A multicentre survey on the perception of palliative care among health professionals working in haematology.

PURPOSE: Patients with haematologic malignancies have less access to palliative care and are referred later than patients with solid tumours. We developed a survey to investigate this phenomenon, with the intention of analysing palliative care perceptions among health professionals who treat haematology patients and identifying barriers and facilitators to referrals to palliative care services. METHODS: This was a multicentre exploratory descriptive web-based survey. A questionnaire was administered to 320 medical and nursing staff members from five Italian haematological units and San Marino's hospital to investigate their perception of palliative care. Quantitative and qualitative analyses were performed. RESULTS: A total of 142/320 healthcare professionals completed the survey, achieving a 44% response rate. Most of the respondents supported the integration of haematology and palliative care and were aware of the role of palliative care. Despite this, only half had an in-hospital palliative care team, and only a few had previously attended a specific training course. The majority agreed with palliative care referral when the prognosis was less than 3 months or when the symptoms were incoercible and with blood transfusions even in the last stages of the disease. Many considered the presence of an in-hospital palliative care team or a case manager, as well as structured palliative care training, as fundamental facilitators of palliative care referrals. CONCLUSION: These results showed that healthcare professionals in haematology generally hold a favourable attitude and a high interest in integrating palliative care into their patients' care. The low referral rate could depend on clinical, cultural, and organisational issues.

Treatments, prognostic factors, and genetic heterogeneity in advanced cholangiocarcinoma: A multicenter real-world study.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real-world data for enhanced understanding and patient care. METHODS: This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan-Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first-line chemotherapy) and OS. Genetic profiling was conducted selectively. RESULTS: Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first-line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one-third received no systemic treatment. After a median 14-month follow-up, 81 CCA-related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first-line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14-0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04-3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes. CONCLUSIONS: Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.

[Haemopoietic stem cells transplantation: a narrative review]. / Il trapianto di cellule staminali emopoietiche: una revisione narrativa.

. Haemopoietic stem cells transpantation: a narrative review. Haematopoietic stem cell transplantation (HSCT) is an effective treatment for many haematological malignancies and its employment is growing thanks to the increased possibility of finding suitable donors and the discovery of therapies to treat major complications. The fourth contribution on emergencies in the oncology setting proposes a narrative literature review to describe the transplant pathway, the types of HSCT, the conditioning regimen, the stem cells reinfusion, the aplasia phase, the major complications and the follow-up. The review included secondary studies published from 2020 to 2022, on adult transplanted patients and written in English; 30 studies were included. In addition, 28 primary studies describing key issues and 11 textbooks were added. Both autologous and allogeneic HSCT expose patients to infectious or drug therapy-related complications, such as mucositis and bleedings. The allogeneic HSCT is at higher risk of major complications such as the graft-versus-host disease and the venous-occlusive disease. The update proposed is accompanied by two cases with multiple choice questions, in patients who underwent autologous stem cells hematopoietic transplantation: case 1 (published in this issue of the AIR journal) on septic shock and case 2 (which will be published in the next issue of the AIR journal) on a massive hemothorax.

Chondro-Cutaneous Autograft for Reconstruction of the Nasal Ala After a Human Bite.

BACKGROUND The nasal ala is a paired structural subunit of the nose that is functionally important in the maintenance of the nasal valve. It consists of 3 anatomically distinct layers: skin, cartilage, and mucosa, all of which need to be restored in reconstructive surgeries to maintain nasal patency. When multiple layers are involved in a defect, the reconstruction requires combining procedures to replace each layer. CASE REPORT We describe a peculiar case of a 58-year-old man with a full-thickness loss of substance of the right nasal ala due to a human bite. The patient came to our hospital after an altercation with another man who bit his nose off. He was initially seen at a smaller regional hospital that did not have a plastic surgery department and was soon after transferred to our facility due to the complexity of the case. To reduce the risk of infection, the patient was treated with a complete course of intravenous antibiotic therapy and the wound was medicated daily with antiseptic solutions. The loss of substance was reconstructed with a composed graft from the auricle concha and the melolabial flap. CONCLUSIONS Defects of the nasal ala are challenging to reconstruct, given its complex 3-dimensional structure. The successful repair of these defects provides aesthetic symmetry and preserves nasal function. A wide variety of reconstructive options have been utilized in many nasal reconstruction cases and have been documented. The combination of a chondro-cutaneous graft from the auricular concha and a melolabial flap graft allowed a good result without local or systemic complications.

The inguinal fold as a flaps bank: the inguinal fold island flap (IFI flap).

