across databases using random-effects meta-analyses. Overall, 118 133 and 267 891 patients initiated third-generation β-blockers (carvedilol and nebivolol) or atenolol, respectively. The pooled hazard ratios (HRs) of acute myocardial infarction, stroke, hospitalization for heart failure, and most metabolic complications were not different between the third-generation β-blockers versus atenolol after propensity score matching and empirical calibration (HR, 1.07 [95% CI, 0.74–1.55] for acute myocardial infarction; HR, 1.06 [95% CI, 0.87–1.31] for stroke; HR, 1.46 [95% CI, 0.99–2.24] for hospitalized heart failure). Third-generation β-blockers were associated with significantly higher risk of stroke than ACE (angiotensin-converting enzyme) inhibitors (HR, 1.29 [95% CI, 1.03–1.72]) and thiazide diuretics (HR, 1.56 [95% CI, 1.17–2.20]). In conclusion, this study found many patients with first-line β-blocker monotherapy for hypertension and no statistically significant differences in the effectiveness and safety comparing atenolol with third-generation β-blockers. Patients on third-generation β-blockers had a higher risk of stroke than those on ACE inhibitors and thiazide diuretics.
Two-Year Responses of Heart Rate and Heart Rate Variability to First Occupational Lead Exposure
Authors: Yu Yu-Ling , Thijs Lutgarde , Yu Cai-Guo , Yang Wen-Yi , Melgarejo Jesus D. , Wei Dong-Mei , Wei Fang-Fei , Nawrot Tim S. , Verhamme Peter , Roels Harry A. , Staessen Jan A. , Zhang Zhen-Yu
Published: March 2021

Because of the falling lead exposure, the literature relating autonomous nervous function to blood lead (BL) has limited relevance. In the longitudinal Study for Promotion of Health in Recycling Lead (URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02243904), we recorded the 2-year responses of heart rate (HR), HR variability (HRV; Cardiax, International Medical Equipment Developing, Budapest, Hungary), and median nerve conduction velocity (Brevio, NeuMed, West Trenton, NJ), a routine test in occupational medicine, to first lead exposure in 195 newly hired workers (91.3% men; mean age, 27.8 years). High- and low-frequency HRV power and orthostatic HRV responses were derived from 5-minute ECGs in the supine and standing positions by Fourier transform and autoregression. BL was determined by inductively coupled plasma mass spectrometry. From baseline to follow-up, BL increased from 4.22 to 14.1 μg/dL and supine/standing HR from 63.6/75.5 to 67.1/78.8 beats per minute. In analyses stratified by fourths of BL changes, trends in HR and Fourier/autoregressive HRV did not reveal a dose-response curve (0.074≤
P
≤0.98). In multivariable-adjusted mixed models, HR, Fourier/autoregressive HRV, and nerve conduction velocity changes were unrelated to BL except for a weak inverse association between supine HR and BL changes (−0.55%;
P
=0.029). The expected associations between HRV and HR changes were preserved with no differences at baseline/follow-up. Analyses dichotomized by baseline median BL or cumulative BL index (4.30 μg/dL or 32.1 μg/dL×year) suggested an HRV increase versus decrease in the low versus high baseline exposure group. Thus, a >3-fold BL increment did not affect autonomous neural function as captured by HRV.
Association Between Periodontitis and Blood Pressure Highlighted in Systemically Healthy Individuals
Authors: Muñoz Aguilera Eva , Suvan Jean , Orlandi Marco , Miró Catalina Queralt , Nart Jose , D’Aiuto Francesco
Published: March 2021

Recent evidence suggests hypertension and periodontitis are closely linked but limited data is available on the nature of the association. We aimed to investigate the relationship between periodontitis and mean arterial blood pressure in a sample of otherwise systemically healthy individuals. A case-control study including 250 cases (participants with periodontitis) and 250 controls (without periodontitis) was designed from a register of clinical trials conducted between 2000 and 2018 in a university setting. Cases were age, sex, and body mass index balanced with controls. Linear, logistic regression, and mediation models were planned to test the association between various periodontal measures and arterial blood pressure. We further investigated the role of systemic inflammation assessed by hs-CRP (high-sensitivity C-reactive protein) and white cell counts. Cases presented with 3.36 mm Hg (95% CI, 0.91–5.82,
P
=0.007) higher mean systolic blood pressure and 2.16 mm Hg (95% CI, 0.24–4.08,
P
=0.027) higher diastolic blood pressure than controls. Diagnosis of periodontitis was associated with mean systolic blood pressure (β=3.46±1.25,
P
=0.005) and greater odds of systolic blood pressure ≥140 mm Hg (odds ratio, 2.3 [95% CI, 1.15–4.60],
P
=0.018) independent of common cardiovascular risk factors. Similar findings were observed when continuous measures of periodontal status were modeled against systolic blood pressure. Measures of systemic inflammation although elevated in periodontitis were not found to be mediators of the association between periodontitis and arterial blood pressure values. Periodontitis is linked to higher systolic blood pressure in otherwise healthy individuals. Promotion of periodontal and systemic health strategies in the dental and medical setting could help reduce the burden of hypertension and its complications.