Biochemical Follow-up Research Articles

Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.

Atrial arrhythmias occur in 20-40% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and are associated with an increased risk of sustained ventricular arrhythmias and inappropriate implantable cardioverter-defibrillator shocks. The pathophysiology of atrial arrhythmias in ARVC remains unclear. Most cases of gene-positive ARVC are linked to pathogenic variants in the desmosomal gene plakophilin-2 (PKP2). Here, we test the hypothesis that loss of PKP2 expression leads to pro-arrhythmic changes in atrial cardiomyocytes. Atrial cells/tissue were obtained from a cardiac-specific, tamoxifen-activated model of PKP2 deficiency (PKP2cKO). By contrast to PKP2cKO ventricular myocytes, PKP2cKO atrial cardiomyocytes presented no significant differences in intracellular calcium (Ca2+ i) transient dynamics, sarcoplasmic reticulum load or action potential morphology. PKP2cKO atrial cardiomyocytes showed elevated reactive oxygen species levels, increased frequency and amplitude of Ca2+ sparks, and increased diastolic [Ca2+]i compared to control; the latter two parameters were further increased by isoproterenol exposure and reversed by exposure to ryanodine receptor blocker dantrolene. We speculate that these isoproterenol-dependent effects may impact on the exercise-related atrial arrhythmia risk in ARVC patients. Despite absence of changes in Ca2+ i transient dynamics, PKP2cKO atrial cardiomyocytes showed enhanced sarcomere shortening and impaired sarcomere relaxation. Orthogonal transcriptomic analysis of human(GTEx) and PKP2cKO atrial tissue led to identification of 41 transcripts depending on PKP2 expression. Biochemical follow-up confirmed reduced abundance of sarcomeric protein myosin binding protein C, potentially playing a role in cellular shortening and relaxation changes observed. Our findings provide novel insights into the role of PKP2 in atrial myocardium with potential implications to therapeutic management of atrial fibrillation in patients with PKP2-related ARVC. KEY POINTS: Atrial arrhythmias occur in a large group of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a cardiac disease mostly caused by pathogenic variants in the desmosomal gene plakophilin-2 (PKP2). Exercise is considered to be an independent risk factor for arrhythmias consequent to PKP2 deficiency. Weshow that loss of PKP2 expression affects cellular calcium handling and electrophysiology differently in left atrial vs. ventricular myocardium and causes extensive atrial fibrosis. PKP2-deficient atrial cardiomyocytes present increased spontaneous sarcoplasmic reticulum calcium release events, furtherenhancedby isoproterenol exposure and reversiblebya ryanodine receptor blocker(dantrolene). In addition, PKP2-deficient atrial myocytes exhibit impaired relaxation and enhanced sarcomere shortening, most probably related to reduced abundance of myosin binding protein C. We speculate that cellular effects reported upon isoproterenol impact on the exercise-related atrial arrhythmia risk in ARVC patients. We further propose that therapeutic approaches aimed at mitigating ventricular damage may be effective to treat the atrial disease in ARVC.

Neuroserpin, IL-33 and IL-17A as potential markers of mild symptoms of depressive syndrome in Toxoplasma gondii-infected pregnant women.

Depressive syndrome (DS) is a common complication during pregnancy and the postpartum period, and is triggered by multiple organic/genetic and environmental factors. Clinical and biochemical follow-up is essential for the early diagnosis and prognosis of DS. The protozoan Toxoplasma gondii causes infectious damage to the fetus during parasite primary-infection. However, in long-term infections, pregnant women develop immune protection to protect the fetus, although they remain susceptible to pathological or inflammatory effects induced by T. gondii. This study aimed to investigate plasma inflammatory biomarkers in pregnant women seropositive and seronegative for T. gondii, with diagnoses of minor and moderate/severe DS. Pregnant women (n=45; age=18-39 years) were recruited during prenatal care at health centers in Ouro Preto, Minas Gerais, Brazil. Participants were asked to complete a socio-demographic questionnaire to be submitted to well-standardized DS scale calculators (Beck Depression Inventory Questionnaire, Edinburgh Postnatal Depression Scale, and Major Depressive Episode Module). Additionally, 4 mL of blood was collected for plasma neuroserpin, CCL2, IL-17A, and IL-33 analysis. Pregnant volunteers with chronic T. gondii contact were all IgG+ (44%; n=21) and exhibited increased plasma IL-33, IL-17A, and neuroserpin levels, but not CCL2, compared to uninfected pregnant women. Using Beck's depression inventory, we observed an increase in plasma IL-17A and IL-33 in women with T. gondii infeCction diagnosed with mild DS, whereas neuroserpin was associated with minor and moderate/severe DS. Our data suggest a close relationship between DS in pregnant women with chronic T. gondii infection and neurological conditions, which may be partially mediated by plasma neuroserpin, IL-33, and IL-17A levels.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study

BackgroundGlycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment.ResultsIn this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients.ConclusionEmpagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

18F]FET PET/MRI: An Accurate Technique for Detection of Small Functional Pituitary Tumors.

Small functional pituitary tumors can cause severely disabling symptoms and early death. The gold standard diagnostic approach includes laboratory tests and MRI, with or without inferior petrosal sinus sampling (IPSS). In up to 40% of patients, however, the source of excess hormone production remains unidentified or uncertain. This excludes patients from surgical, Gamma Knife, and CyberKnife therapy and adversely affects overall cure rates. We here assess the diagnostic yield of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET/MRI for detection of small functional pituitary tumors in these patients. Methods: This retrospective analysis included patients with Cushing disease (CD) but prior negative or inconclusive MRI results who underwent [18F]FET PET/MRI between February 1, 2021, and December 1, 2022. PET/MR images and MR images alone were evaluated by experienced nuclear radiologists, neuroradiologists, or radiologists. Postoperative tissue analysis (when performed) was used as a reference standard to assess diagnostic metrics (i.e., sensitivity and positive predictive value). Results were also compared with previously obtained MR images, preceding IPSS, and clinical or biochemical follow-up. Results: Twenty-two patients (68% female; mean age ± SD, 48 ± 15 y; range, 24-68 y) were scanned. All patients showed a clear metabolic focus on [18F]FET PET, whereas reading of the MRI alone yielded a suspected lesion in only 50%. Fifteen patients underwent surgery directed at the [18F]FET-positive focus. Tissue analysis confirmed a pituitary adenoma/pituitary neuroendocrine tumor of the corticotroph cell type (TPIT lineage) in 10 of 15 and a pituicytoma in 1 of 15, rendering a sensitivity of 100% and a positive predictive value of 73%. Lateralization was more accurate with [18F]FET PET/MRI than with IPSS in 33%. Twelve of 16 (75%) patients who received surgical, Gamma Knife, or CyberKnife therapy after [18F]FET PET/MRI reached short-term remission. Conclusion: [18F]FET PET/MRI shows a high diagnostic yield for localizing small functional pituitary tumors. This multimodal imaging technique provides a welcome improvement for diagnosis, planning of surgery, and clinical outcome in patients with Cushing disease, particularly those with repeated negative or inconclusive MRI results with or without IPSS.

Severe Acute Hepatitis of Unknown Etiology in Pediatric Patients: Multidisciplinary Clinical Approach

Introduction: In mid-2022, the World Health Organization (WHO) declared a moderate-risk outbreak due to an increase in severe acute hepatitis cases of unknown etiology in children. Several reports suggested a viral infection link, with the outbreak spanning over 35 countries. By June 2022, Mexico reported 69 probable cases across 5 entities to the WHO. Case Presentation: A 4-year-old boy presented with vomiting, jaundice, choluria, and hepatomegaly. A multidisciplinary approach was employed, using an algorithm developed exclusively for clinical, epidemiological, and biochemical follow-up. Despite the negative identification of any associated microorganism and the absence of antibodies, liver function tests remained elevated. A fine needle liver biopsy was performed for diagnostic support, followed by histopathological study and sequencing and analysis of the complete high-depth transcriptome. Transcriptome analysis identified dysbiosis-related intestinal microbiota, including increased enterogenic and opportunistic pathogenic bacteria of the genus Clostridium, as well as HERV-K113, implicated in autoimmune disease development. Conclusions: The study's findings suggest possible immune-mediated mechanisms involving dysbiosis of the gut microbiota and the potential role of HERV-K113. Management and control of acute liver disease depend on specific causes, with the main challenge being early determination and implementation of optimal management strategies. The exact pathological mechanisms underlying pediatric acute hepatitis of unknown etiology remain elusive, warranting further studies to confirm or refute these hypotheses and elucidate the underlying pathological mechanisms

Regional variation in incidence and prognosis of acute kidney injury.

