The long-term effect on surgery-free survival of biological compared to conventional therapy in Crohn's disease in real world-data: a retrospective study.

BACKGROUND: The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn's disease (CD) who were never with the surgical option. METHODS: This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L'Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population. RESULTS: Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01-8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69-6.44). CONCLUSION: This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

An unusual case of homicide-suicide: overkilling by stabbing and suicide by hanging.

Background: This case presents a detailed forensic examination of a unique femicide case followed by the perpetrator's suicide. Case report: On a Sunday afternoon, a 52 year old man killed his 43 year old partner in their home with eleven stab wounds. A few minutes later, he committed suicide by suspending himself to a tree in their home garden by means of a rope. This unique case is interesting because of the combination of methods used for both homicide and suicide, as well as the relationship dynamics between the victim and perpetrator. The perpetrator committed homicide by stabbing and then hanged himself. Conclusion: The case adds valuable knowledge to Forensic Medicine, advocating for increased awareness and preventive measures against domestic and gender-based violence. This report provides an in-depth analysis of a homicide-suicide incident, focusing on a unique case of homicide-suicide. It serves to highlight the global crisis of femicide. The case is situated within the context of gender- based violence, illustrating how such acts are deeply rooted in societal norms. It highlights patterns of intimate partner violence, where emotional factors play a significant role. Forensic analysis uncovered the overkill nature of the homicide, indicating excessive injuries beyond what was necessary for death, reflecting the psychological turmoil of the perpetrator. It emphasizes the importance of identifying signs of potential violence in domestic settings and implementing interventions for mental health support and the prevention of genderbased violence.

Applications to augment patient care for Internal Medicine specialists: a position paper from the EFIM working group on telemedicine, innovative technologies & digital health.

Telemedicine applications present virtually limitless prospects for innovating and enhancing established and new models of patient care in the field of Internal Medicine. Although there is a wide range of innovative technological solutions in Europe, there are overarching elements associated with such technologies when applied to the practices of Internal Medicine specialists. The European Federation of Internal Medicine (EFIM) strongly advocates for active leadership and influence from the Internal Medicine societies and specialist physicians across Europe in the development and application of telemedicine and digital technologies in healthcare. This position paper's conclusions were drawn via Delphi method, which was developed collaboratively from July 2021 to December 2023. The panel, consisting of experts in clinical medicine, public health, health economics and statistics, assessed various aspects related to telemedicine. Participants assigned scores on a Likert scale reflecting perceived value and potential risks. The findings were consolidated in a comprehensive checklist aligning with relevant literature and a SWOT analysis. Specifically, key issues that need to be addressed include promoting the professional development of e-health competencies in the healthcare and medical workforce, using educational campaigns to promote digital literacy among patients and caregivers, designing and implementing telemedicine applications tailored to local conditions and needs and considering the ethical and legal contexts under which these applications are employed. Importantly, there is currently no consensus on care models or standardized protocols among European Internal Medicine specialists regarding the utilization of telemedicine. This position paper aims to outline the opportunities and challenges associated with the application of telemedicine in Internal Medical practice in Europe.

Pathological and molecular characteristics distinguishing contralateral metastatic from new primary breast cancer.

BACKGROUND: Breast cancer patients have a cumulative lifetime risk of 2%-15% of developing a contralateral metastatic or ex novo primary cancer. From prognostic and therapeutic viewpoints, it is important to differentiate metastatic from second primary. To distinguish these entities, we investigated whether the pattern of X chromosome inactivation could determine whether the two tumors derived from different progenitor cells. MATERIALS AND METHODS: The clonality of bilateral breast cancer was evaluated through the X-inactivation analysis using the human androgen receptor gene (HUMARA) polymorphism and the histopathologic and molecular results were compared. A different or an identical pattern of X inactivation was considered as indicator of a second primary cancer or not informative, respectively. We considered morphological indicators of a new primary cancer the absence of concordance in the histological type or a better histological differentiation. RESULTS: Ten patients with bilateral breast cancer were evaluated. Morphological criteria indicated that eight were second primary, a conclusion confirmed by the X-inactivation analysis. Two cases classified as recurrence according to morphological criteria were classified as second tumor by molecular analysis. CONCLUSION: Our results show that the HUMARA clonality assay can improve the histological parameters in differentiating metastatic cancer from second primary cancer.

