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Hypoplastic left heart syndrome (HLHS) is a severe form of single ventricle congenital heart disease characterized by an underdevelopment of the left ventricle. Early serial postmortem examinations revealed high rate of coronary artery abnormalities in HLHS fetal hearts, which may impact ventricular development and intra-cardiac hemodynamics, leading to a poor prognosis after surgical palliations. Previous study reported that endothelial cells (ECs) lining the coronary vessels showed DNA damage in the left ventricle of human fetal heart with HLHS, indicating that EC dysfunction may contribute to the coronary abnormalities in HLHS. To investigate the underlying mechanism of HLHS coronary artery abnormalities, we profiled both human fetal heart with an underdeveloped left ventricle (ULV) and ECs differentiated from induced pluripotent stem cells (iPSCs) derived from HLHS patients at single cell resolution. CD144+/NPR3- vascular ECs were selected and further classified as venous EC (NR2F2high), arterial EC (EFNB2high) and late arterial EC (GJA5high) subclusters based on previously reported marker genes. To study the arterial phenotype, we specifically generated iPSC-arterial ECs (AECs, CD34+CDH5+CXCR4+NT5E-/low) derived from three HLHS patients and three age-matched healthy controls to further dissect the phenotype of HLHS-AECs. As compared to normal human heart and control iPSC-ECs respectively, ULV late arterial EC subcluster and HLHS iPSC-EC arterial clusters showed significantly reduced expression of arterial genes GJA5, DLL4, and HEY1. Pathway enrichment analysis based on differentially expressed genes revealed several defects in late AEC cluster from ULV compared to normal human heart, such as impaired endothelial proliferation, development and Notch signaling. HLHS iPSCs exhibited impaired AEC differentiation as evidenced by the significantly reduced CXCR4+NT5E-/low AEC progenitor population. Consistent with human heart transcriptomic data, matured HLHS iPSC-AECs also showed a lower expression of the arterial genes such as GJA5, DLL4, HEY1 which are also downstream of NOTCH signaling. Additionally, matured HLHS iPSC-AECs showed significantly decreased expression of cell proliferation marker Ki67 and G1/S transition genes (CCND1, CCND2) compared with controls. Interestingly, NOTCH ligand Jag1 treatment significantly rescued this cell proliferation defect in HLHS AECs, accompanied by upregulation of various G1/S transition genes. In summary, we found that coronary AECs from HLHS showed impaired arterial development and proliferation downstream of NOTCH signaling. These functional defects in HLHS coronary AECs could contribute to the vascular structure malformation and impaired ventricular development.

The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors. Hepatic mRNA expression of FNDC5/Irisin and stearoyl-CoA desaturase (SCD-1), main enzymatic regulator of DNL, were significantly higher in HCC patients than in donors (p, This pre-print version may be used for non-commercial purposes in accordance with CC BY-NC-ND license terms and conditions.

Isolation of the left subclavian artery or its anomalous origin from the pulmonary artery has been documented in several cases, especially in association with a right-sided aortic arch. However, similar anomaly involving the right subclavian artery has been less frequently reported. Isolated right subclavian artery in association with interrupted aortic arch (IAA) is extremely rare, and only three cases have been reported so far. Here, we have presented yet another case of isolated right subclavian artery associated with ventricular septal defect, type B IAA and bilateral patent ductus arteriosus.

Aim: of this paper is to review the recent literature on the relationship between ectopic fat accumulation and cardiovascular disease. Data synthesis: Ectopic fat is an important predictor of metabolic (in particular insulin resistance) and cardiovascular disease, carrying more risk than general fat accumulation. Recent studies have shown a link between ectopic fat accumulation, as cardiac (epicardial or intra-myocardial fat) and/or visceral and/or hepatic fat, and development of atherosclerosis, coronary heart disease and hypertension. Conclusions: Ectopic fat accumulation is not only a marker of cardiometabolic disease, since through the release of adipocitokines, lipotoxic and glucotoxic agents, participates in the crosstalk with insulin-sensitive organs leading to metabolic, cardiac and vascular dysfunctions., This article version may be used for non-commercial purposes in accordance with CC BY-NC-ND license terms and conditions.

A 67-year-old man presented with 5 months of worsening memory impairment and sensory gait ataxia on the background of symptomatic anaemia. He experienced falls, agitation and became socially withdrawn over 3 weeks, resulting in hospital admission. On examination, he had sensory gait ataxia consistent with a dorsal column syndrome. He scored 13/30 on the Montreal Cognitive Assessment. Serum analysis showed normocytic anaemia and leucopenia, severe hypocupraemia, reduced caeruloplasmin and normal zinc levels. Overuse of zinc-containing denture cream was the cause of excess zinc ingestion and resultant copper deficiency, leading to blood dyscrasia and myelopathy. The cream was withdrawn and intravenous and then oral copper supplementation was implemented. Direct questions with regard to excess zinc in the diet and serological testing of copper and zinc should be considered in any patient with a dorsal column syndrome, particularly with concurrent anaemia. Copper deficiency may also have a role in exacerbating pre-existing cognitive impairment.

A 49-year-old woman presented to the hospital with shortness of breath 2 weeks after a left total hip replacement. She was found to have a submassive pulmonary embolism (PE), with her case complicated by the detection of a large mobile clot in transit extending through a patent foramen ovale between the right and left atria. The presence of this free-floating right heart thrombus (FFRHT) increases her risks of stroke and mortality, yet the optimal approach to her treatment was unclear. Ultimately, intravenous tissue plasminogen activator was administered with resolution of the clot. Treatment was complicated by haemodynamically insignificant bleeding at the site of recent surgery. Herein, we further discuss the implications and treatment options for patients with an FFRHT in the setting of an acute PE.

