Left Ventricular Morphology and Function in Normotensive, Metabolically Healthy Obese Individuals without Fatty Liver Disease.

BACKGROUND: Obesity is one of the major risk factors for the development of heart failure (HF), although the exact underlying mechanism remains unclear. In the clinical setting, assessing the impact of obesity on the cardiovascular system is difficult due to comorbidities. OBJECTIVES: The purpose of this study was to evaluate an independent influence of obesity on the left ventricular (LV) morphology and function. To eliminate hemodynamic and metabolic confounders, we performed an echocardiographic evaluation of severely obese but normotensive and metabolically healthy patients without fatty liver disease. METHODS: The patients were retrospectively selected from the cohort of 180 consecutive obese patients systematically evaluated with transthoracic echocardiography before bariatric surgery. Finally, 25 obese subjects, predominantly females, were evaluated with transthoracic echocardiography. Inclusion criteria were defined as absence of diabetes, hypertension, and hyperlipidemia, no use of medications and no hepatic steatosis on liver biopsy. They were matched with a control group of healthy subjects with normal body mass index. RESULTS: In obese patients, LV hypertrophy (LVH) (expressed as LV mass indexed for height in meters2.7) was significantly more frequent in the obese group (48 vs. 0%, p < 0.001). LV longitudinal systolic function measured by mitral annular systolic velocity was significantly lower in the obese group (S' 8.5 vs. 9.7 cm/s, p = 0.002). All studied indices of the LV diastolic function (E/A, mean E' and E/E' ratio) were impaired in obese subjects, even after adjustment for systolic blood pressure and heart rate (E/A 1.31 vs. 1.64, p < 0.001, E' mean 11 vs. 14.8 cm/s, p < 0.001, E/E' 7.5 vs. 6.4, p = 0.002 for obese vs. controls, respectively). CONCLUSIONS: LVH is significantly more common, and LV diastolic and longitudinal systolic function is significantly impaired in young, metabolically healthy, normotensive, severely obese individuals without fatty liver disease when compared to age and sex-matched lean subjects. These abnormalities may represent the independent effect of the obesity on the heart, which may contribute to the development the obesity-related HF in later life.

Rituximab and Chemotherapy for Newly Diagnosed Follicular Lymphoma: Real-World Report of Polish Lymphoma Research Group.

INTRODUCTION: Follicular lymphoma (FL) is the most common type of indolent B-cell lymphoma with a favorable prognosis in the majority of patients. The induction treatment is still based on rituximab and chemotherapy, though new anti-CD20 antibody and chemo-free regimen have been recently introduced. The aim of the study was to analyze the management, outcomes, and determinants of prognosis of newly diagnosed patients with FL in real-world experience. METHODS: Data of consecutive patients diagnosed with FL in 5 years period (2011-2015) in three oncohematological centers were reviewed. Variables were compared using Mann-Whitney or χ2 test as appropriate, survival outpoints were calculated using Kaplan-Meier method. RESULTS: One hundred eighty-one patients were included in the study. The median patients' age at diagnosis was 56.6 years. Low histological grade (G1-G2) was found in 62.1% of patients and advanced clinical stage in 77.0% of patients. ECOG 0 performance status was observed in 57.1% of patients. The median follow-up was 5.91 years. Initially, 31.5% of the patients were qualified to watch-and-wait (W&W) strategy, and 84.0% of the whole patients' group received systemic treatment during the observation period. As induction treatment, 53.9% and 41.4% of patients received RCVP and RCHOP regimens, respectively; 39.8% received rituximab maintenance (RM) after first-line therapy. During follow-up, transformation to aggressive lymphoma occurred in 7.2% of patients. Median overall survival (OS) was not achieved, and median progression-free survival (PFS) was 8.28 years (95% CI; 7.35, NA), 19.6% of patients relapsed during 24 months from the start of the treatment (POD24). Median PFS for POD24 group was 1.1 years (95% CI; 0.56, 1.45) with a median OS longer than 8 years. ECOG 0, low PRIMA PI, and no POD24 were found as determinants of longer PFS and OS. CONCLUSIONS: Our data from clinical practice showed that rituximab and chemotherapy is still an effective method of FL treatment resulting in survival more than 8 years from diagnosis in most patients. RCVP protocol followed with RM is a reasonable choice for the first-line therapy especially in low/intermediate group of patients. The prognosis was significantly worse in patients with POD24. Therefore, searching for precise initial clinical and biological markers is warranted and development therapies to improve prognosis of POD24 patients.