Examining regional variation in acute kidney injury (AKI) and associated outcomes may reveal inequalities and possibilities for optimization of the quality of care. Using the Danish medical databases, we examined regional variation in the incidence, follow-up, and prognosis of AKI in Denmark. Patients with one or more AKI episodes in 2017 were identified using population-based creatinine measurements covering all Danish residents. Crude and sex-and-age-standardized incidence rates of AKI were estimated using census statistics for each municipality. Adjusted hazard ratios (aHR) of chronic kidney disease (CKD), all-cause death, biochemical follow-up, and outpatient contact with a nephrology department after AKI were estimated across geographical regions and categories of municipalities, accounting for differences in demographics, comorbidities, medication use, lifestyle and social factors, and baseline kidney function. We identified 63382 AKI episodes in 58356 adults in 2017. The regional standardized AKI incidence rates ranged from 12.9 to 14.9 per 1000 person-years. Compared with the Capital Region of Denmark, the aHRs across regions ranged from 1.04 to 1.25 for CKD, from 0.97 to 1.04 for all-cause death, from 1.09 to 1.15 for biochemical follow-up, and from 1.08 to 1.49 for outpatient contact with a nephrology department after AKI. Similar variations were found across municipality categories. Within the uniform Danish healthcare system, we found modest regional variation in AKI incidence. The mortality after AKI was similar; however, CKD, biochemical follow-up, and nephrology follow-up after AKI varied across regions and municipality categories.

Prophylactic Medication during Radioembolization in Metastatic Liver Disease: Is It Really Necessary? A Retrospective Cohort Study and Systematic Review of the Literature.

Trans-arterial radioembolization is a well-studied tumoricidal treatment for liver malignancies; however, consensus and evidence regarding periprocedural prophylactic medication (PPM) are lacking. A single-center retrospective analysis from 2014 to 2020 was performed in patients treated with 90Y-glass microspheres for neuroendocrine or colorectal liver metastases. Inclusion criteria were the availability of at least 3 months of clinical, biochemical, and imaging follow-up and post-treatment 90Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (Dh). Logistic regression models were used to investigate if variables (among which are P/UDCA and Dh) were associated with either clinical toxicity, biochemical toxicity, or hepatotoxicity. Additionally, a structured literature search was performed in November 2022 to identify all publications related to PPM use in radioembolization treatments. Fifty-one patients received P/UDCA as post-treatment medication, while 19 did not. No correlation was found between toxicity and P/UDCA use. Dh was associated with biochemical toxicity (p = 0.05). A literature review resulted in eight relevant articles, including a total of 534 patients, in which no consistent advice regarding PPM was provided. In this single-center, retrospective review, P/UDCA use did not reduce liver toxicity in patients with metastatic liver disease. The whole non-tumorous liver-absorbed dose was the only significant factor for hepatotoxicity. No standardized international guidelines or supporting evidence exist for PPM in radioembolization.

THU410 Retrospective Review Of Adults Patients With Suspected Or Confirmed Hypophosphatasia At The Penn Bone Center