The aim of this article is to describe an island flap, harvested from the inguinal fold, which can be used for vulvar reconstruction: the inguinal fold island flap (IFI flap). IFI flap is indicated for reconstruction of defects of vaginal vestibule and labia minora and it could be raised bilaterally safeguarding regional symmetry and avoiding vaginal introitus or urethral distortion. This flap has been utilized to reconstruct defects after vulvar melanoma and squamous cell carcinoma resections and in one case to restore vaginal vestibule anatomy in a revision surgery in a transgender woman. IFI flap is an example of an "aesthetic/functional" reconstruction which could be proposed to younger patients too.

International on-line questionnaire about severe lower gastrointestinal bleeding management: Do we have it clear? / Encuesta internacional on-line sobre el manejo de la hemorragia digestiva baja grave. ¿Lo tenemos claro?

BACKGROUND AND AIMS: The diagnostic and therapeutic strategy in severe lower gastrointestinal bleeding (LGIB) varies depending on the patient's clinical situation. Actual clinical practice guidelines propose different management strategies. We aim to know the attitude of the gastroenterologists from different hospitalary centers in the management of this entity. METHODS: Descriptive and observational study using an on-line questionnaire, addressed to gastroenterologists in Spain and Latin America, in December 2021. RESULTS: We included 281 anonymous questionnaires of gastroenterologists from Spain and Latin America. Diagnostic and therapeutic management of severe LGIB was heterogeneous among the participants. Regarding to the first diagnostic modalities they showed variability between performing computed tomography angiography (CTA) (44.5%), gastroscopy (33.1%), colonoscopy (20.6%) and arteriography (1.1%). The therapeutic attitude after a positive CTA mostly varied between performing arteriography (38.1%) and colonoscopy (44.1%). If negative CTA, in the majority of cases a gastroscopy was performed. If the patient needed intensive critical unit (ICU) care and to undergo colonoscopy, most participants performed an urgent colonoscopy (<24h) (31% always, 43.4% in most cases); while if the patient did not require ICU admission this percentage was lower (10% always, 33.8% in most cases). The 40.9% of the participants admitted having doubts about the management of this patients and the 98.2% considered the need for a creation of an action protocol. CONCLUSIONS: There is a high interhospitalary variability on the management of severe lower gastrointestinal bleeding among gastroenterologists. It is necessary to unify the diagnostic and therapeutic management of this pathology.

Correlation between Olive Oil Intake and Gut Microbiota in Colorectal Cancer Prevention.

Extra virgin olive oil (EVOO) is a mainstay of the Mediterranean diet with its excellent balance of fats and antioxidant bioactive compounds. Both the phenolic and lipid fractions of EVOO contain a variety of antioxidant and anticancer substances which might protect from the development of colorectal cancer (CRC). The function of the intestinal microbiome is essential for the integrity of the intestinal epithelium, being protective against pathogens and maintaining immunity. Indeed, dysbiosis of the microbiota alters the physiological functions of the organ, leading to the onset of different diseases including CRC. It is known that some factors, including diet, could deeply influence and modulate the colon microenvironment. Although coming from animal models, there is increasing evidence that a diet rich in EVOO is linked to a significant reduction in the diversity of gut microbiome (GM), causing a switch from predominant bacteria to a more protective group of bacteria. The potential beneficial effect of the EVOO compounds in the carcinogenesis of CRC is only partially known and further trials are needed in order to clarify this issue. With this narrative review, we aim at discussing the available evidence on the effect of olive oil consumption on GM in the prevention of CRC.

Effectiveness of clinical and instrumental follow-up for cutaneous melanoma.

INTRODUCTION: Follow-up guidelines for melanoma greatly differ in the methods of screening for recurrence, and timing and duration of the follow up, with many areas of controversy and a lack of general consensus. The aims of this study are to present our protocol and case series for follow up and to summarize and discuss current literature on melanoma follow-up guidelines/recommendations in different countries. METHODS: We retrospectively reviewed 539 patients operated for melanoma between 2004 and 2013 at the same Institution. Data on the diagnostic role of the different clinical and instrumental detection methods were adjusted for sex, age at diagnosis, staging and evaluated by Fisher's exact test and multivariate analysis. Recommendations from the literature were summarized and discussed. RESULTS: Local recurrences and second melanoma were always identified through physical examination, irrespectively of melanoma staging. Regional metastases were most often identified through physical examination and ultrasound, being more frequent in stage II and III, while distant metastases were most often identified through CT scans. Surveillance follow-up schedules vary significantly depending on country, physician specialty, and stage of disease, with a lack of evidence on the efficacy of the different schemes. Similarities and controversies in the different follow-up protocols are presented and discussed. CONCLUSION: Our clinical series showed that physical examination is very powerful in identifying local recurrences and second melanomas. Physical examination and ultrasound are equally powerful in identifying regional metastases, and alternating them over time could allow to reduce the number of follow-up visits. CT scans, differently from chest x-ray, showed a high power in identifying distant metastases. Surveillance follow-up schedules in the literature vary significantly depending on country, physician specialty, and stage of disease, with a lack of evidence on the efficacy of the different schemes. Standard protocols are desirable for a better evaluation of results.