Intracardiac platypnea–orthodeoxia syndrome (POS) is a pathological condition that leads to a reduction in oxygenation in the sitting position. The detection rate of patent foramen ovale that causes POS increases with Valsalva manoeuvre and cough. We report the case of a 92-year-old woman with POS, which could not be diagnosed in the sitting position. The Valsalva manoeuvre could not be performed because of dementia, and POS was diagnosed on the forward-bending position and abdominal compression. It was assumed that forward-bending increases the right atrial pressure by compressing the right ventricle along with elongation of the aorta, and abdominal compression increases the shunt volume by increasing the venous return. If POS is suspected in patients with dementia which cannot be diagnosed in the sitting position, forward-bending and abdominal compression, instead of the Valsalva manoeuvre, might be useful.

A young man presented to the emergency department with seizures and recurrent episodes of polymorphic ventricular tachycardia (PMVT)/torsades de pointes (TdP) requiring cardioversion and administration of intravenous magnesium. A battery of tests performed to identify a cause for his arrhythmias and seizures were all normal. A revisit of history with family revealed he had consumed over 100 tablets/day of loperamide for the past 1 year. A prolonged QT interval on his ECG raised concerns for long QT syndrome (LQTS) (congenital or acquired). Our patient was suspected to have loperamide-induced cardiotoxicity. TdP is a specific PMVT that occurs with a prolonged QT interval and is usually drug-induced. Less frequently, congenital LQTS may be implicated. With supportive care, including mechanical ventilation, vasopressors and temporary transvenous overdrive pacing, our patient recovered completely. We describe the importance of a systematic and time-sensitive approach to diagnosing critical illness. Loperamide overdose may cause QT prolongation, life-threatening arrhythmias/cardiogenic shock, or cardiac arrest. Seizures/epilepsy may also be a manifestation in young patients. There is a substantial need to revisit the safety of over-the-counter medications and increasing awareness of manifestations of drug overdose.

We describe a case of a 42-year-old man who presented with anginal chest pain. He had objective evidence of ongoing cardiac injury. After initial treatment for coronary arterial disease, cardiac catheterisation revealed diffuse coronary arterial thrombosis with embolisation. Follow-up testing implicated new-onset antiphospholipid antibody syndrome as the aetiology.

A 22-year-old woman with a history of type 1 diabetes mellitus (DM) presented with nausea, vomiting and epigastric discomfort for 3 days. On presentation, she had blood pressure of 80/50 mm Hg and a heart rate of 120 bpm. No significant findings were noted on systemic physical examination. She

Transcatheter aortic valve replacement (TAVR) is becoming the standard of care in the management of severe aortic stenosis for patients in all risk stratifications. Many causes have been identified for acute drop in blood pressure during TAVR. Mitral regurgitation (MR) is a rare, but important acute intraprocedural complication that requires rapid assessment and treatment. Two important reasons for acute MR during TAVR include entanglement of the guide wire in papillary muscles and extension of the guidewire into the left atrium. Here, we report a case of acute reversible MR which was assessed using an echocardiogram and rapidly reversed by removing the stiff preshaped Safari2wire from the left ventricle post valve deployment.

Rheumatic heart disease is an important cause of mortality and morbidity in developing countries, and is the leading cause of triple valve replacement. Myocardial infarction (MI) in such cases can be due to the coronary embolism from the prosthetic valves or due to atherosclerotic vascular disease. Intravascular imaging helps in delineating the cause. We present a case of a 34-year-old premenopausal woman with no conventional cardiovascular risk factors and had triple valve replacement 4 years ago and anterior wall MI with cardiogenic shock and left ventricular failure. She was managed with mechanical ventilation, thrombolysis, diuretics, double antiplatelets and anticoagulation with low molecular weight heparin. Intravascular ultrasound showed a lipid-rich plaque with associated plaque rupture and thrombosis. Intravascular imaging helps in delineating the cause of MI and further management. Atherosclerotic MI in a patient with no conventional risk factors is rare and needs to be considered.

Twelve years following gastric bypass surgery, a cachectic 69-year-old woman presented with both fasting and postprandial hypoglycaemia. Postprandial symptoms were relieved by dietary modification and acarbose, as is common in such cases. During a supervised fast, symptomatic hypoglycaemia occurred. Concurrent laboratory testing showed suppression of plasma insulin, c-peptide, proinsulin and insulin-like growth factor II. However, beta-hydroxybutyrate was also low, surprising given insulin deficiency. Elevated plasma free fatty acid (FFA) concentrations suggested that lipolysis was not impaired, making cachexia/malnutrition a less likely cause of hypoglycaemia. The apparent diagnosis was failure to counter-regulate—subsequent plasma carnitine measurements showed carnitine deficiency which presumably prevented FFA transport across mitochondrial membranes for ketogenesis. Repletion with high-dose oral carnitine supplements effected resolution of fasting hypoglycaemia.

A 3-month-old female weighing 3.6 kg, with trisomy 21, who had undergone pulmonary artery banding for atrioventricular septal defect 2.5 months prior to the presentation was referred to our hospital because of nasal discharge and cough for 3 days and wheezing and decreased feeding for 1 day before

Thrombocytopenia with absent radii (TAR) syndrome is a rare genetic condition causing absent radial bones and thrombocytopenia. Management is generally supportive although there may be a role for platelet-stimulating agents such as romiplostim. In this case, we highlight the obstacles in managing end-stage heart failure in a patient with TAR syndrome.