Abstract Disclosure: R. Tran: None. C. Hvisdas: None. M. Riordan: None. L. Novotny: None. S. Kallish: None. K. Patel: None. M. Al Mukaddam: None. Abstract: Hypophosphatasia (HPP) is a rare inherited genetic disorder that affects the mineralization of bones and teeth. HPP is the result of a pathogenic variant involving the tissue nonspecific alkaline phosphatase (ALPL) gene. The clinical presentations of HPP greatly vary from serious perinatal manifestations (respiratory failure, seizures, and death) to mild manifestations in adulthood. In adults, hallmark signs and symptoms include early loss of primary or secondary teeth, osteoporosis, osteomalacia, recurring metatarsal stress fractures, and abnormal laboratory values, such as low alkaline phosphatase (ALP), elevated phosphoethanolamine, and elevated vitamin B6.The treatment and follow up of adults with HPP are not clearly described. This retrospective study characterizes 43 patients referred to the Penn Bone Center for suspected HPP. Twelve of the 43 patients had a confirmed HPP diagnosis based on both clinical presentations and evidence of variant in the ALPL gene. The twelve patients consisted of both female and male adults between the ages of 24 to 74. In addition, the patients had abnormal ALP levels, ranging between less than 5 to 38 units per liter (normal range: 38 to 126 U/L). Six of these patients had previous or current use of asfotase alfa with variable treatment response. Two patients decided to stop treatment due to lack of clinical benefit or worsening of symptoms while on asfotase alfa therapy. Biochemical and bone mineral density follow-up while on therapy has not been shown to be helpful in monitoring treatment response. Asfotase alfa is a subcutaneously administered synthetic human alkaline phosphatase that was approved by the Federal Drug Administration (FDA) in 2015 for treatment of perinatal/infantile- and juvenile-onset hypophosphatasia. However, the efficacy of treatment in adults remain unclear at this time. Further research is required to better define the natural progression of mild or adult-onset hypophosphatasia and the patients who would benefit from enzyme therapy. Presentation: Thursday, June 15, 2023

Birmingham Hip Resurfacing at 20 years.

The Birmingham Hip Resurfacing (BHR) arthroplasty has been used as a surgical treatment of coxarthrosis since 1997. We present 20-year results of 234 consecutive BHRs performed in our unit. Between 1999 and 2001, there were 217 patients: 142 males (65.4%), mean age 52 years (18 to 68) who had 234 implants (17 bilateral). They had patient-reported outcome measures collected, imaging (radiograph and ultrasound), and serum metal ion assessment. Survivorship analysis was performed using Kaplan-Meier estimates. Revision for any cause was considered as an endpoint for the analysis. Mean follow-up was 20.9 years (19.3 to 22.4). Registry data revealed that 19 hips (8.1%) had been revised and 26 patients (12%) had died from causes unrelated to the BHR. Among the remaining 189 hips, 61% were available for clinical follow-up at 20 years (n = 115) and 70% of patients had biochemical follow-up (n = 132). The cumulative implant survival rate at 20 years for male patients was 96.5% (95% confidence interval (CI) 93.5 to 99.6), and for female patients 87% (95% CI 79.7 to 94.9). The difference was statistically significant (p = 0.029). The mean Oxford Hip Score, Hip disability and Osteoarthritis Outcome Score, and Forgotten Joint Score were 45 (29 to 48), 89 (43 to 100), and 84 (19 to 100), respectively. The mean scores for each of the five domains of the EuroQol five-dimension three-level questionnaire were 1.2, 1.0, 1.2, 1.3, and 1.1, and mean overall score 82.6 (50 to 100). Ultrasound showed no pseudotumour. Mean cobalt and chromium levels were 32.1 nmol/l (1 to 374) and 45.5 nmol/l (9 to 408), respectively. This study shows that BHRs provide excellent survivorship and functional outcomes in young male patients. At 20 years, soft-tissue imaging and serum metal ion studies suggest that a metal-on-metal resurfacing implant can be well tolerated in a group of young patients.

Comparison of Neck Ultrasonography, Dual Phase 99mTc-Sestamibi with early SPECT-CT & 18F-Fluorocholine PET-CT as First Line Imaging in Patients with Primary Hyperparathyroidism.

