Management of patients with extensive locally advanced thyroid cancer: results of multimodal treatments.

PURPOSE: Surgery plays a key role in the treatment of thyroid cancer (TC) patients. Locally advanced cases, however, can require an extensive surgical approach with technical issues and a high risk of complications. In these cases, a multidisciplinary evaluation should be carried out to evaluate pros and cons. The aim of this study was to share our experience, as a multidisciplinary team, in the management of patients with locally advanced TC with a particularly extensive local disease, whose surgical approach could be challenging and part of a multimodal treatment. METHODS: We retrospectively evaluated clinical, surgical, and oncologic features of all patients with locally advanced TC who had undergone multidisciplinary surgery from January 2019 to June 2020. RESULTS: Six patients (two cases each of poorly differentiated, papillary, and medullary TC) were included. Four out of six were suffering from symptoms related to the advanced disease. At pre-surgical evaluation, a multidisciplinary team proposed extended surgery with radical intent via cervicotomy and sternotomy, considering other therapies not feasible or probably ineffective without it. No one passed away in intra- or perioperative time. At the end of follow-up (median 2.6 years), all patients presented a remission of symptoms due to the advanced disease, four patients were submitted to adjuvant therapies and only one patient died for a cause unrelated to the disease. CONCLUSION: This series of very advanced TCs shows the effectiveness of a surgery performed by a multidisciplinary team in controlling symptoms, allowing adjuvant therapies, and improving the survival of patients whose cases would otherwise be very difficult to manage.

Corrigendum to "Going for a stroll on lurasidone: Considerations on an atypical case of acute compartment syndrome of both legs" [Heliyon 9(4) (April 2023) e15047].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15047.].

Going for a stroll on lurasidone: Considerations on an atypical case of acute compartment syndrome of both legs.

Non-traumatic acute bilateral compartment syndrome is a rare condition that may lead to limb ischemia. We describe a case of this syndrome occurring after a five-kilometer walk in a young woman receiving chronic treatment with lurasidone, leading to a bilateral foot-drop and rhabdomyolysis of the anterolateral compartment of both legs. Due to her late presentation in the emergency department, we opted for a conservative approach, closely monitoring her renal function. We noticed a subsequent clinical and biochemical improvement over the following days, with the patient returning to her daily routine in a matter of weeks, despite a persisting bilateral foot drop. Since atypical antipsychotics are known to be associated with rhabdomyolysis, while possibly exerting a toxic effect on mitochondria, we hypothesize that a mild aerobic physical exertion might have triggered the event, in the context of an iatrogenic muscle susceptibility to oxidative distress.

Lenvatinib as a salvage therapy for advanced metastatic medullary thyroid cancer.

PURPOSE: Patients with advanced progressive metastatic medullary thyroid cancer (MTC), show poor prognosis and few available systemic therapeutic options. After the loss of clinical benefit with other tyrosine kinase inhibitors (TKI), we evaluated the use of lenvatinib as salvage therapy. METHODS: Ten patients who experienced the loss of clinical benefit after treatment with at least one previous TKI, were treated with lenvatinib. We assessed patient's response immediately before, at the first (first-EV) and last (last-EV) evaluation, after the beginning of treatment. RESULTS: At first-EV, one patient died, while all the remaining 9 showed a stable disease (SD) in the target lesions. At last-EV, SD was still observed in seven patients, while partial response (PR) and progressive disease (PD), in one patient each. Conversely, analyzing all target and non-target lesions, at first-EV, we observed PR in one patient and SD in eight patients. At last-EV, PR was shown in two patients and SD was shown in seven. Bone metastases showed stable disease control at both first-EV and last-EV in only approximately 60% of cases. Tumor markers (CTN and CEA) decreased at first-EV, while they increased at last-EV. Seven patients experienced at least one dose reduction during treatment with lenvatinib. CONCLUSIONS: In this real-life clinical experience, lenvatinib showed interesting results as salvage therapy in patients with advanced progressive metastatic MTC patients. Its usefulness could be effective in patients without any other available treatment, because previously used or unsuitable, especially with negative RET status with no access to the new highly selective targeted therapies.