From the bench to practice - Field integration of community-based services for older citizens with different levels of functional limitation across European Regions.

The meeting of the European Innovation Partnership on Active and Healthy Ageing (EIPonAHA) action group A3 together with members of the Reference site collaborative network (RSCN) in December 2019 in Rome focused on integration of evidence-based approaches on health and care delivery for older citizens at different levels of needs with expertise coming from stakeholder across Europe. It was the final aim of the group to co-create culturally sensitive pathways and facilitate co-ownership for further implementation of the pathways in different care systems across Europe. The study design is a mixed method approach. Based on data analysis from a cohort of community-dwelling over-65 citizens in the framework of a longitudinal observational study in Rome, which included health, social and functional capacity data, three personas profiles were developed: the pre-frail, the frail and the very frail personas. Based on these data, experts were asked to co-create care pathways due to evidence and eminence during a workshop and included into a final report. All working groups agreed on a common understanding that integration of care means person-centered integration of health and social care, longitudinally provided across primary and secondary health care including citizens' individual social, economic and human resources. Elements for consideration during care for pre-frail people are loneliness and social isolation, which, lead to limitation of physical autonomy in the light of reduced access to social support. Frail people need adaption of environmental structures and, again, social resource allocation to maintain at home. Very frail are generally vulnerable patients with complex needs. Most of them remain at home because of a strong individual social support and integrated health care delivery. The approach described in this publication may represent a first approach to scaling-up care delivery in a person-centered approach.

Hyperhomocysteinemia is associated with cognitive impairment in multiple sclerosis.

Hyperhomocysteinemia (HHcy) has been associated with cognitive impairment in various neurological diseases. Cognitive impairment occurs early in multiple sclerosis (MS). Conflicting data have been reported regarding plasma total homocysteine (tHcy) levels in MS patients, and the impact of HHcy on cognitive impairment in MS is not known. This study investigated whether plasma total homocysteine levels are increased in MS and if HHcy is associated with cognitive impairment in MS. We compared tHcy levels in 94 patients with MS and 53 healthy age-matched controls. We used a neuropsychological test battery that included the Raven's Coloured Progressive Matrices, the Visual Search Test, the Trail Making Test A and B, the Immediate and Delayed Recall of a Short Story, the 30 Paired Word Associates, the Rey-Osterrieth Complex Figure Test, and the Semantic and Verbal Fluency Tests. Clinical (sex, age, type of MS, relapse, disease duration, coexisting disease, smoking habit, and physical disability) and laboratory variables (HHcy, low serum levels of folate and vit.B12, MTHFR genotype) were evaluated for their ability to predict cognitive impairment. The mean tHcy was higher in patients (13.19 micromol/L, SD5.58) than in controls (9.81 micromol/L, SD2.53; p < 0.001). Univariate analysis determined the following factors to be associated with cognitive impairment: higher age at observation, chronic progressive course of disease, longer disease duration,moderate or severe physical disability, and frequency of HHcy. With multivariate regression analysis, there remained a significant association only between frequency of HHcy and cognitive impairment (beta 0.262, p = 0.01). We conclude that tHcy levels are increased in MS and that HHcy is associated with cognitive impairment in this disease.

FMECA methodology applied to two pathways in an orthopaedic hospital in Milan.

INTRODUCTION: Adverse events pose a challenge to medical management: they can produce mild or transient disabilities or lead to permanent disabilities or even death; preventable adverse events result from error or equipment failure. METHODS: IRCCS Istituto Ortopedico Galeazzi implemented a clinical risk management program in order to study the epidemiology of adverse events and to improve new pathways for preventing clinical errors: a risk management FMECA-FMEA pro-active analysis was applied either to an existing clinical support pathway or to a new process before its implementation. RESULTS: The application of FMEA-FMECA allowed the clinical risk unit of our hospital to undertake corrective actions in order to reduce the adverse events and errors on high-risk procedure used inside the hospitals.

Minimally invasive right colectomy: challenges and clinical practice.