Successful surgical treatment for primary hyperparathyroidism requires accurate localization of abnormal parathyroid tissue in terms of location and number. Imaging is important for localizing the parathyroid adenoma, and there has been significant interest in 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) for this purpose. This study attempted to ascertain the utility of 18F-FCH PET/CT as a first-line investigation in preoperative localization of abnormal parathyroid tissue in primary hyperparathyroidism, in comparison with 99mTc-sestamibi dual-phase scintigraphy with early single-photon emission computed tomography (SPECT)/CT and neck ultrasonography. Fifty-five patients with biochemical features of primary hyperparathyroidism were enrolled in this study. They underwent neck ultrasonography, 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT, and 18F-FCH PET/CT for localization of parathyroid lesions. Thirty-three patients underwent surgical resection of the detected lesions. For two patients, clinical and biochemical follow-up was used as a gold standard. A total of 40 lesions were resected in the 33 patients who underwent surgery. A further two lesions were localized in two patients with clinical and biochemical follow-up as the gold standard. Of these 42 lesions, 41 were detected in preoperative imaging and 1 lesion was noted intraoperatively and resected. 41/42 lesions were detected by 18F-FCH PET/CT (detection rate: 97.6%), 33/42 by 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT (detection rate: 78.5%), and 30/42 by neck ultrasonography (detection rate: 71.4%). Detection rates on 18F-FCH PET/CT were superior to both 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT and neck ultrasonography in preoperative localization of parathyroid lesions in patients with primary hyperparathyroidism.

Thyrotropin Secreting Pituitary Adenoma: A Clinical Case of Postoperative Re-Onset Thyrotoxicosis with Adenoma Recurrence.

Thyrotropin-secreting pituitary adenomas are rare benign tumours. Proper diagnosis can be challenging, requiring TSH autonomous production and differentiation from resistance to thyroid hormone action (RTH).Undetectable TSH levels one week after surgery and/or positive T3 suppression test or no response to TRH stimulation test seem to be the criteria with the best prognostic value post-treatment.Close clinical, biochemical and imaging follow-up is crucial to detect TSHoma recurrence.

Clinical significance of atypical 68Ga-DOTATOC prostatic uptake on PET/CT: A ten-year review.

Gallium-68-DOTA-D-Phe1-Try3-Octreotide (68Ga-DOTATOC) is a radiolabeled somatostatin receptor (SSTR) analog that is widely used in the imaging of neuroendocrine tumors (NET). Benign and malignant prostate tumors have been observed to express SSTR. Diffuse symmetric DOTATOC uptake in the prostate is a normal positron emission tomography (PET) finding. The aim of this study was to evaluate the frequency and clinical significance of incidental atypical prostatic uptake in men undergoing 68Ga-DOTATOC PET/computed tomography(CT). A retrospective review of consecutive male patients who underwent 68Ga-DOTATOC PET/CT studies at Aalborg University Hospital, Denmark, from November 2010 to April 2020 was performed. Positron emission tomography/CT reports were searched for text words or phrases indicating incidental atypical prostatic uptake. In the resulting cohort, PET/CT were re-evaluated, and DOTATOC uptake in the prostate gland was categorized as focal, diffuse or mixed. The intensity of the uptake was visually graded using the Krenning visual score. Follow-up was based on all available clinical, biochemical, imaging, and pathology follow-up. A total of 178 male patients underwent 193 68Ga-DOTATOC PET/CT scans. Incidental atypical uptake of 68Ga-DOTATOC on PET/CT in the prostatic bed was observed in eight patients (4.5%) (mean age 67 years, range 58-85 years). Six patients (75%) had diffuse uptake; two (25%) patients had focal uptake. Four patients out of eight with incidental findings (50%) had uptake less than or equal to that of the liver (Krenning score 2); four patients (50%) had uptake greater than that of the liver (score 3). All patients had measurements of serum prostate-specific antigen and were referred for urological evaluation. Five patients (62%) underwent a transrectal ultrasound, and three required a biopsy of the prostate. No cases of prostate malignancy (including prostatic cancer) were diagnosed. During a 10-year period, we found that 4.5% of men exhibited prostate incidentalomas on 68Ga-DOTATOC PET/CT. No malignancy was found in the prostate in this population. Our data indicate absent malignancy among incidental 68Ga-DOTATOC findings in the prostate.