No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease.

Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts (group B, n = 27). Median age at diagnosis was 13 years, and 15 years (range 3-49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p < 0.02).

The identification of pathogens associated with periprosthetic joint infection in two-stage revision.

OBJECTIVE: Identification of periprosthetic joint infection (PJI)-related pathogens is crucial to decide what is the correct surgical strategies and the most secure timing to re-implant in case of two-stage revision. The purpose of the present study is to review the literature to identify the features of each exams which are used to identify the pathogens associated with PJI, to evaluate which are the most sensitive and specific and to set up an algorithm to decide when, in the field of two-stage revision, it's the ideal timing to re-implant. MATERIALS AND METHODS: We did a systematic review of the literature to look for peer-reviewed papers of any evidence level focusing on: (1) Microbiological and molecular exams for identification of PJI-related pathogens. (2) Nuclear imaging methods, which can help in the identification of a PJI. Special attention was focused to analyse which is the sensitivity and specificity of these exams. RESULTS: Overall, 64 manuscripts met the criteria of the systematic search at point 1 and 7 manuscripts at point 2. Among microbiological and molecular exams, the average of sensitivity and specificity were respectively 65.6% and 94.4% for cultural exams, 74.1% and 95.2% for molecular diagnosis and 86.9% and 96% for MicroDTTect. Among nuclear imaging methods, the average of sensitivity and specificity were respectively 94% and 69 % for three-phase bone scintigraphy and 100% and 62.5% for [18F] Fluoro-2-deoxyglucose-positron emission tomography/computed tomography. CONCLUSIONS: In two-stage revision after PJI, taking into account the sensitivity and specificity values, just a few microbiological and molecular exams and nuclear imaging methods should be considered in the decision process to re-implant the components.

The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

OBJECTIVE: To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a relationship with HbA1c and episodes of hypoglycemia. METHODS: Multicentric, observational, cross-sectional study in Italy. Adult DM1 (n = 476) and DM2 (n = 541) outpatients, with eGFR >30 mL/min/1.73 m2, on a basal-bolus regimen for at least six months, were recruited from 31 Italian Diabetes services between March and September 2016. Clinicaltrials.govID: NCT03489031. RESULTS: Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9 U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (p = 0.0011). The b/T was significantly higher in the patients taking metformin in both groups, and significantly different according to the type of basal insulin (Degludec, 0.48 in DM1 and 0.44 in DM2; Glargine, 0.44 in DM1 and 0.43 in DM2; Detemir, 0.45 in DM1 and 0.39 in DM2). The b/T ratio was not correlated in either group to HbA1c or incidence of hypoglycemia (<40 mg/dL, or requiring caregiver intervention, in the last three months). In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1. CONCLUSION: The b/T ratio was independent of glycemic control and incidence of hypoglycemia.

Correction to: The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

[This corrects the article DOI: 10.1007/s40200-018-0358-2.].

Gut microbiota and hematopoietic stem cell transplantation: where do we stand?

Advances in biological techniques have potentiated great progresses in understanding the interaction between human beings and the ∼10 to 100 trillion microbes living in their gastrointestinal tract: gut microbiota (GM). In this review, we describe recent emerging data on the role of GM in hematopoietic stem cell transplantation, with a focus on immunomodulatory properties in the immune system recovery and the impact in the development of the main complications, as GvHD and infections.

Two cases of colon LST in transplanted liver patients.

Long-life immunosuppressive therapy increases the risk of de novo tumors in liver transplant recipients by decreasing the immune surveillance against malignant cells and oncogenic viruses. However, no cases of colon precancerous lesions have been reported in these subjects. Patient n. 1, a 73 yrs old male treated with calcineurin and purine synthesis inhibitors, showed at a per-protocol colono-scopy a 3 cm laterally spreading tumor (LST). Patient n. 2, a 73 yrs old male treated with calcineurin inhibitors, showed at a screening colonoscopy an LST occupying one third of the lumen circumference. Both subjects were asymptomatic, had been transplanted 14 years before, and in both cases, lesions showed severe dysplasia. LSTs represent 17.2% of advanced colorectal neoplasia (CRC) and risk factors are multifactorial. Immunosuppression may play a role which is however not completely understood. Based on this report, surveillance colonoscopy in liver transplanted patients should be considered.