AIM: Since the introduction of laparoscopic and robotic technology in surgical practice, there have been multiple reports and a few clinical trials on their use in colorectal surgery. Although the application of laparoscopy to right colectomy has been increasingly adopted in many institutions around the world, there are still several open issues regarding the effective role of robotics and single incision surgery. This is a review of the relevant surgical literature evaluating the risks, benefits, and costs of minimally invasive approaches to right colectomy (RC) surgery. METHODS: Retrospective and prospective articles spanning the past 20 years were reviewed to identify the current application of minimally invasive surgery in RC. A review of the most relevant papers comparing open vs. laparoscopic vs. robotic approaches will illustrate the role of minimally invasive surgery in current clinical practice in terms of surgical outcomes, technical advantages and oncological outcomes. We then pooled the evidence for and against the application of laparoscopy and robotics in intracorporeal vs. extracorporeal anastomosis creation, single incision and natural orifice surgery. RESULTS: Evidence shows that compared to open surgery, laparoscopic RC provides lower postoperative morbidity, faster return to normal bowel function and a shorter length of hospital stay, with a similar oncological outcome. The application of robotics to RC procedure has proven to be safe and feasible, however the intraoperative and postoperative outcomes are similar with the laparoscopic technique and no clear advantages have been demonstrated. When adopted in a single incision technique and natural orifice surgery, robotics can help to overcome the limitations of laparoscopy, enabling the surgeon to perform scar-less surgery. CONCLUSION: Laparoscopy surgery, whenever performed by adequately trained surgeons, can be safely applied to right colectomy and should be considered as the gold standard procedure. In terms of robotic surgery, to date, this technology needs more evidence from multicenter randomized clinical trials. New tools and instruments are needed to expand the field of single incision and natural orifice surgery, and make it available in current clinical practice.

Structural differences in the cell binding region of human fibronectin molecules isolated from cultured normal and tumor-derived human cells.

Fibronectins isolated from human plasma (pFN) and from the conditioned media of normal (N-cFN) and tumor (T-cFN) human cells were compared by cathepsin D digestion followed by immunostaining of released fragments with the monoclonal antibody 3E3, specific for the cell binding site. Two different staining patterns were obtained, one specific for pFN and N-cFN, the second common to fibronectins from the 3 different kinds of tumors studied. This indicates structural differences between N-cFN and T-cFN in the cell binding region of the fibronectin molecule.

Interleukin-3 dependent c-myc protein expression during the cell cycle of murine mast cells.

Aim of the study was to evaluate the relationship between the mitogenic stimulus interleukin-3 to normal murine mast cells and the cell cycle dependent expression of the nuclear c-myc protein. In order to do that on a cell by cell basis, we measured the nuclear c-myc protein simultaneously by flow cytometry, via specific monoclonal antibodies, and the DNA content via the intercalating dye propidium iodide. When cells were deprived from interleukin-3 (IL-3), proliferation was inhibited and the majority of cells arrested in early G1 (G1A, characterized by low c-myc content). Readdition of IL-3 resulted in a slow transition of cells from G1A to late G1 (G1B, at higher c-myc content) before DNA synthesis started. G1A cells with low c-myc content do not undertake DNA synthesis. Using a stathmokinetic methodology we confirmed that the G1A cells are early postmitotic G1 phase cells. The low content of c-myc within these cells appears a direct consequence of reduced c-myc levels during mitosis. Cumulatively, the data suggest that c-myc protein levels of murine mast cells fall at mitosis and that these levels must rise before cells can traverse the G1 phase. Our data are compatible with a model in which c-myc protein content of G1 phase cells has to reach a critical threshold before the cells can move further into the cell cycle.

Neurite outgrowth and cell cycle kinetic changes induced by cis-diamminedichloroplatinum II and retinoic acid in a human neuroblastoma cell line.

The aim of this study was to analyze by flow cytometry the effect of cis-diamminedichloroplatinum II (CDDP) and retinoic acid (RA) on the cell cycle of a neuroblastoma cell line (SK-N-BE (2)C NB) and to correlate the kinetic data with cell morphology. CDDP at 1 microgram/ml induced a dramatic G2 + M cell cycle phases block (nearly 200% increase with respect to control) 2 days after treatment. The G2 + M block was spontaneously reversed starting from the 4th day. The cells treated with 10 microM RA were, instead, induced to irreversibly enter the G0 + G1 phase of the cell cycle (nearly 20% increase with respect to control) 48 h after treatment. Neurite-like structures were observed for both CDDP and RA treated cells. These data suggest different cell cycle dependent molecular mechanisms and different degrees of differentiation during CDDP or RA treatment of NB cells.