Successful Laparoscopic Surgical Removal of a Caesarean Scar Pregnancy (CSP) Using Temporary Uterine Artery Ligation

To demonstrate a laparoscopic technique to remove a scar pregnancy. Stepwise demonstration of the surgical technique. Santa Croce and Carle Hospital, Cuneo. Patient B.B. is a woman referred to our center for a suspected cesarean scar pregnancy (CSP) at 9 weeks gestation. CSP occurs approximately in 6% of all ectopic pregnancies. The estimated incidence is reported to be 1:1800 to 1:2500 in cesarean deliveries. Depending on its location, CSP can be categorized as either type 1, if the growth is in the uterine cavity, or type 2, if it expands toward the bladder and the abdominal cavity. If inadequately managed, it can lead to severe complications; most of them are hemorrhagic and can threaten the woman's life. There are several therapeutic approaches: local excision seems to be the most effective choice in type 2 CSP. In expert hands, the laparoscopic approach is perhaps the best surgical choice as tissue dissection, electrosurgical hemostasis, and vascular control can be effectively managed with minimal invasive access. Because severe intraoperative bleeding can occur, retroperitoneal vascular control is mandatory in this surgery. In type 1 CSP curettage, aspiration or hysteroscopic approach can be considered if the CSP is of small dimensions. A hysteroscopic approach can also be helpful in type 2 CSP during the laparoscopic removal, as intrauterine guidance. A potassium chloride local injection can be considered in a preoperative stage in the presence of a fetal heart rate. The systemic administration of methotrexate is usually ineffective as single agent, but it can be useful if administered as adjuvant therapy. Uterine artery embolization can be useful in an emergency setting to manage severe bleeding, but it can lead to complications in subsequent pregnancies and, more rarely, to premature ovarian failure. Considering poor bleeding at presentation, feasible dimensions, and the woman's desire for future pregnancy, ultrasound-guided aspiration and curettage was attempted. Because endouterine removal was incomplete, methotrexate injection was proposed as adjuvant therapy, but the administration was postponed as the patient tested positive for coronavirus disease 2019. A month later, beta-human chorionic gonadotropin level dropped from over 16 000 to 271 mU/mL, so an ultrasound and biochemical follow-up was performed. A month later, despite a low beta-human chorionic gonadotropin value, an increase in dimensions was observed at ultrasound, so surgical laparoscopic removal was offered. In this video article, laparoscopic removal of scar pregnancy is discussed in the following surgical steps: (1) Temporary closure of uterine arteries at the origin, using removable clips. (2) Retroperitoneal dissection to safely manage the scar pregnancy. (3) Dissection of the myometrial-pregnancy interface. (4) Double layer suture on the anterior uterine wall. Laparoscopic surgical management is a very effective surgical approach to remove CSP. Knowledge of retroperitoneal dissection and vascular control is necessary to carry out this surgical intervention safely and effectively.

Screening for thyroid dysfunction with free T4 instead of thyroid stimulating hormone (TSH) improves efficiency in older adults in primary care.

Subclinical hypothyroidism (SCHT) is defined as a consistently elevated thyroid stimulating hormone (TSH) with a free T4 (fT4) within the reference range. This diagnosis may lead to additional monitoring, levothyroxine therapy and increased patient concerns, despite lack of evidence of treatment benefit in older adults. In order to avoid this diagnosis, we evaluated the efficiency of fT4-based screening for thyroid dysfunction, in older adults in primary care and compared it with TSH-based screening.Individuals aged >65years in primary care were selected for this retrospective study when both TSH and fT4 were individually requested irrespective of the TSH value. Exclusion criteria were C-reactive protein > 10 mg/l or a history of thyroid hormone monitoring in the previous year.Screening based on fT4 instead of TSH decreased reflex testing from 23.8% to 11.2%. The positive predictive value (PPV) for clinical hypothyroidism increased from 17.3% to 52.2%. The negative predictive value was 96.1% with TSH-based screening versus 97.8% with fT4-based screening. Elevation of the TSH cutoff value from 4.2 to 6.5 mU/l resulted in a reflex test percentage of 12.5% and a PPV of 31.0%.Our results suggest that screening for thyroid dysfunction in older individuals in primary care can be improved by screening based on fT4 instead of TSH or by adjusting the TSH cutoff value. Adjustment of the screening strategy may be of interest to health policy makers because of potential cost reduction. From a patient perspective, medical concerns and unnecessary biochemical follow-up might be reduced by circumventing the diagnosis SCHT.

