Surgical treatment of tertiary hyperparathyroidism: does one fit for all?

BackgroundTertiary hyperparathyroidism (3HPT) is defined as a condition of excessive autonomous excretion of intact parathyroid hormone (iPTH) with persistent hypercalcemia (>10.5 mg/dL) that lasts for more than 12 months after a successful kidney transplantation, in the context of a long course secondary hyperparathyroidism (2HPT). The chronic high levels of iPTH cause a worsening of graft function, accompanied by systemic symptoms of hypercalcemia. The only curative therapy is parathyroidectomy (PTX). It remains unclear whether total parathyroidectomy with autotransplantation (TPTX-AT) or subtotal parathyroidectomy (SPTX) lead to better outcomes.AimsThe aim of this retrospective, single-institution cohort study is to evaluate the rate of persistent or recurrent disease and postoperative calcium/iPTH disturbances in patients treated with TPTX-AT or SPTX for 3HPT.MethodsA single-center retrospective analysis of 3HPT patients submitted to TPTX-AT or SPTX between 2007–2020 with at least 24 months follow-up was conducted. The outcome parameters included persistence/recurrence of disease, incidence of transitory hypocalcemia, and temporary/permanent hypoparathyroidism.ResultsA cohort of 52 patients was analyzed and divided in two groups: 38 (73%) were submitted for TPTX-AT, and 14 patients (27%) were submitted for SPTX. The TPTX-AT population showed lower plasmatic calcium concentrations compared with the SPTX group during the entire follow-up period (p<0.001). There were eight cases (21%) of transitory hypocalcemia in the TPTX-AT group and none in the SPTX group, with p=0.065. Two cases (5%) of temporary hypoparathyroidism occurred in the TPTX-AT group and none in the SPTX group, with p= 0.530. There were no cases of permanent hypoparathyroidism and no cases of persistent disease. No statistical difference was assessed for the recurrence of 3HPT between the TPTX-AT group and the SPTX group (N=1, 3% vs N=1, 7%) (p=0.470).ConclusionNo significative difference was registered between the TPTX-AT and SPTX groups in terms of persistence/recurrence of disease, incidence of transitory hypocalcemia, and temporary/permanent hypoparathyroidism. Mean calcium levels iPTH values were statistically lower among the TPTX-AT group compared with the SPTX group while remaining always in the range of normality

High Growth Rate of Benign Thyroid Nodules Bearing RET/PTC Rearrangements

Context: Benign thyroid nodules display a broad range of behaviors from a stationary size to a progressive growth. The RET/PTC oncogene has been documented in a fraction of benign thyroid nodules, besides papillary thyroid carcinomas, and it might therefore influence their growth. Objective: The aim of the present work was to evaluate whether RET/PTC in benign thyroid nodules associates with a different nodular growth rate. Study Design: In this prospective multicentric study, 125 subjects with benign nodules were included. RET rearrangements were analyzed in cytology samples; clinical and ultrasonographic nodule characteristics were assessed at the start and at the end of the study. Results: RET/PTC was present in 19 nodules. The difference between the mean baseline nodular volume of the RET/PTC− and RET/PTC+ nodules was not significant. After 36 months of follow-up, the RET/PTC+ group (n = 16) reached a volume higher than the RET/PTC− group (n = 90) (5.04 ± 2.67 vs. 3.04 ± 2.26 ml; P = 0.0028). We calculated the monthly change of nodule volumes as a percentage of baseline. After a mean follow-up of 36.6 months, the monthly volume increase of nodules bearing a RET rearrangement was 4.3-fold that of nodules with wild-type RET (1.83 ± 1.2 vs. 0.43 ± 1.0% of baseline volume; P < 0.0001). Conclusions: Benign thyroid nodules bearing RET rearrangements grow more rapidly than those with wild-type RET. Searching for RET rearrangements in benign thyroid nodules might be useful to the clinician in choosing the more appropriate and timely therapeutic option

Methicillin-resistant Staphylococcus aureus nasal colonization in a department of pediatrics: a cross-sectional study

BACKGROUND: We describe methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage at admission in patients admitted to a Department of Pediatrics. METHODS: All patients received a nasal swab at admission. A questionnaire was administered and molecular genetics analyses were performed on all identified MRSA isolates. RESULTS: We enrolled 785 patients, affected with both acute and chronic diseases. MRSA nasal colonization prevalence was 1.15% (CI: 0.5607%-2.093%). Methicillin-sensitive Staphylococcus aureus (MSSA) nasal colonization prevalence at admission was 19.75% (CI 17.07%-22.64%). Only one MRSA isolate carried the SCCmec V variant; all other isolates carried the SCCmecIV variant. Five out of 9 MRSA-colonized patients had an underlying condition. Antibiotic therapy in the previous 6 months was a protective factor for both MRSA (OR 0,66; 95% CI: 0,46-0,96) and MSSA (OR 0,65; 95% CI: 0,45-0,97) colonization. A tendency to statistical significance was seen in the association between hospitalization in the 6 months prior to admission and MRSA colonization at admission (OR 4,92; 95% CI: 0,97-24,83). No patient was diagnosed with an S. aureus infection during hospitalization. CONCLUSIONS: The majority of our MRSA colonizing isolates have community origins. Nevertheless, most MRSA-colonized patients had been hospitalized previously, suggesting that strains that circulate in the community also circulate in hospital settings. Further studies should elucidate the role of children with frequent contact with health care institutions in the circulation of antibiotic resistant strains between the hospital and the community

Growing thyroid nodules with benign histology and RET rearrangement.