Heat stroke is a debilitating disease that is characterised by inflammation, coagulation and tissue abnormalities.[1][1] Patients who have experienced heat stroke can manifest complications even after their body temperature has returned to normal.[1][1] However, data on the characteristics of

A 29-year-old woman was referred to our hospital for catheter ablation (CA) due to symptomatic atrial fibrillation (AF), after two failed CA attempts at another hospital. She had presented with left ventricular dysfunction at the age of 1 year, with a suspected diagnosis of endocardial

A 47-year-old man was commenced on levothyroxine following a diagnosis of subclinical hypothyroidism with nonspecific symptoms. Despite increasing doses of levothyroxine, his thyroid-stimulating hormone (TSH) remained elevated and he was referred for further assessment as he was unable to tolerate further titration. On assessment, his thyroid function demonstrated an elevated TSH and elevated free-T4. The initial impression was of iatrogenic thyrotoxicosis, with possible underlying thyroid hormone resistance, TSHoma or assay interference. After discontinuation of levothyroxine, free-T4 normalised but TSH remained elevated. There was a normal response to thyrotropin-releasing hormone (TRH) testing. T3 suppression testing demonstrated free-T4 reduction but persistently high TSH. THRβ sequencing was normal. TSH measurement by alternative assays revealed discrepant results. Gel filtration chromatography revealed the presence of high-molecular weight TSH variant alongside normal TSH. Macro-TSH is a rare phenomenon with spuriously elevated TSH and which may mimic subclinical hypothyroidism. Recognition of macro-TSH avoids misdiagnosis and prevents inappropriate treatment.

A rare case of a hypoplastic internal carotid artery (ICA) terminating in the ophthalmic artery with multiple intracranial saccular aneurysms in the contralateral ICA, anterior communicating artery fenestration and triple A2 was identified. The aetiology and pathogenesis of ICA hypoplasia are subjected to certain hypotheses. Developing several collaterals to preserve the blood supply of the ipsilateral cerebral hemisphere could result in aneurysm formation due to flow overload on the contralateral vasculature, but it could also result in hemicranial hypoplasia, cerebral atrophy and deep watershed infarcts, as in our case.

Hashimoto’s thyroiditis (HT) is the most common form of primary hypothyroidism. Several muscular manifestations like pain, weakness, stiffness and elevated muscle enzymes have been noticed in hypothyroidism. Alcohol is also known to cause myositis and rhabdomyolysis. Patients with thyroid should avoid certain foods like broccoli, cauliflower and cabbage as they contain goitrogens. This is a case of a young man who presented with severe muscle aches and pain and was found to have rhabdomyolysis. Further evaluation revealed an underlying HT. Moreover, he had been consuming raw broccoli, which is goitrogenic, and alcohol which worsened the rhabdomyolysis. He was managed with levothyroxine and intravenous fluids, following which he improved.

The differential diagnosis of acute onset flank pain include renal colic, papillary necrosis, pyelonephritis and renal infarction from renal artery thrombosis or embolism. Here, we describe a case of acute onset flank pain caused by unilateral renal vein thrombosis (RVT) in a previously healthy

The purpose of this study was to determine if an expertnetwork, a form of artificial intelligence, could effectivelystratify cardiac risk in candidates for renal transplant.Input into the expert network consisted of clinical riskfactors and thallium-201 stress test data. Clinical riskfactor screening alone identified 95 of 189 patients ashigh risk. These 95 patients underwent thallium-201stress testing, and 53 had either reversible or fixed defects.The other 42 patients were classified as low risk.This algorithm made up the ‘‘expert system,’’ and duringthe 4-year follow-up period had a sensitivity of 82%,specificity of 77%, and accuracy of 78%. An artificial neural network was added to the expert system, creatingan expert network. Input into the neural networkconsisted of both clinical variables and thallium-201stress test data. There were 5 hidden nodes and the output(end point) was cardiac death. The expert networkincreased the specificity of the expert system alone from77% to 90% (p

Methotrexate is a versatile antineoplastic and immunosuppressive agent. We report a case of a young adult on the Cancer and Leukaemia Group B 10403 treatment protocol for B-cell acute lymphoblastic leukaemia. She has previously completed the induction and consolidation phases with good tolerance then started on Capizzi methotrexate during the interim maintenance phase. Few days after receiving one intermediate dose of methotrexate, she developed severe multiorgan toxicities including pancytopaenia and several dermatologic toxicities. The patient underwent extensive diagnostic workup, with all results negative, pointing eventually towards severe methotrexate toxicity. This case highlights the broad spectrum of toxicities that can occur even with low doses of methotrexate. Capizzi methotrexate therapy implies no leucovorin therapy, hence putting patients at risk for multiorgan toxicity. Our experience reinforces the importance of close monitoring for patients receiving methotrexate, regardless of dose, and the prompt administration of high-dose leucovorin once toxicity suspected.

Background Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection. Methods We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission. Results The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6–23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1–4.9) for the first 2 years, 2.3 (95% CI, 1.6–3.2) for 2 to Conclusions We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6–23 months compared to those whose first severe RSV infection occurred at 0–6 months. This provides new evidence for further assessment of the association and RSV intervention programs.

Ticagrelor is a part of dual antiplatelet therapy (DAPT) which has proven benefits in patients with acute coronary syndrome especially in those undergoing percutaneous coronary intervention (PCI). However, like most other drugs, it can lead to undesired and adverse effects such as dyspnoea, easy bruising and gastrointestinal bleeding. We present a case of 70-year-old woman who developed diarrhoea following initiation of DAPT comprising of aspirin and ticagrelor following PCI. After excluding more common causes, it was attributed to ticagrelor administration and completely resolved after it was replaced with another oral antiplatelet agent. On follow-up, the patient reported complete resolution of symptoms.

