Predicting postoperative hypocortisolism in patients with non-aldosterone-producing adrenocortical adenoma: a retrospective single-centre study.

BACKGROUND: Limited information exists on postoperative hypocortisolism and hypothalamus-pituitary-adrenal axis recovery in patients with adrenal incidentaloma following unilateral adrenalectomy. We evaluated frequency of postoperative hypocortisolism and predictors for recovery in non-aldosterone-producing adrenocortical adenoma patients after unilateral adrenalectomy. METHODS: A retrospective analysis of 32 adrenal incidentaloma patients originally included in the ITACA trial (NCT04127552) with confirmed non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy from September 2019 to April 2023 was conducted. Preoperative assessments included adrenal MRI, anthropometrics, evaluation of comorbidities, adrenal function assessed via ACTH, urinary free cortisol, and 1 mg dexamethasone suppression test. ACTH and serum cortisol or Short Synacthen test were performed within 6 days, 6 weeks, 6 months, and a year after surgery. RESULTS: Six days postoperative, 18.8% of patients had normal adrenal function. Among those with postoperative hypocortisolism, 53.8% recovered by 6 weeks. Patients with earlier adrenal recovery (6 weeks) had lower preoperative 1 mg dexamethasone suppression test (median 1 mg dexamethasone suppression test 76.2 [61.8-111.0] nmol/L vs 260.0 [113.0-288.5] nmol/L, p < 0.001). Univariate analysis showed preoperative 1 mg dexamethasone suppression test negatively related with baseline ACTH levels (r = - 0.376; p = 0.041) and negatively associated with the 6-week baseline (r = - 0.395, p = 0.034) and 30-min cortisol levels during Short Synacthen test (r = - 0.534, p = 0.023). Logistic regression analysis demonstrated preoperative 1 mg dexamethasone suppression test as the only biochemical predictor for 6-week adrenal recovery: ROC curve identified a 1 mg dexamethasone suppression test threshold of 131 nmol/L predicting 6-week recovery with 89.5% sensitivity and 72.7% specificity (AUC 0.87; 95% CI 66.9-98.7, p < 0.001). Other preoperative assessments (tumor size, ACTH levels and anthropometrics) were not associated with postoperative hypothalamus-pituitary-adrenal axis function, but the presence of diabetes was associated with a lower probability of recovery (OR = 24.55, p = 0.036). ACTH levels increased postoperatively in all patients but did not predict hypothalamus-pituitary-adrenal axis recovery. CONCLUSIONS: The preoperative 1 mg dexamethasone suppression test cortisol value and presence of diabetes are the only relevant predictor of hypothalamus-pituitary-adrenal axis recovery in patients with non-aldosterone- producing adrenocortical adenoma undergoing surgery, regardless other clinical and biochemical variables. Notably, pre- and postoperative ACTH levels did not predict hypothalamus-pituitary-adrenal axis recovery. These findings point towards the potential for saving resources by optimizing their allocation during follow-up assessments for patients with non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy.

Long-term results of arthroscopic repair of type II SLAP lesions in sports: assessment of return to pre-injury playing level and critical risk factors for complication.

PURPOSE: The management of isolated SLAP lesions is still debated especially in athletes. Aims of the study were: 1. to analyse our algorithm to treat SLAP lesions starting from the selection of patients for surgery and 2. to correlate the familiarity for diabetes and hypothyroid disorders with post-operative results. METHODS: Seventy-eight patients with isolated SLAP lesion were arthroscopically treated using knotless anchors and microfractures. All patients had a pre-operative and post-operative clinical examination according to Walch-Duplay, Constant, Rowe and Dash scores and interviewed for familiarity to diabetes and hypothyroid disorders. RESULTS: About 68.8% of patients solved pain with rehabilitation. About 29% of patients returned to the sports activities. About 32% of patients were no responder to physiotherapy and were arthroscopically treated. About 53.9% of patients responded excellent, 34.7% good, 3.8% medium and 7.6% poor results according to Walch-Duplay score. The Constant score increased from 64 to 95, the Rowe score from 48 to 96. The outcomes were significantly worse in patients with familiarity for diabetes. CONCLUSIONS: Microfractures and knotless anchor give long-term good results for the treatment of SLAP lesions in athletes. The familiarity for diabetes is an important risk factor that can lead to decreased outcomes.

Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer.

Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear. In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: (1) via cutting-edge digital spatial proteomic and transcriptomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n = 19); and (2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract. PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from mild-moderate (GOLD 1-2) COPD patients compared to severe-very severe (GOLD 3-4) COPD patients and controls. Within all the COPD patients, PD-L1 protein expression was associated with upregulation of genes involved in tumor progression and downregulation of oncosuppressive genes, and strongly directly correlated with the FEV1% predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly directly correlated with the number of functionally active AMs. In BAL, we confirmed that AMs from patients with both GOLD 1-2 COPD and NSCLC had the highest and similar, PD-L1 expression levels versus all the other groups, independently from active cigarette smoking. Intriguingly, AMs from patients with more severe COPD had reduced AM PD-L1 expression compared to patients with mild COPD. Acute CS extract stimulation increased PD-L1 mRNA expression only in never-and not in ever-smoker AMs. Lungs from patients with mild COPD and NSCLC are characterized by a similar strong PD-L1 expression signature in bronchioles and functionally active AMs compared to patients with severe COPD and controls. Active smoking does not affect PD-L1 levels. These observations represent a new resource in understanding the innate immune mechanisms underlying the link between COPD and lung cancer onset and progression and pave the way to future studies focused on the mechanisms by which CS promotes tumorigenesis and COPD.

Articulating spacers in elderly patients affected by periprosthetic knee infection: clinical findings and outcome.

OBJECTIVE: Although the two-stage technique is a validated strategy in periprosthetic joint infections, there is a lack of data on the patients' clinical outcomes after the spacer placement. This study aims at evaluating the quality of life, joint function, and pain in patients over 70 years affected by periprosthetic joint infection treated with a two-stage exchange using metal on polyethylene spacers. PATIENTS AND METHODS: We conducted a follow-up study to evaluate the quality of life and functionality of consecutive patients over 70 years treated for PJI at our institution using a validated assessment set including the Western Ontario and Mac Master University (WOMAC) score, Knee Society Score (KSS), numerical rating scale (NRS). Knee Range of Movement (ROM) before and after the surgery was also analyzed. RESULTS: Forty-five patients with a mean age of 76 ± 5.3 years were included. Coagulase-negative staphylococci were the most isolated microorganisms. In the preoperative study group, the WOMAC score was 48.4 ± 18.9, and the KSS objective and functional scores were 37.6 ± 17.3 and 27.6 ± 22.3, respectively. NRS was 7.3 ± 1.8. After three months of follow-up, we found better results than preoperative clinical evaluation. We retrieved similar results comparing our post-operative PROMS (WOMAC and KSS scores) with published thresholds for treatment success two months after primary total knee arthroplasty. The infection eradication rate was 87%. CONCLUSIONS: The two-stage technique confirmed its efficacy in the treatment of PJI. Patients over 70 years who had undergone the first stage of the two-stage technique for PJI showed a good quality of life and knee function.

Predictors of malignancy in high-risk indeterminate (TIR3B) cytopathology thyroid nodules.