MTARC1 and HSD17B13 Variants Have Protective Effects on Non-Alcoholic Fatty Liver Disease in Patients Undergoing Bariatric Surgery.

The severity of hepatic steatosis is modulated by genetic variants, such as patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, and membrane-bound O-acyltransferase domain containing 7 (MBOAT7) rs641738. Recently, mitochondrial amidoxime reducing component 1 (MTARC1) rs2642438 and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567 polymorphisms were shown to have protective effects on liver diseases. Here, we evaluate these variants in patients undergoing bariatric surgery. A total of 165 patients who underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies and 314 controls were prospectively recruited. Genotyping was performed using TaqMan assays. Overall, 70.3% of operated patients presented with hepatic steatosis. NASH (non-alcoholic steatohepatitis) was detected in 28.5% of patients; none had cirrhosis. The increment of liver fibrosis stage was associated with decreasing frequency of the MTARC1 minor allele (p = 0.03). In multivariate analysis MTARC1 was an independent protective factor against fibrosis ≥ 1b (OR = 0.52, p = 0.03) and ≥ 1c (OR = 0.51, p = 0.04). The PNPLA3 risk allele was associated with increased hepatic steatosis, fibrosis, and NASH (OR = 2.22, p = 0.04). The HSD17B13 polymorphism was protective against liver injury as reflected by lower AST (p = 0.04) and ALT (p = 0.03) activities. The TM6SF2 polymorphism was associated with increased ALT (p = 0.04). In conclusion, hepatic steatosis is common among patients scheduled for bariatric surgery, but the MTARC1 and HSD17B13 polymorphisms lower liver injury in these individuals.

Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant.

Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by norovirus gastroenteritis, acute graft-versus-host disease, and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.

Leukaemia cutis for clinicians, a literature review.

Leukaemia cutis (LC) describes infiltration of the skin by leukaemia cells, resulting in clinically identifiable cutaneous lesions. LC has a wide range of clinical manifestations, which can make it difficult to distinguish LC from other skin changes. In a group of patients, LC can be the first manifestation of leukaemia, therefore skin biopsy is crucial for the diagnosis. In this mini review, we discuss various types of leukaemia most frequently represented in leukaemia cutis, in both children and adults and skin changes in multiple myeloma, focusing on the clinical presentation of LC and prognosis in patients.

Comprehensive histopathological diagnostics of aggressive B-cell lymphomas based on the updated criteria of the World Health Organisation's 2017 classification.

Revision of the fourth edition of the World Health Organisation (WHO) Classification of Haematopoietic and Lymphatic Tissues, which was published in 2017, introduced important changes updating the biology, pathology, genetics, and clinical presentation of aggressive B-cell lymphomas. High grade B-cell lymphomas (HGBLs) replaced B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, the new provisional entity Burkitt-like lymphoma with 11q aberration was identified, and some categories were upgraded, e.g. EBV-positive diffuse large B-cell lymphoma, not otherwise specified. Still the histopathological diagnostics is based on morphology and immunoprofile, but to define the HGBLs evaluation of MYC, BCL2, and BCL6 gene statuses is required. According to the presented WHO criteria, in the comprehensive histopathological diagnostics of aggressive B-cell lymphomas a highly specialised diagnostic team including a pathologist, a molecular biologist, a geneticist, a haematologist, and immunophenotyping technicians is needed.