Abstract. Some benign thyroid nodules are stationary in size over time while others grow progressively, indicating that there is a broad individual variability within benign nodules. To date, it is very difficult to predict if a benign thyroid nodule will grow in size and which will be its trend over time. While BRAFV600E is a highly specific marker of thyroid cancer, RET rearrangements have been disclosed also in non malignant thyroid lesions and their biological significance is debated. We compared the clinical history of three histologically benign thyroid nodules harboring RET rearrangements with that of 6 benign nodules bearing wild type RET. The nodules negative for RET rearrangements were followed for 10 years by ultrasonographic evaluation, showing a slow, constant enlargement. Three patients with benign nodules diagnosed at FNAC, were followed for 11, 9 and 7 years by annual ultrasonographic evaluation. After several years of latency, the nodules had an unexpected and gradual increase in their dimensions, reaching a large final size. A second FNAC confirmed the previous cytologic diagnosis of benign lesion. Because of the increasing size of the nodules, the patients were advised to surgery. Before undergoing thyroidectomy, we performed molecular diagnostic tests that revealed the absence of BRAFV600E and the presence of RET/PTC-1 in one nodule and RET/PTC-3 in the two others. Despite the presence of this oncogene, the samples were histologically classified as benign hyperplastic nodules. These findings lead us to speculate that histologically benign hyperplastic thyroid nodules containing RET rearrangements might represent a subgroup of nodules with a rapid size increase

Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer

Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC

Chemopreventive effect of a milk whey by-product derived from Buffalo (Bubalus bubalis) in protecting from colorectal carcinogenesis

Abstract Background Several studies show that natural foods are a source of compounds with anticancer properties that affect the gut microbiota and its metabolites. In the present study, we investigate the effect of a delactosed buffalo milk whey by-product (DMW) on colorectal carcinogenesis. Methods The effect of DMW on colorectal carcinoma (CRC) was investigated in the established mouse model of azoxymethane (AOM)-induced colon carcinoma, which closely resembles the human clinical condition of CRC. The effect of DMW on CRC immortalized cell lines was also evaluated to further identify the antineoplastic mechanism of action. Results Pretreatment of AOM-treated mice with DMW significantly (P < 0.05) reduced the percentage of mice bearing both aberrant crypt foci with more than four crypts (which are early precancerous lesions that progress to CRC) and tumors. In addition, DMW completely counteracted the effect of AOM on protein expression of caspase-9, cleaved caspase-3 and poly ADP-ribose polymerase in colonic tissue. Administration of DMW alone (i.e. without AOM) resulted in changes in the composition of the gut microbiota, leading to enrichment or depletion of genera associated with health and disease, respectively. DMW was also able to restore AOM-induced changes in specific genera of the gut microbiota. Specifically, DMW reduced the genera Atopobiaceae, Ruminococcus 1 and Lachnospiraceae XPB1014 and increased the genera Parabacteroides and Candidatus Saccharimonas, which were increased and reduced, respectively, by AOM. Blood levels of butyric acid and cancer diagnostic markers (5-methylcytidine and glycerophosphocholine), which were increased by AOM treatment, were reduced by DMW. Furthermore, DMW exerted cytotoxic effects on two human CRC cell lines (HCT116 and HT29) and these effects were associated with the induction of apoptotic signaling. Conclusions Our results suggest that DMW exerts chemopreventive effects and restores the gut microbiota in AOM-induced CRC, and induces cytotoxic effect on CRC cells. DMW could be an important dietary supplement to support a healthy gut microbiota and reduce the prevalence of CRC in humans. Video Abstrac

Prevalence of RET/PTC rearrangement in benign and malignant thyroid nodules and its clinical application.

Fine-needle aspiration cytology (FNAC) is the primary means to distinguish benign thyroid nodules from malignant ones. About 20% of FNAC yields indeterminate results leading to unnecessary or delayed surgery. Many studies of tissue samples, the majority of which are retrospective advocate testing for RET rearrangements as a diagnostic adjunctive tool in thyroid nodules with indeterminate cytological findings. Because of the uncertain prevalence of RET rearrangements, its utility as a tumor marker is still controversial. The goal of this study was to establish the prevalence and the utility of testing for RET rearrangements in FNAC suspicious of cancer in a clinical setting. In this prospective study, we analysed a large series of thyroid aspirates by RT-PCR only and Southern blot on RT-PCR products for type 1 and 3 RET rearrangements. Results were compared with clinical findings, cytological diagnosis and final histopathology. By the higher sensitive Southern-blot on RT-PCR method, RET rearrangements were present in 36% of papillary thyroid carcinomas (RET/PTC-1, 12%; RET/PTC-3, 20%; both, 4%) and of 13.3% of benign nodules. By means of RT-PCR only, RET rearrangements were disclosed only in 14.3% of PTC and in 3.6% of benign nodules. No significant correlation was found between RET rearrangements and clinicopathological features of patients. These results indicate that molecular testing of thyroid nodules for RET/PTC must take into account of its high prevalence in benign nodules, inducing false positive diagnoses when the highly sensitive assay Southern-blot on RT-PCR is used. Its searching by means of RT-PCR only, has a specificity superior of conventional cytology and can be used to refine inconclusive FNAC