Complete remission of recurrent multiple insulin-producing neuroendocrine tumors of the pancreas with somatostatin analogs: a case report and literature review

Hyperinsulinemic hypoglycemia is most commonly caused by a single, sporadic insulinoma. Multicentric insulinoma disease (insulinomatosis) as well as metachronous neuroendocrine tumors of the pancreas, known also as neuroendocrine adenomatosis, represent a very rare condition, if not associated with multiple endocrine neoplasia type 1 syndrome (MEN1) or Von Hippel Lindau disease. We report a 9-year follow-up of a 41-year-old woman, initially presenting with hypoglycemic syndrome caused by two insulin-producing tumors, who underwent subtotal pancreasectomy in 2012, with histology compatible with multiple small neuroendocrine tumors. An approximately 1-cm insulin-producing tumor recurred at subsequent biochemical and radiological follow-up, and was cured with the somatostatin analog octreotide as a single treatment, until remission of symptoms and complete regression of the pancreatic lesion achieved after only 16 months of treatment. The possible mechanisms for these findings are discussed and the literature is briefly reviewed.

18F]FDG PET/MRI in the follow-up of hepatocellular carcinoma after liver transplantation.

There is limited evidence regarding the application of [18F] fluorodeoxyglucose (FDG)-PET/MRI in patients with a suspected clinical recurrence, who underwent liver transplantation for hepatocellular carcinoma (HCC). Therefore, we compared the accuracy of PET/MR and standard-of-care (SOC) imaging in these patients. We retrospectively reviewed 26 patients, whose liver were transplanted for HCC and were suspected of disease relapse based on biochemical analysis or SOC follow-up imaging, and carried out PET/MRI with diffusion-weighted imaging sequences on them. All patients underwent SOC imaging within the 2 months prior to the PET/MRI examination and had follow-up data for at least 12 months after. Reference standards were histopathology, clinical and imaging follow-up data. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for PET/MRI were 100, 94, 91, 100 and 96%, whereas for SOC imaging were 80, 69, 61, 85 and 73%. The accuracy of PET/MRI was higher with respect to SOC imaging, although not significantly. PET/MRI is useful for oncological surveillance of patients who have undergone liver transplantation for HCC, particularly in cases of allergy to contrast media, renal failure or persistently elevated alpha-fetoprotein levels, and with no identification of metastatic/relapsing foci at standard-of-care imaging.

ASO Visual Abstract: Tailored Management with Highly Selective Diversion for Low Colorectal Anastomosis—Biochemical Postoperative Follow-Up and Long-Term Results from a Single-Institution Cohort

ASO Visual Abstract: Tailored Management with Highly Selective Diversion for Low Colorectal Anastomosis—Biochemical Postoperative Follow-Up and Long-Term Results from a Single-Institution Cohort

Tailored Management with Highly-Selective Diversion for Low Colorectal Anastomosis: Biochemical Postoperative Follow-Up and Long-Term Results from a Single-Institution Cohort.

Defunctioning stoma (DS) can decrease the rate of symptomatic anastomotic leakage (AL). Since 2010, we have used tailored, highly selective DS management for low colorectal anastomosis (LCRA). In total, 433 rectal cancer patients underwent the same standardized procedure. Non-stoma (NS) management was used in patients with no surgical difficulties as well as good colonic preparation and quality of anastomoses. In all other cases, DS was used. C-reactive protein was measured during postoperative follow-up. Imbalance in the initial population was adjusted using propensity-score matching according to sex, age, body mass index, tumor location, and American Society of Anesthesiologists score. Rate of AL within 30 days, 5-year overall survival, local relapse-free survival, and disease-free survival were recorded. Anastomosis was mostly ultra-low and was performed equally by laparoscopy or robotic surgery. The overall rate of AL was 13.4%, with no significant differences between groups (DS, 12.2%; NS, 14.6%; p=0.575). Operative time, blood loss, and hospital stay were significantly lower for NS patients. The rate of secondary stoma was 11.4% overall. Pathological results were similar, with a 98% R0 resection rate. With a median follow-up of 5.5 years for the NS and DS groups, the overall survival was 84.9% and 73.4%, respectively (p=0.064), disease-free survival was 67.0% and 55.8%, respectively (p=0.095), and local relapse-free survival was 95.2% and 88.7%, respectively (p=0.084). The long-term, stoma-free rate was 89.1% overall. Tailoring DS for LCRA seems safe and could provide potential benefits in postoperative morbidity with the same long-term oncological results in NS patients. Prospective, multicentric studies should validate this approach.

