Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series.

BACKGROUND: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response. PATIENTS AND METHODS: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified. Data on patient, disease, treatment, and response-specific factors were explored for potential risk factors. Overall treatment numbers were used to estimate incidence. RESULTS: Nine patients from eight European centres were included. Common features were hepatic flexure location (5/9), T4 radiological staging (6/9), annular shape (8/9), radiological stricturing (5/9), and endoscopic obstruction (6/9). All received pembrolizumab and obstructed between 45 and 652 days after starting treatment. Seven patients underwent surgical resection; one was managed with a defunctioning stoma; and one was managed conservatively. One patient died from obstruction. Radiological response was seen in eight patients, including two complete responses. Pathological response was seen in all seven who underwent resection, including four complete responses. The overall incidence of immunotherapy response-related obstruction in these centres was 1.51%. CONCLUSIONS: Bowel obstruction associated with immunotherapy response may represent a rare treatment-related complication in dMMR CC. Clinicians must recognise this safety signal and share experience to maintain patient safety.

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey.

BACKGROUND: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting. PATIENTS AND METHODS: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed. RESULTS: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS. CONCLUSIONS: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.

Short-term effects of a dietary supplement on lower urinary tract symptoms.

Benign prostatic hyperplasia (BPH) is one of the most common conditions affecting men over 40 years of age, typically manifesting itself with lower urinary tract symptoms (LUTS). Recently, research interest has focused in discovering a viable nutraceutical alternative to the drugs that are currently the first line of treatment for BPH. The aim of this study was to investigate the efficacy and safety of a dietary supplement containing curcumin, beta-sitosterol and oligomeric proanthocyanidins in a group of BPH/LUTS patients. One-hundred men with LUTS caused by BPH were enrolled in this study and agreed to take one tablet a day of the test dietary supplement for three months. Several parameters, such as International Prostate Symptom Score (IPSS), degree of urinary obstruction and average urinary flow were evaluated at different time points. Significant improvement in LUTS was seen after one month of treatment and a significant decrease in mean IPSS index was evident after three months of treatment. Moreover, a comparison of the mean urinary flow and of the number of subjects with bladder obstruction at three months versus one month of treatment shows a significant improvement. The study results suggest that the dietary supplement is effective for almost all the symptoms investigated, including the reduction of IPSS score and the increase of urinary flow. Moreover, the dietary supplement proved to be safe and well tolerated by the great majority of the enrolled subjects. .

Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To estimate the patient-specific risk of pre-eclampsia (PE) at 35-37 weeks' gestation by a combination of maternal characteristics and medical history with multiples of the median (MoM) values of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), and stratify women into high-, intermediate- and low-risk management groups. METHODS: This was a prospective observational study in women attending a third-trimester ultrasound scan at 35-37 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at < 4 weeks from assessment and PE at < 42 weeks' gestation were calculated using the competing-risks model to combine the prior risk from maternal characteristics and medical history with MoM values of MAP, UtA-PI, PlGF and sFlt-1. On the basis of these risks, the population was stratified into high-, intermediate- and low-risk groups. Different risk cut-offs were used to vary the proportion of the population stratified into each risk category and the performance of screening for delivery with PE at < 40 and ≥ 40 weeks' gestation was estimated. RESULTS: The study population of 3703 singleton pregnancies included 38 (1.0%) with PE < 40 weeks' gestation and 22 (0.6%) with PE ≥ 40 weeks. Using a risk cut-off of 1 in 50 for PE delivering at < 4 weeks after assessment to define the high-risk group and a risk cut-off of < 1 in 100 for PE delivering at < 42 weeks' gestation to define the low-risk group, the proportion of the population stratified into high, intermediate and low risk was 12.7%, 28.8% and 58.5%, respectively. The high-risk group contained 92% of pregnancies with PE at < 40 weeks' gestation and 73% of those with PE at ≥ 40 weeks. The intermediate-risk group contained a further 27% of women with PE at ≥ 40 weeks. In the low-risk group, none of the women developed PE at < 40 or ≥ 40 weeks' gestation. CONCLUSION: The study presents risk stratification of PE by the combined test at 35-37 weeks, aiming to identify a high-risk group in need of intensive monitoring from the time of the initial assessment and up to 40 weeks' gestation, an intermediate-risk group in need of reassessment at 40 weeks' gestation and a low-risk group that can be reassured that they are unlikely to develop PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[Artificial lighting and blue light in the operating room: what risks for the surgeon?]. / Illuminazione artificiale e luce blu in sala operatoria: quali rischi per il chirurgo?