Pediatric extreme thrombocytosis (EXT, platelet count > 1000 × 10(3)/μL) is rare. In a single center retrospective analysis of hospitalized children with EXT, infants with congenital diaphragmatic hernia (CDH) were overrepresented. In general pediatric patients, EXT is usually secondary to infection or inflammation, but most of the 14 CDH patients with EXT had no identifiable inciting factor. Instead, there was evidence that splenic dysfunction and bone marrow hyperactivity underlied EXT in CDH patients. None were associated with bleeding or thrombosis. Our findings identify mechanisms underlying EXT, and aid clinical interpretation and management of EXT in the pediatric population.

BACKGROUND Models estimating risk for advanced proximal colorectal neoplasia (APN) may be used to select colorectal cancer (CRC) screening test, either prior to knowing distal colorectal findings or afterward. Current models have only fair discrimination and nearly all require knowing distal findings. OBJECTIVE Derive and test risk prediction models for APN with and without distal findings. SETTING Selected endoscopy centers within central Indiana, USA. PARTICIPANTS Average-risk persons undergoing first-time screening colonoscopy. INTERVENTIONS Demographics, personal and family medical history, lifestyle factors and physical measures were linked to the most advanced finding in proximal and distal colorectal segments. For both models, logistic regression identified factors independently associated with APN on a derivation set. Based on equation coefficients, points were assigned to each factor, and risk for APN was examined for each score. Scores with comparable risks were collapsed into risk categories. Both models and their scoring systems were tested on the validation set. MAIN OUTCOME APN, defined as any adenoma or sessile serrated lesion ≥1 cm, one with villous histology or high-grade dysplasia, or CRC proximal to the descending colon. RESULTS Among 3025 subjects in the derivation set (mean age 57.3 ± 6.5 years; 52% women), APN prevalence was 4.5%; 2859 (94.5%) had complete data on risk factors. Independently associated with APN were age, sex, cigarette smoking, cohabitation status, metabolic syndrome, non-steroidal anti-inflammatory drug use and physical activity. This model (without distal findings) was well-calibrated (P = 0.62) and had good discrimination (c-statistic = 0.73). In low-, intermediate- and high-risk groups that comprised 21, 58 and 21% of the sample, respectively, APN risks were 1.47% (95% CI, 0.67-2.77%), 3.09% (CI, 2.31-4.04%) and 11.6% (CI, 9.10-14.4%), respectively (P

Colonic mucosal injury is rare, but may severely fatal, complications following the administration of calcium polystyrene sulfonate resins. The incidence rate is about 0.57%, administered without sorbitol, and increases to 1.8% when it is concomitant with sorbitol, especially in postoperative patients. In this case report, we demonstrated the case of a 77-year-old female with stage 3b chronic kidney disease presented with in-hospital hematochezia after 3 weeks of calcium polystyrene sulfonate administration. The colonoscopic findings showed several serpiginous ulcers with some oozing at descending and sigmoid colon. The histological findings revealed some focal inflammation and ulcerations with crystal-like materials, compatible with cation exchange resins. The recent in vitro study, explaining the pathogenesis of cation exchange resin-associated colonic mucosal injury, was also reviewed.

CelCelem prezentowanego badania była identyfikacja i podsumowanie badań analizujących związek pomiędzy stężeniem witaminy D a ryzykiem i nasileniem objawów depresji, opublikowanych pomiędzy styczniem 2008 a styczniem 2019 r.Materiał i metodyPrzeprowadzono systematyczny przegląd literatury opublikowanej w okresie ostatnich 10 lat i dostępnej w ramach bazy PubMed. Przegląd wykonywany był przez każdego z autorów osobno w oparciu o wcześniej założone kryteria.WynikiZ 823 badań zakwalifikowanych do wstępnej analizy abstraktów, 24 zostały włączone do analizy pełnotekstowej a 18 do meta-analizy. Uzyskano istotne statystycznie ilorazy szans dla wysokiego ryzyka depresji w przebiegu niedoboru witaminy D równe OR=1,51; 95%CI: 1,4-1,62; pWnioskiZaprezentowana analiza literatury wydaje się wskazywać na związek pomiędzy ryzykiem zaburzeń depresyjnych a niedoborem witaminy D. Jednakże, dostępne badania nie pozwalają na szczegółowe wyjaśnienie mechanizmu i kierunku tej zależności.

Accessory breast tissue is a rare aberration of normal breast development, that presents most commonly in the axilla. Similar to normal breast tissue, it can undergo physiologic and pathologic changes, including malignant transformation. We report a rare case of accessory breast cancer, treated with surgical resection and axillary reverse mapping (ARM), and review current literature focusing on management. We report a 68-year-old female with a history of left breast cancer treated with lumpectomy and axillary dissection, who later developed in-breast recurrence treated with re-lumpectomy and sentinel node biopsy which mapped at the contralateral (right) axilla, but was negative. Two years later screening imaging revealed right axillary tail focal asymmetry with two spiculated masses. Core biopsy showed invasive ductal carcinoma (IDC), and histologic examination of the biopsy could not determine whether this represents a new primary breast cancer or axillary metastasis from the contralateral site. She underwent lumpectomy of the two masses and sentinel node biopsy. During surgery, the masses were identified in the axilla itself, rather than the axillary tail. Final pathology revealed IDC, pT1N0(sn), and extensive ductal carcinoma in situ (DCIS). Due to positive margins, she underwent re-lumpectomy with ARM. Final pathology revealed residual DCIS with negative new margins. The patient was referred for adjuvant radiotherapy. Accessory axillary breast tissue can be confused with axillary tail tissue. It is necessary for the surgeon to distinguish between them by meticulous physical examination and radiologic evaluation, as resection of axillary breast tissue may warrant reverse lymphatic mapping for lymphedema prevention.