[Indications for CAR-T cell therapy and management of the complications: an update]. / Indicazioni e gestione delle complicanze della terapia con CAR-T: un aggiornamento.

. Indications for CAR-T cell therapy and management of the complications: an update. INTRODUCTION: The engineering of T lymphocytes with the chimeric antigen receptor (CAR-T) opened a new pattern for the treatment of malignant neoplasms and it was pivotal for the treatment of some haematological malignancies. AIM: To describe the therapy with CAR-T, the mechanism, the management process, the role of the multidisciplinary team and highlight the main complications and management, follow-up, the impact on quality of life and the role of nurse. METHOD: A literature review was conducted. Secondary studies published between 1 January and 17 October 2022, in English and Italian language, on adult population undergoing CAR-T, were included. Of the 335 articles, 64 were, finally, included. RESULTS: New CAR-T products have been tested for the treatment of acute myeloid leukaemia, multiple myeloma and some kind of solid tumours. The two main toxicities are the cytokine release syndrome and the neurotoxicity. Alternative drugs have been tested for minor adverse effects. The multidisciplinary team and the nurse are fundamental, both in the clinical care and in the organization; an emphasis was put on the correct patients' information. Quality of life after CAR-T treatment is still poorly investigated. CONCLUSIONS: The knowledge on CAR-T is in continuous and rapid growth and several questions are still without answer, requiring a continuous update of the transplant centres.

[Cytokine release syndrome in a patients treated with CAR-T cells therapy: a case report]. / Sindrome da rilascio di citochine in paziente sottoposto a CAR-T: un caso clinico.

This is the third contribution of a series of updates on oncological emergencies. The updates are published in the form of a case, with multiple-choice questions to assess knowledge, a brief discussion of the answer, and reference literature, to further explore. This case, which involves the management of a B-cell non-Hodgkin lymphoma, is accompanied by a more extensive update on CAR-T cell treatment.

Replicative DNA polymerases promote active displacement of SSB proteins during lagging strand synthesis.

Genome replication induces the generation of large stretches of single-stranded DNA (ssDNA) intermediates that are rapidly protected by single-stranded DNA-binding (SSB) proteins. To date, the mechanism by which tightly bound SSBs are removed from ssDNA by the lagging strand DNA polymerase without compromising the advance of the replication fork remains unresolved. Here, we aimed to address this question by measuring, with optical tweezers, the real-time replication kinetics of the human mitochondrial and bacteriophage T7 DNA polymerases on free-ssDNA, in comparison with ssDNA covered with homologous and non-homologous SSBs under mechanical tension. We find important differences between the force dependencies of the instantaneous replication rates of each polymerase on different substrates. Modeling of the data supports a mechanism in which strong, specific polymerase-SSB interactions, up to ∼12 kBT, are required for the polymerase to dislodge SSB from the template without compromising its instantaneous replication rate, even under stress conditions that may affect SSB-DNA organization and/or polymerase-SSB communication. Upon interaction, the elimination of template secondary structure by SSB binding facilitates the maximum replication rate of the lagging strand polymerase. In contrast, in the absence of polymerase-SSB interactions, SSB poses an effective barrier for the advance of the polymerase, slowing down DNA synthesis.

Comparative study of overweight and obese patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the western world. Although NAFLD prevalence is higher in patients with a BMI > 25 kg /m2, it is unclear if there are differences between overweight and obese patients. The associated biochemical, dietary and genetic parameters were compared between overweight and obese patients with NAFLD. METHODS: patients with biopsy-proven NAFLD (n = 203) were enrolled in a cross-sectional study. The MEDAS questionnaire was used to assess adherence to the Mediterranean diet. Biochemical, anthropometrical parameters and the I148M variant (rs738409) of the PNPLA3 gene and rs180069 of the TNF-α gene were evaluated. RESULTS: overweight patients had higher serum adiponectin levels (22.5 ± 21.9 vs 11.2 ± 18.1 ng/ml; p < 0.05) and lower resistin (3.3 ± 1.7 vs 8.1 ± 8 ng/ml; p < 0.001) and leptin concentrations (22.9 ± 21.9 vs 55.8 ± 45 ng/ml; p < 0.001) than obese patients. Non-alcoholic steatohepatitis (NASH) was more frequent in the obese group (59.3% vs 41.3%; p = 0.02). The multivariate analysis showed adherence to the Mediterranean diet to be an independent protective factor for NASH and liver fibrosis in overweight patients (OR 0.7, 95% CI 0.5-0.8). CONCLUSIONS: NASH was more prevalent in obese patients than in overweight subjects. HOMA-IR and adherence to the Mediterranean diet provided protection against fibrosis in overweight patients. Adherence to the Mediterranean diet was the only independent factor associated with NASH in these patients.