Liver Function in Patients With Nonalcoholic Fatty Liver Disease Randomized to Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVES: The aim of the study was to compare the influence of sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) on liver function in bariatric patients with non-alcoholic fatty liver disease (NAFLD) in a randomized clinical trial (NCT01806506). BACKGROUND: Rapid weight loss and malabsorption after bariatric surgery in patients with NAFLD or steatohepatitis (NASH) may impair liver function. METHODS: Sixty-six morbidly obese patients randomized to SG or RYGB were included in a secondary outcome analysis. Intraoperative liver biopsies were categorized with NAFLD Activity Score (NAS) and liver function tests were done before surgery and after 1, 6 and 12 months. RESULTS: NASH was present in 54.5% RYGB and 51.5% SG patients (P > 0.05). At 12 months excess weight loss was 68.7 ±â€Š19.7% after SG and 62.8 ±â€Š18.5% after RYGB (P > 0.05). At 1 month international normalized ratio (INR) increased after RYGB (0.98 ±â€Š0.05 vs 1.14 ±â€Š0.11; P < 0.05) and SG (0.99 ±â€Š0.06 vs 1.04 ±â€Š0.06; P < 0.05), RYGB induced significantly greater increase in INR in the whole group and NASH patients than SG. After RYGB albumin decreased at 1 month (41.2 ±â€Š2.7 vs 39.0 ±â€Š3.2 g/L; P < 0.05). At 12 months, INR and albumin returned to baseline. At 12 months in NASH group, SG induced significant improvement in aspartate aminotransferase (32.4 ±â€Š17.4 vs 21.5 ±â€Š6.9U/L), alanine aminotransferase (39.9 ±â€Š28.6U/L vs 23.8 ±â€Š14.1U/L), gamma-glutamyl transpeptidase (34.3 ±â€Š16.6 vs 24.5 ±â€Š16.8U/L), and lactate dehydrogenase (510.8 ±â€Š33 vs 292.4 ±â€Š29). Variables predictive of INR change after 1 month included operation type, NAS ≥ 5, bilirubin, body mass index, hemoglobin A1C, and dyslipidemia. CONCLUSIONS: Patients with NASH undergoing RYGB are more susceptible to early transient deterioration of liver function than after SG.

Expression of resistin in the liver of patients with non-alcoholic fatty liver disease.

Adipokines are cytokines that presumably connect the pathologies of metabolic syndrome. One of the adipokines is resistin, the role of which in insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD) needs to be determined. Liver biopsy specimens were obtained intraoperatively from 214 obese patients. Histological assessment was based on NAFLD activity score according to Kleiner. Statistical analysis involved semi-quantitive immunohistochemistry assessment of resistin staining and: NAFLD status in obese patients compared with a non-obese control group, selected clinical data (age, sex, body mass index - BMI), selected biochemical data, comorbidities (hypertension, type 2 diabetes mellitus, dyslipidaemia), and metformin treatment in patients with type 2 diabetes mellitus. Resistin expression was observed in the histiocytes of inflammatory infiltrate, Kupffer cells, and histiocytes surrounding the hepatocytes with steatosis. There was a positive correlation between the total expression of resistin and: (1) NAFLD advancement (NAFLD Activity Score- NAS), (2) AST, ALT, BMI, glucose, insulin, Homeostasis Model Assessment (HOMA), LDH, GGT, triglycerides (TG), and glycated haemoglobin (HbA1c). Resistin expression was more intense in patients with type 2 diabetes mellitus and dyslipidaemia and less intense in the control group. Resistin probably plays a role in the pathogenesis of hepatic insulin resistance and aggravates pathologic changes in the liver of patients with NAFLD.

Aspergillosis of the Heart and Lung and Review of Published Reports on Fungal Endocarditis.