Background: Many patients in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) had a significant improvement (> 10%) in the left ventricular ejection fraction (LVEF) during the course of the study, but the factors and outcomes associated with such improvement are uncertain. Methods: We examined factors and rates of mortality, cause-specific mortality, and implantable cardioverter defibrillator (ICD) shocks associated with improvement in LVEF by analyzing patients in the SCD-HeFT who were randomized to placebo or an ICD and who had an LVEF checked during follow-up. Results: During a median follow-up of 3.99 years, of 837 patients who had at least two follow-up LVEF measurements, 276 (33%) patients had > 10% improvement in LVEF and 561 (67%) patients had no significant change in LVEF. Factors significantly associated with LVEF improvement included female sex, white race, history of hypertension, a QRS duration < 120 ms, and beta-blocker use. Improvement in LVEF was associated with a significant improvement in survival. There was no significant association between improvement in LVEF and cause-specific death, but there was a significant association between improvement in LVEF and reduced risk of receiving appropriate ICD shocks. Conclusions: About a third of patients in this analysis, who were randomized to placebo or an ICD in SCD-HeFT, had a significant improvement in LVEF during follow-up; improvement in LVEF was associated with improved survival but not with cause-specific death, and with decreased likelihood of receiving appropriate ICD shocks.

Background: The contribution of sex as an independent risk factor for cardiovascular disease still remains controversial. The present study investigated the impact of sex on long-term clinical outcomes in Korean acute myocardial infarction (AMI) patients with a history of current smoking on admission after drug-eluting stents (DESs). Methods: A total of 12,565 AMI patients (male: n = 11767 vs. female: n = 798) were enrolled. Major adverse cardiac events (MACEs) comprising all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization were the primary outcomes that were compared between the two groups. Probable or definite stent thrombosis (ST) was the secondary outcome. Results: After adjustment, the early (30 days) cumulative incidences of MACEs (adjusted hazard ratio [aHR]: 1.457; 95% confidence interval [CI]: 1.021–2.216; p = 0.035) and all-cause death (aHR: 1.699; 95% CI: 1.074–2.687; p = 0.023) were significantly higher in the female group than in the male group. At 2 years, the cumulative incidences of all-cause death (aHR: 1.561; 95% CI: 1.103–2.210; p = 0.012) and Re-MI (aHR: 1.880; 95% CI: 1.089–2.974; p = 0.022) were significantly higher in the female group than in the male group. However, the cumulative incidences of ST were similar between the two groups (aHR: 1.207; 95% CI: 0.583–2.497; p = 0.613). Conclusions: The female group showed worse short-term and long-term clinical outcomes compared with the male group comprised of Korean AMI patients with a history of current smoking after successful DES implantation. However, further studies are required to confirm these results.

Purpose: The use of FDG-PET/TC for cancer staging has been leading to the increasing diagnosis of adrenal lesions, which usually represent a clinical challenge. Our aim was to characterize the adrenal lesions found in FDG-PET of patients followed in a cancer center.Methods: Retrospective analysis of all FDG-PET studies performed in our center in the last 10 years. Exams reporting adrenal lesions in the CT component and/or anomalous adrenal FDG uptake were selected. Cases were characterized regarding clinical, laboratorial, imaging and pathological findings. Results: We identified 27,427 FDG-PET studies. Of those, 7.6% evidenced adrenal findings. We included 1364 exams corresponding to 1021 patients. Only 15.6% were referred to the endocrinology department and 38% of the lesions were not studied.Malignant lesions were present in 38.9% of the studied patients: metastases in 37.5%, carcinoma in 1.2% and other malignant tumors in 0.4%. Median SUVmax of malignant lesions was significantly higher than the SUVmax of the benign findings (p0.05). Conclusion: Occult adrenal lesions discovered during FDG-PET/CT are common in cancer context and are frequently benign. SUVmax may be a useful tool in the workup of adrenal lesions but with several important caveats.

BACKGROUND Burkholderia cepacia complex (BCC) represents a group of multidrug-resistant gram-negative bacteria that cause infections among immunocompromised hosts. Bacteremia occurs in patients who are chronically ill and is associated with substantial morbidity and mortality. The aim of this study was to investigate the clinical characteristics and outcomes of BCC bacteremic patients without cystic fibrosis. METHODS We conducted a retrospective study at the National Taiwan University Hospital. Adults with BCC bacteremia from January 2015 to May 2019 were enrolled. The primary outcome was 14-day mortality. Multivariable logistic regression was performed for outcome analysis. RESULTS One-hundred and ninety-five patients were analyzed and their mean age was 67 years. Over 95% of the BCC isolates were susceptible to trimethoprim/sulfomethoxazole (TMP/SXT). Levofloxacin resistance rates were high, with only 25.1% of isolates being susceptible. Pairwise comparisons were made between different definitive regimens including meropenem-monotherapy, ceftazidime-monotherapy, levofloxacin-monotherapy, TMP/SXT-monotherapy, tigecycline-monotherapy as well as combination versus monotherapy. No regimen was significantly associated with survival in our study. Multivariable logistic regression showed that the Pitt bacteremia score (adjust odds ratio [aOR],1.46; 95% confidence interval [CI],1.19-1.79; p