The influence of interoceptive awareness on functional connectivity in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity likely related to altered processing of sensory stimuli along the brain-gut axis. Previous neuroimaging studies demonstrated structural and functional alteration of several brain areas involved in bodily representation, e.g. the insula, in patients with IBS. By means of resting-state functional magnetic resonance imaging (rs-fMRI) we searched for alteration of functional connectivity within the network involved in self-bodily consciousness. We found significant inverse correlation between hypochondriasis assessed through a clinical questionnaire and connectivity between posterior cingulate cortex and left supramarginal gyrus, extending into the adjacent superior temporal gyrus. Moreover, we observed a significant and positive correlation between a clinical questionnaire assessing interoception and connectivity between left anterior ventral insula and two clusters located in supramarginal gyrus bilaterally.Our findings highlight an "abnormal network synchrony" reflecting functional alteration, in the absence of structural and micro-structural changes, which might represent a possible therapeutic target for Irritable Bowel Syndrome.

Continuous intra jejunal infusion of levodopa-carbidopa intestinal gel by jejunal extension tube placement through percutaneous endoscopic gastrostomy for patients with advanced Parkinson's disease: a preliminary study.

OBJECTIVE: Levodopa is the gold standard in the pharmacological treatment of Parkinson's disease (PD) and its oral administration is associated with the development of disabling motor and non-motor complications in advanced disease. Levodopa is rapidly metabolized and has a short plasma half-life thus requiring frequent, repeated dosing. Impaired gastric emptying is common in PD, and likely contributes to the unpredictable motor responses observed with orally-dosed levodopa. A new therapeutic protocol for patients with advanced PD include a carbidopa/levodopa combination using continuous, modulated enteral administration achieved inserting a Jejunal Extension Tube Placement through Percutaneous Endoscopic Gastrostomy (PEG-J). The aim of this work is to assess efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) delivered continuously through an intrajejunal percutaneous tube (PEG-J). PATIENTS AND METHODS: We enrolled 11 adults with advanced PD and preserved sensitivity to L-dopa. For pre-procedural endoscopic evaluation each patient underwent a diagnostic esophagogastroduodenoscopy (EGD) 7 days before PEG-J placement to evaluate the presence of gastric anatomical or wall anomalies and the presence of oesophageal or gastric varices. Treatment with LCIG, consisting of a water-based suspension containing micronized levodopa (20 mg/mL) and carbidopa (5 mg/mL) in methylcellulose (Duodopa®), was administered by continuous jejunal infusion for 12h/day using a portable pump (CADD-Legacy) by PEG-J. Clinical evaluations were performed at baseline (T0) before LCIG initiation, and after 3 (T3) and 6 (T6) months of therapy. The efficacy and safety outcomes were assessed by using the Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III and IV. RESULTS: Mean age of patients was 71.18 ± 5.4 SD at LCIG initiation. Out of the 11 patients, 2 (18%) dropped-out LCIG at T3. Patients showed statistically significant (p < 0.05) higher performances in activities of daily living and a statistically significant (p < 0.001) lower incidence and severity of motor fluctuations, as rating by UPDRS part IV, compared to their best oral therapy. During observational period, 5 patients experienced adverse events. Success rate for PEG-J placement was 100%. CONCLUSIONS: Our work shows that continuous intrajejunal infusion of LCIG ensures a reduction in motor Fluctuations compared to oral administration of levodopa-carbidopa in advanced PD. Based on our results and on the evidence emerging in the literature, this therapeutic approach should be the gold standard for therapy in these patients.

Language outcomes at 36 months in prematurely born children is associated with the quality of developmental care in NICUs.