Invasive aspergillosis (IA) is increasingly diagnosed in high-risk patients. The lesions are usually located in the lungs and/or sinuses, and the fungus may spread haematogenously to different organs; however, involvement of the heart during IA is very rare. We describe a unique case of invasive aspergillosis of the heart septum and the lungs in the allogeneic haematopoietic stem cell transplant recipient.

[A rare CD5-positive subgroup of diffuse large B-cell lymphoma - clinical, morphological and immunophenotypic features in Polish patients].

The aim of the study was to assess the incidence of CD5-positive diffuse large B-cell lymphoma (DLBCL) in the Polish population and to describe its morphologic and clinical characteristics. The study included 36 patients with CD5-positive DLBCL, diagnosed and treated in the Maria Sklodowska-Curie Institute and Oncology Centre, Warsaw, Poland and the Medical University of Warsaw, Poland in the years 2002-2013. The control group consisted of 28 patients with CD5-negative DLBCL. CD5-positive DLBCL accounted for 6.26% of all DLBCL cases diagnosed in the Maria Sklodowska-Curie Institute and Oncology Centre in the years 2008-2012. The incidence is comparable to other European countries, lower than noted in Japan and higher than in the US. Patients with CD5-positive DLBCL, in comparison to the CD5-negative group, were characterized by: (1) older age (≥ 60 vs. younger) and worse general status (ECOG ≥ 2 vs. < 2), (2) lower frequency of complete remission (CR), (3) higher expression of unfavorable prognostic factors (BCL2, FOXP1, CD44) and MMP-9, and (4) lower expression of favorable prognostic factors (CD30, cyclin D1, cyclin D3) and TIMP-2.

Anti-HLA and anti-MICA antibodies in liver transplant recipients: effect on long-term graft survival.

OBJECTIVE: Presence of anti-HLA antibodies has a well-known impact on kidney grafts survival; however their role in liver transplantation has not been fully elucidated. We conducted a 7-year prospective study to show correlation between presence of anti-HLA and anti-MICA antibodies and liver graft survival. METHODS: Blood samples from 123 liver transplant recipients were collected during patients routine visits. Time from transplantation to blood sample collection was different for each patient. Blood samples were tested for anti-HLA (separately class I and II) and MICA antibodies using Luminex assays. RESULTS: There were 32 (26%) patients with positive anti-HLA and 37 (30%) with positive anti-MICA antibodies. Graft loss occurred in 7 cases (23%) in anti-HLA positive group compared to 20 (22%) in anti-HLA negative group (P = ns) and in 8 cases (22%) in anti-MICA positive group but 19 (23%) in anti-MICA negative group (P = ns). No correlations were detected between presence of antibodies and acute graft rejection (AGR). Presence of any antibodies (anti-HLA or anti-MICA antibodies) correlated with late graft rejection (P = 0.04). CONCLUSION: Presence of anti-HLA or anti-MICA had no impact on long-term liver graft survival; however, detection of any antibodies was correlated with episodes of late graft rejection.

Atrial fibrillation as a first clinical manifestation of right atrial cavernous haemangioma.

Primary heart tumours are rare with an incidence of 0.02% in reported autopsy series. One of the most uncommon is haemangioma. We describe the case of a 51-year-old woman, who presented with a giant cavernous haemangioma, but with no clinical manifestations other than atrial fibrillation. Performed echocardiography showed a giant (6.5 x 7.5 cm) tumour located in the right atrium, modelling other heart chambers. In order to improve atrial haemodynamics, a large portion of the tumour was removed via sternotomy. Examination after 12 months showed no further growth of the unremoved part of the tumour.

