Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Real-World Safety Profile of Biologics Used in Rheumatology: A Six-Year Observational Pharmacovigilance Study in the Calabria Region

Background: The introduction of biological agents into the clinical armamentarium has modified the management of moderate-severe inflammatory arthritis (IA). However, these drugs can lead to serious adverse events (SAEs) and unpredictable adverse events (AEs) that are difficult to detect in pre-marketing clinical trials. This pharmacovigilance project aimed to study the AEs associated with biologics use in rheumatology. Methods: The current investigation is a multicenter, prospective, observational cohort study based on the Calabria Biologics Pharmacovigilance Program. Patients treated with one biologic agent from January 2016 to January 2022 were enrolled. Results: Overall, 729 (86.3%) of a total of 872 patients did not develop AEs or SAEs, whereas 143 (16.4%) patients experienced at least one AE, of which 16 (1.8%) had at least one SAE. The most common AEs were administration site conditions followed by gastrointestinal, nervous system and skin disorders. We reported a total of 173 switches and 156 swaps. Switches mainly occurred for inefficacy (136; 77.7%), whereas only 39 (22.3%) were due to the onset of an AE. Primary/secondary failure was the most frequent reason for swaps (124, 79%), while AEs onset led to 33 (21%) swaps. Conclusions: This study supports the validity of our program in monitoring and detecting AEs in the rheumatological area, confirming the positive beneficial/risk ratio of biologics

Biologics for Inflammatory Bowel Disease in Clinical Practice: A Calabria (Southern Italy) Prospective Pharmacovigilance Study

Background: The use of immune-modifying biological agents has markedly changed the clinical course and the management of Inflammatory bowel diseases (IBDs). Active post-marketing surveillance programs are fundamental to early recognize expected and unexpected adverse events (AEs), representing a powerful tool to better determine the safety profiles of biologics in a real-world setting. Methods: This study aimed to identify the occurrence of AEs and therapeutic failures linked to biological drugs used in gastroenterology units during a prospective pharmacovigilance program in Southern Italy. Patients affected by IBDs and treated with a biologic agent, from 1 January 2019, to 31 December 2021 (study period) in three gastroenterology units were enrolled. Results: Overall, 358 patients with a diagnosis of active Crohn’s disease or ulcerative colitis satisfying inclusion criteria have been enrolled. Infliximab (IFX) was the most administered drug at the index date (214; 59.8%), followed by Adalimumab (ADA; 89; 24.9%), Golimumab (GOL; 37; 10.3%), Vedolizumab (VDZ; 17; 4.7%) and Ustekimumab (UST; 1; 0.3%). Seventy-three patients (20.4%) experienced at least one AE, while 62 patients (17.3%) had therapeutic ineffectiveness. No serious AEs were reported in the follow-up period in the enrolled patients. AEs have been described with IFX (50/214; p = 0.47), GOL (7/37; p = 0.78), ADA (13/89; p = 0.18), and VDZ (3/17; p = 0.52), no AEs have been noticed with UST (0/1). Conclusions: Based on the low rate of AEs observed and withdrawal from treatment, our data seem to corroborate the favorable beneficial/risk profile of biologics for IBDs

Pathologist computer-aided diagnostic scoring of tumor cell fraction: A Swiss national study.

Tumor cell fraction (TCF) estimation is a common clinical task with well-established large inter-observer variability. It thus provides an ideal testbed to evaluate potential impacts of employing a computer-aided diagnostic (TCFCAD) tool to support pathologists' evaluation. During a National Slide Seminar event, pathologists (n=69) were asked to visually estimate TCF in 10 regions of interest (ROI) from hematoxylin and eosin (H&E) colorectal cancer images intentionally curated for diverse tissue compositions, cellularity, and stain intensities. Next, they re-evaluated the same ROIs while being provided a TCFCAD created overlay highlighting predicted tumor versus non-tumor cells, together with the corresponding TCF percentage. Participants also reported confidence levels in their assessments using a 5-tiers scale, indicating no confidence to high confidence, respectively. The TCF ground truth (GT) was defined by manual cell-counting by experts. When assisted, inter-observer variability significantly decreased, showing estimates converging to the GT. This improvement remained even when TCFCAD predictions deviated slightly from the GT. The standard-deviation of estimated TCF to the GT across ROIs was 9.9% vs 5.8% with TCFCAD, p < 0.0001. The intraclass correlation coefficient increased from 0.8 to 0.93 (CI95% [0.65, 0.93] vs [0.86, 0.98]) and pathologists stated feeling more confident when aided (3.67 ± 0.81 vs. 4.17 ± 0.82 with CAD). TCFCAD estimation support demonstrated improved scoring accuracy, inter-pathologist agreement and scoring confidence. Interestingly, pathologists also expressed more willingness to use such a CAD tool at the end of the survey, highlighting the importance of training/education to increase adoption of CAD systems

Connexin implication in the control of the murine beta-cell mass

Diabetes develops when the insulin needs of peripheral cells exceed the availability or action of the hormone. This situation results from the death of most beta-cells in type 1 diabetes, and from an inability of the beta-cell mass to adapt to increasing insulin needs in type 2 and gestational diabetes. We analyzed several lines of transgenic mice and showed that connexins (Cxs), the transmembrane proteins that form gap junctions, are implicated in the modulation of the beta-cell mass. Specifically, we found that the native Cx36 does not alter islet size or insulin content, whereas the Cx43 isoform increases both parameters, and Cx32 has a similar effect only when combined with GH. These findings open interesting perspectives for the in vitro and in vivo regulation of the beta-cell mass

Migration and the Built Environment - Abstract, Projects, Conference Proceedings, Atti del Simposio Internazionale Caumme III/Paumme I, Napoli, novembre 24-25, 2016

The phenomenon of migration is as ancient as human socialization. However, in the last decades both phenomena have become a top political and discursive concern in many countries. The contemporary, more international dimension of migration and the spread of media perfectly epitomizes the “liquid” character of the present: something that changes in a constant fashion, but remains hard to contextualize. The global nature of migrations, linked to their increasing articulation, has been the object of widespread scholarly interest, especially in the humanities, to the point that the social scientists S. Castles e M.J. Miller define the last decades as “the migration era”, even if other, earlier historical periods witnessed even more numerous flows. It is unquestionable that, starting from World War I, migration has assumed a global character that has intensified in the last decade. This global dimension is linked to the host of different places involved in the two directions of the flow, to the formation of multiple migratory systems, to the amplification of the transnational character and, the transformation of the landscape of the transit places. Further, focusing on the long period, the transformations appear to affect even the destination places, as populations bring along their customs, behaviors, cultures and techniques. Such mutations involve numerous aspects beyond the anthropological, physical and spatial ones. They also affect the built environment and the processes of construction and representation of both cities and their architecture. CAUMME III - 2016 addresses a number of relevant concerns regarding the relationship between architecture, urbanism and migrations. What are the relevant impacts of migration on the host communities? What anthropological effects are linked to these phenomena? Are architectural aesthetics, the material use and the building techniques going to mutate under the pressure of migration? How is the urban landscape being transformed by flows of migration? What is happening to the housing environments? What kind of relationships are forming between transformation processes of the built environment and the social system in the presence of migrant communities