Neuroendocrine carcinomas of the cervix are very rare, accounting for only 1–2% of all cervical cancers and <1% of all neuroendocrine tumors. Small-cell carcinoma of the cervix is associated with ...poor prognosis, even in early stages. Despite their neuroendocrine origin, tumors presenting with syndromes due to secreted neuroendocrine hormones are extremely rare. To date, only seven cases of cervical small-cell carcinoma associated with Cushing’s syndrome due to ectopic ACTH secretion have been described. In most reports, Cushing’s syndrome associated with these tumors occurred only in association with liver or lung metastasis. Only one single case of primary uterine cervix carcinoma secreting enough ACTH to induce Cushing’s syndrome in the absence of metastatic disease has been described in 1994. Here, we describe a case of cervical small-cell carcinoma presenting with an acute onset of severe hypokalemia in Cushing’s syndrome without metastatic disease to distant organs.
Response to sorafenib is highly variable in hepatocellular carcinoma (HCC). Baseline inflammatory parameters and treatment toxicities may improve survival prediction in patients on sorafenib therapy.
...442 patients with advanced stage HCC on sorafenib were recruited (follow-up 5096 person-months at risk). 88% had BCLC stage B or greater HCC and 72.3% had Child-Pugh A cirrhosis. On Cox multivariate regression, previously-treated HCC (HR 0.579, 95% CI 0.385-0.872, p=0.009), Cancer of Liver Italian Program (CLIP) score (HR 1.723, 95% CI 1.462-2.047, p<0.0001), baseline red cell distribution width (RDW; HR 1.234, 95% CI 1.115-1.290, p<0.0001) and neutrophil to lymphocyte ratio (NLR; HR 1.218, 95% CI 1.108-1.322, p<0.0001) were significant independent risks for shorter survival, whilst sorafenib-related diarrhoea was associated with prolonged survival (HR 0.533, 95% CI 0.373-0.763, p=0.001). The combination of RD-CLIP score (CLIP score multiplied by RDW) ≥ 70 and no treatment-related diarrhoea had good utility for predicting 3-month survival (AUC of 0.808 (95% CI 0.734-0.882), positive predictive value of 86.4% and negative predictive value of 83.3%), compared with CLIP (AUC=0.642) or BCLC score alone (AUC=0.579). RD-CLIP score ≥ 35 and no treatment-related diarrhoea had an AUC of 0.787 for predicting 12-month survival.
Patients with HCC were consecutively recruited from three tertiary centres (Japan, Italy and UK) and clinical data were prospectively collected. The primary study endpoint was overall survival (OS) after commencing sorafenib.
The novel prognostic index of CLIP score combined with inflammatory marker RDW and treatment-related diarrhoea has good accuracy for predicting overall, 3 month and 12 month survival in patients on sorafenib.
The association between cancer and immune-mediated rheumatic conditions is controversial, especially as far as polymyalgia rheumatica (PMR) is concerned. Furthermore, no clinical feature has been ...shown to be suggestive of a paraneoplastic rheumatic syndrome. With the present study, we aim to address both these issues. The study population comprised
N
= 1750 patients, including
N
= 100 with PMR, who attended our tertiary immuno-rheumatology clinic between January 1, 2005 and November 30, 2012. A rheumatic disease was deemed paraneoplastic if cancer had been diagnosed in the 2 years preceding or following its onset. The probability of a significant association between a specific rheumatic disease and cancer was evaluated by computing the odds ratio (OR):
N
= 702 patients with osteoarthritis serving as controls. Furthermore, clinical features distinguishing paraneoplastic rheumatic diseases were searched for by univariate and multivariate analysis. Sjogren’s syndrome (SS) OR 3.6 (CI 95% 1.7–7.5), PMR (OR 5.1 CI 95% 2.9–8.9), dermatomyositis/polymyositis OR 12.09 (CI 95% 2.6–55.8) and vasculitis OR 3.70 (CI 95% 1.81–7.52) are associated with cancer. At multivariate analysis, older age is associated with cancer among SS patients (
p
= 0.03), while in the PMR group, older age, male gender, and ≥6 tender joints are independent predictors of paraneoplastic PMR (
p
< 0.0004). Cancer frequently either heralds or follows rheumatic manifestations, including PMR. Older age, male gender and a more extensive joint involvement should be considered red flags for paraneoplastic PMR.
Non-traumatic musculoskeletal complaints are often dealt with by emergency room (ER) physicians. We aimed to quantify how many patients with such complaints have conditions requiring immediate ...recognition and treatment, versus specialist referral, versus primary care. We retrieved the clinical records of all the patients admitted to the ER department of our hospital along 1 year. Pediatric (age <14 years) and obstetrics/gynecology cases were excluded. Data from all patients visiting the ER for non-traumatic musculoskeletal complaints were classified as follows: true emergencies (i.e., conditions associated with high morbidity/mortality risk), urgencies (i.e., conditions requiring prompt referral to a specialist), and non-urgent conditions (to be dealt with in primary care). Out of 54,915 patients evaluated in the ER of our hospital, 1652 patients complained of non-traumatic musculoskeletal symptoms (3.0 %): Back pain accounted for 944/1652 ER visits (57.1 %), including 6 emergencies (0.6 %) and 105 urgent conditions (11.1 %). Among the remaining 708 patients (42.9 %) who presented with complaints concerning a peripheral joint, true emergencies were 2/708 (0.3 %) while 210/708 were urgent conditions (29.7 %). Although patients who present to ER physicians with musculoskeletal complaints have rarely true emergencies, many of them are in need of urgent treatment and prompt specialist referral.
COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared ...two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV).
Patients with COVID-19 pneumonia admitted up to May 28
, 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan.
Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes.
Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.
Background:
Both the anti-infective and anti-inflammatory properties of vitamin D, an essential hormone of calcium homeostasis, have ample support in the literature. The high rates of vitamin D ...deficiency among patients with chronic hepatitis C are also well known. That supplementation with vitamin D may boost sustained viral response rates in vitamin D deficient, hepatitis C virus (HCV) infected patients undergoing Interferon-alpha (IFN) treatment, on the other hand, is controversial. Surprisingly, studies considering in this latter setting what are the effects of IFN treatment (with or without vitamin D supplementation) on the other major regulator of mineral metabolism,
i.e.
the Parathyroid hormone (PTH), are lacking.
Aim:
Evaluate the impact of interferon-based treatment against HCV (±cholecalciferol supplementation) on vitamin D and PTH homeostasis.
Methods:
A series of 40 consecutive patients received pegylated IFN plus ribavirin to treat chronic hepatitis C. At the discretion of their physician, some of them (N. = 27) received vitamin D supplementation while others did not (N. = 13). All had measured plasma 25-hydroxycholecalciferol and PTH concentrations at baseline, at completion of the 4
th
(TW4) and 12
th
treatment week (TW12) and at 24 weeks after the end of therapy (SVR24).
Results:
Plasma PTH concentration increased significantly from baseline during treatment, raising to 44.8 30.7-57.2 pg/mL at TW4 (p=0.01), 47.0 37.1-63.2 pg/mL at TW12 (p=0.006) to return to baseline levels in the follow-up (34.5 27.6-43.0; p=0.16). The proportion of patients who satisfied criteria for hyperparathyroidism was higher at TW12 (N=10, 25%) than at TW4 (N=6, 15%). There was no statistical correlation between vitamin D and PTH blood levels (ρ=-0.07; p=0.65).
Conclusion:
An increase in plasma PTH occurs systematically during IFN treatment of HCV patients and cannot be prevented by vitamin D supplementation.
Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of ...different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.
Background
While migraine is markedly prevalent in women, gender-related phenotype differences were rarely assessed. For this reason, we investigated, through a multicenter observational ...cross-sectional study, based on an online questionnaire, gender-related differences in stress factors, emotions, and pain perception in migraine patients and controls and their impact on migraine severity.
Methods
The study was designed as an online questionnaire. The link was emailed to healthy subjects (C) and migraine patients (MIG) (age 18–75, education ≥ 13 years) recruited during the first visit in 8 Italian Headache Centers adhering to Italian Society for Headache Study (SISC). The questionnaire included personal/social/work information, the Perceived Stress Scale, the Romance Quality Scale, the Emotion Regulation Questionnaire, the Beck Anxiety Inventory, the Body Perception Questionnaire, the pain perception, and a self-assessment of migraine severity in the last 3 months.
Results
202 MIG and 202 C completed the survey. Independently from gender, migraine was characterized by higher pain sensitivity and more severe partner relationships. The female gender, in MIG, exhibited higher anxiety scores, body awareness, and reduced emotional suppression. Body awareness and emotional suppression were discriminating factors between genders in control and migraine groups without relevant influence on disease features. Perceived perception of migraine severity was similar between genders.
Conclusion
Gender-related emotional and stress factors did not contribute to delineate a distinct phenotype in migraine men and women. The possible impact of emotional and stress factors characterizing genders could be considered for a single case–tailored therapeutic approach.
It is crucial to identify in large population samples the most important determinants of excessive fetal growth. The aim of the study was to evaluate the independent role of pre-pregnancy body mass ...index (BMI), gestational weight gain and gestational diabetes on the risk of macrosomia.
A prospective study collected data on mode of delivery and maternal/neonatal outcomes in eleven Hospitals in Italy. Multiple pregnancies and preterm deliveries were excluded. The sample included 14109 women with complete records. Associations between exposure variables and newborn macrosomia were analyzed using Pearson's chi squared test. Multiple logistic regression models were built to assess the independent association between potential predictors and macrosomia.
Maternal obesity (adjusted OR 1.7, 95% CI 1.4-2.2), excessive gestational weight gain (adjusted OR 1.9, 95% CI 1.6-2.2) and diabetes (adjusted OR 2.1, 95% CI 1.5-3.0 for gestational; adjusted OR 3.0, 95% CI 1.2-7.6 for pre-gestational) resulted to be independent predictors of macrosomia, when adjusted for other recognized risk factors. Since no significant interaction was found between pre-gestational BMI and gestational weight gain, excessive weight gain should be considered an independent risk factor for macrosomia. In the sub-group of women affected by gestational or pre-gestational diabetes, pre-gestational BMI was not significantly associated to macrosomia, while excessive pregnancy weight gain, maternal height and gestational age at delivery were significantly associated. In this sub-population, pregnancy weight gain less than recommended was not significantly associated to a reduction in macrosomia.
Our findings indicate that maternal obesity, gestational weight gain excess and diabetes should be considered as independent risk factors for newborn macrosomia. To adequately evaluate the clinical evolution of pregnancy all three variables need to be carefully assessed and monitored.
The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 ...antibodies.
To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle.
180 patients (133/180 73.9% males, mean age 66.6 years IQR 57-73) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio RR 1.13; 95% confidence interval CI, 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively.
Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020.
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