BACKGROUND: Lighting in operating rooms must ensure conditions of visual comfort, wellbeing and safety when procedures are being carried out, so as to preserve  the health of both workers and patients. OBJECTIVES: In this study we attempted to develop a methodology for specifically assessing the risk for surgeons of exposure to blue light, simulating the surgeon's real working conditions. Visual comfort was also assessed by measuring maintained illuminance (Em) and the luminance levels in the visual task area within the operating field. METHODS: Blue light exposure was measured by an OCEAN OPTICS-QE65000 spectroradiometer and a LSI-Lastem model Z-Lux radiometer, while for lighting measurements, a videophotometer and luxmeter were used. RESULTS: Results show that the surgeons were exposed to blue light values lower than the limit of effective radiance LB= 100 W m-2 sr-1 foreseen by European Directive 2006/25/EC. For visual comfort, significant differences in illumination were observed between surrounding areas and the visual task areas, with very high luminance values measured in most of the observation points. CONCLUSIONS: In this case the measured values confirm that the workers were daily exposed to unsuitable luminance contrasts that can cause eyestrain. Given such results and considering the task analysis, we proposed to extend health surveillance to workers performing activities such as precision surgery for prolonged periods.

[Risk of non-coherent optical radiation in the operating room]. / Rischio da radiazioni ottiche artificiali non coerenti in sala operatoria.

In this study, we evaluated the exposure of operating room personnel to non-coherent optical radiation by measuring the emission of blue light generated by operating lights. The values we obtained were largely below the exposure limit value of 100 W x m(-2) x sr(-1) provided by Legislative Decree no. 81/08 and European Directive 2006/25/EC, showing how workers can be exposed for longer than 8 hours without risk of acute health effects, confirming what was already said in literature. This work demonstrates, therefore, that the risk of acute nature of photochemical retinal damage, caused by exposure to blue light, is absent, if not exceeded the exposure limit values, on the basis of the current knowledge, however, respect for exposure level cannot protect against a possible retinal damage from chronic exposure, related to the total dose accumulated by the worker in the long-term.

Quantitative evaluation of personal exposure to UV radiation of workers and general public.

Due to meteorological conditions variability and to the variability of exposure patterns, which can be largely different during a working day, personal dosemeters use can be necessary to obtain a correct quantitative evaluation of the radiation dose absorbed by an exposed worker. Different classes of personal dosemeters exist and, among them, electronic dosemeters and polysulphone film dosemeters. An experimental campaign is presented conduced in a cultivated area of Tuscany and some aspects are discussed about an experimental campaign performed on a population of volunteers on a central Italy beach near Rome. The aim of the present work is to show some relevant issues in a dosimetric approach to the exposure evaluation of outdoor workers and, in general, of the public during recreational activities.

Variability among polysulphone calibration curves.

Within an epidemiological study regarding the correlation between skin pathologies and personal ultraviolet (UV) exposure due to solar radiation, 14 field campaigns using polysulphone (PS) dosemeters were carried out at three different Italian sites (urban, semi-rural and rural) in every season of the year. A polysulphone calibration curve for each field experiment was obtained by measuring the ambient UV dose under almost clear sky conditions and the corresponding change in the PS film absorbance, prior and post exposure. Ambient UV doses were measured by well-calibrated broad-band radiometers and by electronic dosemeters. The dose-response relation was represented by the typical best fit to a third-degree polynomial and it was parameterized by a coefficient multiplying a cubic polynomial function. It was observed that the fit curves differed from each other in the coefficient only. It was assessed that the multiplying coefficient was affected by the solar UV spectrum at the Earth's surface whilst the polynomial factor depended on the photoinduced reaction of the polysulphone film. The mismatch between the polysulphone spectral curve and the CIE erythemal action spectrum was responsible for the variability among polysulphone calibration curves. The variability of the coefficient was related to the total ozone amount and the solar zenith angle. A mathematical explanation of such a parameterization was also discussed.

[Work capacity of housewives with complete laceration of the rotator cuff]. / Capacità lavorativa della casalinga con lacerazione completa della cuffia dei rotatori.