Cell cycle variations in azoxymethane-induced rat colorectal carcinogenesis studied by flow cytometry.

Cell cycle variations and DNA aneuploidy, were investigated in different phases of azoxymethane (AOM)-induced colon carcinogenesis in rats by flow cytometry. K-ras gene mutations (transitions Gright curved arrow A) were frequently detected in aberrant crypt foci (ACF) initial pre-neoplastic lesions. The fraction of cells in the G2M-phase of the cell cycle was higher in ACF compared to the normal mucosa of control rats. A similar modification of the cell cycle was found in adenomas and adenocarcinomas but, unexpectedly, also in morphologically normal mucosa from AOM-treated animals indicating that AOM treatment permanently modifies cell cycle control in rat colon mucosa. These alterations, however, were not associated with DNA aneuploidy as reported in human sporadic colorectal cancer, suggesting that tumour development in AOM-treated rats is less dependent on aneuploidy.

Cerebral aspergillosis following intracranial surgery. Case report.

The authors report a case of cerebral aspergillosis. This is only the fifth case following intracranial surgery noted in the literature. Pathogenesis, angiographic findings, and results of cerebrospinal fluid culture are discussed.

DNA flow cytometry of endoscopically examined colorectal adenocarcinomas.

The purpose of the study was to evaluate the correlation of DNA-ploidy of colorectal adenocarcinomas (adk) with histological and clinical parameters including the survival of the patients. Multiple biopsies from 95 adk were taken during colonoscopy prior to surgery. The samples were used to obtain nuclei suspensions for specific staining of DNA content and high resolution flow cytometry. DNA-aneuploidy, i.e. the presence of more than one G0/G1 peak, was detected in 67/95 cases (71%). The individual-specific control mucosa was DNA-diploid in all cases. The mean fraction of S-phase cells was 7.2% in control mucosa and 13.6% in adk. DNA-ploidy did neither correlate with Dukes' stage nor with differentiation degree. Among the patients studied for the correlation of DNA ploidy with survival for a period extending to 30 months (n = 51), the DNA aneuploid group was estimated to be about 5 times as risky as the DNA diploid group with respect to the odds of dying. We conclude that DNA flow cytometry of colorectal adk may predict clinical outcome and be helpful in addition to histopathology.

Autotransfusion program: integrated use of different techniques.

A successful autologous program should enroll all appropriate patients, conserve homologous blood and minimise the exposure to the risks of donor blood. A program of autotransfusion and proper use of blood has been implemented since 1980 with the objectives to include all eligible patients and to transfuse autologous blood only. The following strategies were adopted: critical review of transfusion indications; control of overtransfusion; avoidance of waste; systematic and integrated use of all autotransfusion techniques currently available. Results in 1992 in elective surgery: 98% enrollment, 75% blood conservation. Exposure to homologous blood was completely avoided in 53% of the cases.

One-year use of the Bloodloc system in an orthopedic institute.

UNLABELLED: Human error in patient or specimen identification due to fatigue, stress and lack of attention by technologists, nurses, interns, and physicians, can cause routinely safety procedures to be circumvented. Clerical errors may occur during the specimen collection, the issue of blood unit and the transfusion of blood. The introduction in an increasing number of hospital of preoperative autologous blood donation programs further increases the chance of error, because a single patient can predeposit multiple units of blood. In this cases there is a greater commitment not only to transfuse any blood unit that is ABO compatible but to transfuse the specific units the patient previously donated for his own use. Human error has been recognized as a significant cause of transfusion-associated fatalities. The persistence of the frequency and type of errors observed in spite of extensive efforts to eradicate them, suggests that errors are inevitable as long as large number of repetitive procedures are performed unless major system changes are adopted. A system (Bloodloc System) that physically prevents the possibility of error was adopted since January 1993 and cuncurrently a quality improvement program (QI) was implemented specifically designed to monitor: 1. the absence of the code on the blood samples, 2. the blood bank error in setting the Bloodloc, 3. the misidentification of blood samples, 4. any attempt to transfuse the wrong blood unit, 5. any attempt to transfuse, the wrong patients. RESULTS: 4895 blood units (2469 autologous and 2426 allogeneic units) were transfused to 1478 patients (849 predeposited an average of 3.3 +/- 2.0 units). The methodological errors (absence of three-letter code on the patient's specimen tube, wrong transcription of the code on the blood sample, wrong setting of the Bloodloc in the blood bank)--41 cases--were limited at the first four months of implementation of the system. In the same period however have been reported 3 potentially fatal errors which have been avoided by the Bloodloc. Two cases of misidentification of blood samples at the moment of the specimen collection, and one attempt to transfuse the wrong units to the wrong patients. CONCLUSIONS: The Bloodloc system is effective in preventing potential transfusion-associated fatalities caused by units or recipients misidentification.