PURPOSE: The classification of indeterminate cytopathology at thyroid fine-needle-aspiration (FNA) has been updated to reduce the number of unnecessary surgery; the 2014 Italian classification introduced the low-risk (TIR3A) and high-risk (TIR3B) subcategories. Aim of this study was to identify the ultrasonographic (US), clinical and cytological predictors of malignancy among TIR3B nodules from a single institution. METHODS: A prospective observational study including 1844 patients who underwent thyroid FNA from June 2014 to January 2019. Ultrasonographic, clinical and cytological features were recorded. All TIR3B diagnoses were referred to surgery. According to final histology, patients were divided into thyroid cancer (TC) or benign nodules. Chi-square test, or Fisher exact test when appropriate, were used to compare groups and logistic regression analyses were used to determine independent predictors of malignancy. RESULTS: Of 1844 FNAs, 96 (5.2%) were TIR3B. Histology report was available in 65. Among them, 25 (38.5%) were TC. Predictors of TC were nodule size < 20 mm [Odds Ratio (OR) = 5.88, 95% CI 1.91-18.11, p = 0.002], absence or weak intralesional flow [OR = 0.3, 95% CI 0.09-0.77, p = 0.015], microcalcifications [OR = 6.5, 95% CI 1.90-21.93, p = 0.003] at US; nuclear inclusions [OR = 25.3, 95% CI 1.34-476.07, p = 0.031] and chromatin clearing [OR = 3.7, 95% CI 1.27-10.99, p = 0.017] at cytopathology. Patients aged < 55 years had a significantly higher risk of TC [OR = 9.7, 95% CI 2.79-34.07, p < 0.001]. In multivariate analysis, age < 55 and nodule size < 20 mm resulted as independent risk factors. CONCLUSIONS: Patients < 55 years receiving a diagnosis TIR3B on nodules < 20 mm, with microcalcifications, showing specific nuclear atypia at cytopathology are more likely to have TC. Combining US, cytological and clinical features could help determining which patients with a TIR3B diagnosis should be referred to surgery.

Solution and gas phase evidence of anion binding through the secondary bonding interactions of a bidentate bis-antimony(iii) anion receptor.

The solution and gas phase halide binding to a bis-antimony(iii) anion receptor was studied. This new class of anion receptors utilizes the strong Sb-centered secondary bonding interactions (SBIs) that are formed opposite to the polar Sb-O primary bond. 1H NMR titration data were fitted statistically to binding models and solution-phase binding energetics were extracted, while the formation of anion-to-receptor complexes was observed using ESI-MS. Density functional theory calculations suggest that their affinity towards binding halide anions is mitigated by the strong explicit solvation effect in DMSO, which gives insights into future designs that circumvent direct solvent binding and are anticipated to yield tighter and perhaps more selectivity in anion binding.

Autophagy regulates hepatocyte identity and epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions promoting Snail degradation.

Epithelial-to-mesenchymal transition (EMT) and the reverse process mesenchymal-to-epithelial transition (MET) are events involved in development, wound healing and stem cell behaviour and contribute pathologically to cancer progression. The identification of the molecular mechanisms underlying these phenotypic conversions in hepatocytes are fundamental to design specific therapeutic strategies aimed at optimising liver repair. The role of autophagy in EMT/MET processes of hepatocytes was investigated in liver-specific autophagy-deficient mice (Alb-Cre;ATG7(fl/fl)) and using the nontumorigenic immortalised hepatocytes cell line MMH. Autophagy deficiency in vivo reduces epithelial markers' expression and increases the levels of mesenchymal markers. These alterations are associated with an increased protein level of the EMT master regulator Snail, without transcriptional induction. Interestingly, we found that autophagy degrades Snail in a p62/SQSTM1 (Sequestosome-1)-dependent manner. Moreover, accordingly to a pro-epithelial function, we observed that autophagy stimulation strongly affects EMT progression, whereas it is necessary for MET. Finally, we found that the EMT induced by TGFß affects the autophagy flux, indicating that these processes regulate each other. Overall, we found that autophagy regulates the phenotype plasticity of hepatocytes promoting their epithelial identity through the inhibition of the mesenchymal programme.

DWI findings in a iatrogenic lumbar epidermoid cyst. A case report.