Ultrasound- and biomarker-based assessment of hepatic steatosis in patients with severe obesity.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a common liver abnormality, but its noninvasive diagnosis in patients with severe obesity remains difficult. OBJECTIVES: Our aim was to investigate the usefulness of the ultrasound­based hepatorenal index (HRI) technique and 2 biomarker­based methods, including the hepatic steatosis index (HSI) and NAFLD logit score for the diagnosis of NAFLD in patients referred for bariatric surgery. PATIENTS AND METHODS: A total of 162 patients, including 106 with NAFLD, admitted for bariatric surgery participated in the study. Fat fraction level and the presence of NAFLD were determined using surgical liver biopsy. Each patient underwent liver ultrasound examination and blood tests to determine the HRI, HSI, and NAFLD logit score. RESULTS: For the NAFLD diagnosis, the HRI, HSI, and NAFLD logit score techniques achieved areas under the receiver operating characteristic curves of 0.879, 0.577, and 0.825, respectively. The Spearman correlation coefficients between the liver fat fraction values and the HRI, HSI, and NAFLD logit score were equal to 0.695, 0.215, and 0.595, respectively. The optimal cutoff values for the NAFLD diagnosis for the HRI, HSI, and NAFLD logit score were equal to 1.12, 56.1, and 0.59, respectively, and significantly differed from the cutoff values reported for the general population in the literature. CONCLUSIONS: Our study confirmed the usefulness of only 2 out of 3 techniques, the HRI and the NAFLD logit score for the diagnosis of NAFLD in patients with severe obesity. The methods designed for the general population require different cutoff values to achieve accurate performance in patients with severe obesity.

Anemia, Iron Deficiency, and Iron Regulators in Pancreatic Ductal Adenocarcinoma Patients: A Comprehensive Analysis.

Anemia and iron deficiency (ID) are common complications in patients with pancreatic ductal adenocarcinoma (PDAC), but their underlying causes remain unclear. This study investigated the incidence and characteristics of anemia and micronutrient deficiencies in PDAC patients before initiating chemotherapy. A total of 103 PDAC patients were included, comprising 67 in the palliative and 36 in the adjuvant groups. The overall incidence of anemia was 42.7% (n = 44), with comparable rates in both groups. Normocytic and normochromic anemia were predominant, with mild and moderate cases observed in 32% and 10.7% of the cohort, respectively. ID was evident in 51.4% of patients, with absolute ID more frequent in the adjuvant than in the palliative group (19.4% vs. 13.4%). Functional ID occurred more often in the palliative than in the adjuvant group (41.8% vs. 25%). Vitamin B12 and folate deficiency occurred in <5% (n = 5) of patients. Furthermore, 8.7% (n = 9) of patients had chronic kidney disease and anemia. To elucidate mechanisms of iron deficiency, the study explored the expression of iron regulators (hepcidin (HEP), ferroportin (FPN), and ZIP14 protein) and mitochondrial mass in PDAC tissue with immunohistochemical (IHC) staining and Perl's Prussian blue to detect iron deposits on available tumor samples (n = 56). ZIP14 expression was significantly higher in less advanced tumors (p = 0.01) and correlated with mitochondrial mass (p < 0.001), potentially indicating its role in local iron homeostasis. However, no significant impact of tissue iron regulators on patient survival was observed. Perl's Prussian blue staining revealed iron deposits within macrophages, but not in pancreatic duct cells. Furthermore, the GEPIA database was used to compare mRNA expression of iron regulators (HEP, FPN, and ZIP14) and other genes encoding iron transport and storage, including Transferrin Receptor Protein 1 (TfR1) and both ferritin chain subunits (FTH and FTL), in PDAC and normal pancreatic samples. FPN, TfR1, FTH, and FTL showed higher expression in tumor tissues, indicating increased iron usage by cancer. ZIP14 expression was higher in the pancreas than in PDAC and was correlated with FPN expression. The study highlights the importance of baseline iron status assessment in managing PDAC patients due to the high incidence of anemia and iron deficiency. Furthermore, ZIP14, in addition to HEP and FPN, may play a crucial role in local iron homeostasis in PDAC patients, providing valuable insights into the underlying mechanisms of iron dysregulation.

Expression of ghrelin and its receptors in ovarian endometrioma.