This study aims to find out the possible optimal therapy and assess the prognosis properly for patient with spontaneous rupture of hepatocellular carcinoma (HCC).Propensity score matching (PSM) analysis was used to study the data from 325 patients with ruptured HCC (RHCC) and 2,291 patients with non-RHCC.The incidence and hospital mortality of RHCC were 5.1% and 0.8% respectively, with a median overall survival (OS) time of 17 months. There was no difference between ruptured and non-RHCC patients undergoing conservation treatment in terms of OS. Trans-arterial embolization (TAE) was carried out in 69 (21.2%) cases with RHCC, with a median OS of 7 months, which was no difference from that of non-RHCC (pre- and post-PSM). One hundred and sixty-nine (52.0%) RHCC cases underwent one-stage hepatectomy, with a median OS and disease-free survival (DFS) of 30 and 6 months respectively, which were shorter than that of non-RHCC (post-PSM). TAE plus two-stage hepatectomy was performed in 30 RHCC cases, with a median OS and DFS of 28 and 10 months respectively; these outcomes were better than that from RHCC patients undergoing TAE alone or one-stage hepatectomy (post-PSM), which were no difference from that of non-RHCC patients undergoing hepatectomy. The risk of death for RHCC patient undergoing one-stage hepatectomy is 1.545 times higher than that of one undergoing TAE + two-stage hepatectomy.TAE plus two-stage hepatectomy might be the optimal treatment for RHCC patient. Under the premise of the same pathological properties, there is no difference in prognosis between ruptured and non-RHCC patients if the therapy is appropriate.

Background/aimsFuchs’ uveitis syndrome (FUS) is one of the frequently misdiagnosed uveitis entities, which is partly due to the absence of internationally recognised diagnostic criteria. This study was performed to develop and evaluate a set of revised diagnostic criteria for FUS.MethodsThe clinical data of Chinese patients with FUS and patients with non-FUS were collected and analysed from a tertiary referral centre between April 2008 and December 2020. A total of 593 patients with FUS and 625 patients with non-FUS from northern China were enrolled for the development of diagnostic criteria for FUS. Three hundred and seventy-seven patients with FUS and 503 patients with non-FUS from southern China were used to validate the criteria. Clinical symptoms and ocular signs were collected from all patients with FUS and patients with non-FUS. Multivariate two-step cluster analysis, logistic regression and decision tree algorithms in combination with the clinical judgement of uveitis experts were used to revise diagnostic criteria for FUS.ResultsThree essential findings including diffuse iris depigmentation, absence of posterior synechiae, mild inflammation in the anterior chamber at presentation and five associated findings including mostly unilateral involvement, cataract, vitreous opacities, absence of acute symptoms and characteristic iris nodules were used in the development of FUS diagnostic criteria. All essential findings were required for the diagnosis of FUS, and the diagnosis was further strengthened by the presence of associated findings.ConclusionRevised diagnostic criteria for FUS were developed and validated by analysing data from Chinese patients and showed a high sensitivity (96.55%) and specificity (97.42%).

BACKGROUND Many patients with papillary thyroid cancer (PTC) demonstrate satisfactory outcomes. However, 8%-28% of patients with PTC show tumor recurrence, which may affect prognosis. Therefore, identifying factors associated with tumor recurrence in patients with PTC may be helpful to refine therapeutic strategies. PATIENTS AND METHODS To identify factors associated with PTC recurrence, we retrospectively reviewed demographic features (sex and age), operation method, image character, serum thyroglobulin (Tg), accumulated radioactive iodine (I-131) therapeutic dose, I-131 uptake, and metastases at diagnosis in 829 patients with PTC. Patients were grouped into early (stage I and II; n = 698) and advanced (stage III and IV; n = 131) tumor-node-metastasis (TNM) stages. Recurrence rate, mortality rate, risk factors of recurrence, recurrent free survival and overall survival curve were compared between two groups. RESULTS Patients in the early stage demonstrated a lower recurrence rate (7.2%) than did those in the advanced stage (28.2%, p < 0.05). The mortality rate of patients with recurrence in the advanced stage was higher than that of those in the early stage (51.4% vs. 12.0%). The major impact factors on tumor recurrence in early TNM stage were distant metastasis and lymph node metastasis, while in advanced TNM stage were distant metastasis, male gender, total thyroidectomy with limited lymph node dissection, and a high serum Tg level. CONCLUSIONS Strategies to monitor tumor recurrence might be refined according to the TNM stages of PTC patients.