Clinical and Biochemical Profile of Children on Follow-up with Autoimmune Thyroiditis

Introduction: Hashimotos Thyroiditis (HT) is the most common autoimmune thyroid disease and the most common cause of acquired hypothyroidism in children. Understanding the clinical profile in children with Autoimmune Thyroiditis (AIT) helps in follow-up and appropriate management of the condition. Aim: To assess the clinical, biochemical profile and the course of disease in children with AIT. Materials and Methods: This was a hospital-based longitudinal study done at a Paediatric endocrinology clinic, from January 2018 to June 2019, at southern India on all children with autoimmune thyroiditis on follow-up for at least three years, aged up to18 years, attending the clinic. Clinical examination for thyroid swelling, anthropometry of the child, Tanner staging for pubertal status, Thyroid Stimulating Hormone (TSH), and free Thyroxine (T4) were done at enrollment and also at followup after one year. Results: A total of 33 children were enrolled into the study. Of this, girls constituted 85%, with a female to male ratio of 5.6:1. Mean age at diagnosis was 9.76±1.69 years; 25 (75.7%) were hypothyroid and 8 (24.2%) were euthyroid at presentation; 21 (64%) had a positive family history of thyroid illness. The most common presentation was goitre (88%), 32 (96.9%) of them had positive thyroid antibodies either Antithyroid Peroxidase (TPO) or anti thyroglobulin (Tg) antibody. Of the 32 children with positive antibodies, 26 (78.7%) had raised anti TPO and 17 (51%) had positive anti Tg; 12 (36.3%) were positive for both anti TPO and anti Tg; 29 patients(78.7%) required treatment with thyroxine. All were noted to be pubertal but with no significant growth impairment. On follow-up after 1 year, the percentage of hypothyroid patients increased from 75.7% to 97%, and 1(3%) became hyperthyroid. None of them had other autoimmune disorders during follow-up. Conclusion: Children with AIT were mostly females and the majority had goitre. The prevalence of goitre was 88% and the majority were hypothyroid at presentation. A majority of children with autoimmune thyroiditis had a positive family history of thyroid disease. On follow-up after at 1 year, all the euthyroid patients had become hypothyroid. The thyroid status of children with autoimmune thyroiditis can change over time and needs regular clinical and biochemical follow-up.

Update on Pediatric Hemodialysis Adequacy.

The use of high reflux dialyzers to achieve a Kt/Vurea above 1.2 did not improve patient survival in most literature reports. After an electronic search in many sites, guidelines, systematic reviews, and review articles (cited references): We recommend (1) using the equilibrated double-pool, weekly rather than per session, Kt/Vurea, (2) Use of UF-dry weight to avoid V changes, (3) consider protein catabolic Rate (4) Use of double pool to avoid urea generation rebound effect. Beyond the urea model, other recommended parameters include the middle molecule clearance and patient clinical data as blood pressure control, normal ventricular morphology, and function, absence of anemia, bone mineral disease, vascular calcifications, good nutrition and growth, long-lasting vascular access, less intra-dialysis hypotension, fewer hospitalizations related to complications as infection, long-term patient survival with better life quality. All mentioned parameters are the good markers for adequate dialysis. Since (1) frequent short and (or) slow long dialysis sessions show better solute clearance and hemodynamic stability associated with better control of cardiovascular and bone disease, anemia, nutrition, and growth with better quality of life and survival. (2) The spare in the cost of the antihypertensive medications, erythroid-stimulating drugs, phosphate binders, and frequent hospitalization, compensates for the high dialysis cost. (3) The use of some advisable techniques can minimize access trauma; therefore, HD Model can be changeable according to each patient's clinical and biochemical follow-up dialysis adequacy progress pattern.