Epidermoid cysts comprise less than 1% of intraspinal tumors. They can be congenital, frequently associated with other spinal malformations, or iatrogenic, resulting from the implantation of epidermal cells within the spinal canal during the execution of a variety of procedures such as spinal puncture. At MR imaging epidermoid tumors can mimic cystic lesions with fluid content such as arachnoid cysts. DWI can help obtain a correct diagnosis. We describe a case of iatrogenic lumbar epidermoid cyst with DWI findings in a young woman who had undergone epidural anesthesia for Cesarean section three years before the onset of symptoms.

Growth hormone, prolactin, and sexuality.

GH and PRL, although not considered as 'classical' sexual hormones, could play a role in the endocrine control of sexual function both in men and women. Physiologically, PRL seems to be involved in the central control of sexual behavior and activity, by modulating mainly the effects of dopaminergic and serotoninergic systems on sexual function. Indeed, circulating PRL levels increase after orgasm and may potentially play a role in the acute regulation of further sexual arousal following orgasm both in men and women. On the other hand, either short-term or long-term PRL increase can modulate central nervous system areas involved in the control of sexual function and, peripherally, can directly influence mechanisms of penile erection in men, and presently only as an hypothesis, mechanisms related to the sexual response of genitalia in women. Furthermore, chronic hyperprolactinemia is classically associated with hypogonadotropic hypogonadism and sexual dysfunction in both sexes. Successful treatment of chronic hyperprolactinemia generally restores normal sexual function both in men and women although this effect is not only related to relapse of gonadal function. Hypoprolactinemia is recently recognised as a possible risk factor of arteriogenic erectile dysfunction while a possible role on female sexual function is not known. The physiological role of GH on sexual function is not fully elucidated. GH is an important regulator of hypothalamuspituitary- gonadal axis and seems to participate in the regulation of the sexual response of genitalia in men, and potentially also in women. Sexual function in men and women with GH deficiency (GHD) and GH excess, particularly in acromegaly, is scantily studied and GH- or IGF-I-dependent effects are difficult to quantify. Nevertheless, a decrease of desire and arousability both in men and women, together with an impairment of erectile function in men, have been described both in patients with GHD and acromegaly, although it is not clear whether they are dependent directly on the hormone defect or excess or they are consequence of the hypogonadism or the different clinical complications or the physical disfigurement and psychological imbalance, which are associated with the diseases, and are potentially affecting sexual function. Data on beneficial effects of GH replacement therapy and specific surgical or pharmacological approach for acromegaly are far to be fully elucidated although restoring normal GH/IGF-I levels have been associated to improvement of sexual function.

Quantitative assessment of visual behavior in disorders of consciousness.

The study of eye behavior is of paramount importance in the differential diagnosis of disorders of consciousness (DoC). In spite of this, assessment of eye movement patterns in patients with vegetative state (VS) or minimally conscious state (MCS) only relies on clinical evaluation. In this study we aimed to provide a quantitative assessment of visual tracking behavior in response to moving stimuli in DoC patients. Nine VS patients and nine MCS patients were recruited in a Neurorehabilitation Unit for patients with chronic DoC; 11 matched healthy subjects were tested as the control group. All participants under went a quantitative evaluation of eye-tracking pattern by means of a computerized infrared eye-tracker system; stimuli were represented by a red circle or a small color picture slowly moving on a PC monitor. The proportion of on- or off-target fixations differed significantly between MCS and VS. Most importantly, the distribution of fixations on or off the target in all VS patients was at or below the chance level, whereas in the MCS group seven out of nine patients showed a proportion of on-target fixations significantly higher than the chance level. Fixation length did not differ among the three groups significantly. The present quantitative assessment of visual behaviour in a tracking task demonstrated that MCS and VS patients differ in the proportion of on-target fixations. These results could have important clinical implications since the quantitative analysis of visual behavior might provide additional elements in the differential diagnosis of DoC.