OBJECTIVE: The aim of this study was to examine the relationship between the quality levels of NICU developmental care (DC) and language skills at 36 months in very preterm (VPT) children. STUDY DESIGN: Language skills of 78 VPT children from 19 NICUs and 90 full-term controls was assessed using a standardized language test. We compared children' language task performance by splitting NICUs into units with high- and low-quality of DC according to two main factors: (1) infant centered care (ICC), and (2) infant pain management (IPM). RESULTS: VPT children from low-care units with respect to ICC obtained lower scores in sentence comprehension, compared to children from high-care units. No differences were found between preterm children from high-quality ICC NICUs and full-term children. CONCLUSIONS: Findings suggest that higher quality of DC related to infant centered care can mitigate delays in language skills at 36 months in children born VPT.

Neonatal developmental care in infant pain management and internalizing behaviours at 18 months in prematurely born children.

BACKGROUND: Very preterm infants are exposed to adverse stressful experiences, which may result in long-term behavioural outcomes. The developmental care practices, including pain management and environmental support, can minimize the effects of stress exposure. However, developmental care quality levels may vary among Neonatal Intensive Care Units (NICUs) and little is known about how differences in developmental care quality affect long-term behavioural outcomes. The aim of this study was to examine the relation between quality levels NICUs developmental care and behaviour problems at 18 months corrected age in preterm children. METHODS: The behaviour of 134 preterm children from 22 NICUs and 123 full-term controls was examined using the questionnaire Child Behaviour Checklist 1½-5. We compared the behavioural profile of children by splitting NICUs into units with high- and low quality of developmental care according to two main care factors: (1) infant centered care (ICC) index, and (2) infant pain management (IPM) index. RESULTS: Preterm children from low-care units in IPM group reported higher scores in Internalizing Problems, compared to children from high-care units. No differences were found between preterm children from high-care in IPM and full-term children. No significant IPM effect was found for externalizing problems. No significant ICC effect emerged both for internalizing and externalizing problems. CONCLUSIONS: Findings suggest that higher quality of developmental care related to infant pain management can mitigate behavioural problems at 18 months in children born preterm, to such an extent that preterm children exhibit a behavioural profile similar to that displayed by full-term children.

Prospective Epstein-Barr virus-related post-transplant lymphoproliferative disorder prevention program in pediatric allogeneic hematopoietic stem cell transplant: virological monitoring and first-line treatment.

BACKGROUND: In 28 pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, we aimed to evaluate: (i) the impact of routine Epstein-Barr virus (EBV) DNA monitoring on the development of EBV-related post-transplant lymphoproliferative disorder (EBV-PTLD); (ii) the incidence of EBV infection and the potential risk factors; and (iii) the suitability of whole blood (WB) as clinical specimen to monitor the risk of patients to develop EBV-PTLD. METHODS: Quantitative real-time polymerase chain reaction assay was performed on WB samples for all patients. EBV DNA quantification also in peripheral blood mononuclear cells (PBMCs) samples was adopted for the patients at higher risk of developing EBV-PTLD (≥ 10,000 copies/mL WB). RESULTS: High EBV DNAemia levels were observed in 37.5% of the actively infected recipients (57.1%). Severe aplastic anemia, matched-unrelated donor transplant, the reduced-intensity conditioning regimen and, to a lesser extent, the in vivo T-cell depletion with anti-thymocyte immunoglobulin were associated with high viral load. A significant correlation between EBV DNA levels in WB and PBMC samples was obtained (r = 0.755, P < 0.001). A similar kinetics of EBV DNA in the 2 blood compartments was observed. Clinically, both specimen types appeared to be equally informative to assess the risk of patients to develop PTLD. On the basis of EBV DNAemia levels, in 3 patients (10.7%) immunosuppressive therapy was reduced and 1 patient (3.5%) received early treatment for probable EBV disease. No patients developed EBV-PTLD. CONCLUSION: WB proved to be a suitable clinical specimen to monitor EBV DNA load after allo-HSCT for the management of EBV infection and PTLD prevention.