BACKGROUND: Historically, impaired glucose metabolism has been associated with early and late complicated clinical outcomes after cardiac surgery; however, such a condition is not specific to subjects with diabetes mellitus and involves a larger patient population.METHODS: Databases were screened (January 2000 to December 2020) to identify eligible articles; studies that evaluated the association between preoperative metabolic status, as assessed by glycosylated hemoglobin levels and clinical outcomes, were considered. The studies were stratified in thresholds by baseline glycosylated hemoglobin level (lower vs higher).RESULTS: Thirty studies, involving 34,650 patients, were included in the review. In a meta-analysis stratified by glycosylated hemoglobin levels, early mortality was numerically reduced in each threshold comparison and yielded the highest reductions when less than 5.5% versus greater than 5.5% glycosylated hemoglobin levels were compared (risk ratio, 0.39; 95% confidence interval, 0.18-0.84; P = .02). Comparing higher glycosylated hemoglobin threshold values yielded comparable results. Late mortality was reduced with lower levels of glycosylated hemoglobin. Low preoperative glycosylated hemoglobin was associated with the lowest risk of sternal wound infections (risk ratio, 0.50; 95% confidence interval, 0.32-0.80; P = .003 and risk ratio, 0.53; 95% confidence interval, 0.39-0.70; P < .0001) for comparisons of less than 7.5% versus greater than 7.5% and less than 7.0% versus greater than 7.0% glycosylated hemoglobin thresholds, respectively. Additionally, levels of glycosylated hemoglobin lower than 7% were associated with reduced hospital stay, lower risk of stroke/transient ischemic attack (risk ratio 0.53; 95% confidence interval, 0.39-0.70; P < .0001), and acute kidney injury (risk ratio, 0.65; 95% confidence interval, 0.54-0.79; P < .0001).CONCLUSIONS: Lower levels of glycosylated hemoglobin in patients undergoing cardiac surgery are associated with a lower risk of early and late mortality, as well as in the incidence of postoperative acute kidney injury, neurologic complications, and wound infection, compared with higher levels.

Background Patients surviving a myocardial infarction have progressive cardiac dysfunction and ventricular remodeling. Mitral regurgitation is often diagnosed in these patients, and is a risk factor that portends poor prognosis. Whether such post-infarction mitral regurgitation magnifies adverse left ventricular remodeling is unclear, which was studied in an animal model. Methods Forty-one adult rats were induced with myocardial infarction by left coronary artery ligation and assigned to three groups: (group 1) myocardial infarction only; (group 2) myocardial infarction with severe mitral regurgitation introduced after 4 weeks; and (group 3) myocardial infarction with severe mitral regurgitation introduced after 10 weeks. Valve regurgitation was introduced by advancing a trans-apical, ultrasound guided needle into the mitral valve anterior leaflet. Animals were survived to 20 weeks from the index procedure, with biweekly cardiac ultrasound, and invasive hemodynamics and histology at termination. Results At 20 weeks, end diastolic volume was largest in the groups with mitral regurgitation, compared to the group without the valve lesion (group 1: 760.9±124.6μl, group 2: 958.0±115.1μl, group 3: 968.3±214.9μl). Similarly, end systolic volume was larger in groups with regurgitation (group 1: 431.2±152.6μl, group 2: 533.2±130.8μl, group 3: 533.1±177.5μl). In the infarction only group, left ventricular remodeling was maximal until 6 weeks and plateaued thereafter. In groups with mitral regurgitation, left ventricular remodeling was significantly elevated upon the onset of regurgitation and persisted. Conclusions Mitral regurgitation is a potent driver of adverse cardiac remodeling after a myocardial infarction, irrespective of the timing of its onset.

OBJECTIVES Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction. METHODS New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation. RESULTS Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P = .9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P = .0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P = .2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P = .0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P

Background To determine a reliable method to predict prevalent vertebral fractures (VF) by assessing the association between dysmobility syndrome (DS) and VF in a community-dwelling population. Material and methods This cross-sectional study enrolled 518 participants from fracture-prevention educational activities held in multiple communities in Taiwan. Assessments included questionnaires, fracture risk assessment tool (FRAX), bone mineral density (BMD) and body composition using dual-energy x-ray absorptiometry (DXA), lateral thoracolumbar spine x-rays (specifically T8-S1), grip strength (GS), walking speed, and fall history. Results DS was noted in 257 participants (49.6%) and VF was identified in 196 participants (37.8%). A higher prevalence of VF was noted in those with DS. The prevalence of VF was significantly associated with age, gender, FRAX both with and without BMD, osteoporosis, low GS, and DS. In multivariate models accounting for age and sex, the c-index was greater in those with low GS plus osteoporosis as compared to DS alone. Low GS, osteoporosis, and pre-BMD FRAX all had similar c-indexes. Pre-BMD FRAX plus low GS and osteoporosis was superior in predicting VF compared to pre-BMD FRAX plus low GS or osteoporosis alone. Besides the inclusion of age and gender, the nomogram with pre-BMD FRAX major osteoporosis fracture probability (MOF) plus low GS had improved correlation between the estimated and actual VF probability than those with pre-BMD FRAX MOF plus osteoporosis. Conclusions The constructed nomogram containing pre-BMD FRAX MOF plus low GS may be considered as a first-line prevalent VF screening method. Those with high-risk scores should subsequently undergo vertebral radiography and/or BMD.

Pseudohypoparathyroidism type 1A (PHP1A) is a disorder of multiple hormone resistance, mainly parathyroid hormone. It is associated with Albright hereditary osteodystrophy phenotypes. Patients with PHP1A may initially present with hypothyroidism during infancy and later develop typical PHP1A characteristics during their childhood. Central precocious puberty (CPP) is extremely rare among PHP1A patients in whom gonadotropin resistance is more usual. This study reported a 9.5-year-old boy with congenital hypothyroidism who developed hypocalcemia secondary to pseudohypoparathyroidism. He had relatively short stature with height standard deviation score of -0.9. Obesity had been noted since the age of 2 years. At the presentation of pseudohypoparathyroidism, pubertal-sized testes of 10 mL were observed, and CPP was documented with serum testosterone concentration of 298 ng/dL (normal for Tanner stage III, 100-320), luteinizing hormone of 3.9 IU/L (normal, 0.2-5.0), and follicle-stimulating hormone of 4.8 IU/L (normal, 1.2-5.8). Pituitary magnetic resonance imaging was unremarkable. Genetic analysis confirmed the diagnosis of PHP1A with a novel heterozygous missense variant of GNAS gene in the exon 13, c.1103A>G (p.Asp368Gly). Awareness of PHP1A diagnosis in patients with congenital hypothyroidism and early childhood-onset obesity is crucial for early diagnosis. Apart from multiple hormone resistance, CPP could be manifested in patients with PHP1A.