Growth hormone, prolactin, and sexuality.

GH and PRL, although not considered as 'classi cal' sexual hormones, could play a role in the endocrine control of sexual function both in men and women. Physiologically, PRL seems to be involved in the central control of sexual behavior and activity, by modulating mainly the effects of dopaminergic and serotoninergic systems on sexual function. Indeed, circulating PRL levels increase after orgasm and may potentially play a role in the acute regulation of further sexual arousal following orgasm both in men and women. On the other hand, either short-term or long-term PRL in crease can modulate central nervous system areas involved in the control of sexual function and, peripherally, can directly influence mechanisms of penile erection in men, and presently only as an hypothesis, mechanisms related to the sexual response of genitalia in women. Furthermore, chronic hyperprolactinemia is classically associated with hypogonadotropic hypogonadism and sexual dysfunction in both sexes. Successful treatment of chronic hyperprolactinemia generally restores normal sexual function both in men and women although this effect is not only related to relapse of gonadal function. Hypoprolactinemia is recently recognised as a possible risk factor of arteriogenic erectile dysfunction while a possible role on female sexual function is not known. The physiological role of GH on sexual function is not fully elucidated. GH is an important regulator of hypothalamus-pituitary-gonadal axis and seems to participate in the regulation of the sexual response of genitalia in men, and potentially also in women. Sexual function in men and women with GH deficiency (GHD) and GH excess, particularly in acromegaly, is scantily studied and GH- or IGF-I-dependent effects are difficult to quantify. Nevertheless, a decrease of desire and arousability both in men and women, together with an impairment of erectile function in men, have been described both in patients with GHD and acromegaly, although it is not clear whether they are dependent directly on the hormone defect or excess or they are consequence of the hypogonadism or the different clinical complications or the physical disfigurement and psychological imbalance, which are associated with the diseases, and are potentially affecting sexual function. Data on beneficial effects of GH replacement therapy and specific surgical or pharmacological approach for acromegaly are far to be fully elucidated although restoring normal GH/IGF-I levels have been associated to improvement of sexual function.

An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs.

Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene HNF4α, directly represses the expression of the epithelial microRNAs (miRs)-200c and -34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4α, previously identified as a transcriptional repressor of Snail, induces the miRs-34a and -200a, b, c that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4α and miRs-200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation.

Association study between the LINGO1 gene and Parkinson's disease in the Italian population.

Some studies have suggested an overlap of clinical and genetic findings between essential tremor (ET) and Parkinson's disease (PD). The first genome-wide association study in ET showed a significant association with the rs9652490 SNP of the leucine-rich repeat and Ig domain containing 1 (LINGO1) gene. Since patients with PD have higher LINGO1 expression levels compared to healthy controls, and animal models of PD show elevated LINGO1 protein levels after experimentally induced damage in the striatum, it can be inferred that LINGO1 is probably involved in PD pathophysiology. In this study, we performed a genetic association analysis of the rs9652490 and rs11856808 SNPs in Italian PD patients and controls to assess the role of these variants in our population. A total of 567 patients with PD and 468 control subjects were enrolled in five Movement Disorder centers located in Central-Southern Italy. Both variants were significantly associated with PD under a recessive model of inheritance before applying the Bonferroni correction. The GG genotype of rs9652490 and the TT genotype of rs11856808 were less frequent in patients than in controls, suggesting a protective effect against the disease. However, after stringent correction, only the P-values obtained from allele and genotype comparisons of the rs11856808 SNP remained significant. Our findings suggest that LINGO1 plays a certain role in the development of PD in the Italian population and represents an interesting candidate gene responsible for PD, due to its involvement in neurological processes.

MRI in a woman with late onset ornithine transcarbamylase deficiency.