OBJECTIVE: The aim of the this study is to evaluate the work capacity of housewives with full thickness tear of the rotatory cuff (FTTRC). METHODS: Twenty-five subjects have been studied. The FTTRC was located un the right shoulder in 16 cases, in the left shoulder in 5 cases and was bilateral in 4 patients. All patients were female; the average age was 72.4 +/- 4 (range 62-81). The Assessments were made using the Constant Scale, the Groningen Activity Restriction Scale and the Simon's Test. RESULTS: The result of this study confirmed that none of the housewives was able to carry out the houseworks quite independently and with no effort. 16% of the patients did the houseworks with great effort while 84% was helped in making some activities. Help is necessary for the usual housework and heavy domestic works (washing glasses, using vacuum cleaner to clean the floor). Patient's relatives provided help in 76.2% of cases while 23.8% were assisted by maid. Help was occasional in 33.3% of cases, continuous in 52.3% and full in 14.4% of patients. Disability resulting from FTTRC is heavier in subjects where electrical household appliances are not used (p < 0.05) and in subjects who feel deep pain (p < 0.05). The active movements of shoulder, local shoulder pain and level of use of upper limbs do not affect domestic works. CONCLUSIONS: These study showed that FTTRC reduces work capacity of house wives. These disease is more preventing heavy domestic works.

Bulbar-onset amyotrophic lateral sclerosis in a patient with Chiari I malformation.

We report on a patient with bulbar-onset, clinically defined, sporadic amyotrophic lateral sclerosis (ALS) who also showed a Chiari I malformation. This malformation, otherwise asymptomatic, was detected during the diagnostic work-up for ALS. To our knowledge this is the first report of an association between these two relatively uncommon disorders. Since our patient worked for many years as a bus-driver and because the ALS symptoms began in the brainstem region, we suggest that his hindbrain anomaly, along with the mechanical stress on the spine and cranio-vertebral junction due to the daily driving, might have played a role in the region-specific onset of ALS.

The calibration of personal dosemeters used for evaluating exposure to solar UV in the workplace.

In the framework of an epidemiological study regarding the correlation between solar UV radiation exposure and skin pathologies in a population of outdoor workers, the possibility of using polysulphone film personal dosemeters to quantify the Subjects UVB exposure has been evaluated. An original experimental set-up is presented. in a preliminary version, which ill be used both for solar irradiance spectroradiometric measurements and for the reading of personal dosemeters. The polysulphone absorption is similar to the CIE erythemal response curve. Due to UVB radiation exposure, the polysulphone film dosemeters photodegrade with a measrable absorbance change. The absorbance variation after the dosemeter exposure to UV radiation has been correlated to the UVB effective dose. The calibration curve obtained by this method may be particularly useful for the evaluation of small closes. The method will be used to quantify the personal exposure of workers whose exposure conditions are characterised by high variability.

[Duplex scanner in the diagnosis of vasculogenic impotence]. / Il duplex scanner nella diagnosi dell'impotenza vasculogenica.

This paper is reporting the experience of the Authors in the use of Duplex-scanner and eco-color-doppler in the diagnosis of the erectile dysfunctions and particularly in the importance of vascular (arterious and venous) origin. For this purpose, we selected a sample constituted of 41 patients: 22 with psychogenic, 8 with arterial, 5 with venous impotence, 5 patients with Peyronie's disease and 1 patient with posttraumatic arterio-venous fistula. The Authors, while underlining the remarkable accuracy and diagnostic reliability of eco-doppler, emphasize the indication of the method up to consider it "investigation of prime choice", not only in the patients with the dysfunction of vis erigendi but, in the cases in which a morphological evaluation, besides hemodynamical one, become necessary.

Effects of bendazac L-lysine salt on some metabolic enzymes of glutathione in the rabbit lens after X-irradiation.

The effect of (1-benzoyl-1H-indazol-3-yl)oxylacetate L-Lysine (bendazac-lysine) on some enzymatic activities involved in the metabolism of reduced glutathione (GSH) was studied in the rabbit lens during developing cataract induced by a single dose of X-rays (2000 rads). The specific activities of glutathione reductase (G.R.), glutathione peroxidase (GSH.Px) and glutathione S-transferase (GSHS-tr.) do not change following irradiation and treatment with bendazac-lysine. The activity of the same enzymes expressed as a function of water soluble proteins (WSP) per lens significantly decreases (P less than 0.01) as compared to controls in the irradiated lens not treated with bendazac-lysine (ILNTB) at the 8th week, whereas no significant decrease as compared to controls is observed in the irradiated lens treated with bendazac-lysine (ILTB). In the ILNTB the specific activity of glucose-6-phosphate dehydrogenase (G6PDH) is reduced by 10% after 0.3 weeks and by 29% after 12 weeks. In the ILTB the specific activity of G6PDH is reduced by 8% after 0.3 weeks and by 14.5% after 12 weeks. The specific activity of superoxide dismutase (SOD) in the ILNTB is reduced by 19% after 0.3 weeks and reached 31% after 12 weeks. In the ILTB the specific activity of SOD is reduced by 11% after 0.3 weeks and 19.8% after 12 weeks. The mechanism of protective effect of bendazac-lysine on cataract is discussed.