Background and objectives The highest incidence of death in systemic sclerosis due to pulmonary disease raises the need for early detection and treatment. The study aim is the assessment of interstitial pulmonary disease by Multi Detector High Resolution CT (MDCT) and finds its relationship with the other disease parameters and the Pulmonary Function tests (PFT). Patients and methods A prospective cross-sectional study was performed in Assiut University Hospitals from May 2018 to January 2020 and included 62 consecutive SSc female patients. Demographic, clinical, Laboratory, PFT and MDCT assessment were conducted for all participants. Results The coarseness of fibrosis was 8.32 (range 0.0–17), the average proportion of ground-glass opacification was 28.3% (range, 0.0%–75%). Honey-comb pattern was seen in (52.5%). Mean Extent of disease was 46.25 ± 3.7 (range 5–81). Restrictive deficit found in 42 patients. Significant relation was found between the extent of disease and the percentage predicted FVC (r = 0.373, p 0.018) and FEV1/FVC (r = 0.593, p 0.000) and coarseness of fibrosis and proportion of ground glass opacification correlated inversely with VC (r = −0.385, p = 0.014, r = −0.376, p = 0.017 respectively), Rayanud's phenomena, modified Rodnan Skin Score and Medsger's general are positively correlated with MDCT disease extent. Conclusion Scoring of systemic sclerosis (SSc) related interstitial lung disease (SSc-ILD) could be applicable as one of the important tools for disease assessment.

The aim is to present a rare clinical case of central areolar choroidal dystrophy (CACD), confirmed clinically and electrophysiologically. A 49-year-old man underwent a detailed ophthalmological examination, fundus autofluorescence, fluorescein angiography, optical coherence tomography, visual field testing, electrophysiological (EF) studies – full-field ERG and multifocal ERG, thanks to which the diagnosis was established. A classic CACD phenotype with slightly reduced visual acuity, central scotomas, atrophy of the outer layers of the retina and the choroid in the macula and hypoautofluorescence in the macula were demonstrated. EF studies showed absence of diffuse photoreceptor involvement. The local mfERG photopic response was slightly reduced. The relatively good functional results and the pronounced anatomical changes are due to the later, secondary involvement of the photoreceptors in the macular area, characteristic of choroidal dystrophies. The comprehensive clinical and EF testing of patients with rare hereditary retinal dystrophies is essential for the correct diagnosis given the many clinical trials of new innovative therapies for many of these diseases. It is expected that some of them would become curable in the very near future, and we should be prepared when that moment comes.

World Health Organization (WHO) recommends the use of first-line anti-tuberculosis drugs, that is, rifampicin (RIF) and isoniazid (INH) fixed-dose combination (FDC) therapies in tuberculosis (TB) d...

Aims To estimate prevalence of anxiety and depression in patients with diabetes mellitus and identify their determinants. Methods A cross-sectional study was conducted at Hassan II University-Hospital of Fes in 2019–2020. Anxiety and depression were measured by using the Hospital Anxiety and Depression Scale (HADS). Multivariate analysis by logistic regression was used to determine factors associated with depression and anxiety, adjusting for confounding factors. All statistical analyses were conducted using EPIINFO7. Results A total of 243 diabetics were included in the study. The average age of the participants was 48.07 ± 14.25 years, 58% were females and 72% were diagnosed with diabetes type II. The prevalence of depressive symptoms and anxiety symptoms was (18, 1%, CI95% = (13–23)) and (29.6%, CI95% = (24–35)), respectively. The prevalence of depression and anxiety was higher among women than man and increases with increasing duration of the disease. In multivariate analysis, illiterates (OR = 3.19, CI95% = (1.46–6.98)), those with depression (OR = 3.61, CI95% = (1.78–7.32)), and type 1 diabetics (OR = 3.22, CI95% = (1.44–7.21)) are a higher risk of developing anxiety. Depression was associated with older age (OR = 2, 65, CI95% = (1, 14–6, 14)), use of insulin (OR = 3.77 CI95% = (1.50–9.44)) and anxiety symptoms (OR = 4, 27, CI95% = (2, 05–8, 91)). Conclusion High prevalence of depressive and anxiety symptoms in diabetics suggests consideration of psychological aspect in implementation of diabetes managing program.

An acute ischaemic stroke (AIS) is a non-specific state of brain injury with neuronal dysfunction that has several pathophysiologic causes and is time critical. More than 70% of cases are due to thrombotic or embolic causes with resultant focal ischaemia and an accompanying neurological deficit. Initial assessment, stabilization and early imaging are important aspects of effective stroke management. Over the last two decades, thrombolysis and mechanical thrombectomy have proven beneficial in reversing neurological deficits and improving functional outcomes. Guidelines now support administration of recombinant tissue plasminogen activator (rt- PA ) up to 4.5 hours and extension of thrombectomy windows up to 24 hours after onset of symptoms in a select group of patients. Other important aspects of management include administration of antiplatelet agents (aspirin) within 48 hours, management within a specialist stroke unit, and decompressive hemi-craniectomy for malignant middle cerebral artery (MCA) stroke.

Objectives: With the aging population worldwide, the octogenarians are becoming a substantial group and since cancer incidence increases by age, this group of patients is becoming more affected. Ho...