We describe the brain MR imaging findings of a woman who developed neurologic symptoms due to an acute hyperammonemic encephalopathy resulting from late onset ornithine transcarbamylase deficiency (OCTD). MR images revealed injury (hyperintense foci on long TR images) to the subcortical white matter of the left precentral and supramarginal gyrus and in the left frontal lobe. These findings presumably reflect the distribution of brain injury from hypoperfusion secondary to severe hyperammonemia. If MR findings suggesting hypoperfusion are detected in a patient with hyperammonemia, the diagnosis of OCTD should be considered. Knowledge of the physiopathological mechanisms of OTCD and of MR imaging of hyperammonemic injury may help expedite diagnosis and treatment and prevent the exitus of patients with this genetic disorder.

Illness awareness in terminal cancer patients: an Italian study.

The amount and quality of information and awareness in cancer patients' is a topic frequently debated, but few studies have focussed on terminal patients. This is the objective of the present study that involved two different palliative home-care units in Italy, which recruited 550 terminal cancer patients. Data from patients and their caregivers was prospectively collected with special attention to information patients were provided with when their cancer was diagnosed and patients' awareness of their current health condition. In the case of the information, 67.0% of patients reported they were previously informed about their diagnosis, but only 58.0% seemed to be aware of their terminal condition. The comparison between the caregivers opinions about the level of information provided to the patients and their present awareness and what the patients really know about their own disease shows a high degree of correspondence. Some variables such as age and education level of patients were associated with patient's awareness.

The functional relevance of neurological recovery after lumbar discectomy: a follow-up of more than 20 years.

We have studied 180 patients (128 men and 52 women) who had undergone lumbar discectomy at a mean of 25.4 years (20 to 32) after operation. Pre-operatively, most patients (70 patients; 38.9%) had abnormal reflexes and/or muscle weakness in the leg (96 patients; 53.3%). At follow-up 42 patients (60%) with abnormal reflexes pre-operatively had fully recovered and 72 (75%) with pre-operative muscle impairment had normal muscle strength. When we looked at patient-reported outcomes, we found that the Short form-36 summary scores were similar to the aged-matched normative values. No disability or minimum disability on the Oswestry disability index was reported by 136 patients (75.6%), and 162 (90%) were satisfied with their operation. The most important predictors of patients' self-reported positive outcome were male gender and higher educational level. No association was detected between muscle recovery and outcome. Most patients who had undergone lumbar discectomy had long-lasting neurological recovery. If the motor deficit persists after operation, patients can still expect a long-term satisfactory outcome, provided that they have relief from pain immediately after surgery.

Bowel sonography in adult celiac disease: diagnostic accuracy and ultrasonographic features.

BACKGROUND: Celiac disease (CD) is a chronic intolerance to gluten, which induces intestinal mucosal lesions in genetically predisposed individuals. Transabdominal bowel sonography (TABS) is a safe and noninvasive procedure that allows to detect intestinal abnormalities in many conditions, but actually is not routinely part of the diagnostic management of CD. AIM: To evaluate the diagnostic accuracy of TABS in CD patients. PATIENTS AND METHODS: Fifty CD patients and 50 dyspeptic subjects (control group) underwent TABS. The presence of fluid-distended small bowel loops with thickened valvulae conniventes and increased peristalsis was considered a TABS sign of CD. All clinical, biochemical, and TABS features were assessed at the diagnosis and revaluated after 1 year of gluten-free diet. RESULTS: TABS signs were present in 66% of CD patients. Sensitivity, specificity, positive and negative predictive value were 66%, 96%, 94%, and 74%, respectively. TABS findings were recorded in 82% of patients with endoscopical markers of CD, in 87.5% of symptomatic patients, and in 61% of patients without symptoms. After 1 year of gluten-free diet TABS was still abnormal in 20% patients, with no correlation with laboratory tests e/o symptoms. CONCLUSIONS: Patients with CD frequently present TABS signs of the disease and operators performing sonography every day have to consider the possibility to suggest CD diagnosis and aTTG determination in these subjects.