Endometriosis is a common gynaecological disorder manifesting by implantation and growth of endometrial tissue outside the uterine cavity. The evidence accumulates that endometriosis may be associated with abrogated regulation of energy balance. Ghrelin is one of the most important orexigenic factor which may also play a role in regulation of inflammatory and angiogenic reactions. The present study was aimed at investigating expression profile of ghrelin and its receptors (GHSR1α and GHSR1ß) in endometriotic lesions. The study included ovarian cysts and peritoneal fluid specimens obtained laparoscopically from 20 women with revised American Fertility Society stage III or IV endometriosis. Expression of specific mRNAs was assessed by reverse transcription-polymerase chain reaction. Expression of ghrelin and GHSR1α protein was studied by immunohistochemical staining with specific antibodies. Ghrelin and its receptors mRNA expression was found in all tested specimens. Specific mRNAs for these factors were also expressed in the peritoneal leukocytes. Immunohistochemical staining revealed expression of ghrelin and GHSR1α both in glandular endometrioid epithelium and in some stromal cells, particularly in some fibroblasts, blood vessels and infiltrating leukocytes. Co-localization of ghrelin and its receptors strongly suggests that this neuropeptide may affect development and growth of endometriotic lesions and may influence local inflammatory and angiogenic response.

Lymphangioma Cavernosum with a Rare Location.

Lympangioma cavernosum in the abdominal cavity is a rare benign tumour. In most cases, such tumours are diagnosed in the oral cavity and neck. The aim of this paper is to present our clinical observations and review of existing literature to draw attention to this disease. A 25-year-old woman was admitted to our department for a symptomatic tumour in the lesser curvature of the stomach. The patient was first operated on as a three-year-old child because the tumour extended from the back wall of the stomach to the gastro-colonic ligament. The medical records showed that it was a benign tumour; however, no diagnosis was specified. No symptoms were observed for 22 years. Currently, the patient is admitted for epigastric pain. Abdominal computed tomography revealed an extensive mass located between the left segments of the liver and the lesser curvature of the stomach. The patient was operated on, and the tumour was completely removed. The patient's postoperative course was uneventful. Histopathological examination of the lymphangioma cavernosum was performed. Two months after the operation, the patient did not report any complaints.

Comparison of Post-Transplantation Lymphoproliferative Disorder Risk and Prognostic Factors between Kidney and Liver Transplant Recipients.

Post-transplantation lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation (SOT). Its development risk varies among organ graft recipients. In this study, retrospective data were analyzed to compare PTLD's risk and prognostic factors between adult kidney and liver transplant recipients (KTRs and LTRs, respectively). Over 15 years, 2598 KTRs and 1378 LTRs were under observation at our center. Sixteen KTRs (0.62%) and twenty-three LTRs (1.67%) were diagnosed with PTLD. PTLD developed earlier in LTRs (p < 0.001), SOT patients > 45 years old (p = 0.002), and patients receiving tacrolimus (p < 0.001) or not receiving cyclosporin (p = 0.03) at diagnosis. Tacrolimus use, male sex, and age > 45 years old significantly affected the time of PTLD onset in KTRs (hazard ratio (HR) = 18.6, 7.9 and 5.2, respectively). Survival was longer in LTRs < 45 years old (p < 0.009). LTRs were more likely than KTRs to achieve complete remission (p = 0.039). Factors affecting PTLD development and outcome differ between KTRs and LTRs; thus, these populations should be separately evaluated in future studies.

Cutaneous Rosai-Dorfman Disease: A Treatment Challenge.

Rosai-Dorfman disease (RDD) is a benign histiocytosis that rarely manifests as a purely cutaneous form. Its differential diagnosis and treatment can pose a challenge to both clinicians and pathomorphologists. We present the case of a 69-year-old woman with cutaneous RDD presenting as multiple nodules on the right thigh who was treated with low-dose methotrexate weekly for > 1 year with a partial response.