[Complications of gastroduodenal peptic ulcers]. / Le ulcere peptiche gastroduodenali complicate.

The paper reports that the introduction of H2-antagonist histamine drugs has led to the present drastic contraction of surgical therapy and complications related to gastroduodenal peptic ulcers. Following a brief discussion of the diagnostics of the various complications of the disease, the surgical urgency is then underlined and case studies are presented (A. Vinci). Thirty-seven hemorrhagic ulcers are reported, 32 of which were completely treated with somatostatin and blood transfusions and 5 were operated for gastrosection during hemorrhage; 70 acute gastroduodenal perforations and 8 blocked pyloroduodenal stenoses are also reported. The surgical approach used for each type of complication is discussed, underlining the end-result to be attained in relation to the patient's future. It is stressed, however, that the surgeon's main goal must be to save the patient's life using the simplest and most efficacious method available.

[Modern view of the pathogenesis and therapy of gastroduodenal peptic ulcer]. / Moderne vedute sulla patogenesi e sulla terapia dell'ulcera peptica gastroduodenale.

After a wide analysis of peptic gastroduodenal ulcer medical therapy, before and after the era of cimetidine, the Authors, after a brief account of the Anatomy and Physiology of the stomach, examine surgical therapy, from the end of the last century till now. After giving the results of the surgical cases of one of them (A. Vinci), including 500 operations, from 1955 till now, almost all with gastric resection, without vagotomy, the Authors point out that today, in the era of cimetidine, surgical therapy has considerably diminished and is reserved only for the complications of pathological cases (perforation, hemorrhage, closed duodenum stenosis), and for those cases which don't respond to antisecretory pharmacological therapy. They also emphasize, that nowadays, in spite of the cooperation among gastroenterologists, gastroscopists and surgeons, the etiopathogenesis of peptic ulcer isn't clear yet, and they conclude by saying that our lack of knowledge of its origin and natural evolution, doesn't guarantee a definitive cure, although the therapy with cimetidine and similar medicines, according to the Authors' personal experiences and opinion, must be continued for the patient's entire life.

[Insulin-dependent diabetes mellitus. Study and follow-up of 100 cases]. / Diabete giovanile insulinodipendente. Studio e follow up di 100 casi.

UNLABELLED: Clinical records of one hundred pediatric patients affected by IDDM have been analyzed. All the patients have been followed since the beginning of the disease and they have had a check up on average of four months (weight, height, blood pressure, HbA1, C peptide, Triglyceridemia, renal function were evaluated). The method of home-self-monitoring was applied. After four years, and periodically thereafter, microvascular abnormalities were evaluated in all the patients by fluorescein angiography. Neuropathy was evaluated only in symptomatic patients by peripheral nerve conduction. The average follow up period was 6.1 years (range 1-20). RESULTS: the onset of the disease was expressed in 11% of the cases by coma, in 14% by ketoacidosis, in the remaining cases by hyperglycemia only. The severity of initial symptoms has progressively and significantly decreased in the last years. In 7% of the subjects diabetes affected more members of the same family (4 couples of siblings and 3 couples of parent-child). An infection preceding the onset of the disease was present in the history of 23% of the cases. Islet cell antibodies were found in 83% of the studied cases at the onset of the disease. In 80 out of the 100 patients a detailed history has been obtained about the occurrence of ketoacidosis episodes after the first admission and about the occurrence of severe hypoglycemic crises (seizures and/or coma). 17% of the patients presented at least one ketoacidosis episode after the first admission (the main cause was infection before 12 years of age, an emotional problem thereafter).(ABSTRACT TRUNCATED AT 250 WORDS)