Immunomodulation in Vascularized Composite Allotransplantation: What Is the Role for Adipose-Derived Stem Cells?

Hand and face transplants are becoming increasingly common, recording progressively more penile, uterus, abdominal wall, and allotransplantation cases reported worldwide. Despite current protocols allow long-term survival of the allografts, the ultimate goal of donor-specific tolerance has not been achieved yet. In fact, the harmful adverse effects related to the lifelong administration of immunosuppressive agents are the main drawbacks for vascularized composite allotransplantations. Research is very active in investigating alternative methods to induce greater tolerance while minimizing toxicity. Adipose-derived stem cells (ASCs) represent promising cell therapies for immunomodulation in preclinical and clinical settings. Their clinical appeal is due to their easy harvest in large quantities through a noninvasive and well-accepted approach; they may well promote donor-specific tolerance and potentially reduce immunosuppression. Several experimental studies exist, but lacking review articles reporting current evidence. This work proposes a literature review on the immunomodulatory role of ASCs in vascularized composite allotransplantations. In vitro and in vivo evidence will be summarized. The role that cell passaging and upstream progenitors-the so-called spheroid ASCs-may play in modulating the immune response will also be discussed. Finally, this article will summarize current knowledge on biodistribution, migration, and homing of injected stem cells. This review may well provide useful information for preclinical and clinical studies, aiming at a breakthrough for donor-specific tolerance.

Can sentinel node biopsy be safely omitted in thin melanoma? Risk factor analysis of 1272 multicenter prospective cases.

BACKGROUND: The indication to sentinel node biopsy (SNB) for thin melanomas (Breslow <1 mm) is still subject to controversies. The aim of this paper is to review all SNB performed for thin melanoma and to analyze factors related to lymphatic metastasis. Moreover, the diagnostic performance of the 5th, 6th, 7th and 8th AJCC classifications for cutaneous melanoma were investigated. METHODS: All sentinel node biopsies performed for thin melanomas were selected from a multicentre prospectively-collected database. For each patient the following was collected: age, sex, date of treatment, site of primary melanoma, histopathologic features (Breslow, Clark, number of mitoses/mm2, presence of ulceration) and the results of the sentinel node biopsy. RESULTS: From 1998 to 2017 were performed a total of 1272 SNB for thin melanoma. Mean age was 51years with 48.7% of male patients. Overall, 5.6% positive SNB were found. At univariate and multivariate analyses, Breslow thickness and ulceration were related to the presence of lymphatic metastasis. We compared the four versions of the AJCC classification: among pT1a patients there were respectively 5.32%, 5.63%, 3.72% and 3.49% of positive SNB. CONCLUSIONS: in thin melanoma Breslow thickness and ulceration were the only factors related to a positive SNB. Although convincing improvements resulted from the implementation of AJCC classifications with a reduction of positive biopsies among pT1a, a 10.71% rate among all positive nodes remains in the low-risk group. No recommendations can be drawn from this research and adjunctive evidences are needed to better identify patients at risk of nodal metastasis.

Dynamics of individual molecular shuttles under mechanical force.

Molecular shuttles are the basis of some of the most advanced synthetic molecular machines. In these devices a macrocycle threaded onto a linear component shuttles between different portions of the thread in response to external stimuli. Here, we use optical tweezers to measure the mechanics and dynamics of individual molecular shuttles in aqueous conditions. Using DNA as a handle and as a single molecule reporter, we measure thousands of individual shuttling events and determine the force-dependent kinetic rates of the macrocycle motion and the main parameters governing the energy landscape of the system. Our findings could open avenues for the real-time characterization of synthetic devices at the single molecule level, and provide crucial information for designing molecular machinery able to operate under physiological conditions.

Single-Stranded Condensation Stochastically Blocks G-Quadruplex Assembly in Human Telomeric RNA.

TERRA is an RNA molecule transcribed from human subtelomeric regions toward chromosome ends potentially involved in regulation of heterochromatin stability, semiconservative replication, and telomerase inhibition, among others. TERRA contains tandem repeats of the sequence GGGUUA, with a strong tendency to fold into a four-stranded arrangement known as a parallel G-quadruplex. Here, we demonstrate by using single-molecule force spectroscopy that this potential is limited by the inherent capacity of RNA to self-associate randomly and further condense into entropically more favorable structures. We stretched RNA constructions with more than four and less than eight hexanucleotide repeats, thus unable to form several G-quadruplexes in tandem, flanked by non-G-rich overhangs of random sequence by optical tweezers on a one by one basis. We found that condensed RNA stochastically blocks G-quadruplex folding pathways with a near 20% probability, a behavior that is not found in DNA analogous molecules.